HES6

Summary

HES6 (hes family bHLH transcription factor 6, HGNC:18254) is a protein-coding gene on chromosome 2q37.3, encoding Transcription cofactor HES-6 (Q96HZ4). Does not bind DNA itself but suppresses both HES1-mediated N box-dependent transcriptional repression and binding of HES1 to E box sequences.

This gene encodes a member of a subfamily of basic helix-loop-helix transcription repressors that have homology to the Drosophila enhancer of split genes. Members of this gene family regulate cell differentiation in numerous cell types. The protein encoded by this gene functions as a cofactor, interacting with other transcription factors through a tetrapeptide domain in its C-terminus. Alternatively spliced transcript variants encoding different isoforms have been described.

Source: NCBI Gene 55502 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 39 total
• MANE Select transcript: NM_018645

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18254
Approved symbol	HES6
Name	hes family bHLH transcription factor 6
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Aliases	bHLHb41
Ensembl gene	ENSG00000144485
Ensembl biotype	protein_coding
OMIM	610331
Entrez	55502

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 12 protein_coding

ENST00000272937, ENST00000409002, ENST00000409160, ENST00000409182, ENST00000409356, ENST00000409574, ENST00000417803, ENST00000436051, ENST00000450098, ENST00000898518, ENST00000898519, ENST00000941871

RefSeq mRNA: 3 — MANE Select: NM_018645 NM_001142853, NM_001282434, NM_018645

CCDS: CCDS2527, CCDS46556, CCDS63180

Canonical transcript exons

ENST00000272937 — 4 exons

Exon	Start	End
ENSE00001589004	238239825	238240038
ENSE00001926712	238238267	238239251
ENSE00003579143	238239661	238239747
ENSE00003607380	238239487	238239568

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 99.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.1980 / max 1291.4515, expressed in 1340 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34761	17.1291	1340
34762	0.0689	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.36	gold quality
ventricular zone	UBERON:0003053	97.85	gold quality
secondary oocyte	CL:0000655	96.57	gold quality
cortical plate	UBERON:0005343	94.97	gold quality
oocyte	CL:0000023	94.41	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	92.78	gold quality
mucosa of transverse colon	UBERON:0004991	91.40	gold quality
adenohypophysis	UBERON:0002196	91.29	gold quality
spinal cord	UBERON:0002240	91.27	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.94	gold quality
primary visual cortex	UBERON:0002436	90.61	gold quality
anterior cingulate cortex	UBERON:0009835	90.34	gold quality
pituitary gland	UBERON:0000007	90.19	gold quality
right frontal lobe	UBERON:0002810	89.90	gold quality
amygdala	UBERON:0001876	88.81	gold quality
right uterine tube	UBERON:0001302	88.24	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.96	gold quality
occipital lobe	UBERON:0002021	86.95	gold quality
prefrontal cortex	UBERON:0000451	86.85	gold quality
neocortex	UBERON:0001950	86.84	gold quality
endothelial cell	CL:0000115	86.67	silver quality
hypothalamus	UBERON:0001898	86.30	gold quality
cerebral cortex	UBERON:0000956	86.13	gold quality
right testis	UBERON:0004534	85.94	gold quality
putamen	UBERON:0001874	85.70	gold quality
transverse colon	UBERON:0001157	85.64	gold quality
forebrain	UBERON:0001890	85.60	gold quality
caudate nucleus	UBERON:0001873	85.46	gold quality
Ammon’s horn	UBERON:0001954	85.38	gold quality
left testis	UBERON:0004533	85.37	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	5234.78
E-MTAB-10485	yes	3777.18
E-MTAB-6911	yes	2527.60
E-HCAD-56	yes	2451.25
E-HCAD-5	yes	2150.14
E-MTAB-9435	yes	1508.37
E-MTAB-8894	yes	1350.77
E-CURD-114	yes	1032.50
E-MTAB-7008	yes	273.15
E-GEOD-125970	yes	198.35
E-GEOD-93593	yes	10.45
E-MTAB-6524	no	184.07
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

9 targets.

Target	Regulation
ASCL1	Repression
E2F1	Activation
HES5	Repression
HNF4A
HTR1A	Unknown
INS
LDLR	Unknown
MSC	Repression
PPARG	Unknown

JASPAR motifs

Motif	Name	Family
MA1493.1	HES6	Hairy-related factors

JASPAR matrix evidence (PMIDs): PMID:11959828

Upstream regulators (CollecTRI, top): ASCL1, ATOH1, NR0B2, POU5F1, RARA, SOX2

miRNA regulators (miRDB)

23 targeting HES6, 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-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-3145-5P	98.57	67.83	900
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-3116	97.07	65.78	1324
HSA-MIR-3192-5P	96.98	65.76	1926

Literature-anchored findings (GeneRIF, showing 19)

• Differentially expressed in metastatic colon carcinoma (PMID:12957362)
• Hes6 promotes cortical neurogenesis and inhibits Hes1 transcription repression activity. (PMID:12972610)
• Here, we show that WRPW motif deletion mutant Hes6 protein is substantially stabilized in comparison to the full length protein and that the enhanced stability is due to its resistance to proteasomal degradation. (PMID:15896295)
• Hes6 overexpression using a retroviral vector led to a decrease in Hes1 levels, an increase in beta-cell transcription factors and partial restoration of insulin expression (PMID:17300753)
• Increased expression of Notch3, Jagged1, Hes1, and Hes6 gene transcripts were observed during differentiation of cultured human skeletal muscle cells. (PMID:17301032)
• ATOH1 activates HES6 transcription through binding to three clustered E boxes of its promoter (PMID:17826772)
• the Hes6-CBP complex in PML-NB may influence the proliferation of cells via p53-dependent and -independent pathways. (PMID:18160400)
• These four variants were tested for association with mood disorder diagnosis or antidepressant response in a family study of depression, but no significant associations were observed. (PMID:19481584)
• Data suggest that Hes-6 is a potential oncogene overexpressed in breast cancer, with a tumor-promoting and proliferative function. Hes-6 is a novel estrogen-regulated gene in breast cancer cells. (PMID:19891787)
• HES6 gene is selectively overexpressed in glioma and represents an important transcriptional regulator of glioma proliferation. (PMID:21785461)
• HES6 contributes to the pathogenesis of alveolar rhabdomyosarcoma by enhancing both proliferation and cell motility. (PMID:22982728)
• HES6 is up-regulated in aggressive human prostate cancer and drives tumour growth by enhancing the transcriptional activity of the AR, which is preferentially directed to a regulatory network enriched for transcription factors such as E2F1. (PMID:24737870)
• HES6 mutations are associated with castration resistant and androgen independent tumors in prostate cancer. (PMID:25006183)
• prostate cancer-specific up-regulation of NOTCH3 and HES6, is reported. (PMID:25864518)
• High HES6 expression is associated with metastasis in colorectal cancer. (PMID:30015909)
• Single-cell RNA sequencing reveals intratumoral heterogeneity in primary uveal melanomas and identifies HES6 as a driver of the metastatic disease. (PMID:33462406)
• ERCC5, HES6 and RORA are potential diagnostic markers of coronary artery disease. (PMID:35934844)
• The novel GATA1-interacting protein HES6 is an essential transcriptional cofactor for human erythropoiesis. (PMID:36929421)
• HES6 Mediates Oxidative Phosphorylation Pathway to Promote Immune Infiltration of CD8 + T Cells in Lung Adenocarcinoma. (PMID:39005046)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	her13	ENSDARG00000007097
danio_rerio	hes6	ENSDARG00000019335
mus_musculus	Hes6	ENSMUSG00000067071
rattus_norvegicus	Hes6	ENSRNOG00000020194
drosophila_melanogaster	E(spl)m8-HLH	FBGN0000591
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	Hesr	FBGN0030899
drosophila_melanogaster	cwo	FBGN0259938

Paralogs (12): HES2 (ENSG00000069812), HES1 (ENSG00000114315), BHLHE41 (ENSG00000123095), BHLHE40 (ENSG00000134107), HEY2 (ENSG00000135547), HEYL (ENSG00000163909), HEY1 (ENSG00000164683), HES3 (ENSG00000173673), HES7 (ENSG00000179111), HELT (ENSG00000187821), HES4 (ENSG00000188290), HES5 (ENSG00000197921)

Protein

Protein identifiers

Transcription cofactor HES-6 — Q96HZ4 (reviewed: Q96HZ4)

Alternative names: C-HAIRY1, Class B basic helix-loop-helix protein 41, Hairy and enhancer of split 6

All UniProt accessions (6): Q96HZ4, B8ZZP9, B9A070, C9JF41, H7C020, H7C1R4

UniProt curated annotations — full annotation on UniProt →

Function. Does not bind DNA itself but suppresses both HES1-mediated N box-dependent transcriptional repression and binding of HES1 to E box sequences. Also suppresses HES1-mediated inhibition of the heterodimer formed by ASCL1/MASH1 and TCF3/E47, allowing ASCL1 and TCF3 to up-regulate transcription in its presence. Promotes cell differentiation.

Subunit / interactions. Transcription repression requires formation of a complex with a corepressor protein of the Groucho/TLE family. Interacts with HES1.

Subcellular location. Nucleus.

Domain organisation. 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. 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).

Isoforms (4)

UniProt ID	Names	Canonical?
Q96HZ4-1	1	yes
Q96HZ4-2	2
Q96HZ4-3	3
Q96HZ4-4	4

RefSeq proteins (3): NP_001136325, NP_001269363, NP_061115* (*=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 (16 total): splice variant 4, compositionally biased region 3, domain 2, sequence conflict 2, region of interest 2, chain 1, sequence variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96HZ4-F1	71.57	0.41

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 195 (showing top): GCANCTGNY_MYOD_Q6, CMYB_01, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_NEUROGENESIS, TAL1ALPHAE47_01, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, CAGCTG_AP4_Q5, UEDA_PERIFERAL_CLOCK, MYOD_01, GOBP_ANTERIOR_POSTERIOR_PATTERN_SPECIFICATION, NELSON_RESPONSE_TO_ANDROGEN_UP, MYOD_Q6, SANSOM_APC_TARGETS_UP

GO Biological Process (8): regulation of transcription by RNA polymerase II (GO:0006357), nervous system development (GO:0007399), anterior/posterior pattern specification (GO:0009952), cell differentiation (GO:0030154), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of neurogenesis (GO:0050767), negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (11): 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), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), transcription regulator inhibitor activity (GO:0140416), sequence-specific double-stranded DNA binding (GO:1990837), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), transcription regulator complex (GO:0005667)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	3
regulation of transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
regulation of gene expression	2
transcription regulator activity	2
transcription cis-regulatory region binding	2
system development	1
regionalization	1
cellular developmental process	1
positive regulation of DNA-templated transcription	1
neurogenesis	1
regulation of nervous system development	1
regulation of cell development	1
negative regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	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
protein binding	1
DNA-binding transcription factor binding	1
molecular function inhibitor activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

1076 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HES6	ASCL1	P50553	822
HES6	TLE1	Q04724	814
HES6	MSC	O60682	807
HES6	HES5	Q5TA89	646
HES6	CSNK2A1	P19138	631
HES6	DLL1	O00548	579
HES6	HES3	Q5TGS1	569
HES6	CSNK2A2	P19784	562
HES6	BTG2	P78543	524
HES6	DLL3	Q9NYJ7	510
HES6	NOTCH1	P46531	507
HES6	NEUROD1	Q13562	507
HES6	HNF4A	P41235	500
HES6	GSX2	Q9BZM3	491
HES6	NEUROG2	Q9H2A3	452

IntAct

21 interactions, top by confidence:

A	B	Type	Score
NEUROG3	GXYLT2	psi-mi:“MI:0914”(association)	0.640
RAB2A	HES6	psi-mi:“MI:0915”(physical association)	0.560
SMARCD1	HES6	psi-mi:“MI:0915”(physical association)	0.560
HES6	C14orf119	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	HES6	psi-mi:“MI:0915”(physical association)	0.560
TLE1	HES6	psi-mi:“MI:0915”(physical association)	0.550
HES6	TLE1	psi-mi:“MI:0914”(association)	0.550
HES6	TLE4	psi-mi:“MI:0914”(association)	0.530
HOXC8	ANKRD17	psi-mi:“MI:0914”(association)	0.350
HES6	RGPD3	psi-mi:“MI:0914”(association)	0.350
CHCHD2	ZNF593	psi-mi:“MI:0914”(association)	0.350
TWIST1	PPP2CA	psi-mi:“MI:0914”(association)	0.350
HES6	RAB2A	psi-mi:“MI:0915”(physical association)	0.000
HES6	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.000
SMARCD1	HES6	psi-mi:“MI:0915”(physical association)	0.000
C14orf119	HES6	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (53): HES6 (Synthetic Growth Defect), HES6 (Two-hybrid), HES6 (Affinity Capture-MS), HES6 (Two-hybrid), HES6 (Two-hybrid), C14orf119 (Two-hybrid), KRTAP10-9 (Two-hybrid), HES6 (Affinity Capture-Western), TLE1 (Two-hybrid), HES6 (Affinity Capture-RNA), TLE1 (Affinity Capture-MS), HES1 (Affinity Capture-MS), TLE4 (Affinity Capture-MS), USP4 (Affinity Capture-MS), HES6 (Affinity Capture-MS)

ESM2 similar proteins: A4D2P6, A5PJV8, A6NFD8, D4AE48, O00268, O00287, O35274, O35779, O43566, P04198, P12755, P55199, Q08DA0, Q0D2I5, Q2KJ58, Q504T8, Q5XKK7, Q60698, Q61976, Q6NZ67, Q6P582, Q6R891, Q6T4P5, Q7Z6J2, Q80YR4, Q86UD0, Q86UK7, Q8BXL9, Q8CEG5, Q8R4T5, Q8TF61, Q8VCG9, Q969F2, Q969G9, Q96HZ4, Q96SB3, Q99PV5, Q9BQ61, Q9BUN5, Q9BZE9

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

3 interactions.

A	Effect	B	Mechanism
HES6	“up-regulates quantity by expression”	E2F1	“transcriptional regulation”
ATOH1	“up-regulates quantity by expression”	HES6	“transcriptional regulation”
CSNK2A1	“up-regulates activity”	HES6	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

428 predictions. Top by Δscore:

Variant	Effect	Δscore
2:238239657:GCAC:G	donor_loss	1.0000
2:238239658:CACC:C	donor_loss	1.0000
2:238239660:C:CT	donor_loss	1.0000
2:238239259:C:T	acceptor_gain	0.9900
2:238239260:G:T	acceptor_gain	0.9900
2:238239567:ACCTG:A	acceptor_loss	0.9900
2:238239569:CTG:C	acceptor_loss	0.9900
2:238239570:T:C	acceptor_loss	0.9900
2:238239572:C:CT	acceptor_gain	0.9900
2:238239646:G:A	donor_gain	0.9900
2:238239656:CGCA:C	donor_loss	0.9900
2:238239686:AGCT:A	donor_gain	0.9900
2:238239689:T:TA	donor_gain	0.9900
2:238239819:CCGCA:C	donor_loss	0.9900
2:238239821:GCAC:G	donor_loss	0.9900
2:238239822:CACCT:C	donor_loss	0.9900
2:238239823:ACCTT:A	donor_loss	0.9900
2:238239824:C:A	donor_loss	0.9900
2:238239853:T:TA	donor_gain	0.9900
2:238239259:C:CT	acceptor_gain	0.9800
2:238239264:G:C	acceptor_gain	0.9800
2:238239569:C:CC	acceptor_gain	0.9800
2:238239655:CCGCA:C	donor_loss	0.9800
2:238239687:G:C	donor_gain	0.9800
2:238239743:CGGGC:C	acceptor_gain	0.9800
2:238239858:AT:A	donor_gain	0.9800
2:238239859:T:TA	donor_gain	0.9800
2:238239264:G:GC	acceptor_gain	0.9700
2:238239567:AC:A	acceptor_gain	0.9700
2:238239568:CC:C	acceptor_gain	0.9700

AlphaMissense

1416 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:238239707:A:G	I41T	0.998
2:238239727:C:A	E34D	0.998
2:238239727:C:G	E34D	0.998
2:238239204:A:C	Y100D	0.997
2:238239717:G:T	R38S	0.997
2:238239116:A:G	L129P	0.996
2:238239193:G:C	C103W	0.996
2:238239214:G:C	F96L	0.996
2:238239214:G:T	F96L	0.996
2:238239216:A:G	F96L	0.996
2:238239206:C:T	G99D	0.995
2:238239552:T:A	E62V	0.995
2:238239707:A:T	I41N	0.994
2:238239729:C:T	E34K	0.994
2:238239128:A:G	L125P	0.993
2:238239194:C:T	C103Y	0.993
2:238239537:A:T	L67Q	0.993
2:238239707:A:C	I41S	0.993
2:238239724:C:A	K35N	0.993
2:238239724:C:G	K35N	0.993
2:238239739:C:A	K30N	0.993
2:238239739:C:G	K30N	0.993
2:238239172:G:C	F110L	0.992
2:238239172:G:T	F110L	0.992
2:238239174:A:G	F110L	0.992
2:238239195:A:G	C103R	0.992
2:238239714:C:G	A39P	0.992
2:238239728:T:A	E34V	0.992
2:238239203:T:G	Y100S	0.991
2:238239537:A:G	L67P	0.991

dbSNP variants (sampled 300 via entrez): RS1000121338 (2:238241164 G>A), RS1000415945 (2:238241175 C>T), RS1000770338 (2:238240936 G>A), RS1000867630 (2:238238950 G>A), RS1001158333 (2:238239996 G>A,T), RS1001239532 (2:238237786 A>C), RS1001390714 (2:238239001 C>T), RS1002478598 (2:238238035 ACACAAT>A), RS1003209869 (2:238241455 C>G,T), RS1003472041 (2:238239417 G>A,T), RS1004757983 (2:238241970 G>A), RS1004894752 (2:238240741 G>A,C), RS1005381950 (2:238241792 A>G), RS1005385207 (2:238239937 G>A,C), RS1005767113 (2:238239721 C>G,T)

Disease associations

OMIM: gene MIM:610331 | 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
GCST002629_1	Irritable bowel syndrome	5.000000e-06
GCST007576_371	Chronotype	4.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1374385	HES6		0.00	0
rs56294817	HES6		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Copper	affects binding, increases expression, decreases expression	3
Valproic Acid	increases expression, increases methylation	3
sodium arsenite	decreases expression, increases abundance, increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
terbufos	decreases methylation	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	increases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
licochalcone B	increases expression	1
jinfukang	increases expression, affects cotreatment	1
NSC 689534	affects binding, increases expression	1
(+)-JQ1 compound	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A2N7	SEES3-1V human HES6, clone1	Embryonic stem cell	Male
CVCL_A2N8	SEES3-1V human HES6, clone2	Embryonic stem cell	Male
CVCL_A2N9	SEES3-1V human HES6, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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