HES2

Chr 1

hes family bHLH transcription factor 2

Also known as: bHLHb40

NCBI Gene: 54626 ENSG00000069812 UniProt: Q9Y543 OMIM: 609970

HES2 encodes a transcriptional repressor that inhibits genes requiring basic helix-loop-helix proteins for transcription and is predicted to regulate neurogenesis. The gene shows low constraint against loss-of-function variants (pLI 0.003, LOEUF 1.72), and no definitive disease associations have been established in the provided data.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.72

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.72LOEUF

pLI 0.003

Z-score 0.33

OE 0.84 (0.41–1.72)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.84Z-score

OE missense 0.70 (0.55–0.90)

43 obs / 61.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.84 (0.41–1.72)

0≤0.351.4

Missense OE?0.70 (0.55–0.90)

0≤0.61.4

Synonymous OE?0.77

0≤1.21.6

LoF obs/exp: 4 / 4.8Missense obs/exp: 43 / 61.5Syn Z: 1.00

Background carrier burden — how many people carry a rare variant somewhere in HES2?

gnomAD v4 · ~729k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 370

317 rare PASS variants

Rare truncating (LoF)

1 in 6,600

41 rare PASS variants

Rare synonymous (reference)

1 in 750

130 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for HES2. 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 460	1 in 9,900
South Asian	~43k	1 in 220	1 in 2,400
Remaining (unassigned)	~30k	1 in 370	none seen
European (Finnish)	~26k	1 in 670	≈ 1 in 8,700
Admixed American	~22k	1 in 260	≈ 1 in 8,600
African / African American	~21k	1 in 99	1 in 4,100
East Asian	~20k	1 in 470	1 in 1,200
Ashkenazi Jewish	~13k	1 in 1,300	none seen
Middle Eastern	~2,881	1 in 210	≈ 1 in 2,900

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): 3 of 4 coding exons well covered in gnomAD exomes; exon 4 marginal. Genomes: all 4.? see exons ↓