HES7

Chr 17AR

hes family bHLH transcription factor 7

Also known as: SCDO4, bHLHb37, hHes7

NCBI Gene: 84667 ENSG00000179111 UniProt: Q9BYE0 OMIM: 608059

This gene encodes a transcriptional repressor that functions as a segmentation clock essential for coordinated somite formation and axial skeleton patterning during embryonic development. Mutations cause spondylocostal dysostosis 4, an autosomal recessive disorder characterized by vertebral and rib malformations. The gene shows high constraint against loss-of-function variants (pLI 0.83, LOEUF 0.52), indicating that heterozygous loss-of-function is likely deleterious.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the hairy and enhancer of split family of bHLH transcription factors. The mouse ortholog of this gene is regulated by Notch signaling. The protein functions as a transcriptional repressor, and is implicated in correct patterning of the axial skeleton. A mutation in this gene has been shown to result in spondylocostal dysostosis. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

ARLOEUF 0.521 OMIM phenotype

Clinical Summary— HES7

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.83) — some intolerance to loss-of-function variants.

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ClinVar Variants

6 unique Pathogenic / Likely Pathogenic· 79 VUS of 148 total submissions

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GeneReview available — HES7

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.52LOEUF

pLI 0.827

Z-score 2.23

OE 0.00 (0.00–0.52)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.76Z-score

OE missense 0.79 (0.66–0.95)

79 obs / 100.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.52)

0≤0.351.4

Missense OE?0.79 (0.66–0.95)

0≤0.61.4

Synonymous OE?0.69

0≤1.21.6

LoF obs/exp: 0 / 5.8Missense obs/exp: 79 / 100.4Syn Z: 1.67

ClinVar Variant Classifications

148 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic3

VUS79

Likely Benign49

Benign9

Conflicting4

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	3	0	0	3
Likely Pathogenic	1	2	0	0	3
VUS	2	71	5	1	79
Likely Benign	0	0	14	35	49
Benign	0	0	6	3	9
Conflicting	—				4
Total	3	76	25	39	147

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 37) ClinVar copy-number / structural variants overlap HES7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →