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

• GWAS associations: 43 (top 2% of genes corpus-wide)
• Clinical variants (ClinVar): 163 total — 4 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 17 tissues, sQTL in 2 (q < 0.05)
• Phenotypes (HPO): 2
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.10 (unconstrained)
• MANE Select transcript: NM_005581
• Notable: 163 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 21 — 12 protein_coding, 5 retained_intron, 4 nonsense_mediated_decay

MANE Select: ENST00000270233

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 4, TSL 3: 2, TSL 5: 2

ENST00000270233, ENST00000588303, ENST00000588603, ENST00000588714, ENST00000589558, ENST00000590108, ENST00000590196, ENST00000591520, ENST00000611077, ENST00000852014, ENST00000852015, ENST00000852016, ENST00000852017, ENST00000940906, ENST00000997728, ENST00000997729, ENST00001034279, ENST00001084256, ENST00001120823, ENST00001120824, ENST00001136122

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.

Highest expression (Bgee): metanephros cortex, uterine tube, lobe of thyroid gland, popliteal artery, tibial artery.

Genetic regulation across tissues (GTEx eQTL / sQTL)

BCAM is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 17 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

19 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Lung	eqtl	4.7e-24	-0.38	19:44842451:G:A
Thyroid	eqtl	5.1e-11	-0.72	19:44810411:A:T
Skin Sun Exposed Lower leg	eqtl	1.2e-10	+0.53	19:44795942:G:T
Skin Not Sun Exposed Suprapubic	eqtl	2.7e-07	+0.44	19:44815094:A:G
Esophagus Mucosa	eqtl	1.4e-06	-0.52	19:44810411:A:T
Cells Cultured fibroblasts	eqtl	4.2e-06	-0.16	19:44787220:T:C
Artery Tibial	eqtl	3.4e-04	+0.10	19:44822481:T:G
Stomach	eqtl	1.6e-03	-0.72	19:45358194:G:A
Esophagus Muscularis	sqtl	3.9e-03	-0.65	19:44808667:T:TGG
Artery Tibial	sqtl	5.0e-03	-0.49	19:44806529:T:A
Muscle Skeletal	eqtl	5.9e-03	+0.16	19:44000345:T:TC
Brain Cerebellar Hemisphere	eqtl	9.1e-03	+0.30	19:44796911:TG:T
Esophagus Muscularis	eqtl	1.0e-02	-0.47	19:44682075:T:G
Spleen	eqtl	1.4e-02	+0.26	19:44820881:G:A
Pancreas	eqtl	2.8e-02	-0.30	19:44876489:A:G
Brain Cerebellum	eqtl	3.3e-02	+0.23	19:44794812:G:A
Nerve Tibial	eqtl	3.6e-02	+0.13	19:44892587:G:A
Prostate	eqtl	4.9e-02	+0.56	19:45390876:G:A
Brain Anterior cingulate cortex BA24	eqtl	5.0e-02	-0.77	19:43953495:A:T

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

showing 100 of 283 tissues 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
ectocervix	UBERON:0012249	96.19	gold quality
cardiac atrium	UBERON:0002081	96.04	gold quality
minor salivary gland	UBERON:0001830	96.02	gold quality
sural nerve	UBERON:0015488	95.91	gold quality
cardiac ventricle	UBERON:0002082	95.84	gold quality
heart	UBERON:0000948	95.34	gold quality
skin of leg	UBERON:0001511	95.24	gold quality
prostate gland	UBERON:0002367	95.01	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.00	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.43	gold quality
skin of abdomen	UBERON:0001416	94.40	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.28	gold quality
body of pancreas	UBERON:0001150	94.12	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.09	gold quality
lower esophagus	UBERON:0013473	94.06	gold quality
mucosa of stomach	UBERON:0001199	93.97	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.92	gold quality
adenohypophysis	UBERON:0002196	93.79	gold quality
right ovary	UBERON:0002118	93.63	gold quality
left ventricle myocardium	UBERON:0006566	93.61	gold quality
body of stomach	UBERON:0001161	93.36	gold quality
mouth mucosa	UBERON:0003729	93.32	gold quality
kidney	UBERON:0002113	93.25	gold quality
saliva-secreting gland	UBERON:0001044	93.15	gold quality
cortex of kidney	UBERON:0001225	92.99	gold quality
vagina	UBERON:0000996	92.81	gold quality
left ovary	UBERON:0002119	92.69	gold quality
endometrium epithelium	UBERON:0004811	92.62	gold quality
fundus of stomach	UBERON:0001160	92.46	gold quality
dorsal root ganglion	UBERON:0000044	92.40	gold quality
zone of skin	UBERON:0000014	91.97	gold quality
pituitary gland	UBERON:0000007	91.90	gold quality
right lobe of liver	UBERON:0001114	91.71	gold quality
esophagus	UBERON:0001043	91.56	gold quality
trigeminal ganglion	UBERON:0001675	91.50	gold quality
lung	UBERON:0002048	91.48	gold quality
stomach	UBERON:0000945	91.22	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.64	gold quality
mucosa of transverse colon	UBERON:0004991	90.63	gold quality
myometrium	UBERON:0001296	90.59	gold quality
spleen	UBERON:0002106	90.55	gold quality
lower esophagus mucosa	UBERON:0035834	90.53	gold quality
uterine cervix	UBERON:0000002	90.40	gold quality
gastrocnemius	UBERON:0001388	90.31	gold quality
mammary duct	UBERON:0001765	90.23	gold quality
cardiac muscle of right atrium	UBERON:0003379	90.22	gold quality
muscle of leg	UBERON:0001383	90.15	gold quality
lower lobe of lung	UBERON:0008949	90.10	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.02	gold quality
adipose tissue	UBERON:0001013	89.83	gold quality
esophagus mucosa	UBERON:0002469	89.78	gold quality
transverse colon	UBERON:0001157	89.61	gold quality
metanephros	UBERON:0000081	89.59	gold quality
right adrenal gland cortex	UBERON:0035827	89.56	gold quality
ovary	UBERON:0000992	89.49	gold quality
saphenous vein	UBERON:0007318	89.46	gold quality
epithelium of mammary gland	UBERON:0003244	89.27	gold quality
left adrenal gland cortex	UBERON:0035825	89.25	gold quality
connective tissue	UBERON:0002384	89.08	gold quality
pancreas	UBERON:0001264	88.94	gold quality
adrenal cortex	UBERON:0001235	88.79	gold quality
left adrenal gland	UBERON:0001234	88.77	gold quality
right adrenal gland	UBERON:0001233	88.70	gold quality
fallopian tube	UBERON:0003889	88.69	gold quality
trachea	UBERON:0003126	88.56	gold quality
nipple	UBERON:0002030	88.34	gold quality
vena cava	UBERON:0004087	88.15	silver quality
small intestine	UBERON:0002108	88.00	gold quality
muscle organ	UBERON:0001630	87.89	gold quality
left testis	UBERON:0004533	87.64	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Kidney	tissue	101.5	high
Fallopian tube	tissue	99.4	high
Prostate	tissue	94.1	medium
Vagina	tissue	76.7	low
Adipose tissue	tissue	66.4	low
Lung	tissue	64.8	medium
Choroid plexus	tissue	55.1
Thyroid gland	tissue	49.6	low
Seminal vesicle	tissue	46.5	low
Heart muscle	tissue	45.3	medium
Cervix	tissue	42.6	high
Skeletal muscle	tissue	41.9	low
Placenta	tissue	41.5	medium
Salivary gland	tissue	40.2	low
Pancreas	tissue	40.2	low
Pituitary gland	tissue	39.6
Superior colliculi	tissue	34.7
Endometrium 1	tissue	34.3	low
Spleen	tissue	34.3	low
Substantia nigra	tissue	30.0
Tongue	tissue	28.8
Medulla oblongata	tissue	28.5
Skin 1	tissue	27.7	low
Spinal cord	tissue	26.4
Pons	tissue	26.0
Thalamus	tissue	25.4
Ovary	tissue	23.8	medium
Urinary bladder	tissue	23.8	high
Breast	tissue	23.4	medium
Cerebral cortex	tissue	22.1	low
Motor cortex	tissue	22.1
Periaqueductal gray	tissue	21.9
Hypothalamus	tissue	21.3
Midbrain	tissue	21.2
Somatosensory cortex	tissue	21.1
Epididymis	tissue	20.2	medium
Hippocampal formation	tissue	20.1
Entorhinal cortex	tissue	20.1
Insular cortex	tissue	19.5
Occipital cortex	tissue	19.1
Parathyroid gland	tissue	18.8	low
Smooth muscle	tissue	18.3	low
Retrosplenial and cingulate cortex	tissue	18.3
Prefrontal cortex	tissue	18.2
Temporal cortex	tissue	18.2
Retrosplenial cortex	tissue	18.1
Hippocampus	tissue	18.0	low
Locus coeruleus	tissue	17.4
Nucleus accumbens	tissue	16.1
Putamen	tissue	16.0
Postcentral gyrus	tissue	15.9
Septum	tissue	15.9
Stomach 1	tissue	15.6	low
Adrenal gland	tissue	15.3	low
Basal ganglia	tissue	15.1	low
Ventral forebrain	tissue	14.9
Gallbladder	tissue	14.8	medium
Small intestine	tissue	14.5	medium
Amygdala	tissue	14.4
Liver	tissue	14.3	low

Brain sub-regions (HPA Brain Atlas): detected in 292; highest nTPM — Blood vessel (346.2), Flocculonodular lobe (37.6), Cerebellar cortex (35.7), Posterior thalamic nucleus (32.9), Ventromedial nucleus (32.9).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting BCAM by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 43 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 6.22e-19, LOEUF 1.1, missense Z -0.543 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000270233 — one region, missense o/e 1.02.

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)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q9BH13	94.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
APOC1	protein-coding	341
APOE	protein-coding	348
NECTIN2	protein-coding	5819
MIR8085	ncRNA	102465879
CEACAM16-AS1	ncRNA	107985305
CBLC	protein-coding	23624
CEACAM16	protein-coding	388551
BCL3	protein-coding	602
TOMM40	protein-coding	10452

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 (65 total): strand 18, sequence variant 8, helix 6, glycosylation site 5, disulfide bond 5, domain 5, modified residue 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 by resolution:

PDB	Title	Method	Resolution (Å)
2PET	Lutheran glycoprotein, N-terminal domains 1 and 2.	X-RAY DIFFRACTION	1.7
2PF6	Lutheran glycoprotein, N-terminal domains 1 and 2	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: CD markers, Blood group antigen proteins, Predicted membrane proteins, Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoli fibrillar center

Antibody reliability (HPA): IH enhanced · IF approved

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)

Type	Positions
Phosphoserine	596, 598, 600, 621

Disulfide bonds (5)

Type	Positions
Disulfide bond	53–125, 172–237, 291–337, 384–424, 473–522

Glycosylation sites (5)

Type	Positions
N-linked (glcnac…) asparagine	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 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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

22 GO namespaces:

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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 16 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
cell adhesion	BP	direct assay
cell-matrix adhesion	BP	mutant phenotype
extracellular exosome	CC	high-throughput assay
extracellular matrix	CC	high-throughput assay
extracellular region	CC	high-throughput assay
plasma membrane	CC	direct assay
laminin binding	MF	mutant phenotype
laminin receptor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 549 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCAM	LAMA5	O15230	772
BCAM	KLF1	Q13351	758
BCAM	CNTN6	Q9UQ52	682
BCAM	PDZD4	Q76G19	666
BCAM	SMARCC2	Q8TAQ2	639
BCAM	A0A0J9YYA3	A0A0J9YYA3	594
BCAM	ICAM4	Q14773	570
BCAM	SMARCE1	Q969G3	554
BCAM	BCL11A	Q9H165	554
BCAM	SMARCC1	Q92922	551
BCAM	KEL	P23276	526
BCAM	SMARCB1	Q12824	490
BCAM	SCN2A	Q99250	490
BCAM	CD44	P16070	489
BCAM	HBB	P02023	433

IntAct

Human interaction partners of BCAM in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

11 partners by confidence:

Partner	Interaction type	MIscore	Records
KLHL2	physical association	0.720	6
LAMA5	association	0.640	1
KRTAP1-1	physical association	0.560	3
KRTAP1-3	physical association	0.560	3
MDFI	physical association	0.560	3
NOTCH2NLC	physical association	0.560	3
TRIM7	physical association	0.560	3
FGFR4	physical association	0.400	1
AGRN	association	0.350	1
BMAL1	association	0.350	1
TNPO2	association	0.350	1

BioGRID (77 interactions; top human partners by supporting records): LAMA5 (Affinity Capture-MS; 4 records), UBE2I (Affinity Capture-Western; 3 records), ARNTL (Affinity Capture-MS; 2 records), ATP11C (Affinity Capture-MS; 2 records), ATP6V0A1 (Affinity Capture-MS; 2 records), ATP6V0A2 (Affinity Capture-MS; 2 records), CD79A (Affinity Capture-MS; 2 records), CDH8 (Affinity Capture-MS; 2 records), EPHA7 (Affinity Capture-MS; 2 records), KLHL2 (Two-hybrid; 2 records), LAMA4 (Affinity Capture-MS; 2 records), LAMB1 (Affinity Capture-MS; 2 records), PRCC (Affinity Capture-MS; 2 records), TMEM11 (Affinity Capture-MS; 2 records), TNPO2 (Affinity Capture-MS; 2 records)

Disease & clinical

Genetic variants

Variant evidence for BCAM: 163 ClinVar records (5 pathogenic / likely pathogenic); 43 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	105
Likely benign	21
Benign	10

Top pathogenic / likely-pathogenic (5)

Showing all 5 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
3892999	NM_005581.5(BCAM):c.880dup (p.Asp294fs)	Likely pathogenic	criteria provided, single submitter	1
440	NM_005581.5(BCAM):c.691C>T (p.Arg231Ter)	Pathogenic	no assertion criteria provided	1
441	NG_007480.1:g.(7267_8082)_(8469_9169)del	Pathogenic	no assertion criteria provided	1
442	NM_005581.5(BCAM):c.711C>A (p.Cys237Ter)	Pathogenic	no assertion criteria provided	1
443	NM_005581.5(BCAM):c.361C>T (p.Arg121Ter)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore BCAM’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 1,087):

Position(s)	Effect	Δscore	Sites
19:44809207–44809208	donor_loss	1.0000	4
19:44811223–44811224	acceptor_loss	1.0000	4
19:44811280	donor_gain	1.0000
19:44811336	donor_gain	1.0000
19:44811347–44811348	donor_loss	1.0000	5
19:44812475	acceptor_gain	1.0000
19:44813347–44813348	donor_loss	1.0000	3
19:44813436–44813437	acceptor_loss	1.0000	6
19:44813621–44813622	donor_loss	1.0000	5
19:44814594	acceptor_gain	1.0000

AlphaMissense

589 missense substitutions predicted likely pathogenic (of 4,036 scored), across 200 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
C473	7	0.980	0.993
C522	7	0.977	0.993
C337	7	0.973	0.993
C172	7	0.972	0.990
C424	7	0.970	0.987
C291	7	0.968	0.990
W396	7	0.968	0.997
W485	7	0.967	0.997
C237	7	0.964	0.984
C125	7	0.960	0.985
W185	7	0.958	0.992
C384	7	0.955	0.980
C53	7	0.932	0.972
W66	7	0.917	0.988
N526	7	0.897	0.984
F535	7	0.895	0.977
F235	7	0.880	0.973
D341	7	0.870	0.947
F416	7	0.865	0.965
F537	7	0.814	0.949

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Ovary Serous Cystadenocarcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

5 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.04e-06
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	0.000402
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000453
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000813
Pancreatic Adenocarcinoma (TCGA)	favorable	0.00092

Disease associations

OMIM: gene MIM:612773 | disease phenotypes:

HPO phenotypes

2 phenotypes (HPO-id order):

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

GWAS associations

showing 30 of 43 associations:

Study	Trait	p-value
GCST006612_34	LDL cholesterol	1e-300
GCST007320_75	Alzheimer’s disease or family history of Alzheimer’s disease	2e-143
GCST002422_1	Alzheimer’s disease	9e-116
GCST007827_3	Alzheimer’s disease or HDL levels (pleiotropy)	1e-97
GCST004069_13	Cerebrospinal fluid AB1-42 levels	5e-94
GCST007827_5	Alzheimer’s disease or HDL levels (pleiotropy)	7e-74
GCST007827_6	Alzheimer’s disease or HDL levels (pleiotropy)	7e-54
GCST007012_6	Cerebrospinal fluid AB1-42 levels	1e-51
GCST007827_7	Alzheimer’s disease or HDL levels (pleiotropy)	5e-50
GCST008438_5	Alzheimer’s disease in hypertension	6e-43
GCST007827_8	Alzheimer’s disease or HDL levels (pleiotropy)	3e-36
GCST008437_7	Alzheimer’s disease in hypertension-negative individuals	2e-30
GCST006996_2	Cerebrospinal AB1-42 levels in mild cognitive impairment	6e-27
GCST007007_4	Cerebrospinal fluid t-tau levels	1e-20
GCST90013406_278	Liver enzyme levels (alkaline phosphatase)	1e-20
GCST007009_7	Hippocampal volume	2e-19
GCST007010_3	Logical memory (delayed recall)	2e-18
GCST007008_6	Cerebrospinal fluid p-tau levels	3e-18
GCST009496_25	Alzheimer’s disease (onset between ages 58 and 79)	6e-16
GCST009921_8	Carotid intima media thickness (mean)	6e-15
GCST007600_1	Alzheimer’s disease	3e-14
GCST007600_2	Alzheimer’s disease	7e-14
GCST009738_3	Carotid intima media thickness (maximum)	7e-14
GCST006997_3	Cerebrospinal fluid t-tau levels in mild cognitive impairment	1e-13
GCST007011_3	Logical memory (immediate recall)	2e-13
GCST007320_15	Alzheimer’s disease or family history of Alzheimer’s disease	3e-13
GCST006585_1175	Blood protein levels	1e-12
GCST009496_2	Alzheimer’s disease (onset between ages 58 and 79)	1e-12
GCST007320_22	Alzheimer’s disease or family history of Alzheimer’s disease	6e-12
GCST005952_8	Body mass index (age>50)	9e-12

EFO canonical traits (from GWAS)

13 canonical traits:

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0004343	waist-hip ratio
EFO:0004340	body mass index
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0005035	hippocampal volume
EFO:0004760	t-tau measurement
EFO:0004763	p-tau measurement
EFO:0004874	memory performance
EFO:0009268	family history of Alzheimer’s disease
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	5
Estradiol	decreases expression, affects cotreatment, increases expression	3
bisphenol A	increases expression, affects 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	increases abundance, increases expression, decreases 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	decreases expression, increases abundance, affects cotreatment	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)

Via MONDO — disease-level, not drug-specific.

12 trials:

NCT	Phase	Status	Title
NCT03414970	Phase 3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	Phase 2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	Phase 2	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	Phase 1/2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	Phase 1/2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	Early Phase 1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	Early Phase 1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT07628634	Early Phase 1	RECRUITING	Feasibility Study on the Effect of a Methionine-Reduced Diet on Serum Levels in Pts w/ Solid Tumors
NCT01208974	Not specified	COMPLETED	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