HES1

Chr 3

hes family bHLH transcription factor 1

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

NCBI Gene: 3280 ENSG00000114315 UniProt: Q14469

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]

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

260

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.57

LOEUF

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.57LOEUF

pLI 0.707

Z-score 2.36

OE 0.12 (0.04–0.57)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.80Z-score

OE missense 0.82 (0.71–0.95)

131 obs / 159.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.12 (0.04–0.57)

0≤0.351.4

Missense OE?0.82 (0.71–0.95)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 1 / 8.3Missense obs/exp: 131 / 159.2Syn Z: 0.60

Background carrier burden — how many people carry a rare variant somewhere in HES1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 250

371 rare PASS variants

Rare truncating (LoF)

1 in 10,000

30 rare PASS variants

Rare synonymous (reference)

1 in 320

184 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for HES1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 250	1 in 9,800
South Asian	~43k	1 in 350	≈ 1 in 25,000
Remaining (unassigned)	~30k	1 in 280	none seen
European (Finnish)	~27k	1 in 540	≈ 1 in 12,000
Admixed American	~22k	1 in 200	1 in 1,800
African / African American	~21k	1 in 220	≈ 1 in 5,700
East Asian	~20k	1 in 250	none seen
Ashkenazi Jewish	~13k	1 in 1,000	≈ 1 in 3,700
Middle Eastern	~2,884	≈ 1 in 720	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓