HES1

Chr 3

hes family bHLH transcription factor 1

Also known as: HES-1, HHL, HRY, bHLHb39

This protein belongs to the basic helix-loop-helix family of transcription factors. It is a transcriptional repressor of genes that require a bHLH protein for their transcription. The protein has a particular type of basic domain that contains a helix interrupting protein that binds to the N-box rather than the canonical E-box. [provided by RefSeq, Jul 2008]

OMIMResearchGenerating clinical summary…
LOFmechanismLOEUF 0.57
Clinical SummaryHES1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.71) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
30 VUS of 36 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.57LOEUF
pLI 0.707
Z-score 2.36
OE 0.12 (0.040.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
0.80Z-score
OE missense 0.82 (0.710.95)
131 obs / 159.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.12 (0.040.57)
00.351.4
Missense OE?0.82 (0.710.95)
00.61.4
Synonymous OE?0.91
01.21.6
LoF obs/exp: 1 / 8.3Missense obs/exp: 131 / 159.2Syn Z: 0.60

This gene — mechanism propensity

DN
0.4983th %ile
GOF
0.1899th %ile
LOF
0.74top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

36 submitted variants in ClinVar

Classification Summary

VUS30
Likely Benign1
Benign1
30
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
30
0
0
30
Likely Benign
0
0
0
1
1
Benign
0
0
1
0
1
Total0301132

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

37 pathogenic / likely-pathogenic (of 42) ClinVar copy-number / structural variants overlap HES1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

HES1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →