HES2

protein-coding

hes family bHLH transcription factor 2, the group of Basic helix-loop-helix proteins

Gene summary

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in anterior/posterior pattern specification; negative regulation of transcription by RNA polymerase II; and regulation of neurogenesis. Predicted to be located in chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_019089.5

Inheritance

—

ClinVar variants

U:27

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.84

Max pathogenic AF

—

Genomic locus

chr1:6,412,418-6,424,670

External References & Databases

Ensembl (ENSG00000069812)

Transcript & Mutation Effects

hg38 • Region Span ~12.3 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 HES2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 27

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_019089.5. 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			27 clinvar			27
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	27	0	0	27

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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_019089.5	RefSeq	NP_061962.2	4	MANE Select
ENST00000377834.8	Ensembl	ENSP00000367065.4	4	MANE Select
ENST00000377836.8	Ensembl	ENSP00000367067.4	3	Standard
ENST00000377836.9	Ensembl	ENSP00000367067.4	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
RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
transcription corepressor activity
transcription factor binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377834
Coding exons: 4
Length: 12253
Individuals with no LoFs: 122717
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 122722
p: 0.0000204

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.838	43	61.5	0.699	0.00000291	1029
Missense (PolyPhen)		18	24.256	0.74209		339
Synonymous	0.999	24	31.1	0.772	0.00000148	409
Loss of Function	0.332	4	4.78	0.836	2.11e-7	61

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.00010	0.000099	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcriptional repressor of genes that require a bHLH protein for their transcription. {ECO:0000250}.;

Recessive Scores

pRec: 0.109

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.231

Gene Damage Prediction

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