TSPAN8

Summary

TSPAN8 (tetraspanin 8, HGNC:11855) is a protein-coding gene on chromosome 12q21.1, encoding Tetraspanin-8 (P19075). Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling.

The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein that is known to complex with integrins. This gene is expressed in different carcinomas. The use of alternate polyadenylation sites has been found for this gene.

Source: NCBI Gene 7103 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_004616

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11855
Approved symbol	TSPAN8
Name	tetraspanin 8
Location	12q21.1
Locus type	gene with protein product
Status	Approved
Aliases	CO-029
Ensembl gene	ENSG00000127324
Ensembl biotype	protein_coding
OMIM	600769
Entrez	7103

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 19 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000247829, ENST00000393330, ENST00000546561, ENST00000549421, ENST00000550818, ENST00000552128, ENST00000552786, ENST00000861089, ENST00000861090, ENST00000861091, ENST00000861092, ENST00000861093, ENST00000861094, ENST00000861095, ENST00000861096, ENST00000861097, ENST00000861098, ENST00000861099, ENST00000861100, ENST00000861101, ENST00000861102, ENST00000861103, ENST00000963071

RefSeq mRNA: 2 — MANE Select: NM_004616 NM_001369760, NM_004616

CCDS: CCDS8999

Canonical transcript exons

ENST00000247829 — 9 exons

Exon	Start	End
ENSE00000871916	71139711	71139848
ENSE00001375502	71157930	71157999
ENSE00002428643	71125096	71125387
ENSE00003624744	71144151	71144213
ENSE00003673871	71157619	71157787
ENSE00003720745	71129331	71129414
ENSE00003731583	71138156	71138230
ENSE00003740413	71132693	71132824
ENSE00003750927	71137953	71138060

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 99.94.

FANTOM5 (CAGE): breadth broad, TPM avg 6.6053 / max 1211.2709, expressed in 275 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132091	2.4833	96
132096	1.6271	166
132093	0.6778	60
132099	0.6159	130
132095	0.5539	95
132098	0.2212	74
132092	0.1050	23
132090	0.0916	33
132097	0.0708	31
132094	0.0606	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
colonic mucosa	UBERON:0000317	99.94	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.94	gold quality
jejunal mucosa	UBERON:0000399	99.88	gold quality
ileal mucosa	UBERON:0000331	99.73	gold quality
mucosa of transverse colon	UBERON:0004991	99.73	gold quality
rectum	UBERON:0001052	99.70	gold quality
ileum	UBERON:0002116	99.65	silver quality
duodenum	UBERON:0002114	99.64	gold quality
pancreatic ductal cell	CL:0002079	99.60	gold quality
bronchial epithelial cell	CL:0002328	99.55	gold quality
epithelium of bronchus	UBERON:0002031	99.13	gold quality
gall bladder	UBERON:0002110	99.12	gold quality
bronchus	UBERON:0002185	99.07	gold quality
pylorus	UBERON:0001166	98.87	gold quality
dorsal root ganglion	UBERON:0000044	98.38	gold quality
vermiform appendix	UBERON:0001154	98.13	gold quality
caecum	UBERON:0001153	98.09	gold quality
nasal cavity epithelium	UBERON:0005384	97.47	gold quality
epithelial cell of pancreas	CL:0000083	97.46	gold quality
gluteal muscle	UBERON:0002000	97.12	gold quality
skin of hip	UBERON:0001554	96.66	gold quality
islet of Langerhans	UBERON:0000006	96.65	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.65	gold quality
trachea	UBERON:0003126	96.49	gold quality
jejunum	UBERON:0002115	96.37	gold quality
trigeminal ganglion	UBERON:0001675	96.19	gold quality
small intestine	UBERON:0002108	95.85	gold quality
transverse colon	UBERON:0001157	95.56	gold quality
cardia of stomach	UBERON:0001162	95.45	gold quality
triceps brachii	UBERON:0001509	95.27	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-MTAB-9906	yes	2624.78
E-MTAB-5061	yes	1944.76
E-CURD-46	yes	1839.65
E-CURD-88	yes	1802.98
E-MTAB-8495	yes	1676.35
E-GEOD-83139	yes	1453.86
E-CURD-114	yes	549.97
E-GEOD-130473	yes	540.87
E-GEOD-75688	yes	472.67
E-MTAB-8410	yes	67.87
E-HCAD-1	yes	10.36
E-HCAD-9	yes	8.50
E-ENAD-27	yes	6.93
E-GEOD-125970	no	19.78
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1

miRNA regulators (miRDB)

17 targeting TSPAN8, 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-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-935	98.82	69.36	1072
HSA-MIR-3136-5P	98.53	67.68	793
HSA-MIR-4439	98.53	67.53	793
HSA-MIR-654-3P	98.38	67.61	905
HSA-MIR-8078	98.32	65.73	361
HSA-MIR-124-5P	98.11	67.65	1095
HSA-MIR-10526-3P	97.86	64.97	1342
HSA-MIR-3936	97.64	64.47	732
HSA-MIR-601	95.98	67.59	421
HSA-MIR-4513	95.04	67.06	727
HSA-MIR-6855-3P	95.04	66.57	725

Literature-anchored findings (GeneRIF, showing 40)

• claudin-7-associated EpCAM is recruited into (tetraspanin-enriched membrane microdomains) and forms a complex with CO-029 and CD44v6 that facilitates metastasis formation (PMID:17579117)
• overexpression of TM4SF3 in esophageal cancer conferred advantage to the invasion and metastasis of this destructive disease (PMID:18365756)
• High TSPAN8 is associated with melanoma invasiveness. (PMID:21081927)
• CO-029 functions as a regulator of both cell-matrix and cell-cell adhesion. During colon cancer progression, CO-029 promotes cancer cell movement by deregulating cell adhesions. (PMID:22679508)
• Based on nasopharyngeal TSPAN8 gene expression in readily available Nasopharyngeal aspirate samples , we can discriminate between severity of disease in Respiratory syncytial virus infected infants. (PMID:25261323)
• Tspn8 was over-expressed in multiple clinical malignant glioma tissues, and its expression level correlated with the grade of tumors. (PMID:25680464)
• TSPAN8 is involved in tumor progression and is an independent prognostic classifier in patients with gastric cancer. (PMID:25711980)
• Our data suggest that TSPAN8-LEL may play an important role in mCRC cell invasion, and that the antibody we have developed could be a useful tool for inhibiting the invasion of TSPAN8-expressing mCRCs. (PMID:26562525)
• This novel nuclear localization of TM4SF3 depends on androgen-induced nuclear localization of androgen receptor (AR) in both androgen-dependent and androgen-independent prostate cancer cell lines (PMID:26649804)
• TSPAN8 might be important for the orchestration of meprin beta at the cell surface with impact on certain proteolytic processes (PMID:27180358)
• Tetraspanin-8 has a role in promoting hepatocellular carcinoma metastasis by increasing ADAM12m expression (PMID:27270327)
• Knocking down TSPAN8 in AEG-1-overexpressing human hepatocellular carcinoma (HCC) cells markedly inhibited invasion and migration without affecting proliferation. TSPAN8 knockdown profoundly abrogated AEG-1-induced primary tumor and intrahepatic metastasis in an orthopic xenograft model in athymic nude mice (PMID:27339400)
• LCMR1 modulation was sufficient to positively regulate endogenous Tspan8 expression, with concomitant in vitro phenotypic changes such as loss of melanoma cell-matrix adherence and increase in invasion, and Tspan8 expression promoted tumourigenicity in vivo. (PMID:27375018)
• Results provide evidence that TSPAN8 may contribute to the pathogenesis of lung cancer by promoting cell viability and proliferation. (PMID:27996312)
• Data indicate a regulatory role for tetraspanin 8 (Tspan8) in melanoma progression by modulating cell-matrix interactions through beta1 integrin - integrin-linked kinase (ILK) axis and establish Tspan8 as a negative regulator of ILK activity. (PMID:28188308)
• Knockdown and knockout models revealed that CD151 and Tspan8 act as molecular facilitators in wound healing, angiogenesis and tumor progression. [review] (PMID:28408484)
• these data point to a crucial role of Co-029 in the modulation of colon cancer cell motility which could be related to the protumoral effect reported for this tetraspanin. Among surface molecules able to mediate Co-029 function, E-cadherin, EGFR and CD44 appear as likely candidates. (PMID:28418857)
• Single nucleotide polymorphism in TSPAN8 gene is associated with pathogenesis of bipolar disorder. (PMID:28777493)
• TSPAN8 mediated Wnt/beta-catenin pathway through binding to NOTCH2. The role of TSPAN8 in the drug resistance of gastric cancer. (PMID:29345284)
• miR-324-5p inhibited gastric cancer cell survival by targeting TSPAN8 expression. (PMID:30159900)
• TSPAN8 is a part of a positive feedback loop and plays role in the invasive properties required for tumor progression and melanoma dissemination. (PMID:30679790)
• High TSPAN8 expression is associated with Drug Resistance in Colorectal Cancer. (PMID:30706227)
• Findings show the presence of Tspan8 in breast cancer primary lesion and metastases and indicate its role as a regulator of cell behaviour and extracellular vesicle release in breast cancer. Tspan8 and p120-catenin were co-immunoprecipitated, indicating that they may interact with each other. (PMID:30982971)
• These findings reveal a molecular basis of TSPAN8-enhanced Sonic Hedgehog signaling and highlight a role for TSPAN8 in promoting cancer stemness. (PMID:31253779)
• High TSPAN8 mRNA expression in the colorectal cancer.LSD1 up-regulated TSPAN8 expression and reduced H3K9me2 occupancy on the TSPAN8 promoter in the colorectal cancer cells. (PMID:31790687)
• TSPAN8 directly interacted ss-catenin and enhanced its protein expression, which is necessary for TSPAN8-mediated effects on colorectal cancer stemness. (PMID:31838484)
• TSPAN8 as a Novel Emerging Therapeutic Target in Cancer for Monoclonal Antibody Therapy. (PMID:32138170)
• Extracellular vesicle tetraspanin-8 level predicts distant metastasis in non-small cell lung cancer after concurrent chemoradiation. (PMID:32195353)
• Silencing of long non-coding RNA SOX21-AS1 inhibits lung adenocarcinoma invasion and migration by impairing TSPAN8 via transcription factor GATA6. (PMID:32698071)
• Tspan8 Is Highly Expressed in Clear Cell Renal Cell Carcinoma and Indicates Poor Prognosis. (PMID:33067209)
• Identification of CD318, TSPAN8 and CD66c as target candidates for CAR T cell based immunotherapy of pancreatic adenocarcinoma. (PMID:33674603)
• SOX9 is a critical regulator of TSPAN8-mediated metastasis in pancreatic cancer. (PMID:34163029)
• Tetraspanin8 expression predicts an increased metastatic risk and is associated with cancer-related death in human cutaneous melanoma. (PMID:34600553)
• High TSPAN8 expression in epithelial cancer cell-derived small extracellular vesicles promote confined diffusion and pronounced uptake. (PMID:34796683)
• EGFR signaling promotes nuclear translocation of plasma membrane protein TSPAN8 to enhance tumor progression via STAT3-mediated transcription. (PMID:35197608)
• TSPAN8 alleviates high glucose-induced apoptosis and autophagy via targeting mTORC2. (PMID:35904232)
• Histone demethylase KDM2A suppresses EGF-TSPAN8 pathway to inhibit breast cancer cell migration and invasion in vitro. (PMID:36084547)
• The Transmembrane Protein TM4SF3 Interacts With AR and AR-V7 and is Recruited to AR Target Genes. (PMID:36951301)
• TSPAN8 regulates EGFR/AKT pathway to enhance metastasis in gastric cancer. (PMID:37535246)
• miR-378a-5p represses Barrett’s esophagus cells proliferation, migration and invasion through targeting TSPAN8. (PMID:38430035)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tspan8	ENSMUSG00000034127
rattus_norvegicus	Tspan8	ENSRNOG00000004411

Paralogs (32): TSPAN6 (ENSG00000000003), CD9 (ENSG00000010278), TSPAN9 (ENSG00000011105), TSPAN17 (ENSG00000048140), TSPAN32 (ENSG00000064201), CD82 (ENSG00000085117), TSPAN15 (ENSG00000099282), CD37 (ENSG00000104894), UPK1A (ENSG00000105668), TSPAN12 (ENSG00000106025), TSPAN13 (ENSG00000106537), TSPAN14 (ENSG00000108219), CD81 (ENSG00000110651), TSPAN11 (ENSG00000110900), PRPH2 (ENSG00000112619), UPK1B (ENSG00000114638), TSPAN1 (ENSG00000117472), TSPAN16 (ENSG00000130167), TSPAN2 (ENSG00000134198), CD63 (ENSG00000135404), TSPAN31 (ENSG00000135452), TSPAN3 (ENSG00000140391), CD53 (ENSG00000143119), ROM1 (ENSG00000149489), TSPAN7 (ENSG00000156298), TSPAN18 (ENSG00000157570), TSPAN33 (ENSG00000158457), TSPAN5 (ENSG00000168785), CD151 (ENSG00000177697), TSPAN10 (ENSG00000182612), TSPAN4 (ENSG00000214063), TSPAN19 (ENSG00000231738)

Protein

Protein identifiers

Tetraspanin-8 — P19075 (reviewed: P19075)

Alternative names: Transmembrane 4 superfamily member 3, Tumor-associated antigen CO-029

All UniProt accessions (1): P19075

UniProt curated annotations — full annotation on UniProt →

Function. Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Participates thereby in diverse biological functions such as cell signal transduction, migration and protein trafficking. Promotes ADAM17-mediated TNF processing through recruitment of ADAM17 to tetraspanin-enriched micro-domains (TEMs). Forms a complex with RICTOR and integrin alpha3/ITGA3 to mediate mTORC2 activation and AKT1 phosphorylation leading to cell migration. Reduces apoptosis and autophagy induced by high glucose levels through forming a complex with mTOR and RICTOR. Contributes to the maintenance of intestinal epithelial barrier and plays a role in the regulation of intestine inflammation by switching interferon gamma receptor 1/IFNGR1 from clathrin-dependent to lipid raft-dependent endocytosis route to limit STAT1 activation magnitude and duration. Acts as a modulator of the endothelin axis by associating with endothelin converting enzyme ECE1 and regulating its activity of conversion of the endothelin-1 precursor to endothelin.

Subunit / interactions. Forms homooligomers. Interacts with MEP1B. Interacts with integrin alpha3/ITGA3. Interacts with RICTOR and MTOR. Interacts with ADAM17. Interacts with ECE1.

Subcellular location. Cell membrane.

Tissue specificity. Gastric, colon, rectal, and pancreatic carcinomas.

Similarity. Belongs to the tetraspanin (TM4SF) family.

RefSeq proteins (2): NP_001356689, NP_004607* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000301	Tetraspanin_animals	Family
IPR008952	Tetraspanin_EC2_sf	Homologous_superfamily
IPR018499	Tetraspanin/Peripherin	Family
IPR018503	Tetraspanin_CS	Conserved_site

Pfam: PF00335

UniProt features (16 total): topological domain 5, transmembrane region 4, sequence variant 3, mutagenesis site 2, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P19075-F1	87.75	0.61

Functional residue map

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

Glycosylation sites (1): 118

Mutagenesis-validated functional residues (2):

Position	Phenotype
133	no difference in tspan8-mediated mep1b activity.
135	no difference in tspan8-mediated mep1b activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 200 (showing top): FREAC2_01, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_REGULATION_OF_COAGULATION, BECKER_TAMOXIFEN_RESISTANCE_UP, MODULE_64, GOCC_CELL_SURFACE, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_MALE_GAMETE_GENERATION, RODRIGUES_NTN1_TARGETS_DN, PATIL_LIVER_CANCER, GOBP_NEGATIVE_REGULATION_OF_COAGULATION, MODULE_66, GOBP_WOUND_HEALING, NKX62_Q2, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS

GO Biological Process (3): spermatogenesis (GO:0007283), regulation of gene expression (GO:0010468), negative regulation of blood coagulation (GO:0030195)

GO Molecular Function (2): integrin binding (GO:0005178), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), cell surface (GO:0009986), extracellular exosome (GO:0070062), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
developmental process involved in reproduction	1
male gamete generation	1
gene expression	1
regulation of macromolecule biosynthetic process	1
blood coagulation	1
regulation of blood coagulation	1
negative regulation of coagulation	1
negative regulation of wound healing	1
negative regulation of hemostasis	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
binding	1
membrane	1
cell periphery	1
extracellular vesicle	1

Protein interactions and networks

STRING

1244 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TSPAN8	ITGA4	P13612	985
TSPAN8	CLDN7	O95471	904
TSPAN8	HHEX	Q03014	817
TSPAN8	IGF2BP2	Q9Y6M1	810
TSPAN8	EPCAM	P16422	794
TSPAN8	CDKAL1	Q5VV42	782
TSPAN8	SLC30A8	Q8IWU4	756
TSPAN8	FTO	Q9C0B1	745
TSPAN8	CDC123	O75794	720
TSPAN8	ICAM1	P05362	713
TSPAN8	ATXN3	P54252	712
TSPAN8	IRGM	A1A4Y4	707
TSPAN8	LGR5	O75473	706
TSPAN8	JAZF1	Q86VZ6	696
TSPAN8	CD151	P48509	666

IntAct

25 interactions, top by confidence:

A	B	Type	Score
MEP1B	TSPAN8	psi-mi:“MI:0915”(physical association)	0.560
PNLIPRP1	TSPAN8	psi-mi:“MI:0915”(physical association)	0.560
SLC38A7	TSPAN8	psi-mi:“MI:0915”(physical association)	0.560
TIMM23	TSPAN8	psi-mi:“MI:0915”(physical association)	0.560
STX2	TSPAN8	psi-mi:“MI:0915”(physical association)	0.560
TSPAN8	PNLIPRP1	psi-mi:“MI:0915”(physical association)	0.560
TSPAN8	SLC38A7	psi-mi:“MI:0915”(physical association)	0.560
TSPAN8	STX2	psi-mi:“MI:0915”(physical association)	0.560
	TSPAN8	psi-mi:“MI:0915”(physical association)	0.490
TSPAN8	TSPAN8	psi-mi:“MI:0915”(physical association)	0.370
	CD63	psi-mi:“MI:0914”(association)	0.350
	AGPS	psi-mi:“MI:0914”(association)	0.350
TSPAN8	TP53I11	psi-mi:“MI:0914”(association)	0.350
TSPAN8	POTEF	psi-mi:“MI:0914”(association)	0.350
TSPAN8	UPK2	psi-mi:“MI:0914”(association)	0.350

BioGRID (78): TSPAN8 (Two-hybrid), TSPAN8 (Two-hybrid), PNLIPRP1 (Two-hybrid), TIMM23 (Two-hybrid), SHH (Affinity Capture-Western), PTCH1 (Affinity Capture-Western), PTCH1 (Reconstituted Complex), LETMD1 (Affinity Capture-MS), ARV1 (Affinity Capture-MS), C4orf32 (Affinity Capture-MS), ZDHHC20 (Affinity Capture-MS), AGPAT3 (Affinity Capture-MS), AGPAT4 (Affinity Capture-MS), LPCAT3 (Affinity Capture-MS), USP34 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M2B5N2, A0A8V0ZLT4, A1L157, O00322, O60637, O75841, P11049, P19075, P21926, P30409, P30413, P30932, P31053, P38572, P38573, P40239, P40240, P40241, Q0D289, Q2KHY8, Q2MJQ7, Q3SZR9, Q4R4Z3, Q4R7W6, Q566D0, Q568Y5, Q58CY8, Q5RDV7, Q5RE11, Q5RH71, Q61470, Q6AYR9, Q6GQF5, Q6P0C6, Q6ZUX7, Q80WR1, Q8WMQ3, Q91Y55, Q925N4, Q96FX8

Diamond homologs: A1L157, B5X3I6, O14817, O35566, O60636, O70352, P19075, P24485, P27701, P40241, P48509, P60033, P60034, P61170, P61171, Q0VC33, Q3ZBH3, Q4V8E0, Q568Y5, Q58CY8, Q58DN3, Q5R9S6, Q5RAP3, Q61451, Q80WR1, Q8WMQ3, Q96FV3, Q96SJ8, Q9D1D1, Q9D7W4, Q9DCK3, Q9JJW1, Q9QZA6, A0A8M2B5N2, A0A8V0ZLT4, B0BM39, B3VSC2, O60635, O75954, P19397

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	0
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

3737 predictions. Top by Δscore:

Variant	Effect	Δscore
12:71129415:C:CC	acceptor_gain	1.0000
12:71132687:TCTCA:T	donor_loss	1.0000
12:71132688:CTCAC:C	donor_loss	1.0000
12:71132689:TCA:T	donor_loss	1.0000
12:71132690:CA:C	donor_loss	1.0000
12:71132691:A:AT	donor_loss	1.0000
12:71132692:C:CG	donor_loss	1.0000
12:71132692:CCT:C	donor_gain	1.0000
12:71132820:TTAAA:T	acceptor_gain	1.0000
12:71132821:TAAA:T	acceptor_gain	1.0000
12:71132823:AA:A	acceptor_gain	1.0000
12:71132825:C:CC	acceptor_gain	1.0000
12:71132832:A:AC	acceptor_gain	1.0000
12:71132832:A:C	acceptor_gain	1.0000
12:71137948:ATTAC:A	donor_loss	1.0000
12:71137949:TTA:T	donor_loss	1.0000
12:71137950:TACC:T	donor_loss	1.0000
12:71137951:ACCTC:A	donor_loss	1.0000
12:71137952:C:A	donor_loss	1.0000
12:71137952:CCT:C	donor_gain	1.0000
12:71137978:T:TA	donor_gain	1.0000
12:71138056:TCAGA:T	acceptor_gain	1.0000
12:71138057:CAGA:C	acceptor_gain	1.0000
12:71138057:CAGAC:C	acceptor_gain	1.0000
12:71138058:AGA:A	acceptor_gain	1.0000
12:71138058:AGAC:A	acceptor_loss	1.0000
12:71138059:GA:G	acceptor_gain	1.0000
12:71138060:ACTGA:A	acceptor_loss	1.0000
12:71138061:C:CC	acceptor_gain	1.0000
12:71138062:T:C	acceptor_loss	1.0000

AlphaMissense

1562 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:71132786:C:A	W161C	0.998
12:71132786:C:G	W161C	0.998
12:71132814:C:G	C152S	0.994
12:71132815:A:T	C152S	0.994
12:71132812:C:A	G153C	0.993
12:71132817:C:G	C151S	0.992
12:71132818:A:T	C151S	0.992
12:71138228:A:C	F88L	0.992
12:71138228:A:T	F88L	0.992
12:71138230:A:G	F88L	0.992
12:71139764:C:G	G70R	0.992
12:71132788:A:G	W161R	0.990
12:71132788:A:T	W161R	0.990
12:71132814:C:T	C152Y	0.989
12:71132818:A:G	C151R	0.989
12:71139754:C:T	G73E	0.989
12:71139755:C:G	G73R	0.989
12:71139755:C:T	G73R	0.989
12:71139785:C:G	G63R	0.989
12:71157631:G:C	N16K	0.989
12:71157631:G:T	N16K	0.989
12:71139745:C:T	G76D	0.988
12:71144206:C:T	G23D	0.988
12:71144207:C:G	G23R	0.988
12:71125381:C:G	G223R	0.987
12:71129348:C:G	G215R	0.987
12:71129348:C:T	G215R	0.987
12:71132813:G:C	C152W	0.986
12:71138221:C:G	G91R	0.986
12:71139743:C:G	A77P	0.986

dbSNP variants (sampled 300 via entrez): RS1000036780 (12:71137878 G>A), RS1000067023 (12:71134788 G>A), RS1000182961 (12:71154985 C>T), RS1000241260 (12:71144945 T>A), RS1000350183 (12:71151141 A>G), RS1000397116 (12:71135057 A>T), RS1000455738 (12:71158438 G>A), RS1000513062 (12:71130151 G>T), RS1000523478 (12:71143899 T>G), RS1000591574 (12:71150183 A>G), RS1000591764 (12:71145138 G>A,C), RS1000684894 (12:71149977 T>C), RS1000786445 (12:71156568 T>A,C), RS1000849149 (12:71158718 T>A,C), RS1000902376 (12:71153722 G>A)

Disease associations

OMIM: gene MIM:600769 | disease phenotypes:

GenCC curated gene-disease

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

Orphanet (0):

HPO phenotypes

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

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000167_3	Type 2 diabetes	1.000000e-09
GCST000712_11	Type 2 diabetes	4.000000e-06
GCST003264_1058	Post bronchodilator FEV1/FVC ratio	4.000000e-06
GCST003996_33	Monobrow	9.000000e-21
GCST004894_115	Type 2 diabetes	7.000000e-06
GCST005047_23	Type 2 diabetes	7.000000e-09
GCST005047_67	Type 2 diabetes	2.000000e-06
GCST005413_9	Type 2 diabetes	2.000000e-06
GCST006522_1	Upper eyelid sagging severity	2.000000e-06
GCST006867_117	Type 2 diabetes	6.000000e-10
GCST007941_29	Medication use (adrenergics, inhalants)	2.000000e-08
GCST007993_26	Asthma (adult onset)	7.000000e-07
GCST007995_41	Asthma (childhood onset)	4.000000e-08
GCST009379_339	Type 2 diabetes	2.000000e-14
GCST010002_218	Refractive error	5.000000e-26
GCST010042_2	Asthma	2.000000e-09
GCST010043_59	Asthma	2.000000e-12
GCST010118_132	Type 2 diabetes	5.000000e-11
GCST90014325_53	Asthma	1.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio
EFO:0007906	synophrys measurement
EFO:0009941	Inhalant adrenergic use measurement
EFO:1002011	adult onset asthma

MeSH disease descriptors (1)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Tobacco Smoke Pollution	affects expression	3
Cyclosporine	decreases expression	3
Aflatoxin B1	decreases expression, decreases methylation	3
Acetaminophen	decreases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Nickel	decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tretinoin	decreases expression, increases expression	2
afuresertib	increases expression	1
3,19-(2-bromobenzylidene)andrographolide	decreases response to substance, increases expression	1
dicrotophos	decreases expression	1
propionaldehyde	decreases expression	1
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
kojic acid	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sulindac sulfide	decreases expression	1
benzo(e)pyrene	increases methylation	1
CGP 52608	increases reaction, affects binding	1
acyline	increases expression	1
abrine	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Irinotecan	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Dimethyl Sulfoxide	increases expression	1
Estradiol	increases expression	1

Clinical trials (associated diseases)

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

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