ATF7

Summary

ATF7 (activating transcription factor 7, HGNC:792) is a protein-coding gene on chromosome 12q13.13, encoding Cyclic AMP-dependent transcription factor ATF-7 (P17544). Stress-responsive chromatin regulator that plays a role in various biological processes including innate immunological memory, adipocyte differentiation or telomerase regulation.

Enables several functions, including DNA-binding transcription repressor activity, RNA polymerase II-specific; mitogen-activated protein kinase binding activity; and transcription coactivator binding activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of RNA polymerase II transcription regulator complex. Biomarker of colorectal cancer.

Source: NCBI Gene 11016 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 16 total
• MANE Select transcript: NM_006856

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:792
Approved symbol	ATF7
Name	activating transcription factor 7
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	ATFA
Ensembl gene	ENSG00000170653
Ensembl biotype	protein_coding
OMIM	606371
Entrez	11016

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 16 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000420353, ENST00000456903, ENST00000546661, ENST00000548118, ENST00000548446, ENST00000550373, ENST00000551087, ENST00000551480, ENST00000588078, ENST00000588232, ENST00000589726, ENST00000591397, ENST00000853731, ENST00000853732, ENST00000853733, ENST00000853734, ENST00000853735, ENST00000923853, ENST00000923854, ENST00000923855

RefSeq mRNA: 10 — MANE Select: NM_006856 NM_001130060, NM_001206682, NM_001206683, NM_001366555, NM_001366556, NM_001366558, NM_001366561, NM_001366562, NM_001366563, NM_006856

CCDS: CCDS44905, CCDS44906, CCDS58238

Canonical transcript exons

ENST00000420353 — 12 exons

Exon	Start	End
ENSE00002751329	53626279	53626382
ENSE00002845896	53512054	53517354
ENSE00003466302	53531744	53531896
ENSE00003471393	53600953	53601021
ENSE00003546208	53524564	53524761
ENSE00003570666	53533160	53533259
ENSE00003583783	53523276	53523384
ENSE00003624511	53552541	53552637
ENSE00003638035	53537415	53537552
ENSE00003648541	53534502	53534659
ENSE00003683500	53532510	53532623
ENSE00003684444	53543330	53543448

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 92.19.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0237 / max 1.9378, expressed in 2 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131253	8.5386	1770
131252	2.1057	1209
131250	0.0237	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
popliteal artery	UBERON:0002250	92.19	gold quality
tibial artery	UBERON:0007610	92.19	gold quality
mucosa of stomach	UBERON:0001199	91.88	gold quality
colonic epithelium	UBERON:0000397	91.57	gold quality
aorta	UBERON:0000947	91.54	gold quality
descending thoracic aorta	UBERON:0002345	91.05	gold quality
minor salivary gland	UBERON:0001830	90.84	gold quality
ascending aorta	UBERON:0001496	90.81	gold quality
thoracic aorta	UBERON:0001515	90.81	gold quality
right coronary artery	UBERON:0001625	90.41	gold quality
left coronary artery	UBERON:0001626	90.32	gold quality
sural nerve	UBERON:0015488	90.27	gold quality
right ovary	UBERON:0002118	90.21	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	90.14	gold quality
left ovary	UBERON:0002119	90.08	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.07	gold quality
monocyte	CL:0000576	89.99	gold quality
lower esophagus	UBERON:0013473	89.99	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.99	gold quality
coronary artery	UBERON:0001621	89.89	gold quality
lower esophagus mucosa	UBERON:0035834	89.70	gold quality
tibial nerve	UBERON:0001323	89.58	gold quality
saliva-secreting gland	UBERON:0001044	89.46	gold quality
body of uterus	UBERON:0009853	89.30	gold quality
mononuclear cell	CL:0000842	89.17	gold quality
endocervix	UBERON:0000458	89.15	gold quality
ectocervix	UBERON:0012249	89.10	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.08	gold quality
esophagus	UBERON:0001043	89.01	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	17.84

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

8 targets.

Target	Regulation
CCL3	Repression
CXCL2	Activation
ERBB2	Unknown
PTGDR
SELE
TAF12	Activation
TGFB2	Activation
TNF	Activation

JASPAR motifs

Motif	Name	Family
MA0834.1	ATF7	Jun-related
MA0834.2	ATF7	Jun-related

JASPAR matrix evidence (PMIDs): PMID:2516827

Upstream regulators (CollecTRI, top): MYC, TAF12, TAF4, TP53

Literature-anchored findings (GeneRIF, showing 11)

• The authors characterized the multisite phosphorylation of the ATF7 activation domain and identified one of the involved kinase, p38beta2 mitogen-activated protein kinase. (PMID:18950637)
• Data show that ATF7-4 is an important cytoplasmic negative regulator of ATF7 and ATF2 transcription factors. (PMID:21858082)
• ATF7 interacts with TAF12 and contributes to the hypersensitivity of OCL precursors to 1,25-(OH)D in PD. (PMID:23426901)
• These results suggest that the Cdk1-mediated phosphorylation of ATF7 facilitates G2/M progression, at least in part, by enabling Aurora signaling. (PMID:25545367)
• mitotic stabilized ATF7 protein re-localizes onto chromatin at the end of telophase and contributes to induce the cyclin D1 gene expression. (PMID:26101806)
• It is negatively related between ATF7 expression and pathological stage and positive correlation with OS and PFS in CRC. ATF7 expression is a favorable factor for survival of patients with CRC. (PMID:26148593)
• CARMA1- and MyD88-dependent activation of Jun/ATF-type AP-1 complexes is a hallmark of ABC diffuse large B-cell lymphomas. (PMID:26747248)
• knockdown of the mammalian homologs of PDK1 and ATF7 in HEK293 cells resulted in changes in metallothionein expression, suggesting that this pathway was evolutionarily conserved (PMID:28632756)
• ATF7 is a direct target of miR-103a-3p. In a stomach cancer cohort,miR-103a-3p expression was inversely correlated with ATF7 expression. Silencing ATF7 showed similar cellular and molecular effects as miR-103a-3p overexpression, namely, increased GC cell proliferation, improved CDK2 expression and decreased P27 expression. (PMID:29754469)
• Results found that ATF7 is upregulated in hepatocellular carcinoma (HCC) tissue. Its expression is regulated by miR-340 which directly binds to the mRNA encoding ATF7. Under HBV infection, miR-340 is downregulated resulting in increasing ATF7 expression, leading to enhanced cell proliferation and inhibition of apoptosis. (PMID:30891870)
• lncRNA prostate cancer-associated transcript 18 upregulates activating transcription factor 7 to prevent metastasis of triple-negative breast cancer via sponging miR-103a-3p. (PMID:34787047)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	atf7a	ENSDARG00000011298
mus_musculus	Atf7	ENSMUSG00000099083
rattus_norvegicus	Atf7	ENSRNOG00000015269
caenorhabditis_elegans		WBGENE00000223

Paralogs (2): ATF2 (ENSG00000115966), CREB5 (ENSG00000146592)

Protein

Protein identifiers

Cyclic AMP-dependent transcription factor ATF-7 — P17544 (reviewed: P17544)

Alternative names: Activating transcription factor 7, Transcription factor ATF-A

All UniProt accessions (4): P17544, F8VWG7, K7EKZ7, K7ESA4

UniProt curated annotations — full annotation on UniProt →

Function. Stress-responsive chromatin regulator that plays a role in various biological processes including innate immunological memory, adipocyte differentiation or telomerase regulation. In absence of stress, contributes to the formation of heterochromatin and heterochromatin-like structure by recruiting histone H3K9 tri- and di-methyltransferases thus silencing the transcription of target genes such as STAT1 in adipocytes, or genes involved in innate immunity in macrophages and adipocytes. Stress induces ATF7 phosphorylation that disrupts interactions with histone methyltransferase and enhances the association with coactivators containing histone acetyltransferase and/or histone demethylase, leading to disruption of the heterochromatin-like structure and subsequently transcriptional activation. In response to TNF, which is induced by various stresses, phosphorylated ATF7 and telomerase are released from telomeres leading to telomere shortening. Also plays a role in maintaining epithelial regenerative capacity and protecting against cell death during intestinal epithelial damage and repair. Acts as a dominant repressor of the E-selectin/NF-ELAM1/delta-A promoter. Acts as a negative regulator, inhibiting both ATF2 and ATF7 transcriptional activities. It may exert these effects by sequestrating in the cytoplasm the Thr-53 phosphorylating kinase, preventing activation.

Subunit / interactions. Homodimer; binds DNA as homodimer. Heterodimer; heterodimerizes with other members of ATF family and with JUN family members. Interacts with JNK2; the interaction does not phosphorylate ATF7 but acts as a docking site for other ATF-associated partners such as JUN family members. Interacts (via its transactivation domain) with TAF12 (isoforms TAFII15 and TAFII20); the interaction potentiates the transactivation activity (isoform TAFII20 only) and is inhibited by ATF7 sumoylation. Interacts with TAF4; the interaction inhibits the TAF12-dependent transactivation. Interacts with MAPK9; the interaction does not phosphorylate ATF7 but acts as a docking site for ATF7-associated partners such as JUN. Interacts with Ku complex components XRCC6 and XRCC7. Interacts with TERT. (Microbial infection) Interacts with adenovirus 2 E1A; the interaction enhances the ATF7-mediated viral transactivation activity which requires the zinc-binding domains of both E1A and ATF7.

Subcellular location. Nucleus. Nucleoplasm. Chromosome. Telomere Cytoplasm.

Tissue specificity. Expressed in various tissues including heart, brain, placenta, lung and skeletal muscle. Highest levels in skeletal muscle. Lowest in lung and placenta. Strongly expressed in skeletal muscle. Also expressed at lower levels in heart and lung.

Post-translational modifications. On EGF stimulation, phosphorylated first on Thr-53 allowing subsequent phosphorylation on Thr-51. This latter phosphorylation prevents sumoylation, increases binding to TAF12 and enhances transcriptional activity. Sumoylation delays nuclear localization and inhibits transactivation activity through preventing binding to TAF12. RANBP2 appears to be the specific E3 ligase. On EGF stimulation, phosphorylated first on Thr-53 allowing subsequent phosphorylation on Thr-51. This latter phosphorylation prevents sumoylation, increases binding to TAF12 and enhances transcriptional activity. Social isolation stress as well as TNF also induce the phosphorylation of ATF7. Phosphorylated in proliferating colonic and small intestinal epithelial cells.

Similarity. Belongs to the bZIP family.

Isoforms (6)

UniProt ID	Names	Canonical?
P17544-6	1	yes
P17544-1	6, ATF-A1
P17544-2	2, ATF-A
P17544-3	3, ATF-A-delta
P17544-4	4, ATF-A0
P17544-5	5, ATF-4

RefSeq proteins (10): NP_001123532, NP_001193611, NP_001193612, NP_001353484, NP_001353485, NP_001353487, NP_001353490, NP_001353491, NP_001353492, NP_006847* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004827	bZIP	Domain
IPR013087	Znf_C2H2_type	Domain
IPR016378	TF_CRE-BP1-typ	Family
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR046347	bZIP_sf	Homologous_superfamily
IPR051027

Pfam: PF00170

UniProt features (40 total): mutagenesis site 14, region of interest 7, modified residue 5, splice variant 5, compositionally biased region 4, chain 1, domain 1, cross-link 1, zinc finger region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17544-F1	61.08	0.17

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 (6): 51, 53, 101, 413, 423, 107

Mutagenesis-validated functional residues (14):

Position	Phenotype
9	severely reduced taf12-mediated enhancement of transcriptional activity.
14	greatly reduced jnk2- or adenovirus e1a-mediated transactivation. abolishes adenovirus 2 e1a-mediated transactivation; w
22	no effect on binding adenovirus 2 e1a. abolishes atf7-mediated e1a responsiveness.
27	no effect on binding adenovirus 2 e1a. abolishes atf7-mediated e1a responsiveness.
33	severely reduced taf12-induced transcriptional activity; when associated with s-35.
35	severely reduced taf12-induced transcriptional activity; when associated with d-33.
51	severely reduced taf12-induced transcriptional activity. no effect on mapk9-mediated phosphorylation; when associated wi
51	completely abolishes mapk9- and adenovirus e1a-mediated transactivation; when associated with d-53.
53	severely reduced taf12-induced transcriptional activity. no effect on mapk9-mediated phosphorylation; when associated wi
53	completely abolishes mapk9- and adenovirus e1a-mediated transactivation; when associated with d-51.
101	some reduction in transactivation but, completely abolishes mapk9-mediated activation. abolishes mapk9-mediated and grea
107	abolishes sumoylation. exclusive nucleoplasmic location. increase in binding the e-selectin promoter.
145	no effect on transactivation; when associated with a-147.
147	no effect on transactivation; when associated with a-145.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 188 (showing top): NKX25_02, KYNG_DNA_DAMAGE_BY_4NQO, GGGTGGRR_PAX4_03, GRE_C, AACTTT_UNKNOWN, VDR_Q3, FOXJ2_02, DANG_BOUND_BY_MYC, GOCC_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATOR_COMPLEX, GOCC_CHROMOSOMAL_REGION, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, GOCC_CHROMOSOME_TELOMERIC_REGION, GOMF_MITOGEN_ACTIVATED_PROTEIN_KINASE_BINDING, GOMF_TRANSCRIPTION_COREGULATOR_BINDING, GOMF_CAMP_RESPONSE_ELEMENT_BINDING

GO Biological Process (4): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (14): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), transcription coactivator binding (GO:0001223), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), enzyme binding (GO:0019899), cAMP response element binding (GO:0035497), mitogen-activated protein kinase binding (GO:0051019), sequence-specific double-stranded DNA binding (GO:1990837), transcription cis-regulatory region binding (GO:0000976), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): chromosome, telomeric region (GO:0000781), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), RNA polymerase II transcription regulator complex (GO:0090575), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
regulation of DNA-templated transcription	2
negative regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
transcription coregulator binding	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
transition metal ion binding	1
protein binding	1
RNA polymerase II cis-regulatory region sequence-specific DNA binding	1
protein kinase binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
nucleic acid binding	1
binding	1
cation binding	1
chromosomal region	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
transcription regulator complex	1
nuclear protein-containing complex	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1456 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATF7	FOS	P01100	906
ATF7	PTP4A1	Q93096	892
ATF7	JUND	P17535	851
ATF7	SETDB1	Q15047	819
ATF7	ATF7IP	Q6VMQ6	811
ATF7	JUN	P05412	809
ATF7	ATF5	Q9Y2D1	750
ATF7	GABBR1	Q9UBS5	666
ATF7	CREB1	P16220	634
ATF7	TAF12	Q16514	620
ATF7	UBE2B	P23567	609
ATF7	GDNF	P39905	598
ATF7	MAPK9	P45984	563
ATF7	JUNB	P17275	537
ATF7	MAFK	O60675	519

IntAct

99 interactions, top by confidence:

A	B	Type	Score
JUN	ATF2	psi-mi:“MI:0914”(association)	0.950
ATF2	JUN	psi-mi:“MI:0914”(association)	0.950
JUNB	FOS	psi-mi:“MI:0914”(association)	0.950
FOSL2	JUN	psi-mi:“MI:0914”(association)	0.930
BACH1	MAFG	psi-mi:“MI:0914”(association)	0.870
ODAD1	HGS	psi-mi:“MI:0914”(association)	0.850
ATF2	BACH1	psi-mi:“MI:0914”(association)	0.780
ATF2	JUND	psi-mi:“MI:0914”(association)	0.760
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
PPP2R2D	YEATS4	psi-mi:“MI:0914”(association)	0.730
ATF7	JUN	psi-mi:“MI:0407”(direct interaction)	0.720
JUN	ATF7	psi-mi:“MI:0407”(direct interaction)	0.720
ATF7	FOS	psi-mi:“MI:0407”(direct interaction)	0.690
ATF7	BACH1	psi-mi:“MI:0407”(direct interaction)	0.690
ATF2	ATF7	psi-mi:“MI:0407”(direct interaction)	0.690
ATF7	JUNB	psi-mi:“MI:0407”(direct interaction)	0.690
ATF7	FOSL2	psi-mi:“MI:0407”(direct interaction)	0.690
JUNB	ATF7	psi-mi:“MI:0407”(direct interaction)	0.690
FOSL2	ATF7	psi-mi:“MI:0407”(direct interaction)	0.690
FOSB	JUN	psi-mi:“MI:0914”(association)	0.690
CREB5	JUN	psi-mi:“MI:0914”(association)	0.690
JUN	NFATC1	psi-mi:“MI:0914”(association)	0.610
ATF7	ATF3	psi-mi:“MI:0407”(direct interaction)	0.590
ATF7	CEBPG	psi-mi:“MI:0407”(direct interaction)	0.590
ATF7	DDIT3	psi-mi:“MI:0407”(direct interaction)	0.590

BioGRID (94): ATF7 (Two-hybrid), CCDC155 (Two-hybrid), FAM9B (Two-hybrid), TMEM239 (Two-hybrid), ATF7 (Affinity Capture-MS), ATF7 (Affinity Capture-MS), ATF7 (Affinity Capture-MS), ATF7 (Affinity Capture-MS), ATF7 (Co-fractionation), MBD3 (Two-hybrid), ATF7 (Affinity Capture-MS), ATF7 (Affinity Capture-MS), ATF7 (Affinity Capture-MS), ATF7 (Affinity Capture-MS), ATF7 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JTY4, A0JNC2, A2AQ25, E1BEQ5, O09000, O57539, O70305, O93602, P15336, P16951, P17544, P70365, P97305, Q00969, Q02930, Q12968, Q14157, Q15032, Q15596, Q15788, Q1LY51, Q4PJW2, Q4VCS5, Q5R9C9, Q5SFM8, Q5T5P2, Q5T6F2, Q61026, Q62415, Q6GP15, Q80TM6, Q80X50, Q86YP4, Q8CHY6, Q8IY63, Q8VCB2, Q8VHG2, Q8VHR5, Q8WXI9, Q91VX2

Diamond homologs: A0A0A2J9B3, A7YY54, B8NLU5, O77627, O93602, P05411, P05412, P05627, P09450, P11939, P12981, P15066, P15336, P16951, P17275, P17325, P17535, P17544, P18870, P23050, P24898, P27921, P52890, P52909, P54864, P56432, P78962, P79703, Q00969, Q02100, Q02930, Q09771, Q09926, Q0VBZ5, Q2U616, Q4WVQ7, Q59VR1, Q5R9C9, Q8K1L0, Q8R0S1

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TAF12	“up-regulates activity”	ATF7	binding
TAF4	“down-regulates activity”	ATF7	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 77 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
NGF-stimulated transcription	6	35.0×	6e-06
Response of EIF2AK4 (GCN2) to amino acid deficiency	5	11.3×	4e-03
Regulation of PD-L1(CD274) transcription	5	11.1×	4e-03
Intracellular signaling by second messengers	5	9.3×	6e-03
Cellular responses to stress	7	5.3×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
integrated stress response signaling	8	80.2×	3e-11
cellular response to calcium ion	6	17.2×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

2590 predictions. Top by Δscore:

Variant	Effect	Δscore
12:53523271:CTCA:C	donor_loss	1.0000
12:53523272:TCA:T	donor_loss	1.0000
12:53523272:TCAC:T	donor_loss	1.0000
12:53523273:CAC:C	donor_loss	1.0000
12:53523274:ACCT:A	donor_loss	1.0000
12:53523275:C:CT	donor_loss	1.0000
12:53523383:TT:T	acceptor_gain	1.0000
12:53523383:TTCTG:T	acceptor_loss	1.0000
12:53523384:TCTG:T	acceptor_loss	1.0000
12:53523384:TCTGA:T	acceptor_loss	1.0000
12:53523385:C:CC	acceptor_gain	1.0000
12:53523385:CTGA:C	acceptor_loss	1.0000
12:53523386:T:A	acceptor_loss	1.0000
12:53524558:A:AC	donor_gain	1.0000
12:53524559:C:CC	donor_gain	1.0000
12:53524562:A:AC	donor_gain	1.0000
12:53524563:C:CC	donor_gain	1.0000
12:53524563:CA:C	donor_gain	1.0000
12:53524563:CACT:C	donor_gain	1.0000
12:53524569:G:C	donor_gain	1.0000
12:53524760:ACCTG:A	acceptor_loss	1.0000
12:53524761:CC:C	acceptor_loss	1.0000
12:53524761:CCTGG:C	acceptor_gain	1.0000
12:53524762:CTG:C	acceptor_loss	1.0000
12:53524763:T:C	acceptor_loss	1.0000
12:53524770:C:CT	acceptor_gain	1.0000
12:53524770:C:T	acceptor_gain	1.0000
12:53524771:A:T	acceptor_gain	1.0000
12:53531739:CTGA:C	donor_loss	1.0000
12:53531740:TGAC:T	donor_loss	1.0000

AlphaMissense

3123 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:53523311:A:T	V400D	1.000
12:53523316:G:C	C398W	1.000
12:53523317:C:A	C398F	1.000
12:53523317:C:G	C398S	1.000
12:53523317:C:T	C398Y	1.000
12:53523318:A:C	C398G	1.000
12:53523318:A:G	C398R	1.000
12:53523318:A:T	C398S	1.000
12:53523325:A:C	H395Q	1.000
12:53523325:A:T	H395Q	1.000
12:53523326:T:C	H395R	1.000
12:53523326:T:G	H395P	1.000
12:53523327:G:C	H395D	1.000
12:53523327:G:T	H395N	1.000
12:53523330:C:G	A394P	1.000
12:53523335:A:C	L392R	1.000
12:53523335:A:G	L392P	1.000
12:53523335:A:T	L392Q	1.000
12:53523338:A:G	L391P	1.000
12:53523343:T:A	K389N	1.000
12:53523343:T:G	K389N	1.000
12:53523344:T:A	K389I	1.000
12:53523347:A:C	L388W	1.000
12:53523347:A:G	L388S	1.000
12:53523354:C:G	A386P	1.000
12:53523365:C:G	R382P	1.000
12:53523368:A:G	L381P	1.000
12:53523377:A:T	V378D	1.000
12:53524568:A:G	L374P	1.000
12:53524589:A:G	L367P	1.000

dbSNP variants (sampled 300 via entrez): RS1000002990 (12:53527390 G>A,C), RS1000003316 (12:53609698 C>T), RS1000013048 (12:53579531 G>A), RS1000061032 (12:53615984 T>C,G), RS1000066596 (12:53525222 G>A,T), RS1000091800 (12:53615627 A>G), RS1000107906 (12:53562856 C>A,T), RS1000110086 (12:53519047 C>G,T), RS1000112755 (12:53583034 A>G), RS1000135108 (12:53531581 T>C), RS1000224629 (12:53559215 T>A), RS1000258184 (12:53554177 C>A,T), RS1000312708 (12:53614945 T>C), RS1000326417 (12:53551812 T>C), RS1000365360 (12:53547643 T>A,C)

Disease associations

OMIM: gene MIM:606371 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST000611_9	Height	9.000000e-07
GCST001263_1	Height	5.000000e-06
GCST002702_64	Height	9.000000e-15
GCST002709_16	Electroencephalogram traits	8.000000e-06
GCST005956_70	Waist-to-hip ratio adjusted for BMI	4.000000e-13
GCST005957_6	Waist-to-hip ratio adjusted for BMI (age <50)	6.000000e-06
GCST005958_9	Waist-to-hip ratio adjusted for BMI (age >50)	1.000000e-08
GCST005962_20	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	7.000000e-13
GCST006979_1059	Heel bone mineral density	3.000000e-09
GCST008839_548	Height	5.000000e-22
GCST90002379_51	Basophil count	6.000000e-13
GCST90002389_463	Lymphocyte percentage of white cells	5.000000e-11
GCST90002393_414	Monocyte count	2.000000e-13
GCST90002393_415	Monocyte count	6.000000e-11
GCST90002394_368	Monocyte percentage of white cells	9.000000e-39
GCST90002398_143	Neutrophil count	5.000000e-17
GCST90002399_337	Neutrophil percentage of white cells	2.000000e-22

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004357	electroencephalogram measurement
EFO:0006871	beta wave measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0009270	heel bone mineral density
EFO:0005090	basophil count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes
EFO:0004833	neutrophil count
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases expression, increases methylation	3
Cadmium	increases expression, increases reaction, decreases expression, increases abundance	2
Cadmium Chloride	decreases expression, increases abundance	2
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
bisphenol A	decreases methylation	1
trichostatin A	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
coumarin	decreases phosphorylation	1
Resveratrol	affects cotreatment, decreases expression	1
Vorinostat	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Caffeine	increases phosphorylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Nickel	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Dronabinol	increases expression	1
Cyclosporine	increases methylation	1
Palmitic Acid	decreases phosphorylation	1
Lactic Acid	increases expression	1
Particulate Matter	increases expression, increases abundance	1

Clinical trials (associated diseases)

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