ATF7IP

Summary

ATF7IP (activating transcription factor 7 interacting protein, HGNC:20092) is a protein-coding gene on chromosome 12p13.1, encoding Activating transcription factor 7-interacting protein 1 (Q6VMQ6). Recruiter that couples transcriptional factors to general transcription apparatus and thereby modulates transcription regulation and chromatin formation.

ATF7IP is a multifunctional nuclear protein that associates with heterochromatin. It can act as a transcriptional coactivator or corepressor depending upon its binding partners (summary by Liu et al., 2009 [PubMed 19106100]).

Source: NCBI Gene 55729 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 178 total — 1 likely-pathogenic
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 2 cancer types
• MANE Select transcript: NM_018179

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20092
Approved symbol	ATF7IP
Name	activating transcription factor 7 interacting protein
Location	12p13.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10688, p621, ATF7IP1, MCAF1, MCAF, AM
Ensembl gene	ENSG00000171681
Ensembl biotype	protein_coding
OMIM	613644
Entrez	55729

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 28 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000261168, ENST00000396279, ENST00000428217, ENST00000534828, ENST00000535132, ENST00000535179, ENST00000535738, ENST00000536279, ENST00000536444, ENST00000537653, ENST00000538511, ENST00000539057, ENST00000539659, ENST00000540793, ENST00000541056, ENST00000541654, ENST00000542508, ENST00000542514, ENST00000542967, ENST00000542991, ENST00000543189, ENST00000544627, ENST00000545723, ENST00000545769, ENST00000884191, ENST00000884192, ENST00000884193, ENST00000936267, ENST00000969301, ENST00000969302, ENST00000969303, ENST00000969304

RefSeq mRNA: 10 — MANE Select: NM_018179 NM_001286514, NM_001286515, NM_001388179, NM_001388180, NM_001388181, NM_001388182, NM_001388183, NM_001388184, NM_018179, NM_181352

CCDS: CCDS66326, CCDS66327, CCDS73449, CCDS8663

Canonical transcript exons

ENST00000261168 — 15 exons

Exon	Start	End
ENSE00001159562	14496231	14496343
ENSE00001159567	14481003	14481185
ENSE00001159582	14478317	14478472
ENSE00001330788	14475890	14475968
ENSE00001371929	14365682	14365827
ENSE00003483412	14466526	14466590
ENSE00003491837	14434337	14434423
ENSE00003570427	14457207	14457295
ENSE00003607942	14460495	14461133
ENSE00003616719	14436106	14436251
ENSE00003617162	14438130	14438267
ENSE00003651643	14446988	14447053
ENSE00003656862	14423909	14425473
ENSE00003661551	14456561	14456634
ENSE00003716013	14497654	14502930

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 99.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.4467 / max 575.8240, expressed in 1796 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
124440	20.5613	1771
124444	4.9697	1128
124439	2.6083	1187
124443	0.6420	303
124441	0.3326	150
124438	0.1661	46
124445	0.1532	73
124448	0.0134	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	99.75	gold quality
cardia of stomach	UBERON:0001162	98.84	gold quality
nipple	UBERON:0002030	98.52	gold quality
renal medulla	UBERON:0000362	98.40	gold quality
tendon of biceps brachii	UBERON:0008188	98.40	gold quality
pylorus	UBERON:0001166	98.38	gold quality
visceral pleura	UBERON:0002401	98.38	gold quality
ventral tegmental area	UBERON:0002691	98.34	gold quality
superior surface of tongue	UBERON:0007371	98.29	gold quality
trigeminal ganglion	UBERON:0001675	98.24	gold quality
inferior vagus X ganglion	UBERON:0005363	98.14	gold quality
dorsal root ganglion	UBERON:0000044	97.95	gold quality
superior vestibular nucleus	UBERON:0007227	97.93	gold quality
subthalamic nucleus	UBERON:0001906	97.90	gold quality
tibia	UBERON:0000979	97.87	gold quality
parietal pleura	UBERON:0002400	97.87	gold quality
pericardium	UBERON:0002407	97.81	gold quality
superficial temporal artery	UBERON:0001614	97.73	gold quality
medial globus pallidus	UBERON:0002477	97.72	gold quality
globus pallidus	UBERON:0001875	97.71	gold quality
germinal epithelium of ovary	UBERON:0001304	97.62	gold quality
pharyngeal mucosa	UBERON:0000355	97.61	gold quality
endothelial cell	CL:0000115	97.58	gold quality
lateral globus pallidus	UBERON:0002476	97.44	gold quality
saphenous vein	UBERON:0007318	97.38	gold quality
vena cava	UBERON:0004087	97.32	gold quality
urethra	UBERON:0000057	97.31	gold quality
pleura	UBERON:0000977	97.29	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.11	gold quality
trabecular bone tissue	UBERON:0002483	97.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.43

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF5

miRNA regulators (miRDB)

184 targeting ATF7IP, 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-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6867-5P	100.00	82.21	3464
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-340-5P	100.00	72.50	4437
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910

Literature-anchored findings (GeneRIF, showing 16)

• mAM/hAM facilitates conversion of H3-K9 dimethyl to trimethyl by ESET/SETDB1 (PMID:14536086)
• These data suggest that MBD1.MCAF1.SETDB1 complex facilitates the formation of heterochromatic domains, emphasizing the role of MCAF/AM family proteins in epigenetic control, and describe a new family member, MCAF2. (PMID:15691849)
• MBD1- and MCAF1-mediated heterochromatin formation involves SUMO modification (PMID:16757475)
• the acidic stretch of the SIM of MCAF1 plays an important role in the binding to SUMO-3. (PMID:18842587)
• Two evolutionarily conserved domains of MCAF1 directly interact with Sp1 and the general transcriptional apparatus. Selective depletion of MCAF1 or Sp1 down-regulates TERT and TERC genes in cultured cells, which results in decreased telomerase activity. (PMID:19106100)
• Studies identified three new susceptibility loci DMRT1, TERT and ATF7IP associated with testicular germ cell cancer. (PMID:20543847)
• Genetic variants at ATF7IP and KLK2 contribute to the variance of %fPSA. (PMID:23359319)
• The transcriptional cofactor MCAF1/ATF7IP is involved in histone gene expression and cellular senescence. (PMID:23935871)
• We demonstrated the importance of Aire’s interaction with the ATF7ip-MBD1 protein complex in maintaining central tolerance (PMID:24464130)
• these results indicate a critical role for MCAF1 in AP-1-dependent Rta activation of BZLF1 transcription. (PMID:24598729)
• results indicate that ATF7IP does not directly modulate SETDB1 catalytic activity, suggesting alternate roles, such as affecting cellular localization or mediating interaction with additional binding partners. (PMID:26813693)
• these data identify a critical functional role for ATF7IP in heterochromatin formation by regulating SETDB1 abundance in the nucleus. (PMID:27732843)
• Here we report on a special case of a Ph-like acute lymphoblastic leukemia patient who had a variant ATF7IP/PDGFRB fusion. In this case, a variant fusion was created between ATF7IP exon 9 (instead of exon 13) and PDGFRB exon 11, resulting in the loss of 411 nucleotides and 137 amino acids in the ATF7IP/PDGFRB fusion cDNA and its encoded chimeric protein, respectively. (PMID:29133777)
• Although these genes are normally expressed at low amounts in hESCs, HTT knockdown (KD) reduces their induction during neural differentiation. Notably, mutant expanded polyglutamine repeats in HTT diminish its interaction with ATF7IP-SETDB1 complex and trigger H3K9me3 in HD-iPSCs. (PMID:30452683)
• ATF7IP promotes the nuclear localization of SETDB1. (PMID:31576654)
• Mutational Alterations of DNA Methylation-related Genes CTCF, ZFP57, and ATF7IP Genes in Colon Cancers. (PMID:35175239)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	atf7ip	ENSDARG00000069619
mus_musculus	Atf7ip	ENSMUSG00000030213
rattus_norvegicus	Atf7ip	ENSRNOG00000008870
drosophila_melanogaster	wde	FBGN0027499

Paralogs (1): ATF7IP2 (ENSG00000166669)

Protein

Protein identifiers

Activating transcription factor 7-interacting protein 1 — Q6VMQ6 (reviewed: Q6VMQ6)

Alternative names: ATF-interacting protein, ATF7-interacting protein, ATFa-associated modulator, MBD1-containing chromatin-associated factor 1, P621

All UniProt accessions (16): A8MV73, Q6VMQ6, F5GYR7, F5GZ10, F5GZ98, F5H1K9, F5H221, F5H2H9, F5H2W9, F5H3C4, F5H502, F5H592, F5H6X8, F5H8I0, F8WE35, H0YFA3

UniProt curated annotations — full annotation on UniProt →

Function. Recruiter that couples transcriptional factors to general transcription apparatus and thereby modulates transcription regulation and chromatin formation. Can both act as an activator or a repressor depending on the context. Required for HUSH-mediated heterochromatin formation and gene silencing. Mediates MBD1-dependent transcriptional repression, probably by recruiting complexes containing SETDB1. Stabilizes SETDB1, is required to stimulate histone methyltransferase activity of SETDB1 and facilitates the conversion of dimethylated to trimethylated H3 ‘Lys-9’ (H3K9me3). The complex formed with MBD1 and SETDB1 represses transcription and couples DNA methylation and histone H3 ‘Lys-9’ trimethylation (H3K9me3). Facilitates telomerase TERT and TERC gene expression by SP1 in cancer cells.

Subunit / interactions. Interacts with MBD1; the interaction is enhanced when MBD1 is sumoylated. Interacts with SETDB1; the interaction protects SETDB1 from proteasomal degradation and is required to stimulate histone methyltransferase activity and facilitate the conversion of dimethylated to trimethylated H3 ‘Lys-9’. Interacts with SUMO ubiquitin-like proteins (SUMO1, SUNO2 and SUMO3), with a preference for SUMO2 and SUMO3. Interacts with SP1, ATF7 and ZHX1. Interacts with the general transcription machinery, including ERCC2, ERCC3, GTF2E1, GTF2E2 and POLR2A. (Microbial infection) Interacts with Epstein-Barr virus BRLF1/Rta protein, leading to the regulation of host genes in Epstein-Barr virus-infected cells.

Subcellular location. Nucleus.

Tissue specificity. Detected at low levels in breast, lung and stomach; highly up-regulated in the corresponding cancerous tissues (at protein level).

Similarity. Belongs to the MCAF family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6VMQ6-1	1	yes
Q6VMQ6-2	2
Q6VMQ6-4	3
Q6VMQ6-5	4

RefSeq proteins (10): NP_001273443, NP_001273444, NP_001375108, NP_001375109, NP_001375110, NP_001375111, NP_001375112, NP_001375113, NP_060649, NP_851997 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR026085	ATF7-int	Family
IPR031870	ATF7IP_BD	Domain
IPR036116	FN3_sf	Homologous_superfamily
IPR056565	Fn3_ATF7IP	Domain

Pfam: PF16788, PF16794

UniProt features (60 total): compositionally biased region 16, modified residue 13, region of interest 11, cross-link 4, splice variant 4, sequence variant 3, mutagenesis site 3, sequence conflict 2, chain 1, domain 1, coiled-coil region 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2RPQ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6VMQ6-F1	48.39	0.08

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 (17): 1, 57, 113, 118, 445, 473, 474, 477, 479, 496, 559, 673, 899, 33, 558, 910, 938

Mutagenesis-validated functional residues (3):

Position	Phenotype
968	abolishes the interaction with sumo.
969	abolishes the interaction with sumo.
1224	abolishes interaction with mbd1 and subsequent transcriptional repression.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-3214841	PKMTs methylate histone lysines
R-HSA-9843940	Regulation of endogenous retroelements by KRAB-ZFP proteins
R-HSA-9843970	Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization
R-HSA-74160	Gene expression (Transcription)
R-HSA-9842860	Regulation of endogenous retroelements

MSigDB gene sets: 316 (showing top): TGCGCANK_UNKNOWN, GCANCTGNY_MYOD_Q6, RACCACAR_AML_Q6, FOXO4_01, FOXO1_01, CAGCTG_AP4_Q5, GTGCCTT_MIR506, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_DNA_METHYLATION_DEPENDENT_CONSTITUTIVE_HETEROCHROMATIN_FORMATION, MYCMAX_01, KORKOLA_EMBRYONAL_CARCINOMA_DN, FISCHER_G2_M_CELL_CYCLE, USF_01, FISCHER_DREAM_TARGETS, USF_02

GO Biological Process (5): negative regulation of transcription by RNA polymerase II (GO:0000122), DNA methylation-dependent constitutive heterochromatin formation (GO:0006346), regulation of DNA-templated transcription (GO:0006355), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (4): transcription coregulator activity (GO:0003712), transcription corepressor activity (GO:0003714), ATP hydrolysis activity (GO:0016887), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cytosol (GO:0005829), nuclear body (GO:0016604)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Regulation of endogenous retroelements	2
Chromatin modifying enzymes	1
Gene expression (Transcription)	1
Chromatin organization	1
Epigenetic regulation of gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	3
negative regulation of DNA-templated transcription	2
regulation of DNA-templated transcription	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
constitutive heterochromatin formation	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
transcription regulator activity	1
transcription coregulator activity	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
protein-containing complex	1
cytoplasm	1
nucleoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1551 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATF7IP	SETDB1	Q15047	991
ATF7IP	ATF7	P17544	811
ATF7IP	DMRT1	Q9Y5R6	777
ATF7IP	MBD1	Q9UIS9	741
ATF7IP	H3-5	Q6NXT2	727
ATF7IP	SUMO1	P55856	724
ATF7IP	H3-3A	P06351	722
ATF7IP	H3C14	Q71DI3	721
ATF7IP	H3C1	P02295	721
ATF7IP	H3-4	Q16695	721
ATF7IP	H3-7	Q5TEC6	721
ATF7IP	CLPTM1L	Q96KA5	708
ATF7IP	MPHOSPH8	Q99549	690
ATF7IP	TERT	O14746	637
ATF7IP	SUMO2	P55855	581

IntAct

115 interactions, top by confidence:

A	B	Type	Score
RYBP	BMI1	psi-mi:“MI:0914”(association)	0.850
TADA3	TADA2A	psi-mi:“MI:0914”(association)	0.740
HSPB2	BAG3	psi-mi:“MI:0914”(association)	0.670
YAF2	E2F6	psi-mi:“MI:0914”(association)	0.640
ATF7IP	ARL14EP	psi-mi:“MI:0915”(physical association)	0.560
ATF7IP	SMAD4	psi-mi:“MI:0915”(physical association)	0.550
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	SEC16A	psi-mi:“MI:0914”(association)	0.530
SETDB1	CCDC85C	psi-mi:“MI:0914”(association)	0.530
PRR20E	SIAH2	psi-mi:“MI:0914”(association)	0.530
SUV39H1	MAGEC1	psi-mi:“MI:0914”(association)	0.530
ATF7IP	GTF2IRD1	psi-mi:“MI:0915”(physical association)	0.510
GTF2IRD1	ATF7IP	psi-mi:“MI:0915”(physical association)	0.510
ATF7IP	SP1	psi-mi:“MI:0915”(physical association)	0.400
ATF7IP	H1-1	psi-mi:“MI:0915”(physical association)	0.400
HMGB1	ATF7IP	psi-mi:“MI:0915”(physical association)	0.370
PIAS3	ATF7IP	psi-mi:“MI:0915”(physical association)	0.370
SPTBN1	ATF7IP	psi-mi:“MI:0915”(physical association)	0.370
ATF7IP	PAPPA2	psi-mi:“MI:0915”(physical association)	0.370
ATF7IP	HEYL	psi-mi:“MI:0915”(physical association)	0.370
ZNF518A	ATF7IP	psi-mi:“MI:0915”(physical association)	0.370
ATF7IP	STBD1	psi-mi:“MI:0915”(physical association)	0.370
ATF7IP	CEP250	psi-mi:“MI:0915”(physical association)	0.370
PLEKHB2	ATF7IP	psi-mi:“MI:0915”(physical association)	0.370
ATF7IP	ZNF350	psi-mi:“MI:0915”(physical association)	0.370
ATF7IP	ZBTB6	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (131): ATF7IP (Reconstituted Complex), ATF7IP (Affinity Capture-MS), ATF7IP (Affinity Capture-MS), ATF7IP (Affinity Capture-MS), ATF7IP (Co-fractionation), SETDB1 (Co-fractionation), ATF7IP (Proximity Label-MS), ATF7IP (Affinity Capture-MS), ATF7IP (Affinity Capture-MS), ATF7IP (Affinity Capture-MS), ATF7IP (Affinity Capture-MS), ATF7IP (Affinity Capture-MS), ATF7IP (Affinity Capture-MS), ATF7IP (Affinity Capture-MS), ARL14EP (Affinity Capture-MS)

ESM2 similar proteins: A2AEY4, A2RRX6, A4FU49, A6NCI8, E9Q0C6, O54963, O55112, O75952, O95197, P10636, P10637, P11137, P15146, P16128, P19332, P20357, P23226, P27546, P27816, P36225, P49342, P51125, P70399, Q12888, Q13127, Q4R729, Q5M7W5, Q5PNS0, Q5R9I1, Q5S6V2, Q5VV67, Q5YCV9, Q5YCW0, Q5YCW1, Q6NZN1, Q6RJR6, Q6VMQ6, Q7SZL5, Q7TT18, Q8C4A5

Diamond homologs: A0JME2, Q3UL97, Q5U623, Q5ZIE8, Q6VMQ6, Q7TT18

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 133 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
Formation of the dystrophin-glycoprotein complex (DGC)	6	20.4×	2e-04
Adherens junctions interactions	5	13.6×	3e-03
Cell-cell junction organization	5	13.6×	3e-03
SUMOylation of transcription cofactors	5	13.3×	3e-03
Cell junction organization	5	10.3×	6e-03
Non-integrin membrane-ECM interactions	6	10.2×	3e-03
Cell-Cell communication	6	9.1×	4e-03
L1CAM interactions	6	7.9×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of embryonic development	7	18.6×	9e-05
regulation of cell adhesion	5	12.3×	7e-03
positive regulation of transcription initiation by RNA polymerase II	5	11.0×	1e-02
transcription by RNA polymerase II	9	5.1×	8e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 2 cancer types — LUAD, UCEC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	131
Likely benign	14
Benign	8

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
443436	GRCh37/hg19 12p13.1-12.3(chr12:14269084-14855982)x1	Likely pathogenic

SpliceAI

3172 predictions. Top by Δscore:

Variant	Effect	Δscore
12:14365786:G:GT	donor_gain	1.0000
12:14390433:C:G	donor_gain	1.0000
12:14395109:A:AG	acceptor_gain	1.0000
12:14423905:A:AG	acceptor_gain	1.0000
12:14423906:A:AG	acceptor_gain	1.0000
12:14423907:A:G	acceptor_gain	1.0000
12:14423908:G:GT	acceptor_gain	1.0000
12:14423908:GA:G	acceptor_gain	1.0000
12:14423908:GATTC:G	acceptor_gain	1.0000
12:14425432:A:G	donor_gain	1.0000
12:14425469:TCCAG:T	donor_loss	1.0000
12:14425470:CCAG:C	donor_loss	1.0000
12:14425471:CAGG:C	donor_loss	1.0000
12:14425472:AG:A	donor_loss	1.0000
12:14425473:GG:G	donor_loss	1.0000
12:14425474:G:GC	donor_loss	1.0000
12:14425475:T:A	donor_loss	1.0000
12:14434335:A:AG	acceptor_gain	1.0000
12:14434336:G:GG	acceptor_gain	1.0000
12:14434336:GCA:G	acceptor_gain	1.0000
12:14434419:GAAAA:G	donor_gain	1.0000
12:14434423:AG:A	donor_loss	1.0000
12:14434424:G:GG	donor_gain	1.0000
12:14434424:GTAT:G	donor_loss	1.0000
12:14434425:T:G	donor_loss	1.0000
12:14436102:TCA:T	acceptor_loss	1.0000
12:14436102:TCAG:T	acceptor_gain	1.0000
12:14436103:CA:C	acceptor_loss	1.0000
12:14436103:CAGA:C	acceptor_gain	1.0000
12:14436104:A:AC	acceptor_loss	1.0000

AlphaMissense

8322 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:14497685:T:C	L1142S	1.000
12:14497742:C:A	P1161H	1.000
12:14497742:C:G	P1161R	1.000
12:14497750:C:T	P1164S	1.000
12:14497751:C:A	P1164Q	1.000
12:14497751:C:G	P1164R	1.000
12:14497757:T:C	L1166S	1.000
12:14497757:T:G	L1166W	1.000
12:14497763:T:C	L1168S	1.000
12:14497786:G:C	G1176R	1.000
12:14497787:G:A	G1176D	1.000
12:14497787:G:T	G1176V	1.000
12:14497790:T:A	I1177K	1.000
12:14497790:T:C	I1177T	1.000
12:14497790:T:G	I1177R	1.000
12:14497793:T:A	V1178E	1.000
12:14497796:T:A	L1179Q	1.000
12:14497796:T:C	L1179P	1.000
12:14497796:T:G	L1179R	1.000
12:14497798:T:C	S1180P	1.000
12:14497801:T:A	W1181R	1.000
12:14497801:T:C	W1181R	1.000
12:14497802:G:C	W1181S	1.000
12:14497803:G:C	W1181C	1.000
12:14497803:G:T	W1181C	1.000
12:14497838:T:A	V1193D	1.000
12:14497846:T:A	Y1196N	1.000
12:14497846:T:C	Y1196H	1.000
12:14497846:T:G	Y1196D	1.000
12:14497853:T:A	L1198H	1.000

dbSNP variants (sampled 300 via entrez): RS1000009134 (12:14427600 G>A,T), RS1000022191 (12:14371209 C>T), RS1000035915 (12:14464295 A>G), RS1000065155 (12:14473941 A>G), RS1000069095 (12:14457700 T>C), RS1000085915 (12:14382053 A>G), RS1000095816 (12:14365216 G>A), RS1000107385 (12:14497464 ATTGT>A), RS1000145581 (12:14481518 A>G), RS1000160728 (12:14402237 C>T), RS1000168749 (12:14488035 A>C), RS1000206477 (12:14395223 G>C), RS1000242848 (12:14365580 T>A,C), RS1000264521 (12:14409415 A>G), RS1000276401 (12:14452010 ATGTT>A)

Disease associations

OMIM: gene MIM:613644 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST000701_6	Testicular germ cell cancer	6.000000e-10
GCST001799_1	Prostate-specific antigen levels	2.000000e-09
GCST002022_10	Testicular germ cell tumor	1.000000e-13
GCST002234_4	Breast cancer	7.000000e-06
GCST004635_23	Testicular germ cell tumor	9.000000e-13
GCST004713_29	Testicular germ cell tumor	3.000000e-08
GCST005141_10	Cognitive ability (MTAG)	4.000000e-09
GCST005316_365	Intelligence (MTAG)	3.000000e-10
GCST008595_114	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	2.000000e-12
GCST008839_27	Height	3.000000e-09
GCST009524_326	Household income (MTAG)	6.000000e-14
GCST009856_31	Leukocyte telomere length	2.000000e-06
GCST90002396_522	Mean reticulocyte volume	3.000000e-11
GCST90002397_421	Mean spheric corpuscular volume	6.000000e-10
GCST90013406_12	Liver enzyme levels (alkaline phosphatase)	1.000000e-12
GCST90013466_69	Height	2.000000e-08

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0009695	household income
EFO:0010701	mean reticulocyte volume
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, increases expression	3
methylmercuric chloride	decreases expression, affects cotreatment	2
sodium arsenite	increases abundance, increases expression	2
Arsenic	increases abundance, increases expression, affects methylation	2
Estradiol	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
bisphenol A	decreases methylation	1
arsenite	decreases reaction, affects binding	1
coumarin	decreases phosphorylation	1
resorcinol	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
dorsomorphin	affects cotreatment, decreases expression, increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Atrazine	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1

Clinical trials (associated diseases)

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