CDCP1

Summary

CDCP1 (CUB domain containing protein 1, HGNC:24357) is a protein-coding gene on chromosome 3p21.31, encoding CUB domain-containing protein 1 (Q9H5V8). May be involved in cell adhesion and cell matrix association.

This gene encodes a transmembrane protein which contains three extracellular CUB domains and acts as a substrate for Src family kinases. The protein plays a role in the tyrosine phosphorylation-dependent regulation of cellular events that are involved in tumor invasion and metastasis. Alternative splicing results in multiple transcript variants of this gene.

Source: NCBI Gene 64866 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 132 total
• MANE Select transcript: NM_022842

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24357
Approved symbol	CDCP1
Name	CUB domain containing protein 1
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	CD318, SIMA135
Ensembl gene	ENSG00000163814
Ensembl biotype	protein_coding
OMIM	611735
Entrez	64866

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000296129, ENST00000425231, ENST00000490471, ENST00000903155, ENST00000903156, ENST00000932324, ENST00000932325, ENST00000932326

RefSeq mRNA: 2 — MANE Select: NM_022842 NM_022842, NM_178181

CCDS: CCDS2727, CCDS46812

Canonical transcript exons

ENST00000296129 — 9 exons

Exon	Start	End
ENSE00001078528	45089054	45089141
ENSE00001078534	45091173	45091538
ENSE00001078535	45093277	45093657
ENSE00001156416	45082277	45086067
ENSE00001166285	45095347	45095568
ENSE00001166292	45110473	45110841
ENSE00001166298	45112083	45112445
ENSE00003492545	45118412	45118621
ENSE00003848211	45146206	45146378

Expression profiles

Bgee: expression breadth ubiquitous, 211 present calls, max score 93.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.3940 / max 337.2342, expressed in 1067 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41887	12.8157	995
41888	0.9192	414
41882	0.6511	257
41886	0.5632	287
41884	0.1933	106
41881	0.1077	62
41879	0.0729	21
41880	0.0709	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gingival epithelium	UBERON:0001949	93.33	gold quality
islet of Langerhans	UBERON:0000006	92.36	gold quality
cervix squamous epithelium	UBERON:0006922	92.24	gold quality
gingiva	UBERON:0001828	91.53	gold quality
squamous epithelium	UBERON:0006914	91.49	gold quality
esophagus mucosa	UBERON:0002469	90.31	gold quality
esophagus squamous epithelium	UBERON:0006920	90.03	gold quality
lower esophagus mucosa	UBERON:0035834	89.80	gold quality
tongue squamous epithelium	UBERON:0006919	89.50	gold quality
epithelium of esophagus	UBERON:0001976	88.59	gold quality
mucosa of transverse colon	UBERON:0004991	87.46	gold quality
rectum	UBERON:0001052	85.81	gold quality
cartilage tissue	UBERON:0002418	85.54	gold quality
skin epidermis	UBERON:0001003	85.47	silver quality
hair follicle	UBERON:0002073	85.47	silver quality
pancreatic ductal cell	CL:0002079	85.09	silver quality
duodenum	UBERON:0002114	84.87	gold quality
palpebral conjunctiva	UBERON:0001812	84.61	gold quality
skin of abdomen	UBERON:0001416	84.36	gold quality
cervix epithelium	UBERON:0004801	83.73	gold quality
colonic mucosa	UBERON:0000317	83.71	gold quality
upper leg skin	UBERON:0004262	83.25	gold quality
skin of leg	UBERON:0001511	82.86	gold quality
ileal mucosa	UBERON:0000331	82.85	gold quality
zone of skin	UBERON:0000014	82.79	gold quality
jejunal mucosa	UBERON:0000399	82.62	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.54	gold quality
mucosa of sigmoid colon	UBERON:0004993	82.45	gold quality
germinal epithelium of ovary	UBERON:0001304	82.00	gold quality
skin of hip	UBERON:0001554	81.31	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	349.53
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ZBTB7B

miRNA regulators (miRDB)

123 targeting CDCP1, 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-1252-5P	100.00	69.80	2774
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-944	99.82	70.85	3042

Literature-anchored findings (GeneRIF, showing 40)

• antibodies generated by subtractive immunization used to purify, identify and partially characterize SIMA135/CDCP1; properties indicate it is a multidomain cell surface antigen, highly expressed by certain cancer cells and normal and cancerous colon (PMID:12660814)
• tyrosine phosphorylation of CDCP1 is regulated by adhesion or plasmin in epithelial cells (PMID:14739293)
• CDCP1 is not only a novel marker for immature hematopoietic progenitor cell subsets but also unique in its property to recognize cells with phenotypes reminiscent of MSC and NPC. (PMID:15153610)
• When CDCP1 promoter was transfected exogenously, Jurkat showed comparable promoter activity with K562, suggesting that the factor to enhance transcription was present but interfered to function in Jurkat (PMID:16926850)
• quantitated CDCP1 gene expression in matched normal colon and tumour tissue and compared the level of expression to other genes upregulated in colorectal tumourigenesis (PMID:17335815)
• CUB-domain-containing protein 1 (CDCP1), is identified as an Src family kinases-binding phosphoprotein associated with the anchorage independence of human lung adenocarcinoma. (PMID:17785447)
• The clustering of Gp140 and signaling components in membrane microdomains in cell-cell contacts contributes to changes in cell behavior. (PMID:18269919)
• CDCP1 promotes invasion and peritoneal dissemination of cancer cells through the regulation of cell migration and anchorage independence. (PMID:18467693)
• CDCP1 may have a role in neoplasm metastasis; targeting it with a monoclonal antibody inhibits metastasis in a prostate cancer model (PMID:18483259)
• Overexpression of CUB-domain containing protein 1 is associated with metastasis and recurrence in renal cell carcinoma. (PMID:18483744)
• CDCP1 expression level is a useful marker for prediction of patients with lung adenocarcinoma (PMID:19077003)
• abberant Trask phosphorylation is seen in many epithelial tumors from all stages including preinvasive, invasive, and metastatic tumors. (PMID:19318475)
• These findings confirm that CDCP1 functions as an antiapoptotic molecule and indicate that during metastasis CDCP1 facilitates tumor cell survival likely during or soon after extravasation. (PMID:19671673)
• findings indicate a functional role for CDCP1 in cancer and underscore the therapeutic potential of function-blocking anti-CDCP1 antibodies targeting both primary and metastatic carcinoma cells (PMID:19916495)
• In endometrioid adenocarcinoma low CDCP1 and advanced stage were independent poor prognostic factors for both overall and disease-free survival. (PMID:20372833)
• Overexpression of CDCP1 is associated with pancreatic cancers. (PMID:20501830)
• biological role of this protein and, potentially, its function in cancer, may be mediated by both 70-kDa cell retained and 65-kDa shed fragments, as well as the full-length 135-kDa protein. (PMID:20551327)
• Trask signaling and focal adhesion signaling inactivate each other and signal in exclusion with each other, constituting a switch that underlies cell anchorage state. (PMID:21189288)
• Data provide molecular mechanisms for the metastasis-enhancing functions of CDCP1. (PMID:21220330)
• Signal transduction from CDCP1 to PKCdelta leads to its activation, increasing migration of CC-RCC. Furthermore, patient survival can be stratified by CDCP1 expression at the cell surface of the tumor (PMID:21233420)
• Src-Trask signaling and Src-focal adhesion signaling inactivate each other, constituting two opposing modes of phosphotyrosine signaling that define a switch underlining cell anchorage state. (PMID:21490433)
• analysis of structural features of Trask that mediate its anti-adhesive functions (PMID:21559459)
• CDCP1 is selectively expressed in ovarian tumor vasculature (PMID:21617380)
• Trask as one of several potential candidates for functionally relevant tumor suppressors on the 3p21.3 region of the genome frequently lost in human cancers. (PMID:21706059)
• Data show that the signaling events that accompany the CDCP1 tyrosine phosphorylation observed in cell lines and lung tumors may explain how the CDCP1/SFK complex regulates motility and adhesion. (PMID:21725358)
• CUB domain-containing protein 1 (CDCP1) is a substrate of Src family kinases and has been shown to regulate anoikis resistance, migration and matrix degradation during tumor invasion and metastasis in a tyrosine phosphorylation-dependent manner. Review. (PMID:21812858)
• analysis of cellular settings mediating Src Substrate switching between focal adhesion kinase tyrosine 861 and CUB-domain-containing protein 1 (CDCP1) tyrosine 734 (PMID:21994943)
• a novel role for CDCP1 in EGF/EGFR-induced cell migration and indicate that targeting of CDCP1 may be a rational approach to inhibit progression of cancers driven by EGFR signaling (PMID:22315226)
• Secreted CDCP1 can be a useful genetic marker for the diagnosis of metastatic prostate cancer. (PMID:22457534)
• Complexing of beta1 integrin the 70-kDa with CDCP1 fragment induced intracellular phosphorylation signaling, involving focal adhesion kinase-1 (FAK) and PI3 kinase (PI3K)-dependent Akt activation (PMID:23208492)
• strongly expressed in tumors derived from lung, colon, ovary, or kidney. for a full transformation capacity, the intact amino- and carboxy-termini of CDCP1 are essential. (PMID:23300860)
• These data support a critical role for CDCP1 as a unique HIF-2alpha target gene involved in the regulation of cancer metastasis. (PMID:23378636)
• CDCP1 is an essential regulator of the trafficking and function of MT1-MMP- and invadopodia-mediated invasion of cancer cells. (PMID:23439492)
• Expression and phosphorylation of exogenous CDCP1 by Fyn kinase reduced the formation of autophagosomes. (PMID:23510015)
• In migrating cancer stem cells isolated from primary human colorectal cancers, CD110(+) and CDCP1(+) subpopulations mediate organ-specific lung and liver metastasis. (PMID:23747337)
• CDCP1 represses the epithelial phenotype of pancreatic cancer cells. (PMID:24384474)
• EGF increases the lifespan of CDCP1 promoting its availability on the cell surface where the data indicate it is available to mediate procancer phenotypes such as cell migration. (PMID:24681947)
• decreased CDCP1 expression promoted the invasive and migratory abilities of esophageal cancer cell lines. (PMID:24849519)
• CDCP1 protein induced by oncogenic Ras/Erk signaling is essential for Ras-mediated metastatic potential of cancer cells. (PMID:24939643)
• These data suggest CDCP1 expression can be used to identify a subset of marrow fibroblasts functionally distinct from CD146+ fibroblasts. (PMID:25275584)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdcp1a	ENSDARG00000058943
danio_rerio	CDCP1	ENSDARG00000110186
mus_musculus	Cdcp1	ENSMUSG00000035498
rattus_norvegicus	Cdcp1	ENSRNOG00000004743

Protein

Protein identifiers

CUB domain-containing protein 1 — Q9H5V8 (reviewed: Q9H5V8)

Alternative names: Membrane glycoprotein gp140, Subtractive immunization M plus HEp3-associated 135 kDa protein, Transmembrane and associated with src kinases

All UniProt accessions (1): Q9H5V8

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in cell adhesion and cell matrix association. May play a role in the regulation of anchorage versus migration or proliferation versus differentiation via its phosphorylation. May be a novel marker for leukemia diagnosis and for immature hematopoietic stem cell subsets. Belongs to the tetraspanin web involved in tumor progression and metastasis.

Subunit / interactions. Interacts with CDH2/N-cadherin, CDH3/P-cadherin, SDC1/syndecan-1, SDC4/syndecan-4 and the serine protease ST14/MT-SP1. Also interacts with SRC and PRKCG/protein kinase C gamma.

Subcellular location. Cell membrane Secreted.

Tissue specificity. Highly expressed in mitotic cells with low expression during interphase. Detected at highest levels in skeletal muscle and colon with lower levels in kidney, small intestine, placenta and lung. Up-regulated in a number of human tumor cell lines, as well as in colorectal cancer, breast carcinoma and lung cancer. Also expressed in cells with phenotypes reminiscent of mesenchymal stem cells and neural stem cells.

Post-translational modifications. Phosphorylated on tyrosine by kinases of the SRC family such as SRC and YES as well as by the protein kinase C gamma/PRKCG. Dephosphorylated by phosphotyrosine phosphatases. Also phosphorylated by suramin, a heparin analog. Tyrosine phosphorylated in response to dissociation of integrin alpha-6 beta-4 from laminin-5. N-glycosylated. A soluble form may also be produced by proteolytic cleavage at the cell surface (shedding). Another peptide of 80 kDa (p80) is present in cultured keratinocytes probably due to tryptic cleavage at an unidentified site on its N-terminal side. Converted to p80 by plasmin, a trypsin-like protease.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H5V8-1	1	yes
Q9H5V8-2	2
Q9H5V8-3	3

RefSeq proteins (2): NP_073753, NP_835488 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR035914	Sperma_CUB_dom_sf	Homologous_superfamily
IPR038811	CDCP1	Family
IPR056266	CDCP1_CUB_3rd_6th	Domain
IPR056268	CUB_CDCP1_1st	Domain
IPR056269	CUB_CDCP1_2nd_5th	Domain
IPR056965	CUB_CDCP1_4th	Domain

Pfam: PF23665, PF23667, PF23668, PF25142

UniProt features (30 total): glycosylation site 7, sequence conflict 5, splice variant 3, sequence variant 3, topological domain 2, mutagenesis site 2, signal peptide 1, chain 1, disulfide bond 1, transmembrane region 1, domain 1, region of interest 1, site 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H5V8-F1	78.13	0.46

Functional residue map

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

Catalytic / active sites (1): 368–369 (cleavage; by st14/mt-sp1)

Post-translational modifications (1): 734

Disulfide bonds (1): 476–499

Glycosylation sites (7): 122, 180, 205, 270, 310, 386, 39

Mutagenesis-validated functional residues (2):

Position	Phenotype
734	impaired association with src.
762	impaired association with protein kinase prkcg but not with src.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 153 (showing top): DITTMER_PTHLH_TARGETS_UP, XU_HGF_SIGNALING_NOT_VIA_AKT1_48HR_UP, BILD_HRAS_ONCOGENIC_SIGNATURE, RICKMAN_METASTASIS_DN, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, KOYAMA_SEMA3B_TARGETS_UP, ROZANOV_MMP14_TARGETS_UP, MCBRYAN_PUBERTAL_BREAST_3_4WK_UP, RIGGI_EWING_SARCOMA_PROGENITOR_DN, GOBP_RESPONSE_TO_HEPATOCYTE_GROWTH_FACTOR, CHARAFE_BREAST_CANCER_LUMINAL_VS_BASAL_DN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_UP, GOBP_RESPONSE_TO_GROWTH_FACTOR, RYTTCCTG_ETS2_B

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
binding	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

788 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDCP1	ZBTB7B	O15156	900
CDCP1	SRC	P12931	830
CDCP1	CD6	P30203	786
CDCP1	EGFR	P00533	750
CDCP1	PTGER3	P43115	695
CDCP1	EPHA2	P29317	682
CDCP1	PRKCD	Q05655	678
CDCP1	SPADH	A0A494C103	624
CDCP1	CDH2	P19022	570
CDCP1	ITGB1	P05556	562
CDCP1	AKT1	P31749	558
CDCP1	MET	P08581	556
CDCP1	CD34	P28906	480
CDCP1	ST14	Q9Y5Y6	478
CDCP1	COL1A1	P02452	438

IntAct

50 interactions, top by confidence:

A	B	Type	Score
SRC	CDCP1	psi-mi:“MI:0915”(physical association)	0.790
CDCP1	SDCBP	psi-mi:“MI:0915”(physical association)	0.720
SDCBP	CDCP1	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CDCP1	PRKCD	psi-mi:“MI:0403”(colocalization)	0.670
CDCP1	PRKCD	psi-mi:“MI:0915”(physical association)	0.670
PRKCD	CDCP1	psi-mi:“MI:0915”(physical association)	0.670
YES1	CDCP1	psi-mi:“MI:0915”(physical association)	0.560
EGFR	XPOT	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
CDCP1	E2	psi-mi:“MI:0915”(physical association)	0.370
		psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
	SNAP23	psi-mi:“MI:0914”(association)	0.350
LMP2	WWP2	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
ALB	CDC45	psi-mi:“MI:0914”(association)	0.350

BioGRID (33): CDCP1 (Two-hybrid), CDCP1 (Biochemical Activity), VWA1 (Affinity Capture-MS), LEPR (Affinity Capture-MS), MAN1A1 (Affinity Capture-MS), LRFN1 (Affinity Capture-MS), CLSTN1 (Affinity Capture-MS), CDCP1 (Affinity Capture-RNA), CDCP1 (Proximity Label-MS), FBXL14 (Affinity Capture-Western), CDCP1 (Affinity Capture-Western), FBXL14 (Co-localization), CDCP1 (Affinity Capture-MS), CDCP1 (Proximity Label-MS), CDCP1 (Two-hybrid)

ESM2 similar proteins: A0A8M9PDM1, B8JI67, D3YX43, D5K8A9, E9Q8Q8, F1LW30, O70535, O95256, O95727, P20352, P27931, P42703, P43303, Q05928, Q0VCB1, Q14956, Q149L7, Q2YDG7, Q3SXY7, Q5BVD1, Q5U462, Q6AXW8, Q6AY06, Q6GMZ9, Q6P7C7, Q6P7N7, Q6PHB0, Q6PNM1, Q6UXZ4, Q7Z6A9, Q80VH0, Q8C4Q9, Q8C5C9, Q8IYV9, Q8K1S2, Q8K4B4, Q8NDB2, Q8NEA5, Q8QHJ9, Q90VY2

Diamond homologs: Q5U462, Q9H5V8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SRC	unknown	CDCP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 32 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
Signaling by ERBB2	5	61.8×	4e-06
Platelet activation, signaling and aggregation	5	18.9×	2e-04
Cytokine Signaling in Immune system	6	8.7×	1e-03
Innate Immune System	6	5.5×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of apoptotic process	6	7.0×	7e-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	6
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1894 predictions. Top by Δscore:

Variant	Effect	Δscore
3:45086064:TTTC:T	acceptor_gain	1.0000
3:45086068:C:CC	acceptor_gain	1.0000
3:45086068:CT:C	acceptor_loss	1.0000
3:45086072:T:C	acceptor_gain	1.0000
3:45086072:T:TC	acceptor_gain	1.0000
3:45089052:A:AC	donor_gain	1.0000
3:45089053:C:CC	donor_gain	1.0000
3:45089053:CTT:C	donor_gain	1.0000
3:45089055:T:TA	donor_gain	1.0000
3:45091175:ACAGT:A	donor_gain	1.0000
3:45091176:CAGTC:C	donor_gain	1.0000
3:45091295:T:TA	donor_gain	1.0000
3:45095349:A:AC	donor_gain	1.0000
3:45095350:T:C	donor_gain	1.0000
3:45110468:CTCA:C	donor_gain	1.0000
3:45110471:A:AC	donor_gain	1.0000
3:45110471:ACTG:A	donor_gain	1.0000
3:45110472:C:CC	donor_gain	1.0000
3:45110472:CT:C	donor_gain	1.0000
3:45110472:CTG:C	donor_gain	1.0000
3:45110472:CTGC:C	donor_gain	1.0000
3:45110472:CTGCT:C	donor_gain	1.0000
3:45112081:A:AC	donor_gain	1.0000
3:45112082:C:CC	donor_gain	1.0000
3:45086063:TTTTC:T	acceptor_gain	0.9900
3:45086065:TTC:T	acceptor_gain	0.9900
3:45086066:TC:T	acceptor_gain	0.9900
3:45086067:CC:C	acceptor_gain	0.9900
3:45089047:CACCT:C	donor_loss	0.9900
3:45089048:ACCTA:A	donor_loss	0.9900

AlphaMissense

5515 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:45110550:C:G	C316S	0.999
3:45110551:A:T	C316S	0.999
3:45110565:A:G	L311P	0.999
3:45110743:A:G	W252R	0.999
3:45110743:A:T	W252R	0.999
3:45110514:A:G	L328P	0.998
3:45110550:C:T	C316Y	0.998
3:45110559:A:G	L313P	0.998
3:45110676:C:G	C274S	0.998
3:45110677:A:T	C274S	0.998
3:45110741:C:A	W252C	0.998
3:45110741:C:G	W252C	0.998
3:45091440:A:G	W576R	0.997
3:45091440:A:T	W576R	0.997
3:45110508:A:G	F330S	0.997
3:45110551:A:G	C316R	0.997
3:45110676:C:T	C274Y	0.997
3:45110549:A:C	C316W	0.996
3:45110550:C:A	C316F	0.996
3:45110650:A:C	Y283D	0.996
3:45110650:A:G	Y283H	0.996
3:45110655:A:T	V281D	0.996
3:45110675:A:C	C274W	0.996
3:45110677:A:G	C274R	0.996
3:45110706:A:T	V264D	0.996
3:45112359:A:G	W127R	0.996
3:45112359:A:T	W127R	0.996
3:45110563:A:G	S312P	0.995
3:45110571:A:G	F309S	0.995
3:45110658:C:G	R280P	0.995

dbSNP variants (sampled 300 via entrez): RS1000019301 (3:45140929 G>A), RS1000059862 (3:45122382 G>A), RS1000107796 (3:45107190 T>C,G), RS1000189027 (3:45116436 A>G), RS1000202769 (3:45092851 C>A,G,T), RS1000327304 (3:45109578 A>G), RS1000366222 (3:45117243 G>A), RS1000447588 (3:45103962 G>C), RS1000612555 (3:45097572 C>A,G), RS1000623357 (3:45139188 A>C), RS1000624682 (3:45116010 T>C), RS1000714573 (3:45105458 C>A), RS1000727456 (3:45127699 A>C), RS1000751810 (3:45133886 C>G,T), RS1000781077 (3:45103440 A>T)

Disease associations

OMIM: gene MIM:611735 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): myoepithelial tumor (MONDO:0002380)

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002481_7	Acne (severe)	3.000000e-06
GCST006585_2244	Blood protein levels	6.000000e-09
GCST006976_13	Macular thickness	3.000000e-30
GCST007001_3	Cerebrospinal AB1-42 levels in normal cognition	5.000000e-07
GCST008553_1	Statin-induced myopathy (severe)	2.000000e-07
GCST009391_494	Metabolite levels	4.000000e-06
GCST009391_662	Metabolite levels	4.000000e-07
GCST012501_1	Achilles tendon injury	2.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0005001	phenylalanine measurement
EFO:0009770	leucine measurement
EFO:0600078	Achilles tendon injury

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	4
Valproic Acid	increases expression	4
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
sodium arsenite	increases abundance, increases expression, affects cotreatment, decreases expression	2
entinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	decreases expression	2
Arsenic	affects expression, affects cotreatment, decreases expression, increases abundance	2
Doxorubicin	decreases expression, increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases methylation	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1
pyrazolo(3,4-d)pyrimidine	affects expression	1
3,4-dichloroaniline	increases expression	1
beta-lapachone	increases expression	1
o,p’-DDT	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
pentanal	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis