HES5

Summary

HES5 (hes family bHLH transcription factor 5, HGNC:19764) is a protein-coding gene on chromosome 1p36.32, encoding Transcription factor HES-5 (Q5TA89). Transcriptional repressor of genes that require a bHLH protein for their transcription.

This gene encodes a member of a family of basic helix-loop-helix transcriptional repressors. The protein product of this gene, which is activated downstream of the Notch pathway, regulates cell differentiation in multiple tissues. Disruptions in the normal expression of this gene have been associated with developmental diseases and cancer.

Source: NCBI Gene 388585 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 33 total
• MANE Select transcript: NM_001010926

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19764
Approved symbol	HES5
Name	hes family bHLH transcription factor 5
Location	1p36.32
Locus type	gene with protein product
Status	Approved
Aliases	bHLHb38
Ensembl gene	ENSG00000197921
Ensembl biotype	protein_coding
OMIM	607348
Entrez	388585

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000378453

RefSeq mRNA: 1 — MANE Select: NM_001010926 NM_001010926

CCDS: CCDS41233

Canonical transcript exons

ENST00000378453 — 3 exons

Exon	Start	End
ENSE00001410539	2529846	2530011
ENSE00001434113	2528745	2529749
ENSE00001477587	2530111	2530263

Expression profiles

Bgee: expression breadth ubiquitous, 106 present calls, max score 88.66.

FANTOM5 (CAGE): breadth broad, TPM avg 13.2526 / max 1939.9430, expressed in 391 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
9916	9.5324	368
9909	2.6276	70
9915	0.4807	70
9914	0.3983	60
9911	0.0721	32
9910	0.0612	24
9913	0.0585	25
9912	0.0219	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.66	gold quality
ventricular zone	UBERON:0003053	88.29	gold quality
ganglionic eminence	UBERON:0004023	78.05	gold quality
nucleus accumbens	UBERON:0001882	77.86	gold quality
amygdala	UBERON:0001876	76.22	gold quality
temporal lobe	UBERON:0001871	76.14	gold quality
hypothalamus	UBERON:0001898	74.07	gold quality
apex of heart	UBERON:0002098	71.41	gold quality
anterior cingulate cortex	UBERON:0009835	70.80	gold quality
caudate nucleus	UBERON:0001873	70.73	gold quality
putamen	UBERON:0001874	70.52	gold quality
superior frontal gyrus	UBERON:0002661	69.69	gold quality
primary visual cortex	UBERON:0002436	68.60	gold quality
right frontal lobe	UBERON:0002810	68.54	gold quality
brain	UBERON:0000955	67.54	gold quality
skin of leg	UBERON:0001511	67.42	gold quality
Brodmann (1909) area 9	UBERON:0013540	67.23	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	67.20	gold quality
cerebral cortex	UBERON:0000956	67.10	gold quality
mucosa of transverse colon	UBERON:0004991	66.61	gold quality
frontal cortex	UBERON:0001870	66.55	gold quality
zone of skin	UBERON:0000014	66.35	gold quality
right hemisphere of cerebellum	UBERON:0014890	65.93	gold quality
Ammon’s horn	UBERON:0001954	65.16	gold quality
skin of abdomen	UBERON:0001416	65.12	gold quality
prefrontal cortex	UBERON:0000451	65.06	gold quality
substantia nigra	UBERON:0002038	64.95	gold quality
cerebellum	UBERON:0002037	63.26	gold quality
cerebellar cortex	UBERON:0002129	63.25	gold quality
cerebellar hemisphere	UBERON:0002245	63.13	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-10485	yes	1199.01
E-MTAB-11121	yes	1011.57
E-HCAD-56	yes	893.33
E-MTAB-8559	yes	143.33
E-GEOD-93593	yes	14.10
E-MTAB-8894	no	271.07
E-ANND-3	no	0.29

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
ASCL1	Repression
ATOH1	Repression
HTR1A	Repression
IL12A
NEUROG1	Repression
NEUROG2	Repression
NOTCH1

JASPAR motifs

Motif	Name	Family
MA0821.1	HES5	Hairy-related factors
MA0821.2	HES5	Hairy-related factors

JASPAR matrix evidence (PMIDs): PMID:15186484

Upstream regulators (CollecTRI, top): ASCL1, BCL6, ETV1, FEZF1, FEZF2, H1-4, H4C2, HES6, HEY1, NOTCH1, PAX6, RBPJ, SERPINF1, SIRT1, SOX21, SOX2, SSRP1, ZNF423

miRNA regulators (miRDB)

23 targeting HES5, 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-548AN	99.97	70.91	2817
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4477B	99.23	70.49	1733
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-500A-5P	98.76	69.13	1241
HSA-MIR-384	98.71	67.34	1229
HSA-MIR-541-5P	98.24	67.77	1181
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-337-3P	97.90	69.37	1052
HSA-MIR-676-3P	97.86	65.70	668
HSA-MIR-3921	97.81	67.45	1431
HSA-MIR-4653-5P	97.22	67.72	1429
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-6775-3P	95.76	65.91	982
HSA-MIR-3679-5P	94.75	66.46	862
HSA-MIR-1185-5P	94.47	65.95	725

Literature-anchored findings (GeneRIF, showing 17)

• The HLH gene HES5 on the other hand was only detected in chondrocytes. (PMID:17072841)
• Human HES5 gene is coupled to the Notch receptor family and expression of Notch markers (including HES5) decreases during cartilage differentiation. (PMID:17093926)
• expression significantly higher in squamous cervical carcinoma than in CIN as well as higher in CIN than normal cervical epithelia (PMID:17388915)
• Data show that HES5 are abundantly expressed in osteoarthritis. (PMID:18354251)
• regulates brain development process.[review] (PMID:18524252)
• The expression of HES5 in adenocarcinoma was significantly higher than those in adenoma and normal control (PMID:20091184)
• In this study, HES 5 transcription factor was detected in the lining epithelium of human periapical cysts with limited inflammation, showing Notch pathway activation in those cells. (PMID:21238798)
• Hes5 overactivation is associated with cell differentiation, thereby resulting in uterine carcinogenesis. (PMID:21495212)
• Notch3 and Hes5 are hypermethylated in human B cell acute lymphoblastic leukemia (ALL). (PMID:23637910)
• the downstream Notch signalling effector HES5 directly represses transcription of the E3 ligase Fbw7beta. (PMID:23776410)
• these data identify HES5 as a key mediator of the Wnt-3a proneurogenic effect occurring independently of the classical Wnt/beta-catenin signaling cascade thus further deciphering crosstalk mechanisms of Wnt and Notch signaling pathways regulating cell fate (PMID:24548083)
• HES5 silencing is an early and recurrent change in prostate tumourigenesis (PMID:25560400)
• that suppression of the HES5 leading to inhibition of proliferation may be one of the mechanisms against Hepatocellular carcinoma (PMID:26342546)
• HES5 might contribute to the proliferation of non-small cell lung cancer by STAT3 signaling. (PMID:27878283)
• NOTCH target gene HES5 mediates oncogenic and tumor suppressive functions in hepatocarcinogenesis. (PMID:32055024)
• Repression of FBXW7 by HES5 contributes to inactivation of the TGF-beta signaling pathway and alleviation of endometriosis. (PMID:33496006)
• Notch3/Hes5 Induces Vascular Dysfunction in Hypoxia-Induced Pulmonary Hypertension Through ER Stress and Redox-Sensitive Pathways. (PMID:37254738)

Cross-species orthologs

21 orthologs

Organism	Symbol	Gene ID
danio_rerio	her4.4	ENSDARG00000009822
danio_rerio	her7	ENSDARG00000017917
danio_rerio	heyl	ENSDARG00000055798
danio_rerio	her4.5	ENSDARG00000056729
danio_rerio	her4.1	ENSDARG00000056732
danio_rerio	her4.3	ENSDARG00000070770
danio_rerio	her4.2	ENSDARG00000094426
mus_musculus	Hes5	ENSMUSG00000048001
rattus_norvegicus	Hes5	ENSRNOG00000013850
drosophila_melanogaster	E(spl)m8-HLH	FBGN0000591
drosophila_melanogaster	hry	FBGN0001168
drosophila_melanogaster	E(spl)m3-HLH	FBGN0002609
drosophila_melanogaster	E(spl)m5-HLH	FBGN0002631
drosophila_melanogaster	E(spl)m7-HLH	FBGN0002633
drosophila_melanogaster	E(spl)mbeta-HLH	FBGN0002733
drosophila_melanogaster	E(spl)mdelta-HLH	FBGN0002734
drosophila_melanogaster	E(spl)mgamma-HLH	FBGN0002735
drosophila_melanogaster	dpn	FBGN0010109
drosophila_melanogaster	Hesr	FBGN0030899
drosophila_melanogaster	Sidpn	FBGN0032741
drosophila_melanogaster	cwo	FBGN0259938

Paralogs (12): HES2 (ENSG00000069812), HES1 (ENSG00000114315), BHLHE41 (ENSG00000123095), BHLHE40 (ENSG00000134107), HEY2 (ENSG00000135547), HES6 (ENSG00000144485), HEYL (ENSG00000163909), HEY1 (ENSG00000164683), HES3 (ENSG00000173673), HES7 (ENSG00000179111), HELT (ENSG00000187821), HES4 (ENSG00000188290)

Protein

Protein identifiers

Transcription factor HES-5 — Q5TA89 (reviewed: Q5TA89)

Alternative names: Class B basic helix-loop-helix protein 38, Hairy and enhancer of split 5

All UniProt accessions (1): Q5TA89

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor of genes that require a bHLH protein for their transcription. Plays an important role as neurogenesis negative regulator.

Subunit / interactions. Transcription repression requires formation of a complex with a corepressor protein of the Groucho/TLE family.

Subcellular location. Nucleus.

Tissue specificity. Expressed in fetal heart and brain tumors.

Domain organisation. Has a particular type of basic domain (presence of a helix-interrupting proline) that binds to the N-box (CACNAG), rather than the canonical E-box (CANNTG). The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with Groucho/TLE family members, transcriptional corepressors recruited to specific target DNA by Hairy-related proteins.

RefSeq proteins (1): NP_001010926* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003650	Orange_dom	Domain
IPR011598	bHLH_dom	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR050370	HES_HEY	Family

Pfam: PF00010, PF07527

UniProt features (5 total): domain 2, chain 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TA89-F1	74.93	0.36

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-2122947	NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2197563	NOTCH2 intracellular domain regulates transcription
R-HSA-2644606	Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2894862	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-9013508	NOTCH3 Intracellular Domain Regulates Transcription
R-HSA-9013695	NOTCH4 Intracellular Domain Regulates Transcription

MSigDB gene sets: 255 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_METANEPHRIC_NEPHRON_MORPHOGENESIS, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, REACTOME_SIGNALING_BY_NOTCH, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_METANEPHROS_DEVELOPMENT, GOBP_CARTILAGE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_OLIGODENDROCYTE_DIFFERENTIATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT

GO Biological Process (55): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), cell adhesion (GO:0007155), Notch signaling pathway (GO:0007219), smoothened signaling pathway (GO:0007224), brain development (GO:0007420), positive regulation of cell population proliferation (GO:0008284), anterior/posterior pattern specification (GO:0009952), oligodendrocyte development (GO:0014003), telencephalon development (GO:0021537), glial cell fate commitment (GO:0021781), neural tube development (GO:0021915), central nervous system neuron differentiation (GO:0021953), central nervous system myelination (GO:0022010), BMP signaling pathway (GO:0030509), positive regulation of BMP signaling pathway (GO:0030513), regulation of myelination (GO:0031641), inner ear auditory receptor cell differentiation (GO:0042491), camera-type eye development (GO:0043010), regulation of cell differentiation (GO:0045595), negative regulation of inner ear auditory receptor cell differentiation (GO:0045608), negative regulation of neuron differentiation (GO:0045665), positive regulation of Notch signaling pathway (GO:0045747), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of receptor signaling pathway via JAK-STAT (GO:0046427), cell maturation (GO:0048469), positive regulation of smooth muscle cell proliferation (GO:0048661), astrocyte differentiation (GO:0048708), negative regulation of astrocyte differentiation (GO:0048712), negative regulation of oligodendrocyte differentiation (GO:0048715), regulation of epithelial cell proliferation (GO:0050678), regulation of neurogenesis (GO:0050767), cartilage development (GO:0051216), inner ear receptor cell stereocilium organization (GO:0060122), protein-containing complex assembly (GO:0065003), comma-shaped body morphogenesis (GO:0072049), S-shaped body morphogenesis (GO:0072050), specification of loop of Henle identity (GO:0072086), metanephric nephron tubule morphogenesis (GO:0072282)

GO Molecular Function (6): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), protein dimerization activity (GO:0046983), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Signaling by NOTCH1	1
Signaling by NOTCH2	1
Signaling by NOTCH1 PEST Domain Mutants in Cancer	1
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	1
Signaling by NOTCH3	1
Signaling by NOTCH4	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
cell surface receptor signaling pathway	2
central nervous system development	2
myelination	2
regulation of cellular process	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
regulation of DNA-templated transcription	1
cellular process	1
animal organ development	1
head development	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regionalization	1
glial cell development	1
oligodendrocyte differentiation	1
forebrain development	1
anatomical structure development	1
glial cell differentiation	1
cell fate commitment	1
nervous system development	1
tube development	1
chordate embryonic development	1
epithelium development	1
neuron differentiation	1
oligodendrocyte development	1
axon ensheathment in central nervous system	1
cellular response to BMP stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
regulation of nervous system development	1
hair cell differentiation	1
inner ear receptor cell differentiation	1
eye development	1
cell differentiation	1

Protein interactions and networks

STRING

1314 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HES5	NOTCH1	P46531	872
HES5	NOTCH3	Q9UM47	865
HES5	DLL1	O00548	853
HES5	JAG1	P78504	836
HES5	NOTCH2	Q04721	793
HES5	LFNG	Q8NES3	769
HES5	STAT3	P40763	729
HES5	RBPJ	Q06330	726
HES5	NRARP	Q7Z6K4	726
HES5	DLL3	Q9NYJ7	719
HES5	ATOH1	Q92858	706
HES5	ASCL1	P50553	696
HES5	FABP7	O15540	680
HES5	OLIG2	Q13516	671
HES5	JAK2	O60674	651

IntAct

7 interactions, top by confidence:

A	B	Type	Score
	HES5	psi-mi:“MI:0915”(physical association)	0.400
	HES5	psi-mi:“MI:0915”(physical association)	0.370
TNFSF14	HES5	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (5): HES5 (Synthetic Growth Defect), HES5 (Synthetic Growth Defect), STAT3 (Affinity Capture-Western), HES5 (Reconstituted Complex), JAK2 (Affinity Capture-Western)

ESM2 similar proteins: A5PJV0, A5PKJ4, A7YY73, O15525, O42290, O42406, O54790, O54791, O57337, O57342, O60675, O73916, O93307, O95343, O95475, P10360, P13097, P35428, P50538, P54845, P54846, Q01068, Q01069, Q04666, Q13164, Q14469, Q14582, Q2KIN4, Q3ZBG4, Q5FWS6, Q5TA89, Q5ZK92, Q60948, Q61827, Q62232, Q62233, Q674X7, Q69ZS8, Q6P730, Q76MX4

Diamond homologs: A0MLS5, A6NFD8, O00327, O14503, O35779, O54792, O57337, O61734, O88529, P13097, P14003, P29303, P35428, P35429, P70120, Q00P32, Q01069, Q03062, Q04666, Q14469, Q26263, Q28HA8, Q2KIN4, Q2NL18, Q3ZBG4, Q5PPM5, Q5R4T2, Q5RAI7, Q5TA89, Q66KK8, Q6IRB2, Q6PBD4, Q6QB00, Q6YGZ5, Q7KM13, Q7TS99, Q8AVU4, Q8AXV5, Q8AXV6, Q8BKT2

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
HES5	“down-regulates quantity by repression”	NEUROG1	“transcriptional regulation”
HES5	“down-regulates quantity by repression”	NEUROG2	“transcriptional regulation”
HES5	“down-regulates quantity by repression”	ATOH1	“transcriptional regulation”
HES5	“down-regulates quantity by repression”	ASCL1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

117 predictions. Top by Δscore:

Variant	Effect	Δscore
1:2529841:CTCA:C	donor_loss	1.0000
1:2529842:TCACC:T	donor_loss	1.0000
1:2529843:CACC:C	donor_loss	1.0000
1:2529844:A:AC	donor_gain	1.0000
1:2529844:AC:A	donor_gain	1.0000
1:2529844:ACCT:A	donor_loss	1.0000
1:2529845:C:CC	donor_gain	1.0000
1:2529845:C:CG	donor_loss	1.0000
1:2529845:CC:C	donor_gain	1.0000
1:2529845:CCT:C	donor_gain	1.0000
1:2530007:CGCAG:C	acceptor_gain	1.0000
1:2530009:CAG:C	acceptor_gain	1.0000
1:2530010:AG:A	acceptor_gain	1.0000
1:2530011:GCT:G	acceptor_loss	1.0000
1:2530012:C:CC	acceptor_gain	1.0000
1:2530106:CTT:C	donor_loss	1.0000
1:2530107:TTA:T	donor_loss	1.0000
1:2530108:TAC:T	donor_loss	1.0000
1:2530109:A:AC	donor_gain	1.0000
1:2530109:A:T	donor_loss	1.0000
1:2530109:ACT:A	donor_gain	1.0000
1:2530110:C:CA	donor_gain	1.0000
1:2530110:CT:C	donor_gain	1.0000
1:2530110:CTC:C	donor_gain	1.0000
1:2530110:CTCG:C	donor_gain	1.0000
1:2530110:CTCGG:C	donor_gain	1.0000
1:2529747:AGG:A	acceptor_gain	0.9900
1:2529748:GG:G	acceptor_gain	0.9900
1:2529748:GGCTG:G	acceptor_loss	0.9900
1:2529749:GCTG:G	acceptor_loss	0.9900

AlphaMissense

1072 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:2529881:A:G	L62P	1.000
1:2529881:A:T	L62Q	1.000
1:2529892:C:A	K58N	1.000
1:2529892:C:G	K58N	1.000
1:2529894:T:G	K58Q	1.000
1:2529896:T:A	E57V	1.000
1:2529950:A:G	L39P	1.000
1:2529959:A:T	I36N	1.000
1:2529967:G:C	N33K	1.000
1:2529967:G:T	N33K	1.000
1:2529969:T:C	N33D	1.000
1:2529971:A:C	I32S	1.000
1:2529971:A:G	I32T	1.000
1:2529971:A:T	I32N	1.000
1:2529974:C:G	R31P	1.000
1:2529975:G:T	R31S	1.000
1:2529980:C:G	R29P	1.000
1:2529980:C:T	R29H	1.000
1:2529981:G:A	R29C	1.000
1:2529981:G:T	R29S	1.000
1:2529984:G:T	R28S	1.000
1:2529988:C:A	K26N	1.000
1:2529988:C:G	K26N	1.000
1:2529991:C:A	E25D	1.000
1:2529991:C:G	E25D	1.000
1:2529992:T:A	E25V	1.000
1:2529993:C:T	E25K	1.000
1:2530003:C:A	K21N	1.000
1:2530003:C:G	K21N	1.000
1:2530005:T:C	K21E	1.000

dbSNP variants (sampled 300 via entrez): RS1000353942 (1:2531307 C>T), RS1000617807 (1:2530295 C>A), RS1000739681 (1:2530375 C>A,G), RS1001619656 (1:2529347 C>G), RS1002738976 (1:2528617 C>T), RS1003663508 (1:2531740 C>T), RS1004260791 (1:2528815 G>C), RS1004748286 (1:2528636 G>A), RS1005573201 (1:2531951 T>C,G), RS1006210005 (1:2532186 C>A,T), RS1006954152 (1:2530976 A>T), RS1007159766 (1:2530785 C>G,T), RS1007904113 (1:2529260 G>A,C), RS1008214132 (1:2530023 G>A,T), RS1008578529 (1:2528846 A>T)

Disease associations

OMIM: gene MIM:607348 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_35	Body mass index	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation, affects cotreatment, decreases expression	7
trichostatin A	affects cotreatment, decreases expression	3
MRK 003	decreases expression	3
methylmercuric chloride	decreases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
belinostat	affects cotreatment, decreases expression	2
bisphenol S	decreases methylation, increases expression	2
Vorinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Rotenone	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
ascorbate-2-phosphate	affects binding, affects cotreatment, decreases expression	1
sodium arsenite	increases expression	1
ferrous chloride	decreases expression	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	affects cotreatment, decreases expression	1
evodiamine	increases expression	1
avobenzone	decreases expression	1
azoxystrobin	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
Chir 99021	affects cotreatment, decreases expression, affects binding	1
thifluzamide	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
XAV939	affects binding, affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
picoxystrobin	decreases expression	1
3-(4-pyridyl)-1H-indole	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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