BCAM

Summary

BCAM (basal cell adhesion molecule (Lutheran blood group), HGNC:6722) is a protein-coding gene on chromosome 19q13.32, encoding Basal cell adhesion molecule (P50895). Transmembrane glycoprotein that functions as both a receptor and an adhesion molecule playing a crucial role in cell adhesion, motility, migration and invasion.

This gene encodes Lutheran blood group glycoprotein, a member of the immunoglobulin superfamily and a receptor for the extracellular matrix protein, laminin. The protein contains five extracellular immunoglobulin domains, a single transmembrane domain, and a short C-terminal cytoplasmic tail. This protein may play a role in epithelial cell cancer and in vaso-occlusion of red blood cells in sickle cell disease. Polymorphisms in this gene define some of the antigens in the Lutheran system and also the Auberger system. Inactivating variants of this gene result in the recessive Lutheran null phenotype, Lu(a-b-), of the Lutheran blood group. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 4059 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 160 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 2
• MANE Select transcript: NM_005581

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6722
Approved symbol	BCAM
Name	basal cell adhesion molecule (Lutheran blood group)
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	CD239, B-CAM, F8/G253
Ensembl gene	ENSG00000187244
Ensembl biotype	protein_coding
OMIM	612773
Entrez	4059

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 8 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000270233, ENST00000588303, ENST00000588603, ENST00000588714, ENST00000589558, ENST00000590108, ENST00000590196, ENST00000591520, ENST00000611077, ENST00000852014, ENST00000852015, ENST00000852016, ENST00000852017, ENST00000940906

RefSeq mRNA: 2 — MANE Select: NM_005581 NM_001013257, NM_005581

CCDS: CCDS12644, CCDS42575

Canonical transcript exons

ENST00000270233 — 15 exons

Exon	Start	End
ENSE00000953048	44819582	44819726
ENSE00000953049	44820705	44820822
ENSE00002935245	44820916	44821421
ENSE00003704835	44812478	44812548
ENSE00003705020	44819056	44819192
ENSE00003706231	44811225	44811346
ENSE00003706343	44818522	44818637
ENSE00003709316	44813438	44813620
ENSE00003709594	44818741	44818882
ENSE00003710285	44813250	44813346
ENSE00003710797	44819346	44819490
ENSE00003710857	44814152	44814288
ENSE00003711431	44812163	44812391
ENSE00003711486	44814604	44814760
ENSE00003734000	44809103	44809206

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 99.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 38.0940 / max 908.8842, expressed in 1436 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176301	32.0347	1375
176300	4.4878	1191
176304	0.7768	364
176306	0.2365	123
176312	0.1855	104
176305	0.1654	81
176313	0.1444	71
176314	0.0629	18

Top tissues by expression

283 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
metanephros cortex	UBERON:0010533	99.38	gold quality
right uterine tube	UBERON:0001302	99.37	gold quality
left lobe of thyroid gland	UBERON:0001120	99.05	gold quality
popliteal artery	UBERON:0002250	99.04	gold quality
tibial artery	UBERON:0007610	99.04	gold quality
right lobe of thyroid gland	UBERON:0001119	99.01	gold quality
right coronary artery	UBERON:0001625	98.89	gold quality
renal medulla	UBERON:0000362	98.88	gold quality
artery	UBERON:0001637	98.88	gold quality
left coronary artery	UBERON:0001626	98.48	gold quality
thyroid gland	UBERON:0002046	98.43	gold quality
coronary artery	UBERON:0001621	98.42	gold quality
apex of heart	UBERON:0002098	98.38	gold quality
aorta	UBERON:0000947	98.01	gold quality
endocervix	UBERON:0000458	97.95	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.88	gold quality
left uterine tube	UBERON:0001303	97.54	gold quality
descending thoracic aorta	UBERON:0002345	97.43	gold quality
adult mammalian kidney	UBERON:0000082	97.41	gold quality
upper lobe of left lung	UBERON:0008952	97.30	gold quality
body of uterus	UBERON:0009853	97.14	gold quality
thoracic aorta	UBERON:0001515	96.80	gold quality
ascending aorta	UBERON:0001496	96.79	gold quality
tibial nerve	UBERON:0001323	96.73	gold quality
right lung	UBERON:0002167	96.73	gold quality
upper lobe of lung	UBERON:0008948	96.67	gold quality
right atrium auricular region	UBERON:0006631	96.60	gold quality
omental fat pad	UBERON:0010414	96.44	gold quality
peritoneum	UBERON:0002358	96.39	gold quality
heart left ventricle	UBERON:0002084	96.26	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 17.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	2346.07
E-GEOD-124472	yes	1464.89
E-MTAB-6701	yes	846.92
E-CURD-114	yes	657.54
E-ANND-5	yes	542.11
E-MTAB-9154	yes	541.88
E-MTAB-7407	yes	522.13
E-HCAD-56	yes	498.48
E-HCAD-24	yes	478.44
E-MTAB-10662	yes	470.53
E-MTAB-10287	yes	63.77
E-GEOD-134144	yes	53.86
E-HCAD-11	yes	44.16
E-HCAD-1	yes	35.57
E-MTAB-8410	yes	27.83

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting BCAM, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-3196	98.96	63.91	326
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-3180	98.46	64.68	348
HSA-MIR-3180-3P	98.46	64.68	348
HSA-MIR-6816-5P	98.46	64.35	364

Literature-anchored findings (GeneRIF, showing 36)

• Results demonstrate that the alpha5 LG3 module is essential for the Lutheran blood group glycoprotein (Lu) binding to laminin alpha5. (PMID:12244066)
• B-CAM/LU is the most critical receptor mediating adhesion to laminin under both static and flow conditions in sickle cell anemia. (PMID:14755370)
• interactions of B-CAM and laminin may be involved in progression of epithelial skin tumors (PMID:15278364)
• Lu mediates the adhesion of human endothelial cells to alpha5 laminins in collaboration with integrins beta(1) and alpha(v)beta(3). (PMID:16236823)
• B-CAM spliceoform seems to be overexpressed by a variety of different malignant tumors and may be involved, along with other adhesion receptor proteins, in malignant transformation and tumor metastasis. (review) (PMID:16584446)
• The Laminin 511/521-binding site on the Lutheran blood group glycoprotein is located at the flexible junction of Ig domains 2 and 3. (PMID:17638854)
• study presents a combined modeling & small angle X-ray scattering approach that extends the structural analysis of Lu gp to all five extracellular domains & provides further insight to its interaction with laminins (Ln511 & Ln521) (PMID:18302987)
• Lu/BCAM gps expressed on erythroid or on endothelial cells are involved in SS RBC-endothelium interactions & could play a role in abnormal adhesion of SS RBCs to vascular endothelium contributing to vaso-occlusive crises reported for sickle cell disease. (PMID:18514010)
• These results suggest that laminins containing alpha 5 serve as functional substrates regulating progression of hepatocellular carcinoma. (PMID:18635166)
• the interaction of the Lu cytoplasmic tail with the cytoskeleton regulates its adhesive receptor function (PMID:18815288)
• CD239 was expressed in a constitutive fashion in polycythaemia vera-derived bone marrow cells and thus a pro-thrombotic function does not seem to be mediated by increased CD239 expression alone. (PMID:18972067)
• Lutheran blood group glycoprotein (Lu) is one of the proteins cleaved by MT1-MMP. (PMID:19667067)
• Aggregation of mononuclear and red blood cells through an {alpha}4{beta}1-Lu/basal cell adhesion molecule interaction in sickle cell disease (PMID:20562314)
• BCAM glycoproteins are the unique erythroid receptors of laminin alpha5 chain, a major component of the extracellular matrix and are involved in several erythrocyte diseases. (PMID:20655789)
• Data indicate that the function-blocking antibody against Lu/B-CAM should be useful for not only investigating cell adhesion to laminin alpha5 but also for developing drugs to inhibit sickle cell vaso-occlusion. (PMID:21858073)
• Increases in adhesion frequency provide significant evidence of the role of epinephrine in BCAM/Lu-laminin and ICAM-4-alpha(v)beta(3) bonding, and suggest mechanisms of vaso-occlusion during physical exertion in sickle cell trait. (PMID:22404936)
• DARC and BCAM expression was associated with pathogenesis of thyroid carcinoma and correlated with clinical-pathological features. (PMID:23168236)
• Glu425 in the Lu glycoprotein is required for expression of Lu7, and Ala425 is associated with the LU:-7 phenotype. This completes the molecular basis associated with all antigens known to be in the Lutheran blood group system. (PMID:23421542)
• tumor cell migration on LM-511 requires that Lu/B-CAM competitively modulates cell attachment through integrins. (PMID:24036115)
• These studies revealed amino acids 720 to 1014 of CNF1 as the binding site for Lu/BCAM. (PMID:24453976)
• Adhesion of sickle reticulocytes to HC-treated endothelial cells was decreased despite the HC-derived increase of Lu/BCAM expression. (PMID:24616094)
• High BCAM expression is associated with hepatocellular carcinoma. (PMID:25051049)
• Through molecular genotyping we also identified polymorphisms in RhCE, Kell, Duffy, Colton, Lutheran and Scianna loci in donors and patients. (PMID:25582271)
• The variable levels of expression of mutated JAK2 and BCAM proteins determine different adhesion patterns of erythrocytes from polycythemia vera patients. (PMID:25809027)
• Cytometry analysis evidenced a specific expression profile on reticulocytes of SCA infants, with notably an increased expression of the adhesion molecules Lu/BCAM, ICAM-4 and LFA-3, both in percentage of positive cells and in surface density. (PMID:26137540)
• The serum levels of IL-8, MIP-1 alpha, MIP-1 beta, MMP-8, Resistin, FLRG, and BCAM were significantly higher in breast cancer patients, but LAP and TSH-beta levels were lower. (PMID:26898119)
• four new alleles with coding sequence variants were identified in the LU gene (PMID:27043150)
• data show that the BCAM/LAMA5 system plays a functional role in the metastatic spreading of KRAS-mutant colorectal cancer (PMID:27143691)
• This is the first report showing that Lu/BCAM, in the presence of its ligand laminin, is oncogenic in human urothelial cancers and may have potential as a novel therapeutic target. (PMID:28841878)
• Lu/BCAM-mediated binding to laminin-alpha5 is restricted by interacting, in cis, with glycophorin-C-derived sialic acid residues. (PMID:29344581)
• Lu expression by erythrocytes from patients with myeloproliferative neoplasms and splanchnic venous thrombosi is significantly increased compared to erythrocytes from healthy individuals (PMID:29756283)
• Lutheran (Lu)/Basal cell adhesion molecule (BCAM) regulates the morphogenesis of DR depending on liver disease models. (PMID:30059007)
• Upregulation of BCAM and its sense lncRNA BAN are associated with gastric cancer metastasis and poor prognosis. (PMID:31951095)
• Novel variants in Krueppel like factor 1 that cause persistence of fetal hemoglobin in In(Lu) individuals. (PMID:34535703)
• Cell trajectory modeling identifies a primitive trophoblast state defined by BCAM enrichment. (PMID:35020896)
• Basal cell adhesion molecule promotes metastasis-associated processes in ovarian cancer. (PMID:36647260)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bcam	ENSDARG00000090190
		ENSDARG00000109267
mus_musculus	Bcam	ENSMUSG00000002980
rattus_norvegicus	Bcam	ENSRNOG00000029399

Paralogs (3): MCAM (ENSG00000076706), ALCAM (ENSG00000170017), AGER (ENSG00000204305)

Protein

Protein identifiers

Basal cell adhesion molecule — P50895 (reviewed: P50895)

Alternative names: Auberger B antigen, B-CAM cell surface glycoprotein, F8/G253 antigen, Lutheran antigen, Lutheran blood group glycoprotein

All UniProt accessions (4): A0A087WXM8, P50895, K7ENU8, K7ERB7

UniProt curated annotations — full annotation on UniProt →

Function. Transmembrane glycoprotein that functions as both a receptor and an adhesion molecule playing a crucial role in cell adhesion, motility, migration and invasion. Extracellular domain enables binding to extracellular matrix proteins, such as laminin, integrin and other ligands while its intracellular domain interacts with cytoskeletal proteins like hemoglobin, facilitating cell signal transduction. Serves as a receptor for laminin alpha-5/LAMA5 to promote cell adhesion. Mechanistically, JAK2 induces BCAM phosphorylation and activates its adhesion to laminin by stimulating a Rap1/AKT signaling pathway in the absence of EPOR.

Subunit / interactions. Homodimer. Interacts with ITGA4:ITGB1. Interacts with spectrins SPTA1 and SPTB1.

Subcellular location. Cell membrane.

Tissue specificity. Wide tissue distribution (highest in the pancreas and very low in brain). Closely associated with the basal layer of cells in epithelia and the endothelium of blood vessel walls.

Post-translational modifications. Epinephrine-stimulated phosphorylation of Ser-621 by PKA enhances adhesion to laminin. Ser-621 can also be phosphorylated by AKT1.

Polymorphism. BCAM is responsible for the Lutheran blood group system (LU) [MIM:111200]. Lutheran is a complex blood group system consisting of 19 antigens. Antigens Lu(a) and Lu(b) are defined by a polymorphism at position 77: Lu(a) has His-77 and Lu(b) has Arg-77. Inactivating variants in BCAM are responsible for the recessive Lutheran null phenotype Lu(a-b-) of the Lutheran blood group [MIM:247420]. Autosomal recessive inheritance of the Lutheran null blood group phenotype is extremely rare. There is no obvious associated clinical or hematologic pathology, and all patients have been identified through identification of anti-Lu3 antibodies in their serum.

RefSeq proteins (2): NP_001013275, NP_005572* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013162	CD80_C2-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR051116	Surface_Rcpt/Adhesion_Mol	Family

Pfam: PF07686, PF08205, PF13895, PF13927

UniProt features (63 total): strand 18, sequence variant 8, glycosylation site 5, disulfide bond 5, domain 5, modified residue 4, helix 4, mutagenesis site 3, sequence conflict 3, region of interest 2, topological domain 2, signal peptide 1, chain 1, compositionally biased region 1, transmembrane region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2PET	X-RAY DIFFRACTION	1.7
2PF6	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P50895-F1	84.29	0.62

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 596, 598, 600, 621

Disulfide bonds (5): 53–125, 172–237, 291–337, 384–424, 473–522

Glycosylation sites (5): 321, 377, 383, 419, 439

Mutagenesis-validated functional residues (3):

Position	Phenotype
584	extremely reduced binding to spectrins; when associated with a-585.
585	extremely reduced binding to spectrins; when associated with a-584.
621	dramatically reduced cell adhesion.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 202 (showing top): KOBAYASHI_EGFR_SIGNALING_24HR_UP, YAGI_AML_WITH_INV_16_TRANSLOCATION, ROVERSI_GLIOMA_COPY_NUMBER_UP, GOCC_CELL_SURFACE, HUMMERICH_SKIN_CANCER_PROGRESSION_DN, RODRIGUES_NTN1_TARGETS_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_BLOOD_VESSEL_MORPHOGENESIS, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, SCHLOSSER_SERUM_RESPONSE_DN, MODULE_88, CAIRO_HEPATOBLASTOMA_UP, VDR_Q3, IK3_01, GOBP_CELL_SUBSTRATE_ADHESION

GO Biological Process (4): angiogenesis (GO:0001525), cell adhesion (GO:0007155), cell-matrix adhesion (GO:0007160), signal transduction (GO:0007165)

GO Molecular Function (4): transmembrane signaling receptor activity (GO:0004888), laminin receptor activity (GO:0005055), laminin binding (GO:0043236), protein binding (GO:0005515)

GO Cellular Component (7): extracellular region (GO:0005576), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062), cell surface (GO:0009986), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cellular process	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
cell-substrate adhesion	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signaling receptor activity	1
laminin binding	1
cell adhesion mediator activity	1
protein binding	1
extracellular matrix binding	1
binding	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
external encapsulating structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

729 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCAM	LAMA5	O15230	846
BCAM	CNTN6	Q9UQ52	788
BCAM	PDZD4	Q76G19	749
BCAM	ICAM4	Q14773	581
BCAM	KEL	P23276	549
BCAM	FUT2	Q10981	491
BCAM	CD151	P48509	468
BCAM	DAG1	Q14118	408
BCAM	ZNF888	P0CJ79	398
BCAM	KAT2A	Q92830	397
BCAM	RPSA	P08865	392
BCAM	IFNB1	P01574	380
BCAM	UBE2I	P50550	379
BCAM	SRC	P12931	372
BCAM	ENG	P17813	333

IntAct

79 interactions, top by confidence:

A	B	Type	Score
TSPAN15	ADAM10	psi-mi:“MI:0914”(association)	0.840
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
TSPAN14	ADAM10	psi-mi:“MI:0914”(association)	0.740
KLHL2	BCAM	psi-mi:“MI:0915”(physical association)	0.720
BCAM	KLHL2	psi-mi:“MI:0915”(physical association)	0.720
BMAL1	CLOCK	psi-mi:“MI:0914”(association)	0.720
BCAM	LAMA5	psi-mi:“MI:0914”(association)	0.640
BCAM	TRIM7	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	BCAM	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	BCAM	psi-mi:“MI:0915”(physical association)	0.560
BCAM	KRTAP1-1	psi-mi:“MI:0915”(physical association)	0.560
BCAM	MDFI	psi-mi:“MI:0915”(physical association)	0.560
SLC4A1	FLOT1	psi-mi:“MI:0914”(association)	0.530
CD79A	METTL15	psi-mi:“MI:0914”(association)	0.530
PRCC	BCAS2	psi-mi:“MI:0914”(association)	0.530
ZSWIM2	SEMG1	psi-mi:“MI:0914”(association)	0.530
CLEC4A	SEMA7A	psi-mi:“MI:0914”(association)	0.530
CDH8	ARVCF	psi-mi:“MI:0914”(association)	0.530

BioGRID (76): KLHL2 (Two-hybrid), KLHL2 (Two-hybrid), LAMA4 (Affinity Capture-MS), BCAM (Affinity Capture-MS), BCAM (Affinity Capture-MS), BCAM (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), TMEM11 (Affinity Capture-MS), LAMA5 (Affinity Capture-MS), BCAM (Affinity Capture-MS), BCAM (Affinity Capture-MS), ATP6V0A2 (Affinity Capture-MS), BCAM (Affinity Capture-MS), ATP11C (Affinity Capture-MS), TNPO2 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LHF2, A6H8M9, A7LCJ3, A8E0Y8, D3YX43, D3YZF7, O14498, O15197, O70394, O70540, P01877, P0C0K6, P0C788, P0DP72, P35590, P40223, P43121, P50895, P70289, Q00657, Q06418, Q06805, Q15109, Q28173, Q5BK54, Q5NVQ6, Q5TJE4, Q61790, Q61826, Q62151, Q62230, Q63495, Q64612, Q6UVK1, Q6UWB1, Q7Z442, Q86VR7, Q8IZF5, Q8R2Y2, Q8VHY0

Diamond homologs: P43121, P50895, Q8R2Y2, Q9BH13, Q9EPF2, Q9ESS6, Q9MZ08, Q9R069, A0A0R4IGV4, A2AJ76, O60229, P05622, P07722, P09619, P54296, P85171, Q02173, Q05030, Q0PMG2, Q0WYX8, Q15772, Q1WIM1, Q1WIM2, Q1WIM3, Q28730, Q5IS82, Q62407, Q63638, Q66KX2, Q6AYP5, Q6DJ83, Q7T2H2, Q7ZXX1, Q8BLQ9, Q8N126, Q8N3J6, Q8NDA2, Q8NFP4, Q8NFZ8, Q8R464

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 67 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
protein localization to plasma membrane	7	11.9×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

160 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	105
Likely benign	18
Benign	10

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
440	NM_005581.5(BCAM):c.691C>T (p.Arg231Ter)	Pathogenic
441	NG_007480.1:g.(7267_8082)_(8469_9169)del	Pathogenic
442	NM_005581.5(BCAM):c.711C>A (p.Cys237Ter)	Pathogenic
443	NM_005581.5(BCAM):c.361C>T (p.Arg121Ter)	Pathogenic
3892999	NM_005581.5(BCAM):c.880dup (p.Asp294fs)	Likely pathogenic

SpliceAI

2113 predictions. Top by Δscore:

Variant	Effect	Δscore
19:44809203:CCAG:C	donor_loss	1.0000
19:44809205:AG:A	donor_loss	1.0000
19:44809206:GG:G	donor_loss	1.0000
19:44811223:A:AG	acceptor_gain	1.0000
19:44811224:G:A	acceptor_loss	1.0000
19:44811224:G:GA	acceptor_gain	1.0000
19:44811224:GAT:G	acceptor_gain	1.0000
19:44811280:A:T	donor_gain	1.0000
19:44811335:G:GT	donor_gain	1.0000
19:44811336:A:T	donor_gain	1.0000
19:44811344:CTTGT:C	donor_loss	1.0000
19:44811345:TT:T	donor_gain	1.0000
19:44811345:TTG:T	donor_loss	1.0000
19:44811346:TGT:T	donor_loss	1.0000
19:44811347:G:C	donor_loss	1.0000
19:44811347:G:GG	donor_gain	1.0000
19:44811348:T:A	donor_loss	1.0000
19:44811349:GAGT:G	donor_loss	1.0000
19:44812475:C:G	acceptor_gain	1.0000
19:44812476:A:AG	acceptor_gain	1.0000
19:44812477:G:GG	acceptor_gain	1.0000
19:44812477:GC:G	acceptor_gain	1.0000
19:44812477:GCA:G	acceptor_gain	1.0000
19:44812477:GCAA:G	acceptor_gain	1.0000
19:44812477:GCAAA:G	acceptor_gain	1.0000
19:44812546:G:GT	donor_gain	1.0000
19:44813345:AGGT:A	donor_loss	1.0000
19:44813347:G:GG	donor_gain	1.0000
19:44813348:T:A	donor_loss	1.0000
19:44813425:C:CA	acceptor_gain	1.0000

AlphaMissense

4036 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:44818631:G:C	W396C	0.997
19:44818631:G:T	W396C	0.997
19:44819174:G:C	W485C	0.997
19:44819174:G:T	W485C	0.997
19:44819632:A:C	S557R	0.996
19:44819634:C:A	S557R	0.996
19:44819634:C:G	S557R	0.996
19:44814691:T:A	C337S	0.993
19:44814692:G:C	C337S	0.993
19:44819136:T:A	C473S	0.993
19:44819137:G:C	C473S	0.993
19:44819436:T:A	C522S	0.993
19:44819437:G:C	C522S	0.993
19:44813298:T:A	W185R	0.992
19:44813298:T:C	W185R	0.992
19:44813300:G:C	W185C	0.992
19:44813300:G:T	W185C	0.992
19:44818629:T:A	W396R	0.992
19:44818629:T:C	W396R	0.992
19:44819172:T:A	W485R	0.991
19:44819172:T:C	W485R	0.991
19:44813259:T:A	C172S	0.990
19:44813260:G:C	C172S	0.990
19:44814238:T:A	C291S	0.990
19:44814239:G:C	C291S	0.990
19:44819136:T:C	C473R	0.990
19:44811340:G:C	W66C	0.988
19:44811340:G:T	W66C	0.988
19:44814691:T:C	C337R	0.987
19:44818816:T:A	C424S	0.987

dbSNP variants (sampled 300 via entrez): RS1000214875 (19:44814721 G>A,C), RS1000245755 (19:44814909 T>C,G), RS1000396926 (19:44810109 G>C,T), RS1000685265 (19:44808108 G>A), RS1000869047 (19:44810435 T>TC), RS1001453928 (19:44815177 G>A), RS1001459417 (19:44807165 G>A), RS1001490626 (19:44807463 G>A), RS1001745147 (19:44813418 C>T), RS1002563096 (19:44816084 G>A,T), RS1002627297 (19:44821418 A>G), RS1002740847 (19:44819261 T>A,C), RS1003099564 (19:44816101 T>A), RS1003149682 (19:44821087 C>T), RS1003340213 (19:44812038 C>T)

Disease associations

OMIM: gene MIM:612773 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0010971	Absence of Lutheran antigen on erythrocytes

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	5
Estradiol	increases expression, decreases expression, affects cotreatment	3
bisphenol A	affects expression, increases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	2
Doxorubicin	affects expression, decreases expression	2
Nickel	decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
tremortin	decreases expression	1
2,4,6-tribromophenol	increases expression	1
deoxynivalenol	decreases expression	1
decabromobiphenyl ether	increases expression	1
beta-lapachone	decreases expression	1
sulforaphane	decreases expression	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
sulindac sulfide	decreases expression	1
ochratoxin A	decreases expression	1
benazol P	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	affects phosphorylation	1
Calcitriol	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E1FF	Abcam A-431 BCAM KO	Cancer cell line	Female

Clinical trials (associated diseases)

11 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery