MCAM

Summary

MCAM (melanoma cell adhesion molecule, HGNC:6934) is a protein-coding gene on chromosome 11q23.3, encoding Cell surface glycoprotein MUC18 (P43121). Plays a role in cell adhesion, and in cohesion of the endothelial monolayer at intercellular junctions in vascular tissue.

Predicted to enable laminin receptor activity. Involved in glomerular filtration and vascular wound healing. Acts upstream of or within angiogenesis. Located in external side of plasma membrane. Biomarker of chronic obstructive pulmonary disease and uveal melanoma.

Source: NCBI Gene 4162 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 132 total
• Druggable target: yes
• MANE Select transcript: NM_006500

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6934
Approved symbol	MCAM
Name	melanoma cell adhesion molecule
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	MUC18, CD146, MelCAM, METCAM, HEMCAM
Ensembl gene	ENSG00000076706
Ensembl biotype	protein_coding
OMIM	155735
Entrez	4162

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 12 protein_coding, 11 protein_coding_CDS_not_defined, 5 retained_intron

ENST00000264036, ENST00000524940, ENST00000525555, ENST00000525586, ENST00000526190, ENST00000526992, ENST00000528502, ENST00000528533, ENST00000528976, ENST00000529257, ENST00000529295, ENST00000529686, ENST00000530006, ENST00000530144, ENST00000530706, ENST00000530937, ENST00000534522, ENST00000856035, ENST00000856036, ENST00000856037, ENST00000920895, ENST00000957745, ENST00000957746, ENST00000957747, ENST00000957748, ENST00000957749, ENST00000957750, ENST00000957751

RefSeq mRNA: 1 — MANE Select: NM_006500 NM_006500

CCDS: CCDS31690

Canonical transcript exons

ENST00000264036 — 16 exons

Exon	Start	End
ENSE00001415913	119308529	119309915
ENSE00002156356	119317035	119317130
ENSE00003479490	119310756	119310903
ENSE00003497650	119311280	119311421
ENSE00003502988	119315139	119315263
ENSE00003526128	119311530	119311651
ENSE00003556741	119314489	119314576
ENSE00003557102	119314833	119315040
ENSE00003563488	119311090	119311185
ENSE00003570070	119312052	119312170
ENSE00003583740	119312770	119312949
ENSE00003592349	119312266	119312428
ENSE00003608698	119312527	119312648
ENSE00003610284	119311808	119311949
ENSE00003677214	119314679	119314749
ENSE00003682271	119310349	119310466

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.4235 / max 953.2459, expressed in 1332 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122699	31.4235	1332

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood vessel layer	UBERON:0004797	99.84	gold quality
popliteal artery	UBERON:0002250	99.80	gold quality
tibial artery	UBERON:0007610	99.79	gold quality
artery	UBERON:0001637	99.76	gold quality
right coronary artery	UBERON:0001625	99.74	gold quality
saphenous vein	UBERON:0007318	99.71	gold quality
aorta	UBERON:0000947	99.69	gold quality
coronary artery	UBERON:0001621	99.61	gold quality
left coronary artery	UBERON:0001626	99.61	gold quality
ascending aorta	UBERON:0001496	99.56	gold quality
thoracic aorta	UBERON:0001515	99.56	gold quality
descending thoracic aorta	UBERON:0002345	99.53	gold quality
mucosa of stomach	UBERON:0001199	99.29	gold quality
subcutaneous adipose tissue	UBERON:0002190	99.23	gold quality
adipose tissue	UBERON:0001013	99.19	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.11	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.06	gold quality
lower esophagus	UBERON:0013473	99.05	gold quality
left uterine tube	UBERON:0001303	99.02	gold quality
nipple	UBERON:0002030	98.93	gold quality
urethra	UBERON:0000057	98.89	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.89	gold quality
omental fat pad	UBERON:0010414	98.86	gold quality
peritoneum	UBERON:0002358	98.84	gold quality
pericardium	UBERON:0002407	98.66	gold quality
body of uterus	UBERON:0009853	98.66	gold quality
connective tissue	UBERON:0002384	98.55	gold quality
vena cava	UBERON:0004087	98.54	gold quality
muscle layer of sigmoid colon	UBERON:0035805	98.40	gold quality
nerve	UBERON:0001021	98.33	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-MTAB-10662	yes	1879.60
E-HCAD-36	yes	1109.21
E-GEOD-137537	yes	657.74
E-MTAB-8142	yes	125.90
E-MTAB-10287	yes	55.31
E-HCAD-10	yes	49.10
E-GEOD-135922	yes	36.24
E-HCAD-11	yes	26.98
E-MTAB-8410	yes	25.57
E-MTAB-6678	yes	17.61
E-GEOD-134144	yes	11.30
E-CURD-46	yes	10.60
E-MTAB-6142	no	359.52
E-MTAB-10137	no	224.98
E-MTAB-8271	no	178.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, NR1I2, SP1, TFAP2A

miRNA regulators (miRDB)

65 targeting MCAM, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-3692-5P	99.29	67.04	1421

Literature-anchored findings (GeneRIF, showing 40)

• Increased expression of MUC18 is implicated to play an important role in developing and malignant progression of human prostate cancer. (PMID:11722842)
• Acute hyperglycaemia induces an up-regulation of seven major genes, four of which were not previously reported in the literature. Northern blot analyses, performed on these 4 genes, confirm macroarrays results for alphav, beta4, c-myc, and MUC18. (PMID:11848444)
• The 28mer peptides are structural equivalents of the MAd18-5D7 epitope of Mel-CAM. (PMID:12406332)
• MCAM and akt protein are reciprocally regulated. (PMID:14534536)
• sCD146 circulates in the plasma of healthy subjects; significantly increased levels of sCD146 in blood and CD146 in kidney endothelial cells of patients with chronic renal failure were observed. (PMID:14597988)
• endothelin-1 (ET-1) upregulates MCAM protein in primary human melanocytes (PMID:15610525)
• Elevation of adiponectin may be a defense mechanism against endothelial damage, reflected by elevated CD146 and thrombomodulin. (PMID:15897668)
• When cell surface glycoprotein gp130 was purified and analyzed by peptide mass fingerprinting, we could demonstrate that it is MUC18 (Mel-CAM, CD146) (PMID:16098047)
• CD146 is a new marker of activated lymphocytes, not just an adhesion marker of endothelial cells (PMID:16204154)
• results demonstrate that CD146 plays a key role in vascular endothelial cell activity and angiogenesis (PMID:16541130)
• Our data indicate a correlation between MUC18 expression and the invasiveness of uveal melanoma cells. (PMID:16570276)
• M-CAM is a marker of early relapse and poorer outcome in epithelial ovarian cancer (PMID:16804906)
• Results identify melanoma cell adhesion molecule as a novel marker for myogenic progenitors in human fetal muscle and confirm that downregulation of this protein promotes myoblast fusion. (PMID:16835268)
• MCAM expression doees not correlates with progression to advanced-stage melanoma. (PMID:16969099)
• These data provide the first evidence that CD146 dimerization occurs in living cells and is regulated within the tumor microenvironment, implying that dimerization of CD146 may be associated with malignancy. (PMID:17320204)
• Plasma levels may be involed in the development of vascular complication in end stage of diabetic nephropathy. (PMID:17490776)
• CD146(an endothelial cell marker)is also expressed on lymphocytes,implicating its role in T cell adherence and activation to vascular endothelium (PMID:17545460)
• Vasculature in tumours and in retina and choroid of all melanoma-affected and normal eyes showed intense MUC18 immunostaining. observations further suggest a role for MUC18 in uveal melanoma growth. (PMID:17786470)
• CD146 and platelet-derived growth factor-receptor beta are expressed in colony-forming endometrial stromal cells which may be mesenchymal stem cells, and have roles in the cells’ cyclical growth (PMID:17872908)
• MCAM might be involved in the recruitment of activated T cells to inflammation sites. (PMID:17982057)
• Elevated adiponectin correlated to CD146 may be the expression of a counterregulatory response aimed at mitigating the consequences in endothelial damage and increased cardiovascular risk in renal failure. (PMID:18160586)
• A decrease in serum adiponectin levels and an increase in serum CD146 may be closely associated with the development of arteriosclerosis obliterans, regardless of renal function. (PMID:18175063)
• The immunoreactivity of the polyclonal CD146 antibody (Abcam, ab28360) is prognostic of PSA-relapse in prostate cancer patients (PMID:18604730)
• Reflux laryngitis is associated with down-regulation of mucin gene expression. (PMID:18834073)
• A subset of host B lymphocytes controls melanoma metastasis through a melanoma cell adhesion molecule/MUC18-dependent interaction. (PMID:18922915)
• CD146(+) cell involvement in bone marrow stromal changes occurring in primary myelofibrosis are consistent with the capability of these cells to participate in fiber deposition, angiogenesis, and bone formation (PMID:19029148)
• CD146 might be a novel marker for RTECs, correlating with cell proliferation and cell-cell conjunctions. High glucose up-regulates both CD146 and sCD146 expression. (PMID:19034879)
• CD146 downmodulation is associated with the reversal of several biological characteristics associated with epithelial to mesenchymal transition, and the phenomenon associated with the metastatic process in human breast tumors. (PMID:19123925)
• may play an important role in the carcinogenesis, progression and perineural invasion activity of adenoid cystic carcinoma (PMID:19200179)
• Identification of MCAM/CD146 as the surface antigen bound by one of the mesothelioma-targeting human single chain antibodies in cultured tumor cells. (PMID:19221091)
• CD146 is regulated by the inflammatory cytokine Tumor necrosis factor alpha and that CD146 and solubleCD146 are both involved in monocyte transendothelial migration during inflammation. (PMID:19229070)
• analysis of the cross-talk between protease-activated receptor 1 and platelet-activating factor receptor regulates melanoma cell adhesion molecule (MCAM/MUC18) expression and melanoma metastasis (PMID:19703903)
• This study for the first time uncovered the pro-angiogenic role of CD146 and also pinpointed the key structural basis responsible for its signaling function and dimerization. (PMID:19782948)
• CD146 was mainly expressed in renal tubular epithelial cells, and might play an important role in the progression of IgA nephropathy. (PMID:20067117)
• CD146 may serve as a marker of multipotency in human mesenchymal stem cells, with higher expression in tripotent vs. unipotent clonal populations. (PMID:20127798)
• CD146 short isoform overexpression displays a distinct function in blood vessel regeneration. (PMID:20448216)
• mRNA levels of CD31, CD144, CD146 and vWf in whole blood as detected by real time RT-PCR cannot be used as biomarkers for end-stage endothelial cells such as circulating endothelial cells. (PMID:20589320)
• Propose that CD146 is a sensitive and specific immunocytochemical marker enabling differential diagnosis of malignant pleural mesothelioma from reactive mesothelium. (PMID:20657552)
• CD146 may be a key gene both in neoplasm invasion and blastocyst embedding because of its ability in regulating cell invasion. (PMID:21095067)
• an allergic airway milieu (e.g., IL-13) increases MUC18 expression, which may contribute to increased bacterial infection/colonization in asthma and other lung diseases (PMID:21239604)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mcamb	ENSDARG00000005368
danio_rerio	mcama	ENSDARG00000089643
mus_musculus	Mcam	ENSMUSG00000032135
rattus_norvegicus	Mcam	ENSRNOG00000007726

Paralogs (3): ALCAM (ENSG00000170017), BCAM (ENSG00000187244), AGER (ENSG00000204305)

Protein

Protein identifiers

Cell surface glycoprotein MUC18 — P43121 (reviewed: P43121)

Alternative names: Cell surface glycoprotein P1H12, Melanoma cell adhesion molecule, Melanoma-associated antigen A32, Melanoma-associated antigen MUC18, S-endo 1 endothelial-associated antigen

All UniProt accessions (1): P43121

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in cell adhesion, and in cohesion of the endothelial monolayer at intercellular junctions in vascular tissue. Its expression may allow melanoma cells to interact with cellular elements of the vascular system, thereby enhancing hematogeneous tumor spread. Could be an adhesion molecule active in neural crest cells during embryonic development. Acts as a surface receptor that triggers tyrosine phosphorylation of FYN and PTK2/FAK1, and a transient increase in the intracellular calcium concentration.

Subcellular location. Membrane.

Tissue specificity. Detected in endothelial cells in vascular tissue throughout the body. May appear at the surface of neural crest cells during their embryonic migration. Appears to be limited to vascular smooth muscle in normal adult tissues. Associated with tumor progression and the development of metastasis in human malignant melanoma. Expressed most strongly on metastatic lesions and advanced primary tumors and is only rarely detected in benign melanocytic nevi and thin primary melanomas with a low probability of metastasis.

Isoforms (2)

UniProt ID	Names	Canonical?
P43121-1	1	yes
P43121-2	2

RefSeq proteins (1): NP_006491* (*=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, PF13927

UniProt features (54 total): strand 14, glycosylation site 8, disulfide bond 5, domain 5, sequence conflict 4, region of interest 3, modified residue 3, compositionally biased region 2, topological domain 2, splice variant 2, helix 2, signal peptide 1, chain 1, transmembrane region 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6LYN	X-RAY DIFFRACTION	2.78

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43121-F1	80.79	0.57

Antibody-complex structures (SAbDab): 1 — 6LYN

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 (3): 606, 614, 628

Disulfide bonds (5): 48–116, 161–223, 272–320, 365–407, 452–499

Glycosylation sites (8): 56, 418, 449, 467, 508, 518, 527, 544

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013405	RHOD GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-9035034	RHOF GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 248 (showing top): ATF_B, AGGAAGC_MIR5163P, GCANCTGNY_MYOD_Q6, MODULE_64, VICENT_METASTASIS_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GOCC_CELL_SURFACE, JOHANSSON_GLIOMAGENESIS_BY_PDGFB_UP, AREB6_01, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_UP, DARWICHE_PAPILLOMA_RISK_HIGH_UP, CREBP1_Q2, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, LIEN_BREAST_CARCINOMA_METAPLASTIC

GO Biological Process (6): angiogenesis (GO:0001525), glomerular filtration (GO:0003094), cell adhesion (GO:0007155), anatomical structure morphogenesis (GO:0009653), positive regulation of cell migration (GO:0030335), vascular wound healing (GO:0061042)

GO Molecular Function (2): laminin receptor activity (GO:0005055), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), plasma membrane (GO:0005886), focal adhesion (GO:0005925), external side of plasma membrane (GO:0009897), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RHO GTPase cycle	9
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
renal filtration	1
cellular process	1
developmental process	1
anatomical structure development	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
angiogenesis involved in wound healing	1
laminin binding	1
cell adhesion mediator activity	1
binding	1
membrane	1
cell periphery	1
cell-substrate junction	1
plasma membrane	1
cell surface	1
side of membrane	1

Protein interactions and networks

STRING

2110 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MCAM	KDR	P35968	932
MCAM	PECAM1	P16284	849
MCAM	ENG	P17813	827
MCAM	FZD3	Q9NPG1	806
MCAM	THY1	P04216	790
MCAM	NT5E	P21589	778
MCAM	CD34	P28906	773
MCAM	PTPRC	P08575	771
MCAM	WNT5A	P41221	749
MCAM	RHOB	P01121	743
MCAM	LAMA4	Q16363	732
MCAM	ITGB1	P05556	701
MCAM	CD44	P16070	696
MCAM	EZR	P15311	677
MCAM	RDX	P35241	654

IntAct

67 interactions, top by confidence:

A	B	Type	Score
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
MCAM	CNTN1	psi-mi:“MI:0914”(association)	0.750
CNTN1	MCAM	psi-mi:“MI:0915”(physical association)	0.750
MCAM	CNTN1	psi-mi:“MI:0407”(direct interaction)	0.750
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CLEC4A	SEMA7A	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
MCAM	LGALS8	psi-mi:“MI:0914”(association)	0.530
ANKH	FAM234B	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
SELE	MCAM	psi-mi:“MI:0915”(physical association)	0.400
MCAM	NPM1	psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
MCAM	FUT2	psi-mi:“MI:0915”(physical association)	0.400
	MCAM	psi-mi:“MI:2364”(proximity)	0.380
	MCAM	psi-mi:“MI:0403”(colocalization)	0.380
PCNA	MCAM	psi-mi:“MI:0915”(physical association)	0.370
UBE2O	MCAM	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (522): MCAM (Affinity Capture-MS), ATP6V0A2 (Affinity Capture-MS), ATP6V0A1 (Affinity Capture-MS), ATP11C (Affinity Capture-MS), LAMA4 (Affinity Capture-MS), CNTN1 (Affinity Capture-MS), ATP6V0D1 (Affinity Capture-MS), MCAM (Proximity Label-MS), MCAM (Proximity Label-MS), MCAM (Proximity Label-MS), LAMA4 (Affinity Capture-MS), CNTN1 (Affinity Capture-MS), ATP6V0A2 (Affinity Capture-MS), MCAM (Affinity Capture-MS), ATP6V0A1 (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: P15364, P43121, Q7Z5N4, Q8AV58, Q8AXY6, Q8R2Y2, Q9EPF2, Q9MZ08, Q9R069, P50895, Q9BH13, Q9ESS6, O73895, Q5R8H1, Q5TJE4, Q6PZD2, Q8VD31, Q9BX59, A0JM20, A0N0X6, A1KZ92, A4IGL7, D3ZEY0, E9Q8Q6, G5EGI7, O15146, O60229, O97394, P0C192, P0C5J5, P0C6S8, P0CC10, P29320, P55144, P55146, Q00993, Q01974, Q14896, Q16270, Q3KNY0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 62 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Neutrophil degranulation	7	3.9×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	111
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2747 predictions. Top by Δscore:

Variant	Effect	Δscore
11:119310755:CAT:C	donor_gain	1.0000
11:119310766:T:TA	donor_gain	1.0000
11:119310767:C:A	donor_gain	1.0000
11:119311181:ATTGA:A	acceptor_gain	1.0000
11:119311182:TTGA:T	acceptor_gain	1.0000
11:119311183:TGA:T	acceptor_gain	1.0000
11:119311186:C:CC	acceptor_gain	1.0000
11:119311274:CCTCA:C	donor_loss	1.0000
11:119311275:CTCA:C	donor_loss	1.0000
11:119311276:TCA:T	donor_loss	1.0000
11:119311277:CACCC:C	donor_loss	1.0000
11:119311278:A:AC	donor_gain	1.0000
11:119311278:AC:A	donor_gain	1.0000
11:119311278:ACCCA:A	donor_loss	1.0000
11:119311279:C:CC	donor_gain	1.0000
11:119311279:CC:C	donor_gain	1.0000
11:119311279:CCCAG:C	donor_gain	1.0000
11:119311282:AGCT:A	donor_gain	1.0000
11:119311283:G:C	donor_gain	1.0000
11:119311417:CTTGC:C	acceptor_gain	1.0000
11:119311418:TTGC:T	acceptor_gain	1.0000
11:119311419:TGC:T	acceptor_gain	1.0000
11:119311420:GC:G	acceptor_gain	1.0000
11:119311421:CC:C	acceptor_gain	1.0000
11:119311422:C:CC	acceptor_gain	1.0000
11:119311422:C:CG	acceptor_loss	1.0000
11:119311425:C:CT	acceptor_gain	1.0000
11:119311426:G:T	acceptor_gain	1.0000
11:119311653:T:C	acceptor_gain	1.0000
11:119311806:ACCAA:A	donor_loss	1.0000

AlphaMissense

4200 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:119312064:C:A	W377C	0.998
11:119312064:C:G	W377C	0.998
11:119311545:C:A	W464C	0.997
11:119311545:C:G	W464C	0.997
11:119311873:C:G	C407S	0.997
11:119311874:A:T	C407S	0.997
11:119314526:C:A	W174C	0.997
11:119314526:C:G	W174C	0.997
11:119314528:A:G	W174R	0.997
11:119314528:A:T	W174R	0.997
11:119311333:C:G	C499S	0.996
11:119311334:A:T	C499S	0.996
11:119311547:A:G	W464R	0.996
11:119311547:A:T	W464R	0.996
11:119312573:C:G	C272S	0.996
11:119312574:A:T	C272S	0.996
11:119312066:A:G	W377R	0.995
11:119312066:A:T	W377R	0.995
11:119312574:A:G	C272R	0.995
11:119312331:C:G	C320S	0.994
11:119312332:A:T	C320S	0.994
11:119311874:A:G	C407R	0.993
11:119312101:C:T	C365Y	0.993
11:119312332:A:G	C320R	0.993
11:119312841:C:G	C223S	0.993
11:119312841:C:T	C223Y	0.993
11:119312842:A:T	C223S	0.993
11:119311582:C:G	C452S	0.992
11:119311583:A:T	C452S	0.992
11:119312101:C:G	C365S	0.991

dbSNP variants (sampled 300 via entrez): RS1000022573 (11:119318792 A>G), RS1000143348 (11:119313953 T>C,G), RS1001098778 (11:119312622 C>T), RS1001343806 (11:119309350 GCAGA>G), RS1001376773 (11:119314895 A>G), RS1001551617 (11:119312414 C>A,G), RS1001569951 (11:119315879 G>A), RS1001627138 (11:119315448 G>A), RS1001809075 (11:119310075 G>A), RS1002648432 (11:119308190 C>G,T), RS1002787158 (11:119313414 T>C), RS1003046728 (11:119317169 C>A,G,T), RS1003295798 (11:119316958 C>A,T), RS1003885205 (11:119311081 C>G), RS1004328912 (11:119317168 G>A,T)

Disease associations

OMIM: gene MIM:155735 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002400_480	Plateletcrit	1.000000e-27

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3712863 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Immunoglobulin C2-set domain-containing proteins

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
imaprelimab	Binding	8.06	pKd

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects expression, increases expression	6
Doxorubicin	decreases expression, decreases response to substance	3
Tobacco Smoke Pollution	affects expression, decreases expression	3
Aflatoxin B1	increases expression, increases methylation	3
bisphenol A	decreases expression, increases expression	2
sodium arsenite	decreases expression	2
perfluoro-n-nonanoic acid	affects expression, decreases expression	2
Resveratrol	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Estradiol	increases expression, affects cotreatment	2
Lipopolysaccharides	affects response to substance, increases expression, increases reaction	2
Methylnitronitrosoguanidine	increases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Smoke	decreases expression, increases abundance	2
Cadmium Chloride	decreases expression, increases abundance	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
geldanamycin	increases expression	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
decabromobiphenyl ether	increases expression	1
arsenite	increases methylation	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
phenanthrene	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1WW	Abcam HeLa MCAM KO	Cancer cell line	Female
CVCL_SX57	HAP1 MCAM (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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