HES7

Chr 17AR

hes family bHLH transcription factor 7

Also known as: SCDO4, bHLHb37, hHes7

NCBI Gene: 84667ENSG00000179111UniProt: Q9BYE0

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]

Primary Disease Associations & Inheritance

Spondylocostal dysostosis 4, autosomal recessiveMIM #613686
AR
181
ClinVar variants
27
Pathogenic / LP
0.83
pLI score
0
Active trials
Clinical Summary— HES7
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.83) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 92 VUS of 181 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.76Z-score
OE missense 0.79 (0.66–0.95)
79 obs / 100.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.52)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.66–0.95)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.69
0≤1.21.6
LoF obs/exp: 0 / 5.8Missense obs/exp: 79 / 100.4Syn Z: 1.67

ClinVar Variant Classifications

181 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic3
VUS92
Likely Benign49
Benign9
Conflicting4
24
Pathogenic
3
Likely Pathogenic
92
VUS
49
Likely Benign
9
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
21
0
24
Likely Pathogenic
1
2
0
0
3
VUS
1
67
23
1
92
Likely Benign
0
0
14
35
49
Benign
0
0
6
3
9
Conflicting
—4
Total2726439181

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

View in ClinVar →

Protein Context — Lollipop Plot

HES7 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spondylocostal dysostosis 4, autosomal recessive

MIM #613686

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — HES7
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Efficient Generation of Megakaryocyte Progenitors and Platelets From HSPCs via JAK2/STAT3 Signaling.
Liu H et al.·Adv Sci (Weinh)
2025
Whole exome sequencing in an Indian family links Coats plus syndrome and dextrocardia with a homozygous novel CTC1 and a rare HES7 variation.
Netravathi M et al.·BMC Med Genet
2015Case report
Canine disorder mirrors human disease: exonic deletion in HES7 causes autosomal recessive spondylocostal dysostosis in miniature Schnauzer dogs.
Willet CE et al.·PLoS One
2015
Identification of bi-allelic LFNG variants in three patients and further clinical and molecular refinement of spondylocostal dysostosis 3.
Lecca M et al.·Clin Genet
2023Cohort
Autosomal dominant spondylocostal dysostosis in three generations of a Macedonian family: Negative mutation analysis of DLL3, MESP2, HES7, and LFNG.
Gucev ZS et al.·Am J Med Genet A
2010Case report
A Confirmatory Case of Severe Spondylocostal Dysostosis Caused by Biallelic Loss-of-Function of DMRT2.
Rips J et al.·Am J Med Genet A
2026Case report
Diagnostic strategy in segmentation defect of the vertebrae: a retrospective study of 73 patients.
Lefebvre M et al.·J Med Genet
2018Cohort
Cancer stem cell-related gene expression as a potential biomarker of response for first-in-class imipridone ONC201 in solid tumors.
Prabhu VV et al.·PLoS One
2017
Epithelial-mesenchymal transition markers screened in a cell-based model and validated in lung adenocarcinoma.
Song J et al.·BMC Cancer
2019Functional
Identification of novel LFNG mutations in spondylocostal dysostosis.
Otomo N et al.·J Hum Genet
2019Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools