EBAG9

Summary

EBAG9 (estrogen receptor binding site associated antigen 9, HGNC:3123) is a protein-coding gene on chromosome 8q23.2, encoding Receptor-binding cancer antigen expressed on SiSo cells (O00559). May participate in suppression of cell proliferation and induces apoptotic cell death through activation of interleukin-1-beta converting enzyme (ICE)-like proteases.

This gene was identified as an estrogen-responsive gene. Regulation of transcription by estrogen is mediated by estrogen receptor, which binds to the estrogen-responsive element found in the 5’-flanking region of this gene. The encoded protein is a tumor-associated antigen that is expressed at high frequency in a variety of cancers. Alternate splicing results in multiple transcript variants. A pseudogene of this gene has been defined on chromosome 10.

Source: NCBI Gene 9166 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_004215

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3123
Approved symbol	EBAG9
Name	estrogen receptor binding site associated antigen 9
Location	8q23.2
Locus type	gene with protein product
Status	Approved
Aliases	EB9, RCAS1, PDAF
Ensembl gene	ENSG00000147654
Ensembl biotype	protein_coding
OMIM	605772
Entrez	9166

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 15 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000337573, ENST00000395785, ENST00000527709, ENST00000529502, ENST00000529931, ENST00000530629, ENST00000531677, ENST00000534318, ENST00000614147, ENST00000620557, ENST00000699338, ENST00000699339, ENST00000699340, ENST00000903040, ENST00000903041, ENST00000903042, ENST00000933076, ENST00000933077, ENST00000933078

RefSeq mRNA: 3 — MANE Select: NM_004215 NM_001278938, NM_004215, NM_198120

CCDS: CCDS6313

Canonical transcript exons

ENST00000337573 — 7 exons

Exon	Start	End
ENSE00000981092	109560838	109560929
ENSE00001132150	109540173	109540461
ENSE00002152940	109564439	109565996
ENSE00003501492	109550810	109550907
ENSE00003525105	109554729	109554887
ENSE00003571589	109556935	109557042
ENSE00003636927	109553865	109553943

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 99.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.5929 / max 229.6578, expressed in 1808 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
90268	9.1287	1700
90263	5.6418	1632
90266	4.0791	1573
90265	0.9886	554
90264	0.6812	428
90270	0.5136	249
90267	0.3499	205
90269	0.1878	56
205290	0.0222	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.21	gold quality
corpus epididymis	UBERON:0004359	98.20	gold quality
caput epididymis	UBERON:0004358	97.55	gold quality
endothelial cell	CL:0000115	97.53	gold quality
calcaneal tendon	UBERON:0003701	97.17	gold quality
nephron tubule	UBERON:0001231	97.16	gold quality
cauda epididymis	UBERON:0004360	97.09	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.04	gold quality
choroid plexus epithelium	UBERON:0003911	96.89	gold quality
renal glomerulus	UBERON:0000074	96.46	gold quality
germinal epithelium of ovary	UBERON:0001304	96.35	gold quality
kidney epithelium	UBERON:0004819	96.26	gold quality
tendon of biceps brachii	UBERON:0008188	96.22	gold quality
tendon	UBERON:0000043	96.19	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.19	gold quality
mammary duct	UBERON:0001765	96.15	gold quality
epithelial cell of pancreas	CL:0000083	96.06	gold quality
metanephric glomerulus	UBERON:0004736	96.01	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.95	gold quality
epithelium of mammary gland	UBERON:0003244	95.91	gold quality
cranial nerve II	UBERON:0000941	95.88	gold quality
biceps brachii	UBERON:0001507	95.83	gold quality
parietal pleura	UBERON:0002400	95.78	gold quality
renal medulla	UBERON:0000362	95.67	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.64	gold quality
visceral pleura	UBERON:0002401	95.58	gold quality
palpebral conjunctiva	UBERON:0001812	95.56	gold quality
bronchial epithelial cell	CL:0002328	95.55	gold quality
colonic mucosa	UBERON:0000317	95.47	gold quality
buccal mucosa cell	CL:0002336	95.17	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.20
E-MTAB-6524	no	98.79

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, ESR2

miRNA regulators (miRDB)

84 targeting EBAG9, 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-3163	100.00	77.23	8605
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311

Literature-anchored findings (GeneRIF, showing 40)

• Overrepresentation of EBAG9 may play a specific role in early stages of breast carcinogenesis. (PMID:11705872)
• High expression of tumor-associated antigen RCAS1 in pancreatic ductal adenocarcinoma is an unfavorable prognostic marker (PMID:11992411)
• RCAS1 is associated with ductal breast cancer progression (PMID:12054692)
• modulates surface expression of tumor-associated, normally cryptic O-linked glycan structures and contributes indirectly to the antigenicity of tumor cells (PMID:12672804)
• RCAS1 expressed on macrophages may play an important role in the induction of activated T-cell apoptosis in cases of HNL (PMID:12774924)
• Overexpression of EBAG9 is correlated with advanced pathologic stages of prostate cancer (PMID:12845666)
• RCAS1 may have role endometrial cancer invasiveness; overexpression associated with significantly poorer prognosis (PMID:12888828)
• RCAS1 gene or protein expression may not correlate with tumor progression in esophageal squamous cell carcinoma (PMID:14534714)
• The mean survival of patients who had primary hepatocellular carcinoma with high RCAS1 protein expression was significantly longer than that of patients with low expression. (PMID:14981953)
• wide distribution of EBAG9 and its relation to advanced disease suggest that this protein may play important roles in epithelial ovarian cancer (PMID:15164121)
• RCAS1 expression might be associated with progression of oral squamous cell carcinoma (PMID:15254686)
• Serum RCAS1 appears to be valuable as a diagnostic index for biliary carcinomas, as well as for evaluating the progression of cancers during therapy. (PMID:15460847)
• EBAG9 and Snapin have roles in controlling exocytosis processes (PMID:15635093)
• Macrophages may negatively regulate erythropoiesis at least in part through the production of RCAS1 molecules. (PMID:15813909)
• EBAG9 is a crucial regulator of tumor progression and a potential prognostic marker for RCC. (PMID:15867365)
• the estrogen-inducible EBAG9 gene-product and the 22-1-1 defined antigen are structurally and functionally separate antigens (PMID:15904507)
• RCAS1 expression is informative for the follow-up of malignant mesothelioma patients and sRCAS1 in pleural fluid may be useful for the diagnosis of malignant mesothelioma. (PMID:16012715)
• RCAS1 may contribute to acquisition of malignant uterine cervical phenotypic characteristics including invasion, metastasis, and tumor growth via connective tissue remodeling. (PMID:16112176)
• RCAS1 and CAP may play a role in the downregulation of the maternal immune response during pregnancy and may participate in the initiation of the labor (PMID:16113565)
• distribution of RCAS1 expression in normal female genital organs; significant positive correlation between age and RCAS1 expression; RCAS1 may affect metaplastic processes and tumor progression (PMID:16175077)
• expression of RCAS1 is correlated with recurrence not only in carcinomas, but also in mesenchymal tumors (PMID:16211275)
• metastatic lymph nodes from bile duct, gastric, colon and pancreatic cancer were investigated for RCAS1 expression (PMID:16273616)
• RCAS1 expression in gliomas may play roles in tumor progression and tumor immune escape. (PMID:16595162)
• The expression of RCAS1 by endometrial cells may favor the persistence of these cells in ectopic localization both in scar following cesarean section and in ovarian endometriosis. (PMID:16907986)
• Significantly higher RCAS1 expression was noticed in tumor in comparison to stroma in patients with the presence of lymph nodes metastases. No such difference was observed in patients without the metastases. (PMID:17187007)
• RCAS1 expression was simultaneous to the infiltration of activated immunological cells of tumor environment as well as decidua. The activity of immunological cells was selectively suppressed. (PMID:17187008)
• High-level expression of RCAS1 is involved in the malignant transformation of endometrium, and RCAS1 coexpression with ER-alpha may be associated with development and metastasis of endometrial carcinoma (PMID:17466050)
• The expression of RCAS1 in cervical cancer is significantly increased, and has correlation with malignant degree of cervical carcinoma. Some RCAS1-positive cervical cancer tissues are infected by HPV16. (PMID:17562271)
• possible role of the RCAS1 protein in the development of pre-eclampsia through an immunological pathway. (PMID:17604121)
• the drop of the RCAS1 level, which could be a result of an insufficiency of the compensatory immune response mechanisms in tubal mucosa (although these mechanisms are simultaneously preserved in endometrium), leads to tubal perforation. (PMID:17717421)
• Results show that the suppression of RCAS1 expression effectively recover T cell proliferation, reduce apoptosis and partially reverse the T cell function of IFN-gamma secretion. (PMID:17825484)
• The limited immune cells infiltration in decidua during severe pre-eclampsia is associated with increase in RCAS1 decidual level. (PMID:17845206)
• RCAS1 may be a pivotal regulator of tumor growth through angiogenesis. (PMID:17849467)
• RCAS1 is a bioactive marker that induces connective tissue remodeling and lymphocyte apoptosis [review] (PMID:17981616)
• The presence of an enhanced number of immune cells of higher activity in ectopic decidua during the final step of decidualization seems to be associated with an increase in the immunoreactivity level of RCAS1. (PMID:18032910)
• The lowest level of RCAS1 endometrial expression was found during the early secretory cycle phase, and significantly higher expression was found in the endometrium during the mid-secretory as compared to the early secretory cycle phase. (PMID:18292826)
• In rheumatoid arthritis, the lack of RCAS1 is thought to induce CTL infiltration through loss of the ability to evade immune attack, thus leading to apoptosis of the synovial lining cells. (PMID:18688918)
• EBAG9 may have a role in promoting progression of bladder cancer (PMID:19030177)
• The level of RCAS1 in the decidua seems to influence effectiveness of stillbirth induction. (PMID:19032612)
• The lack of alterations in the sRCAS1 blood serum concentration levels observed in patients with adenomyosis may favor the development of the condition (PMID:19122463)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ebag9	ENSDARG00000040021
mus_musculus	Ebag9	ENSMUSG00000022339
rattus_norvegicus	Ebag9	ENSRNOG00000004220
drosophila_melanogaster	CG32536	FBGN0052536
caenorhabditis_elegans		WBGENE00022666

Protein

Protein identifiers

Receptor-binding cancer antigen expressed on SiSo cells — O00559 (reviewed: O00559)

Alternative names: Cancer-associated surface antigen RCAS1, Estrogen receptor-binding fragment-associated gene 9 protein

All UniProt accessions (7): O00559, A0A8V8TNL5, A0A8V8TPH5, E9PJ38, E9PJ40, E9PN10, E9PND3

UniProt curated annotations — full annotation on UniProt →

Function. May participate in suppression of cell proliferation and induces apoptotic cell death through activation of interleukin-1-beta converting enzyme (ICE)-like proteases.

Subunit / interactions. Homodimer.

Subcellular location. Golgi apparatus membrane.

Tissue specificity. Widely expressed. Expressed in ovary, testis, prostate, thymus, muscle and heart, but not in small intestine, colon, lymph nodes, or peripherical blood lymphocytes. The protein is not detected in any of the above organs.

Domain organisation. The coiled coil domain is necessary for the homodimerization.

Induction. By estrogen.

Miscellaneous. May serve as a prognostic marker for cancers such as adenocarcinomas of the lung and breast cancers. It is present and overexpressed in many patients suffering from breast carcinomas, its level of expression correlates with tumor grade, suggesting that it may be involved in cancer immune escape. According to PubMed:12672804, it is however not directly a tumor-associated antigen, but it rather modulates surface expression of tumor-associated O-linked glycan Tn when it is overexpressed, suggesting that it contributes indirectly to the antigenicity of tumor cells.

Isoforms (2)

UniProt ID	Names	Canonical?
O00559-1	1	yes
O00559-2	2

RefSeq proteins (3): NP_001265867, NP_004206, NP_936056 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017025	Cancer-assoc_antigen_RCAS1	Family

UniProt features (13 total): modified residue 3, topological domain 2, sequence conflict 2, chain 1, splice variant 1, transmembrane region 1, region of interest 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00559-F1	66.63	0.06

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): 36, 41, 94

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9018519	Estrogen-dependent gene expression

MSigDB gene sets: 182 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MORF_MBD4, MORF_RAB5A, GOCC_SECRETORY_GRANULE, BECKER_TAMOXIFEN_RESISTANCE_UP, GOBP_GROWTH, MORF_RAD21, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, AP2_Q3, MORF_PSMC2, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY

GO Biological Process (4): regulation of cell growth (GO:0001558), T cell mediated cytotoxicity (GO:0001913), adaptive immune memory response involving T cells and B cells (GO:0090717), apoptotic process (GO:0006915)

GO Molecular Function (2): peptidase activator activity involved in apoptotic process (GO:0016505), protein binding (GO:0005515)

GO Cellular Component (4): Golgi membrane (GO:0000139), secretory granule (GO:0030141), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
ESR-mediated signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	2
cell growth	1
regulation of growth	1
regulation of cellular component organization	1
leukocyte mediated cytotoxicity	1
T cell mediated immunity	1
adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
adaptive immune memory response	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
apoptotic process	1
peptidase activator activity	1
binding	1
Golgi apparatus	1
bounding membrane of organelle	1
secretory vesicle	1
cytoplasm	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

630 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EBAG9	COX7A2L	O14548	948
EBAG9	ESR1	P03372	884
EBAG9	GRIN2D	O15399	856
EBAG9	TM9SF1	O15321	615
EBAG9	IGDCC3	Q8IVU1	593
EBAG9	UNC119	Q13432	582
EBAG9	NUDCD1	Q96RS6	541
EBAG9	CALML3	P27482	500
EBAG9	COX7A1	P24310	497
EBAG9	CALML6	Q8TD86	488
EBAG9	CALML5	Q9NZT1	488
EBAG9	ENY2	Q9NPA8	451
EBAG9	CAGE1	Q8TC20	449
EBAG9	SIDT1	Q9NXL6	447
EBAG9	PF4	P02776	437

IntAct

86 interactions, top by confidence:

A	B	Type	Score
SLC35A4	EBAG9	psi-mi:“MI:0915”(physical association)	0.560
SLC30A2	EBAG9	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	REEP6	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	CFHR5	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	STX2	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	CIAO2A	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	TPRG1	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	VAPA	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	SLC35B4	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	STX1A	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	NRAC	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	BNIP3	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	PEX16	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	CLN6	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	PRAF2	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	ACSL5	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	TMEM107	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	CLEC4G	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	SLC35A4	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	TRAF3IP3	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	STX3	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	APOL2	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	SLC35A1	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	SLC30A2	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	ORMDL1	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	VAPB	psi-mi:“MI:0915”(physical association)	0.560
EBAG9	OR10AG1	psi-mi:“MI:0915”(physical association)	0.560
MGLL	EBAG9	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (326): EBAG9 (Proximity Label-MS), EBAG9 (Proximity Label-MS), EBAG9 (Proximity Label-MS), EBAG9 (Affinity Capture-RNA), EBAG9 (Proximity Label-MS), EBAG9 (Proximity Label-MS), EBAG9 (Two-hybrid), EBAG9 (Two-hybrid), EBAG9 (Two-hybrid), EBAG9 (Two-hybrid), EBAG9 (Two-hybrid), EBAG9 (Two-hybrid), EBAG9 (Two-hybrid), EBAG9 (Two-hybrid), EBAG9 (Two-hybrid)

ESM2 similar proteins: A4PB26, A8E4M4, A9JSQ8, B0BN72, B2RX88, O00559, Q1MSJ5, Q32LE2, Q3MHI4, Q3MHS2, Q3U155, Q3UGS4, Q4V891, Q4VAA2, Q504E7, Q5BJ78, Q5I0B5, Q5M8L3, Q5PQP2, Q5PQS7, Q5RC87, Q5VSY0, Q5XIG5, Q5ZIH9, Q5ZLY0, Q63068, Q63ZM9, Q6AZH0, Q6DD53, Q6DIS2, Q6DJ13, Q6GNQ4, Q6INR1, Q6NWC9, Q6PII3, Q7SXU0, Q7T370, Q7ZYA6, Q803P1, Q865S0

Diamond homologs: O00559, Q5PQP2, Q865S0, Q9D0V7

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	30
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1531 predictions. Top by Δscore:

Variant	Effect	Δscore
8:109550804:CCACA:C	acceptor_loss	1.0000
8:109550805:CACA:C	acceptor_loss	1.0000
8:109550807:CAGG:C	acceptor_loss	1.0000
8:109550809:G:T	acceptor_loss	1.0000
8:109550903:TGCAG:T	donor_loss	1.0000
8:109550904:GCAGG:G	donor_loss	1.0000
8:109550905:CAG:C	donor_loss	1.0000
8:109550906:AGGTA:A	donor_loss	1.0000
8:109550907:GGTA:G	donor_loss	1.0000
8:109550908:G:GA	donor_loss	1.0000
8:109550909:T:G	donor_loss	1.0000
8:109553857:T:TA	acceptor_gain	1.0000
8:109553863:A:AG	acceptor_gain	1.0000
8:109553863:AGAT:A	acceptor_loss	1.0000
8:109553864:G:GT	acceptor_gain	1.0000
8:109553864:GA:G	acceptor_gain	1.0000
8:109553864:GAT:G	acceptor_gain	1.0000
8:109553864:GATC:G	acceptor_gain	1.0000
8:109553864:GATCT:G	acceptor_gain	1.0000
8:109553939:AGCAG:A	donor_gain	1.0000
8:109553940:GCAG:G	donor_gain	1.0000
8:109553940:GCAGG:G	donor_gain	1.0000
8:109553941:CAG:C	donor_gain	1.0000
8:109553941:CAGG:C	donor_loss	1.0000
8:109553942:AG:A	donor_gain	1.0000
8:109553943:GG:G	donor_gain	1.0000
8:109553944:G:GG	donor_gain	1.0000
8:109554727:A:AG	acceptor_gain	1.0000
8:109554728:G:GG	acceptor_gain	1.0000
8:109554728:GACA:G	acceptor_gain	1.0000

AlphaMissense

1398 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:109554744:T:A	W60R	0.999
8:109554744:T:C	W60R	0.999
8:109554746:G:C	W60C	0.999
8:109554746:G:T	W60C	0.999
8:109554753:T:A	W63R	0.999
8:109554753:T:C	W63R	0.999
8:109554755:G:C	W63C	0.999
8:109554755:G:T	W63C	0.999
8:109554849:T:C	F95L	0.999
8:109554850:T:C	F95S	0.999
8:109554850:T:G	F95C	0.999
8:109554851:T:A	F95L	0.999
8:109554851:T:G	F95L	0.999
8:109560883:T:A	W159R	0.999
8:109560883:T:C	W159R	0.999
8:109560885:G:C	W159C	0.999
8:109560885:G:T	W159C	0.999
8:109554865:C:A	P100Q	0.998
8:109564469:A:C	R184S	0.998
8:109564469:A:T	R184S	0.998
8:109554864:C:T	P100S	0.997
8:109557005:T:C	L131S	0.997
8:109564444:A:C	Q176P	0.997
8:109564460:A:C	R181S	0.997
8:109564460:A:T	R181S	0.997
8:109554849:T:A	F95I	0.996
8:109554849:T:G	F95V	0.996
8:109560926:T:C	L173P	0.996
8:109564468:G:C	R184T	0.996
8:109564473:G:C	A186P	0.996

dbSNP variants (sampled 300 via entrez): RS1000151421 (8:109559282 TC>T,TCC), RS1000193470 (8:109538791 C>A,T), RS1000417105 (8:109559690 C>T), RS1000490939 (8:109563639 C>A,T), RS1000492902 (8:109551337 A>T), RS1000585502 (8:109539137 T>C), RS1000679372 (8:109544765 A>G), RS1001098358 (8:109564802 T>C), RS1001172236 (8:109547938 G>T), RS1001181441 (8:109551607 A>C), RS1001222612 (8:109555177 C>T), RS1001342845 (8:109541907 T>G), RS1001626495 (8:109542553 G>A,T), RS1001662499 (8:109542291 GAA>G,GA,GAAA), RS1001781226 (8:109561606 A>T)

Disease associations

OMIM: gene MIM:605772 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006631_4	Nicotine dependence and major depression (severity of comorbidity)	5.000000e-06
GCST009391_1530	Metabolite levels	3.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007006	depressive symptom measurement
EFO:0009262	nicotine dependence symptom count
EFO:0009771	methionine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
Air Pollutants	affects expression, decreases expression, increases abundance	3
Estradiol	increases expression, increases phosphorylation, decreases reaction	3
Cadmium	increases abundance, increases expression, decreases reaction, decreases expression	2
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
daidzein	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
arsenite	decreases expression	1
1,6-hexamethylene diisocyanate	increases methylation	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Sunitinib	increases expression	1
Fulvestrant	increases expression, decreases expression, decreases reaction	1
Caffeine	decreases phosphorylation	1
Diethylstilbestrol	decreases expression	1
Dust	increases abundance, decreases expression	1
Ozone	affects expression, increases abundance	1
Vitallium	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Metribolone	increases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	increases abundance, decreases expression	1
Copper Sulfate	decreases expression	1
Genistein	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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