gene_symbol uniprot_acc class ground_truth_verdict ground_truth_signal ground_truth_reason rationale hgnc_id hgnc_symbol ncbi_gene_id ensembl_gene ensembl_canonical_protein n_db_votes sonnet_verdict sonnet_reason CD19 P15391 validated_positive yes likely_accessible classical_surface_receptor Approved CAR-T + ADC; classical B-cell surface marker HGNC:1633 CD19 930 ENSG00000177455 ENSP00000313419.4 4 yes classical_surface_receptor FOLR1 P15328 validated_positive yes likely_accessible gpi_anchored Approved Mirvetuximab (ELAHERE); GPI-anchored on outer leaflet HGNC:3791 FOLR1 2348 ENSG00000110195 ENSP00000308137.4 4 yes gpi_anchored MUC1 P15941 disagreement_rich_positive yes likely_accessible classical_surface_receptor TROP-2-adjacent validated tumor antigen; large mucin ECD; multiple antibody programs HGNC:7508 MUC1 4582 ENSG00000185499 ENSP00000338983.5 4 yes classical_surface_receptor CD74 P04233 disagreement_rich_positive yes likely_accessible classical_surface_receptor Invariant chain on B/dendritic cell surface; clinical-stage Milatuzumab ADC HGNC:1697 CD74 972 ENSG00000019582 ENSP00000009530.7 4 yes classical_surface_receptor PMEL P40967 dual_localization_borderline contextual possibly_accessible dual_localization Single-pass type I TM glycoprotein with a large extracellular domain. Canonical residence is melanosomal (lysosome-related organelle), but the protein transits the PM during melanosome biogenesis and surface biotinylation / flow cytometry / HMB-45 IHC detect a minority PM pool on melanocytes and melanoma cells — gene-specific evidence for `contextual / dual_localization`. The separate tebentafusp / gp100·HLA pMHC story does not affect this verdict either way (pMHC is not credited for protein-body surface accessibility, but PMEL has its own documented PM transit independent of MHC presentation). HGNC:10880 PMEL 6490 ENSG00000185664 ENSP00000402758.2 2 contextual dual_localization SLC34A2 O95436 disagreement_rich_positive yes likely_accessible multipass_with_exposed_loops Apical phosphate transporter; clinical Lifastuzumab vedotin ADC HGNC:11020 SLC34A2 10568 ENSG00000157765 ENSP00000371483.3 4 yes multipass_with_exposed_loops PRAME P78395 pmhc_only_negative no unlikely pmhc_only_intracellular Cancer-testis antigen; intracellular at baseline. Clinical T-cell engagers (brenetafusp / IMC-F106C) target the HLA-A*02-restricted peptide, but the protein body is not surface — `no` / `pmhc_only_intracellular`. HGNC:9336 PRAME 23532 ENSG00000185686 ENSP00000381726.1 1 no pmhc_only_intracellular CALR P27797 induced_borderline contextual possibly_accessible cell_state_induced ER-resident at baseline; reaches outer leaflet during immunogenic cell death HGNC:1455 CALR 811 ENSG00000179218 ENSP00000320866.4 3 contextual cell_state_induced HSPA1A P0DMV8 induced_borderline contextual possibly_accessible cell_state_induced Cytoplasmic at baseline; tumor-stress-induced surface presentation HGNC:5232 HSPA1A 3303 ENSG00000204389 ENSP00000364802.5 0 contextual cell_state_induced HSPA5 P11021 induced_borderline contextual possibly_accessible cell_state_induced ER chaperone at baseline; ER-stress/oncogenic-state translocation to outer leaflet HGNC:5238 HSPA5 3309 ENSG00000044574 ENSP00000324173.6 1 contextual cell_state_induced KRAS P01116 wrong_side_negative no unlikely inner_leaflet_anchored "Membrane-anchored on the cytoplasmic face; tests ""membrane = surface"" trap" HGNC:6407 KRAS 3845 ENSG00000133703 ENSP00000256078.5 1 no inner_leaflet_anchored LAMP1 P11279 induced_borderline contextual possibly_accessible lysosomal_exocytosis Classical lysosomal membrane glycoprotein; reaches plasma membrane via lysosomal exocytosis (CD107a degranulation marker on NK / cytotoxic T cells, surface staining on metastatic tumor cells). Conditional surfacing puts it in the contextual class. HGNC:6499 LAMP1 3916 ENSG00000185896 ENSP00000333298.4 2 contextual lysosomal_exocytosis ABCB9 Q9NP78 wrong_compartment_negative no unlikely endomembrane_resident Polytopic TM but lysosomal; TM topology does not imply PM accessibility HGNC:50 ABCB9 23457 ENSG00000150967 ENSP00000280560.8 1 contextual lysosomal_exocytosis APPL1 Q9UKG1 opencell_vesicle_negative no unlikely endomembrane_resident Imaged-confirmed signaling endosome; M1 false positive HGNC:24035 APPL1 26060 ENSG00000157500 ENSP00000288266.3 1 no cytoplasmic ATG9A Q7Z3C6 wrong_compartment_negative no unlikely endomembrane_resident Cycles between Golgi/endosomes/autophagosomal precursors; multi-pass TM but never PM in steady state HGNC:22408 ATG9A 79065 ENSG00000198925 ENSP00000355173.4 2 no endomembrane_resident TGOLN2 O43493 induced_borderline contextual possibly_accessible dual_localization TGN46 — **cycles continuously between TGN and PM** via the secretory recycling pathway; canonical marker for the TGN-PM trafficking cycle. Transient but routine surface presence. HGNC:15450 TGOLN2 10618 ENSG00000152291 ENSP00000366603.3 2 no endomembrane_resident STEAP1 Q9UHE8 disagreement_rich_positive yes possibly_accessible multipass_with_exposed_loops TCR-T + bispecific: GSK4427296 TCR-T + AMG509 bispecific. 6-pass TM with small ECLs — also tests minimal_ectoloops case HGNC:11378 STEAP1 26872 ENSG00000164647 ENSP00000297205.2 0 yes multipass_with_exposed_loops KLK2 P20151 disagreement_rich_positive contextual possibly_accessible tissue_restricted_surface KLK2 (hK2) — kallikrein-family secreted serine protease with no TM/GPI of its own. Surface accessibility is real but context-dependent: documented surface association on prostate epithelium and stable deposition on the sperm plasma membrane during seminal transit, plus PSMA-axis prostate-cell-surface co-targeting in clinical programs. Web-enabled triage runs across multiple models converge on contextual, never yes — the surface pool is tissue/cell-type restricted, not a canonical extracellular-face receptor. HGNC:6363 KLK2 3817 ENSG00000167751 ENSP00000313581.2 0 no secreted_only CLDN6 P56747 disagreement_rich_positive yes likely_accessible multipass_with_exposed_loops CAR-T + ADC + bispecific: BNT211 CAR-T (BioNTech), AMG794 bispecific, multiple ADCs. Tight-junction claudin HGNC:2048 CLDN6 9074 ENSG00000184697 ENSP00000328674.4 2 contextual cell_state_induced GPRC5D Q9NZD1 disagreement_rich_positive yes likely_accessible multipass_with_exposed_loops approved bispecific + CAR-T: Talquetamab approved 2023 (multiple myeloma); orphan GPCR HGNC:13310 GPRC5D 55507 ENSG00000111291 ENSP00000228887.1 2 yes multipass_with_exposed_loops GUCY2C P25092 disagreement_rich_positive yes likely_accessible classical_surface_receptor approved bispecific + ADC: M9140 ADC; multiple approved/clinical programs HGNC:4688 GUCY2C 2984 ENSG00000070019 ENSP00000261170.3 2 yes classical_surface_receptor PSCA O43653 disagreement_rich_positive yes likely_accessible gpi_anchored clinical CAR-T + ADC: Multiple PSCA programs; GPI-anchored HGNC:9500 PSCA 8000 ENSG00000167653 ENSP00000301258.4 2 yes gpi_anchored SEZ6 Q53EL9 disagreement_rich_positive yes likely_accessible classical_surface_receptor clinical ADC: ABBV-011 ADC (AbbVie SCLC) HGNC:15955 SEZ6 124925 ENSG00000063015 ENSP00000312942.11 2 contextual dual_localization FZD7 O75084 disagreement_rich_positive yes likely_accessible multipass_with_exposed_loops clinical mAb: Vantictumab (OMP-18R5, Ipsen/OncoMed); 7TM Wnt receptor HGNC:4045 FZD7 8324 ENSG00000155760 ENSP00000286201.1 2 yes multipass_with_exposed_loops LGR5 O75473 disagreement_rich_positive yes likely_accessible multipass_with_exposed_loops clinical ADC: Multiple Wnt-receptor ADC programs HGNC:4504 LGR5 8549 ENSG00000139292 ENSP00000266674.4 2 yes multipass_with_exposed_loops EFNA4 P52798 disagreement_rich_positive yes likely_accessible gpi_anchored clinical ADC: PF-06647263 ADC HGNC:3224 EFNA4 1945 ENSG00000243364 ENSP00000352789.4 2 yes gpi_anchored EREG O14944 disagreement_rich_positive contextual possibly_accessible dual_localization Epiregulin — EGF-family ligand. TM precursor transits PM transiently before ADAM/MMP shedding; dominant detected and biologically active form is the soluble shed ligand. Clinical anti-epiregulin mAb programs exist but target the shed soluble pool. HGNC:3443 EREG 2069 ENSG00000124882 ENSP00000244869.2 2 contextual dual_localization ROS1 P08922 disagreement_rich_positive yes likely_accessible classical_surface_receptor approved TKI + clinical ADC: Crizotinib/lorlatinib approved (small molecule); ADC programs in development HGNC:10261 ROS1 6098 ENSG00000047936 ENSP00000357494.3 2 yes classical_surface_receptor DLL3 Q9NYJ7 disagreement_rich_positive yes likely_accessible classical_surface_receptor approved bispecific: Tarlatamab/Imdelltra approved 2024 SCLC HGNC:2909 DLL3 10683 ENSG00000090932 ENSP00000205143.3 3 yes classical_surface_receptor ROR1 Q01973 disagreement_rich_positive yes likely_accessible classical_surface_receptor clinical CAR-T + ADC: Cirmtuzumab, Zilovertamab vedotin, Lyell CAR-T HGNC:10256 ROR1 4919 ENSG00000185483 ENSP00000360120.1 3 yes classical_surface_receptor ROR2 Q01974 disagreement_rich_positive yes likely_accessible classical_surface_receptor clinical ADC: BA3021 conditionally-active ADC (BioAtla) HGNC:10257 ROR2 4920 ENSG00000169071 ENSP00000364860.3 3 yes classical_surface_receptor CCR8 P51685 disagreement_rich_positive yes likely_accessible multipass_with_exposed_loops clinical mAb: Multiple anti-CCR8 mAb programs (Treg depletion) HGNC:1609 CCR8 1237 ENSG00000179934 ENSP00000326432.4 3 yes multipass_with_exposed_loops EPHB4 P54760 disagreement_rich_positive yes likely_accessible classical_surface_receptor clinical mAb: Soluble EphB4 fusion programs HGNC:3395 EPHB4 2050 ENSG00000196411 ENSP00000350896.3 3 yes classical_surface_receptor FLT3 P36888 disagreement_rich_positive yes likely_accessible classical_surface_receptor clinical ADC + CAR-T: AMG553 CAR-T, FLT3xCD3 bispecifics HGNC:3765 FLT3 2322 ENSG00000122025 ENSP00000241453.7 3 yes classical_surface_receptor GFRA1 P56159 disagreement_rich_positive yes likely_accessible gpi_anchored clinical ADC: Multiple GFRalpha-1 ADC programs HGNC:4243 GFRA1 2674 ENSG00000151892 ENSP00000347591.6 3 yes gpi_anchored GPNMB Q14956 disagreement_rich_positive yes likely_accessible classical_surface_receptor clinical ADC: Glembatumumab vedotin (Celldex) HGNC:4462 GPNMB 10457 ENSG00000136235 ENSP00000258733.5 3 yes classical_surface_receptor FZD10 Q9ULW2 disagreement_rich_positive yes likely_accessible multipass_with_exposed_loops clinical mAb: OTSA101-DTPA (radioimmunoconjugate) HGNC:4039 FZD10 11211 ENSG00000111432 ENSP00000229030.4 3 yes multipass_with_exposed_loops ADORA3 P0DMS8 gpcr_extracellular_pocket yes likely_accessible multipass_with_exposed_loops clinical small molecule: Adenosine A3 receptor; multiple clinical programs HGNC:268 ADORA3 140 ENSG00000282608 ENSP00000241356.4 1 yes multipass_with_exposed_loops GIPR P48546 gpcr_extracellular_pocket yes likely_accessible multipass_with_exposed_loops approved peptide drug: Tirzepatide (GIP/GLP-1 dual agonist) approved HGNC:4271 GIPR 2696 ENSG00000010310 ENSP00000263281.3 2 yes multipass_with_exposed_loops GCGR P47871 gpcr_extracellular_pocket yes likely_accessible multipass_with_exposed_loops clinical peptide drug: Multiple glucagon receptor programs HGNC:4192 GCGR 2642 ENSG00000215644 ENSP00000383558.3 2 yes multipass_with_exposed_loops HTR2C P28335 gpcr_extracellular_pocket yes likely_accessible multipass_with_exposed_loops approved small molecule: Lorcaserin (was approved); 7TM serotonin receptor HGNC:5295 HTR2C 3358 ENSG00000147246 ENSP00000276198.1 2 yes multipass_with_exposed_loops MC1R Q01726 gpcr_extracellular_pocket yes likely_accessible multipass_with_exposed_loops approved peptide: Afamelanotide (Scenesse) approved; melanocortin HGNC:6929 MC1R 4157 ENSG00000258839 ENSP00000451605.1 2 yes multipass_with_exposed_loops GPBAR1 Q8TDU6 gpcr_extracellular_pocket yes likely_accessible multipass_with_exposed_loops clinical small molecule: Bile acid receptor TGR5; multiple programs HGNC:19680 GPBAR1 151306 ENSG00000179921 ENSP00000430698.1 2 yes multipass_with_exposed_loops BDKRB1 P46663 gpcr_extracellular_pocket yes likely_accessible multipass_with_exposed_loops clinical small molecule: Bradykinin B1 receptor; multiple programs HGNC:1029 BDKRB1 623 ENSG00000100739 ENSP00000216629.6 2 yes multipass_with_exposed_loops HRH2 P25021 gpcr_extracellular_pocket yes likely_accessible multipass_with_exposed_loops approved small molecule: H2 receptor (ranitidine/famotidine class) HGNC:5183 HRH2 3274 ENSG00000113749 ENSP00000366506.2 2 yes multipass_with_exposed_loops NPY5R Q15761 gpcr_extracellular_pocket yes likely_accessible multipass_with_exposed_loops clinical small molecule: Neuropeptide Y receptor 5; obesity programs HGNC:7958 NPY5R 4889 ENSG00000164129 ENSP00000339377.3 2 yes multipass_with_exposed_loops GRM4 Q14833 gpcr_extracellular_pocket yes likely_accessible multipass_with_exposed_loops clinical small molecule: Metabotropic glutamate receptor 4; CNS programs HGNC:4596 GRM4 2914 ENSG00000124493 ENSP00000363292.3 2 yes multipass_with_exposed_loops AVPR1A P37288 gpcr_extracellular_pocket yes likely_accessible multipass_with_exposed_loops clinical small molecule: Vasopressin V1A receptor; conivaptan family HGNC:895 AVPR1A 552 ENSG00000166148 ENSP00000299178.3 2 yes multipass_with_exposed_loops SRC P12931 wrong_side_borderline contextual possibly_accessible cell_state_induced Proto-oncogene tyrosine kinase; canonically myristoylated/palmitoylated to inner leaflet (cytoplasmic face). Ecto-SRC has been reported on cancer cell surfaces (melanoma, other tumors) — borderline conditional/pathological surfacing. M1 votes 3/6. HGNC:11283 SRC 6714 ENSG00000197122 ENSP00000350941.5 2 no inner_leaflet_anchored RHOA P61586 wrong_side_negative no unlikely inner_leaflet_anchored Rho GTPase; geranylgeranylated to inner leaflet. Cytoplasmic signaling. HGNC:667 RHOA 387 ENSG00000067560 ENSP00000400175.1 2 no inner_leaflet_anchored GNAQ P50148 wrong_side_negative no unlikely inner_leaflet_anchored Heterotrimeric G-alpha-q; lipidated cytoplasmic-side anchor. HGNC:4390 GNAQ 2776 ENSG00000156052 ENSP00000286548.4 2 no inner_leaflet_anchored GNB1 P62873 wrong_side_negative no unlikely inner_leaflet_anchored G-protein beta-1 subunit; peripheral on inner leaflet via Gγ prenylation. HGNC:4396 GNB1 2782 ENSG00000078369 ENSP00000367872.3 2 no inner_leaflet_anchored LYN P07948 wrong_side_borderline no possibly_accessible inner_leaflet_anchored Src-family tyrosine kinase; canonically inner-leaflet myristoylated/palmitoylated. **Cell-surface LYN reported on B cells and in some cancer contexts**, parallel to ecto-SRC. Borderline pathological surfacing. HGNC:6735 LYN 4067 ENSG00000254087 ENSP00000428924.1 2 no inner_leaflet_anchored HCK P08631 wrong_side_negative no unlikely inner_leaflet_anchored Hematopoietic cell kinase (Src family); inner-leaflet lipid-anchored. HGNC:4840 HCK 3055 ENSG00000101336 ENSP00000365012.3 2 no inner_leaflet_anchored NRAS P01111 wrong_side_negative no unlikely inner_leaflet_anchored Ras GTPase; lipidated inner leaflet (same family as KRAS in benchmark). HGNC:7989 NRAS 4893 ENSG00000213281 ENSP00000358548.4 1 no inner_leaflet_anchored RAC1 P63000 wrong_side_negative no unlikely inner_leaflet_anchored Rac1 GTPase; geranylgeranylated to inner leaflet. HGNC:9801 RAC1 5879 ENSG00000136238 ENSP00000258737.7 1 no inner_leaflet_anchored RPN1 P04843 wrong_compartment_negative no unlikely endomembrane_resident Ribophorin 1; ER membrane subunit of OST glycosylation complex. HGNC:10381 RPN1 6184 ENSG00000163902 ENSP00000296255.3 2 no endomembrane_resident RPN2 P04844 wrong_compartment_negative no unlikely endomembrane_resident Ribophorin 2; ER membrane subunit of OST. HGNC:10382 RPN2 6185 ENSG00000118705 ENSP00000237530.6 1 no endomembrane_resident SCAP Q12770 wrong_compartment_negative no unlikely endomembrane_resident SREBP cleavage-activating protein; ER cholesterol sensor. HGNC:30634 SCAP 22937 ENSG00000114650 ENSP00000265565.5 2 no endomembrane_resident ITPR3 Q14573 wrong_compartment_negative no unlikely endomembrane_resident IP3 receptor type 3; ER membrane calcium channel. HGNC:6182 ITPR3 3710 ENSG00000096433 ENSP00000363435.4 2 no endomembrane_resident ITPR1 Q14643 wrong_compartment_negative no unlikely endomembrane_resident IP3 receptor type 1; ER membrane calcium channel. HGNC:6180 ITPR1 3708 ENSG00000150995 ENSP00000349597.4 1 no endomembrane_resident SEC61G P60059 wrong_compartment_negative no unlikely endomembrane_resident Sec61 translocon γ subunit; ER protein-translocation channel. HGNC:18277 SEC61G 23480 ENSG00000132432 ENSP00000341538.4 1 no endomembrane_resident B4GALT1 P15291 induced_borderline contextual possibly_accessible tissue_restricted_surface β-1,4-galactosyltransferase 1; primarily Golgi-resident, but **a cell-surface form on sperm mediates zona pellucida adhesion**; also reported on tumor cells. Conditional/cell-type-restricted surfacing. HGNC:924 B4GALT1 2683 ENSG00000086062 ENSP00000369055.4 2 contextual dual_localization TMED9 Q9BVK6 wrong_compartment_negative no unlikely endomembrane_resident TMED9 p24-family cargo receptor; ER ↔ ERGIC ↔ cis-Golgi cycling for traffic of GPI-anchored cargo. Golgi-residence dominant; no documented stable PM pool. Adversarial M1 hit testing whether secretory-pathway cycling is conflated with PM accessibility. HGNC:24878 TMED9 54732 ENSG00000184840 ENSP00000330945.6 1 no endomembrane_resident TMED10 P49755 dual_localization_borderline contextual possibly_accessible dual_localization TMED10 p24-family cargo receptor — same ER-Golgi cycling pattern as TMED9 but with documented minority PM pool from secretory cycling and reports of cell-surface display in some cancer contexts. Distinguishable from TMED9 by the more frequent surface-detection reports; dual-localization with Golgi-dominant residence + minority PM fraction qualifies for contextual / dual_localization. HGNC:16998 TMED10 10972 ENSG00000170348 ENSP00000303145.4 1 contextual dual_localization GALNT1 Q10472 wrong_compartment_negative no unlikely endomembrane_resident N-acetylgalactosaminyltransferase 1; Golgi glycosyltransferase. HGNC:4123 GALNT1 2589 ENSG00000141429 ENSP00000269195.4 1 no endomembrane_resident NUP210 Q8TEM1 wrong_compartment_negative no unlikely nuclear_envelope Nuclear pore complex transmembrane component; nuclear envelope. HGNC:30052 NUP210 23225 ENSG00000132182 ENSP00000254508.5 2 no nuclear_envelope SUN1 O94901 wrong_compartment_negative no unlikely nuclear_envelope SUN domain protein 1; inner nuclear membrane (LINC complex). HGNC:18587 SUN1 23353 ENSG00000164828 ENSP00000374225.3 1 no nuclear_envelope SUN2 Q9UH99 wrong_compartment_negative no unlikely nuclear_envelope SUN domain protein 2; inner nuclear membrane. HGNC:14210 SUN2 25777 ENSG00000100242 ENSP00000385616.1 1 no nuclear_envelope SYNE1 Q8NF91 wrong_compartment_negative no unlikely nuclear_envelope Nesprin-1; outer nuclear membrane (LINC complex), cytoskeleton-coupled. HGNC:17089 SYNE1 23345 ENSG00000131018 ENSP00000356222.4 1 no nuclear_envelope SYNE2 Q8WXH0 wrong_compartment_negative no unlikely nuclear_envelope Nesprin-2; outer nuclear membrane. HGNC:17084 SYNE2 23224 ENSG00000054654 ENSP00000344528.5 1 no nuclear_envelope VDAC1 P21796 induced_borderline contextual possibly_accessible dual_localization Mitochondrial outer-membrane porin; **plasma-membrane VDAC1 (pl-VDAC) is well-documented** in B cells, neurons, sperm, cancer cells, erythrocytes. Anti-VDAC1 antibodies in development. Borderline due to dual-localization. HGNC:12669 VDAC1 7416 ENSG00000213585 ENSP00000265333.3 1 contextual dual_localization BAX Q07812 induced_borderline no possibly_accessible cytoplasmic Pro-apoptotic Bcl-2 family; canonically translocates to mitochondrial outer membrane during apoptosis. **Surface BAX has been reported as an apoptotic-cell marker** (parallel to CALR's ICD-induced surface translocation). HGNC:959 BAX 581 ENSG00000087088 ENSP00000293288.8 1 no cytoplasmic TGFB1 P01137 surface_attachment_borderline contextual possibly_accessible stable_surface_attachment TGF-β1 is secreted as a precursor cleaved into LAP + mature TGF-β1 (small latent complex). On Tregs / platelets the complex is **covalently disulfide-bonded to surface GARP (LRRC32)** via specific intermolecular cysteine pairs, co-trafficked from the ER as a single unit. Livmoniplimab (ABBV-151) is a clinical antibody specifically targeting the GARP:latent-TGF-β1 complex. Covalent surface attachment is the right mechanism category. HGNC:11766 TGFB1 7040 ENSG00000105329 ENSP00000221930.4 3 contextual stable_surface_attachment C3 P01024 surface_attachment_borderline contextual possibly_accessible stable_surface_attachment Complement C3 secreted plasma protein; cleavage fragment **C3b is covalently deposited on cell surfaces during opsonization**. Borderline because C3 itself is soluble but its activation product is surface-anchored. HGNC:1318 C3 718 ENSG00000125730 ENSP00000245907.4 2 no secreted_only TF P02787 secreted_negative no unlikely secreted_only Transferrin; secreted iron-transport plasma protein. HGNC:11740 TF 7018 ENSG00000091513 ENSP00000385834.3 2 no secreted_only IL6 P05231 secreted_negative no unlikely secreted_only Interleukin-6; secreted cytokine. HGNC:6018 IL6 3569 ENSG00000136244 ENSP00000258743.5 1 no secreted_only IGF1 P05019 secreted_negative no unlikely secreted_only Insulin-like growth factor 1; secreted hormone. HGNC:5464 IGF1 3479 ENSG00000017427 ENSP00000302665.8 1 no secreted_only F2 P00734 secreted_negative no unlikely secreted_only Prothrombin secreted coagulation zymogen. Recruits to activated-platelet surfaces during prothrombinase-complex assembly via Gla-domain binding to phosphatidylserine, but **the protein has no membrane anchor of its own** — surface association is via Ca²⁺-dependent reversible binding, not membrane insertion. Recruitment ≠ surface accessibility. HGNC:3535 F2 2147 ENSG00000180210 ENSP00000308541.5 2 no secreted_only FN1 P02751 secreted_negative contextual unlikely stable_surface_attachment Fibronectin secreted ECM glycoprotein. Forms cell-surface fibronectin matrix via integrin α5β1 binding (recruitment), and EDB-fibronectin antibodies target tumor-stromal fibronectin, but **the protein has no membrane anchor of its own** — it's a soluble protein that binds surface receptors. Recruitment ≠ surface accessibility. HGNC:3778 FN1 2335 ENSG00000115414 ENSP00000323534.6 1 contextual stable_surface_attachment APOB P04114 secreted_negative no unlikely secreted_only Apolipoprotein B-100; secreted on lipoprotein particles. HGNC:603 APOB 338 ENSG00000084674 ENSP00000233242.1 1 no secreted_only VEGFA P15692 secreted_negative no unlikely secreted_only Vascular endothelial growth factor A; secreted angiogenic factor. HGNC:12680 VEGFA 7422 ENSG00000112715 ENSP00000317598.7 1 no secreted_only A2M P01023 secreted_negative no unlikely secreted_only α2-macroglobulin; secreted plasma protease inhibitor. HGNC:7 A2M 2 ENSG00000175899 ENSP00000323929.8 1 no secreted_only JAK3 P52333 approved_drug_intracellular_negative no unlikely cytoplasmic JAK3 tyrosine kinase; cytoplasmic (associates with γc of cytokine receptors). Tofacitinib target. HGNC:6193 JAK3 3718 ENSG00000105639 ENSP00000391676.1 2 no cytoplasmic SYK P43405 approved_drug_intracellular_negative no unlikely cytoplasmic Spleen tyrosine kinase; cytoplasmic. Fostamatinib target. HGNC:11491 SYK 6850 ENSG00000165025 ENSP00000364898.1 2 no cytoplasmic BRAF P15056 approved_drug_intracellular_negative no unlikely cytoplasmic "B-Raf serine/threonine kinase; cytoplasmic. **Vemurafenib/dabrafenib approved**. Tests ""approved drug ⇒ surface"" trap." HGNC:1097 BRAF 673 ENSG00000157764 ENSP00000493543.1 1 no cytoplasmic BTK Q06187 approved_drug_intracellular_negative no unlikely cytoplasmic Bruton's tyrosine kinase; cytoplasmic. **Ibrutinib approved**. HGNC:1133 BTK 695 ENSG00000010671 ENSP00000308176.8 1 no inner_leaflet_anchored JAK1 P23458 approved_drug_intracellular_negative no unlikely cytoplasmic JAK1 tyrosine kinase; cytoplasmic. Multiple approved JAK inhibitors. HGNC:6190 JAK1 3716 ENSG00000162434 ENSP00000343204.4 1 no inner_leaflet_anchored JAK2 O60674 approved_drug_intracellular_negative no unlikely cytoplasmic JAK2 tyrosine kinase; cytoplasmic. **Ruxolitinib approved** (myelofibrosis). HGNC:6192 JAK2 3717 ENSG00000096968 ENSP00000371067.4 1 no inner_leaflet_anchored TYK2 P29597 approved_drug_intracellular_negative no unlikely cytoplasmic TYK2 tyrosine kinase; cytoplasmic. Deucravacitinib approved (psoriasis). HGNC:12440 TYK2 7297 ENSG00000105397 ENSP00000431885.1 1 no cytoplasmic AKT2 P31751 approved_drug_intracellular_negative no unlikely cytoplasmic AKT2 serine/threonine kinase; cytoplasmic. Capivasertib clinical/approved. HGNC:392 AKT2 208 ENSG00000105221 ENSP00000309428.6 1 no inner_leaflet_anchored MAP2K1 Q02750 approved_drug_intracellular_negative no unlikely cytoplasmic MEK1 kinase; cytoplasmic. **Cobimetinib/trametinib approved**. HGNC:6840 MAP2K1 5604 ENSG00000169032 ENSP00000302486.5 1 no cytoplasmic MAP2K2 P36507 approved_drug_intracellular_negative no unlikely cytoplasmic MEK2 kinase; cytoplasmic. HGNC:6842 MAP2K2 5605 ENSG00000126934 ENSP00000262948.4 1 no cytoplasmic HDAC6 Q9UBN7 approved_drug_intracellular_negative no unlikely cytoplasmic Histone deacetylase 6; cytoplasmic/perinuclear with no membrane anchor. 'Extracellular HDAC6' reports are mostly vesicular cargo (in EVs, not cell-surface accessible) or recruitment-style binding. **No own membrane anchor** — recruitment ≠ surface accessibility. Multiple clinical small-molecule inhibitors target the intracellular catalytic pocket. HGNC:14064 HDAC6 10013 ENSG00000094631 ENSP00000334061.5 1 no cytoplasmic IKBKB O14920 approved_drug_intracellular_negative no unlikely cytoplasmic IKK-β; cytoplasmic. Multiple clinical NF-κB-pathway programs. HGNC:5960 IKBKB 3551 ENSG00000104365 ENSP00000430684.1 1 no cytoplasmic LRRK2 Q5S007 approved_drug_intracellular_negative no unlikely cytoplasmic LRRK2 kinase; cytoplasmic/peripheral. **Parkinson's clinical programs**. HGNC:18618 LRRK2 120892 ENSG00000188906 ENSP00000298910.7 1 no cytoplasmic STIM1 Q13586 induced_borderline contextual possibly_accessible dual_localization ER calcium sensor; canonically ER-resident, but **clusters at ER-PM junctions during store-operated calcium entry (SOCE)**; some PM staining reports. Borderline due to ER-PM junction localization. HGNC:11386 STIM1 6786 ENSG00000167323 ENSP00000300737.4 4 yes classical_surface_receptor TFRC P02786 disagreement_rich_positive yes likely_accessible classical_surface_receptor Transferrin receptor 1 (CD71); classical iron-uptake receptor; **multiple clinical antibody programs** (CX-2029 EpCAM-conditional ADC, TROP-2/TFRC dual-targeting), plus the standard transferrin-conjugate brain-shuttle approaches. Type II single-pass TM with large ECD. Missed by SURFY and HPA despite being a canonical surface receptor. HGNC:11763 TFRC 7037 ENSG00000072274 ENSP00000353224.4 3 yes classical_surface_receptor B2M P61769 stable_complex_positive yes likely_accessible stable_complex_partner β2-microglobulin; structural light chain of MHC class I (and CD1 family). **No anchor of its own**, but is stably present on the surface of every nucleated cell as the non-covalent partner of TM-anchored MHC-I heavy chain — assembled in the ER and co-trafficked. Canonical example of accessibility via stable complex partnership. Clinical anti-B2M programs exist (historical mAb work, current B2M-directed CAR-T approaches in multiple myeloma). HGNC:914 B2M 567 ENSG00000166710 ENSP00000453350.1 3 yes stable_complex_partner LRRC32 Q14392 disagreement_rich_positive yes likely_accessible classical_surface_receptor GARP — single-pass type I TM glycoprotein with a large LRR extracellular domain. Restricted expression on Tregs and platelets. Anchors latent TGF-β1 to the cell surface via covalent disulfide bonds. Clinical antibody program: **livmoniplimab (ABBV-151)** targets the GARP:latent-TGF-β1 complex in solid-tumor combination trials with anti-PD1. HGNC:4161 LRRC32 2615 ENSG00000137507 ENSP00000260061.5 4 yes classical_surface_receptor LAMP2 P13473 induced_borderline contextual possibly_accessible lysosomal_exocytosis Second canonical lysosomal membrane glycoprotein (CD107b). Reaches the PM via lysosomal exocytosis on activated cytotoxic lymphocytes / NK cells — same conditional-surfacing mechanism as LAMP1. Surface staining is a marker of degranulation. HGNC:6501 LAMP2 3920 ENSG00000005893 ENSP00000200639.4 3 contextual lysosomal_exocytosis OR1A1 Q9P1Q5 disagreement_rich_positive yes likely_accessible multipass_with_exposed_loops Olfactory receptor 1A1 — classical 7TM rhodopsin-family GPCR. Stably surface on olfactory sensory neurons (and reported in some ectopic-expression contexts). Expression is tissue-restricted to a specialized cell type but the surface architecture is unambiguous when expressed. HGNC:8179 OR1A1 8383 ENSG00000172146 ENSP00000492897.1 2 yes multipass_with_exposed_loops DSG3 P32926 disagreement_rich_positive yes likely_accessible classical_surface_receptor Desmoglein 3 — single-pass type I TM cadherin in desmosomes of basal keratinocytes and oral mucosa. **Pemphigus vulgaris autoantigen** — patient autoantibodies bind cell-surface DSG3 on keratinocytes (validation of surface accessibility). Tissue-restricted expression. HGNC:3050 DSG3 1830 ENSG00000134757 ENSP00000257189.4 3 yes classical_surface_receptor GYPA P02724 disagreement_rich_positive yes likely_accessible classical_surface_receptor Glycophorin A (MNS blood group antigen) — single-pass type I TM sialoglycoprotein on the erythrocyte surface. Classical surface architecture; RBC-restricted expression. Targeted by anti-GYPA in blood-group serology and as an RBC marker in clinical immunology. HGNC:4702 GYPA 2993 ENSG00000170180 ENSP00000324483.10 3 yes classical_surface_receptor PRNP P04156 gpi_anchored_positive yes likely_accessible gpi_anchored Cellular prion protein — canonical GPI-anchored outer-leaflet protein, abundant on neurons. Dominant localization is the plasma membrane; intracellular pools are routine biosynthesis / endolysosomal recycling. Anti-PRNP antibodies recognize the surface form clinically; conformational variant PrP^Sc is the disease antigen. HGNC:9449 PRNP 5621 ENSG00000171867 ENSP00000368752.4 3 yes gpi_anchored NRROS Q86YC3 disagreement_rich_positive yes likely_accessible classical_surface_receptor NRROS (legacy alias LRRC33) — single-pass type I TM glycoprotein with a large LRR extracellular domain on myeloid cells (microglia, monocytes); the myeloid-cell analog of GARP / LRRC32 on Tregs. Anchors latent TGF-β1 to the cell surface via covalent disulfide bonds; clinical antibody programs target the NRROS:latent-TGF-β1 complex in CNS / myeloid contexts. HGNC:24613 NRROS 375387 ENSG00000174004 ENSP00000328625.4 3 contextual tissue_restricted_surface HSPD1 P10809 dual_localization_borderline contextual possibly_accessible dual_localization HSP60 — canonically mitochondrial matrix chaperonin. **Reported on the cell surface** in tumor cells, stress contexts, and as a damage-associated molecular pattern (DAMP). Mechanism of surface translocation is debated (chaperone export, mitochondrial leakage, vesicular). Tests whether the model recognizes the minority-surface dual-localization pattern. HGNC:5261 HSPD1 3329 ENSG00000144381 ENSP00000340019.2 1 contextual cell_state_induced MSLN Q13421 gpi_anchored_positive yes likely_accessible gpi_anchored Mesothelin — GPI-anchored on the outer leaflet of mesothelial cells and overexpressed in mesothelioma / ovarian / pancreatic / lung adenocarcinoma. Clinical anti-MSLN ADC (anetumab ravtansine), CAR-T, and bispecific programs. 4/7 surface DB sources flag it; classical GPI mechanism. HGNC:7371 MSLN 10232 ENSG00000102854 ENSP00000372313.3 4 yes gpi_anchored CEACAM5 P06731 gpi_anchored_positive yes likely_accessible gpi_anchored Carcinoembryonic antigen (CEA) — GPI-anchored, oncofetal surface antigen on epithelial tumors. Tusamitamab ravtansine (anti-CEACAM5 ADC) in clinical trials; classical clinical surface target. 4/7 surface DB sources. HGNC:1817 CEACAM5 1048 ENSG00000105388 ENSP00000221992.5 4 yes gpi_anchored CD24 P25063 gpi_anchored_positive yes likely_accessible gpi_anchored CD24 — small GPI-anchored sialoglycoprotein on B cells, neutrophils, and many tumors. Macrophage 'don't eat me' signal via Siglec-10. Clinical-stage anti-CD24 antibodies (e.g. SNS-101). 2/7 surface DB sources — disagreement-rich GPI. HGNC:1645 CD24 100133941 ENSG00000272398 ENSP00000475625.1 2 yes gpi_anchored BST2 Q10589 gpi_anchored_positive yes likely_accessible gpi_anchored Tetherin (BST-2 / CD317) — interferon-induced GPI-anchored antiviral. Unusual N-terminal TM + C-terminal GPI dual-anchor architecture but functionally outer-leaflet on the cell surface. 4/7 surface DB sources. HGNC:1119 BST2 684 ENSG00000130303 ENSP00000252593.6 4 yes gpi_anchored DPEP1 P16444 gpi_anchored_positive yes likely_accessible gpi_anchored Renal dipeptidase — GPI-anchored ectoenzyme on kidney brush border, lung endothelium, and colon cancer. Clinical-stage anti-DPEP1 antibody (LSALT peptide / DC-101 platform). 4/7 surface DB sources; classical GPI. HGNC:3002 DPEP1 1800 ENSG00000015413 ENSP00000261615.4 4 yes gpi_anchored ZP3 P21754 dual_localization_borderline contextual possibly_accessible dual_localization Zona pellucida glycoprotein 3 — single-pass TM precursor at the oocyte surface; furin cleavage releases the ectodomain into the surrounding zona pellucida matrix during oogenesis. The TM-anchored precursor stage is the textbook `dual_localization` pattern (parallel to EREG): a TM precursor that transits the PM before regulated proteolysis releases the dominant form. The mature matrix-deposited ZP3 itself is `secreted_only` (no own anchor), but the documented TM-precursor stage on the oocyte PM is enough for `contextual / dual_localization`. Restricted to the female germline / oocyte lineage. HGNC:13189 ZP3 7784 ENSG00000188372 ENSP00000337310.4 2 contextual tissue_restricted_surface IZUMO1 Q8IYV9 induced_borderline contextual possibly_accessible cell_state_induced IZUMO1 — single-pass TM with Ig-like extracellular domain, required for sperm-egg fusion. **Sequestered in the acrosomal cap of spermatids at baseline; PM-exposed only after the acrosome reaction** (a sperm-specific cell-state event). Target of contraceptive immunology research. 2/7 surface DB sources. HGNC:28539 IZUMO1 284359 ENSG00000182264 ENSP00000327786.2 2 contextual tissue_restricted_surface DSG4 Q86SJ6 disagreement_rich_positive yes likely_accessible classical_surface_receptor Desmoglein 4 — type I single-pass TM cadherin restricted to hair follicle and stratified epithelia. Same classical TM cadherin architecture as DSG1/2/3 — tissue-restricted expression, classical surface mechanism where expressed. 3/7 surface DB sources. HGNC:21307 DSG4 147409 ENSG00000175065 ENSP00000311859.4 3 yes classical_surface_receptor LAMP3 Q9UQV4 lysosomal_exocytosis_borderline contextual possibly_accessible lysosomal_exocytosis DC-LAMP (CD208) — third member of the LAMP family. Single-pass TM glycoprotein on late-endosomal / lysosomal membranes in mature dendritic cells. Reaches the PM via lysosomal exocytosis during DC maturation and antigen presentation. 3/7 surface DB sources. HGNC:14582 LAMP3 27074 ENSG00000078081 ENSP00000265598.3 3 contextual lysosomal_exocytosis CD63 P08962 lysosomal_exocytosis_borderline contextual possibly_accessible lysosomal_exocytosis CD63 (LAMP-3 in old literature; tetraspanin TSPAN30) — multi-pass tetraspanin on late-endosomes / MVBs / lysosomes. Reaches the PM via lysosomal exocytosis and is a canonical exosomal-surface marker. Surface-displayed in activated platelets and degranulating immune cells. 4/7 surface DB sources. HGNC:1692 CD63 967 ENSG00000135404 ENSP00000257857.4 4 contextual lysosomal_exocytosis CD68 P34810 lysosomal_exocytosis_borderline contextual possibly_accessible lysosomal_exocytosis Macrosialin / CD68 — single-pass TM sialomucin on macrophage / monocyte late-endosomes and lysosomes. Cycles to the PM during phagocytosis / lysosomal exocytosis. Used as a histological pan-macrophage marker; clinical anti-CD68 imaging agents in development. 3/7 surface DB sources. HGNC:1693 CD68 968 ENSG00000129226 ENSP00000250092.6 3 contextual dual_localization SCARB2 Q14108 lysosomal_exocytosis_borderline contextual possibly_accessible lysosomal_exocytosis LIMP-2 (SCARB2) — multi-pass TM lysosomal integral membrane protein, mannose-6-phosphate-independent receptor for β-glucocerebrosidase trafficking to lysosomes. Reaches the PM via lysosomal exocytosis; also the cellular entry receptor for enterovirus 71. 2/7 surface DB sources. HGNC:1665 SCARB2 950 ENSG00000138760 ENSP00000264896.2 2 contextual lysosomal_exocytosis HMGB1 P09429 induced_borderline contextual possibly_accessible cell_state_induced High mobility group box 1 — chromatin-binding nuclear protein and soluble DAMP, but **surface-displayed on activated platelets**: cytoplasmic translocation followed by plasma-membrane exposure detected by flow cytometry and immunofluorescence on viable thrombin/collagen-activated platelets, including HMGB1+ microparticles released into circulation (Maugeri et al. 2014, PMID 24634472; Vogel et al. 2015, PMID 26330544). Contextual surface accessibility — restricted to the activated-platelet cell state (and HMGB1+ EV exteriors in inflammatory disease), not constitutive on nucleated cells. HGNC:4983 HMGB1 3146 ENSG00000189403 ENSP00000343040.4 1 contextual cell_state_induced HNRNPK P61978 nuclear_negative no unlikely nuclear Heterogeneous nuclear ribonucleoprotein K — nucleoplasmic RNA-binding protein involved in pre-mRNA processing. No documented membrane anchor; ectopic surface reports in tumor proteomics studies are likely contamination. Adversarial M1 hit (1 CSPA mass-spec source). HGNC:5044 HNRNPK 3190 ENSG00000165119 ENSP00000353552.5 1 no nuclear ATP5F1B P06576 dual_localization_borderline contextual possibly_accessible dual_localization ATP synthase F1 β subunit — primarily a mitochondrial matrix component of complex V. **Plasma-membrane 'ecto-F1-ATPase' is documented** on hepatocytes (HDL receptor), endothelium (apoA-I receptor), and multiple tumor lineages; multiple anti-ecto-ATP-synthase antibody / aptamer programs. Minority but stable PM pool alongside the dominant mitochondrial localization. HGNC:830 ATP5F1B 506 ENSG00000110955 ENSP00000262030.3 1 contextual cell_state_induced IZUMO4 Q1ZYL8 induced_borderline no possibly_accessible endomembrane_resident IZUMO4 — IZUMO family single-pass TM with Ig-like ECD; same acrosomal-cap → PM trafficking biology as IZUMO1 (sequestered in the acrosomal cap of spermatids at baseline; PM-exposed after the acrosome reaction). Forms heterodimer with IZUMO1 during sperm-egg fusion. 0/5 surface DB sources. HGNC:26950 IZUMO4 113177 ENSG00000099840 ENSP00000378712.3 0 no nuclear CRISP1 P54107 surface_attachment_borderline contextual possibly_accessible stable_surface_attachment CRISP1 (AEG / DE) — CAP-superfamily glycoprotein secreted by epididymal epithelium that **stably attaches to the sperm plasma membrane during epididymal maturation in a wash-resistant manner** (mechanism candidates: GPI re-tethering, disulfide cross-linking, or very stable non-covalent association). Surface-accessible on ejaculated mature sperm through transit and fertilization; anti-CRISP1 contraceptive immunology programs. 0/5 surface DB sources. HGNC:304 CRISP1 167 ENSG00000124812 ENSP00000331317.5 0 contextual stable_surface_attachment EPCAM P16422 disagreement_rich_positive yes likely_accessible classical_surface_receptor Epithelial cell adhesion molecule — single-pass type I TM glycoprotein on epithelial cells. Cytokeratin-positive carcinoma marker; catumaxomab (anti-EpCAM x CD3 trifunctional, EMA-approved 2009 then voluntarily withdrawn 2017); solitomab and multiple EpCAM-targeted bispecifics / CAR-T programs clinical. 5/5 surface DB sources. HGNC:11529 EPCAM 4072 ENSG00000119888 ENSP00000263735.4 5 yes classical_surface_receptor CSPG4 Q6UVK1 disagreement_rich_positive yes likely_accessible classical_surface_receptor Melanoma chondroitin sulfate proteoglycan (CSPG4 / MCSP / NG2) — single-pass type I TM chondroitin-sulfate proteoglycan on melanoma, glioma, sarcoma. Clinical anti-CSPG4 CAR-T programs. 5/5 surface DB sources. HGNC:2466 CSPG4 1464 ENSG00000173546 ENSP00000312506.5 5 yes classical_surface_receptor TACSTD2 P09758 validated_positive yes likely_accessible classical_surface_receptor TROP-2 / TACSTD2 — single-pass type I TM glycoprotein on epithelial tumors. **Sacituzumab govitecan (Trodelvy) approved** 2020 for mTNBC and urothelial; datopotamab deruxtecan (Dato-DXd) approved 2024. 5/5 surface DB sources. HGNC:11530 TACSTD2 4070 ENSG00000184292 ENSP00000360269.2 5 yes classical_surface_receptor CD276 Q5ZPR3 disagreement_rich_positive yes likely_accessible classical_surface_receptor B7-H3 / CD276 — single-pass type I TM Ig-superfamily checkpoint molecule on tumor cells and tumor stroma. Multiple clinical ADC / CAR-T / radioligand programs (ifinatamab deruxtecan, omburtamab radioconjugate, mirzotamab clezutoclax). 4/5 surface DB sources. HGNC:19137 CD276 80381 ENSG00000103855 ENSP00000320058.5 4 yes classical_surface_receptor CEACAM6 P40199 gpi_anchored_positive yes likely_accessible gpi_anchored CEACAM6 / NCA / CD66c — GPI-anchored carcinoembryonic-antigen family member on epithelial tumors. Multiple anti-CEACAM6 ADC / mAb / CAR-T programs (NEO-201, tinurilimab / BAY1834942). 4/5 surface DB sources. HGNC:1818 CEACAM6 4680 ENSG00000086548 ENSP00000199764.6 4 yes gpi_anchored MUC16 Q8WXI7 disagreement_rich_positive yes likely_accessible classical_surface_receptor MUC16 / CA-125 — single-pass type I TM with a massive O-glycosylated mucin ectodomain; ovarian-cancer serum biomarker and surface antigen. Oregovomab clinical; ubamatamab and multiple mucin-targeted T-cell engagers / ADCs. 4/5 surface DB sources. HGNC:15582 MUC16 94025 ENSG00000181143 ENSP00000381008.2 4 yes classical_surface_receptor PTK7 Q13308 disagreement_rich_positive yes likely_accessible classical_surface_receptor Protein tyrosine kinase 7 — single-pass type I TM pseudokinase and Wnt-pathway co-receptor; oncofetal antigen on multiple carcinomas. Cofetuzumab pelidotin (PF-06647020) anti-PTK7 ADC clinical. 4/5 surface DB sources. HGNC:9618 PTK7 5754 ENSG00000112655 ENSP00000230418.4 4 yes classical_surface_receptor CLDN18 P56856 disagreement_rich_positive yes likely_accessible multipass_with_exposed_loops Claudin-18 isoform 2 (CLDN18.2) — 4-pass TM tight-junction claudin, gastric-restricted isoform. **Zolbetuximab (Vyloy) approved** 2024 for HER2-negative gastric / GEJ adenocarcinoma; multiple CAR-CLDN18.2 T-cell programs in clinic. Tissue-restricted to gastric epithelia but architectural surface story is unambiguous. 3/5 surface DB sources. HGNC:2039 CLDN18 51208 ENSG00000066405 ENSP00000183605.5 3 yes multipass_with_exposed_loops FOLH1 Q04609 validated_positive yes likely_accessible classical_surface_receptor PSMA / folate hydrolase 1 — single-pass type II TM with a large extracellular glutamate-carboxypeptidase domain; prostate-cancer overexpressed. **Lutetium-PSMA-617 (Pluvicto) approved** 2022 for metastatic CRPC; multiple PSMA radioligands and PSMA-CAR-T programs. 3/5 surface DB sources. HGNC:3788 FOLH1 2346 ENSG00000086205 ENSP00000256999.2 3 yes classical_surface_receptor GPC3 P51654 gpi_anchored_positive yes likely_accessible gpi_anchored Glypican-3 — GPI-anchored heparan sulfate proteoglycan on hepatocellular carcinoma. Codrituzumab (GC33) clinical mAb; multiple GPC3-CAR-T programs in clinical development. 3/5 surface DB sources. HGNC:4451 GPC3 2719 ENSG00000147257 ENSP00000359854.3 3 yes gpi_anchored NECTIN4 Q96NY8 validated_positive yes likely_accessible classical_surface_receptor Nectin-4 — single-pass type I TM Ig-superfamily adhesion molecule on urothelial / breast / lung cancers. **Enfortumab vedotin (Padcev) approved** 2019 for urothelial cancer. 3/5 surface DB sources. HGNC:19688 NECTIN4 81607 ENSG00000143217 ENSP00000356991.3 3 yes classical_surface_receptor CA9 Q16790 disagreement_rich_positive yes likely_accessible classical_surface_receptor Carbonic anhydrase IX — single-pass type I TM with extracellular PG + catalytic CA domain; hypoxia-induced HIF target on clear-cell RCC. **Girentuximab approved diagnostic** (PET imaging) 2024; therapeutic CA9-ADC and CAR-T programs clinical. 2/5 surface DB sources. HGNC:1383 CA9 768 ENSG00000107159 ENSP00000367608.4 2 yes classical_surface_receptor DLK1 P80370 disagreement_rich_positive yes likely_accessible classical_surface_receptor Delta-like non-canonical Notch ligand 1 (DLK1 / pref-1) — single-pass type I TM with EGF-like repeats; oncofetal antigen on neuroblastoma, hepatoblastoma, adrenal cortex carcinoma. ADCT-701 anti-DLK1 ADC clinical. ADAM17 ectodomain shedding releases a soluble form, but the TM precursor IS the surface form. 2/5 surface DB sources. HGNC:2907 DLK1 8788 ENSG00000185559 ENSP00000331081.6 2 contextual dual_localization GPC2 Q8N158 gpi_anchored_positive yes likely_accessible gpi_anchored Glypican-2 — GPI-anchored heparan sulfate proteoglycan; oncofetal antigen on neuroblastoma. CHOP D3-based GPC2-CAR-T programs in clinical development. 2/5 surface DB sources. HGNC:4450 GPC2 221914 ENSG00000213420 ENSP00000292377.2 2 yes gpi_anchored LYPD1 Q8N2G4 gpi_anchored_positive yes likely_accessible gpi_anchored LY6/PLAUR domain containing 1 — GPI-anchored LY6/uPAR-family surface protein; emerging tumor-associated antigen. 2/5 surface DB sources. HGNC:28431 LYPD1 116372 ENSG00000150551 ENSP00000340563.6 2 yes gpi_anchored SSTR2 P30874 gpcr_extracellular_pocket yes likely_accessible multipass_with_exposed_loops Somatostatin receptor 2 — 7TM rhodopsin-family GPCR on neuroendocrine tumors. **177Lu-DOTATATE (Lutathera) approved** 2018 for GEP-NETs; multiple SSTR-targeted radioligands and bispecifics. 2/5 surface DB sources. HGNC:11331 SSTR2 6752 ENSG00000180616 ENSP00000350198.2 2 yes multipass_with_exposed_loops TYRP1 P17643 dual_localization_borderline contextual possibly_accessible dual_localization Tyrosinase-related protein 1 — single-pass type I TM melanin-biosynthesis enzyme. **Canonical dominant compartment is the melanosome** (lysosome-related organelle); surface display on melanoma cells documented and clinically targeted (TA99 mAb, anti-TYRP1 ADC programs). Dual-localization biology: melanosomal-dominant with documented melanoma-cell-surface fraction. Borderline analog of PMEL but with cleaner surface evidence. 2/5 surface DB sources. HGNC:12450 TYRP1 7306 ENSG00000107165 ENSP00000373570.4 2 contextual lysosomal_exocytosis STEAP2 Q8NFT2 disagreement_rich_positive yes likely_accessible multipass_with_exposed_loops STEAP family member 2 — 6-pass TM metalloreductase / paralog of STEAP1; prostate-cancer overexpressed. Clinical STEAP2-targeted CAR-T and bispecific programs. **Not detected by any of the 5 retained M1 DBs** — adversarial M1 escape, tests whether the agent recognizes the STEAP1/STEAP2 architecture by family extrapolation. 0/5 surface DB sources. HGNC:17885 STEAP2 261729 ENSG00000157214 ENSP00000287908.3 0 yes multipass_with_exposed_loops AMHR2 Q16671 disagreement_rich_positive yes likely_accessible classical_surface_receptor Anti-Müllerian hormone receptor 2 — single-pass type I TM serine/threonine kinase receptor (TGF-β receptor superfamily). Surface on developing Müllerian-duct epithelium, granulosa / theca cells, and ovarian cancer. Clinical anti-AMHR2 ADC and CAR-T programs (e.g., murlentamab). Architectural surface story is unambiguous despite low DB cover. 2/5 surface DB sources (UP, SFY). HGNC:465 AMHR2 269 ENSG00000135409 ENSP00000257863.3 2 yes classical_surface_receptor TM4SF1 P30408 disagreement_rich_positive yes likely_accessible multipass_with_exposed_loops TM4SF1 / L6 — 4-pass TM tetraspanin-superfamily surface protein on lung / colorectal / pancreatic / breast carcinoma and tumor endothelium. Multiple clinical anti-TM4SF1 ADC programs. Same tetraspanin architecture as CD63 (also in benchmark) but more constitutively at the PM. 2/5 surface DB sources (UP, SFY). HGNC:11853 TM4SF1 4071 ENSG00000169908 ENSP00000304277.3 2 yes multipass_with_exposed_loops ALPG P10696 disagreement_rich_positive contextual possibly_accessible tissue_restricted_surface ALPG (legacy alias ALPPL2) — germ cell alkaline phosphatase, GPI-anchored ectoenzyme. When expressed (testis, placenta, germ-cell tumors, oncofetal pattern), the protein is stably surface-displayed; expression itself is narrow / tissue-restricted (cancer-testis pattern). Multiple clinical anti-ALPPL2 ADC/CAR-T programs. contextual/tissue_restricted_surface captures the expression-restricted cancer-testis surface pattern. HGNC:441 ALPG 251 ENSG00000163286 ENSP00000295453.3 2 contextual tissue_restricted_surface LY6K Q17RY6 gpi_anchored_positive contextual possibly_accessible tissue_restricted_surface LY6/uPAR family GPI-anchored cancer-testis antigen. Stable GPI display when expressed, but expression is narrow (testis/sperm and cancer cells). contextual/tissue_restricted_surface captures the expression-restricted cancer-testis surface pattern. HGNC:24225 LY6K 54742 ENSG00000160886 ENSP00000292430.6 2 contextual tissue_restricted_surface LYPD3 O95274 gpi_anchored_positive yes likely_accessible gpi_anchored LYPD3 / C4.4A — LY6/PLAUR domain containing 3, uPAR paralog; GPI-anchored surface protein on lung / pancreatic / esophageal carcinomas. **Lupartumab amadotin (BAY1129980), anti-LYPD3 ADC clinical**. LY6-family GPI architecture is unambiguous. 2/5 surface DB sources (SFY, CSPA). HGNC:24880 LYPD3 27076 ENSG00000124466 ENSP00000244333.2 2 yes gpi_anchored