HES4

protein-coding

hes family bHLH transcription factor 4, the group of Basic helix-loop-helix proteins

Gene summary

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in anterior/posterior pattern specification and negative regulation of transcription by RNA polymerase II. Predicted to be located in chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_021170.4

Inheritance

—

ClinVar variants

U:59

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.7

Max pathogenic AF

—

Genomic locus

chr1:998,962-1,000,172

External References & Databases

Ensembl (ENSG00000188290)

Transcript & Mutation Effects

hg38 • Region Span ~1.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HES4 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 66

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021170.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			58 clinvar			58
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	59	0	0	59

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021170.4	RefSeq	NP_066993.1	4	MANE Select
ENST00000304952.11	Ensembl	ENSP00000304595.7	4	MANE Select
NM_001142467.2	RefSeq	NP_001135939.1	3	Standard
NM_001410700.1	RefSeq	NP_001397629.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Human papillomavirus infection - Homo sapiens (human)

Biological Process

negative regulation of transcription by RNA polymerase II
somitogenesis
Notch signaling pathway
cell differentiation
regulation of neurogenesis

Molecular Function

RNA polymerase II regulatory region sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
transcription corepressor activity
transcription factor binding
sequence-specific DNA binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000428771
Coding exons: 3
Length: 1211
Individuals with no LoFs: 124573
Homozygous LoFs: 0
Heterozygous LoFs: 44
Defined: 124617
p: 0.000177

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.470	103	90.4	1.14	0.00000414	1473
Missense (PolyPhen)		30	30.382	0.98741		389
Synonymous	-1.37	53	41.8	1.27	0.00000199	588
Loss of Function	-1.22	6	3.53	1.70	1.53e-7	49

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00014	0.00013	rare
Latino/Admixed American	0.000089	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0011	0.0010	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0.00023	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional repressor. Binds DNA on N-box motifs: 5'-CACNAG-3' (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.119

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.995

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium