BHLHA9

Chr 17AR

basic helix-loop-helix family member a9

Also known as: BHLHF42, CCSPD

NCBI Gene: 727857ENSG00000205899UniProt: Q7RTU4OMIM: 615416

This transcription factor regulates gene expression during limb development and morphogenesis. Mutations cause autosomal recessive syndactyly with mesoaxial synostotic features and phalangeal reduction, as well as complex camptosynpolydactyly. The gene shows tolerance to loss-of-function variants (LOEUF 1.9), consistent with recessive inheritance where both copies must be affected to cause disease.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 1.892 OMIM phenotypes
Clinical Summary— BHLHA9
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.
📋
ClinVar Variants
112 unique Pathogenic / Likely Pathogenic· 84 VUS of 232 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.89LOEUF
pLI 0.296
Z-score 0.35
OE 0.00 (0.00–1.89)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.02Z-score
OE missense 0.98 (0.65–1.53)
14 obs / 14.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–1.89)
0≤0.351.4
Missense OE0.98 (0.65–1.53)
0≤0.61.4
Synonymous OE1.55
0≤1.21.6
LoF obs/exp: 0 / 0.1Missense obs/exp: 14 / 14.2Syn Z: -1.16

ClinVar Variant Classifications

232 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic90
Likely Pathogenic22
VUS84
Likely Benign29
Benign3
Conflicting2
90
Pathogenic
22
Likely Pathogenic
84
VUS
29
Likely Benign
3
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
88
0
90
Likely Pathogenic
0
2
20
0
22
VUS
0
58
25
1
84
Likely Benign
0
4
8
17
29
Benign
0
0
1
2
3
Conflicting
—2
Total06614220230

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

View in ClinVar →

Protein Context — Lollipop Plot

BHLHA9 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Genetic determinants of syndactyly: perspectives on pathogenesis and diagnosis
Cassim A et al.·Orphanet J Rare Dis
2022
Developmental genomics of limb malformations: Allelic series in association with gene dosage effects contribute to the clinical variability
Duan R et al.·HGG Adv
2022Cohort
Cloning of down-regulated genes under cold stress and identification of important genes related to cold tolerance in zebrafish (Danio rerio).
Zhang L et al.·Comp Biochem Physiol A Mol Integr Physiol
2024Functional
Refining the Clinical Spectrum of the 17p13.3 Microduplication Syndrome: Case-Report of a Familial Small Microduplication
Da Silva JD et al.·Biomedicines
2022
Transcriptional Alterations of Mouse Trigeminal Ganglion Neurons Following Orofacial Inflammation Revealed by Single-Cell Analysis
Liu Q et al.·Front Cell Neurosci
2022Functional
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
A novel frameshift variant in BHLHA9 underlies mesoaxial synostotic syndactyly associated with postaxial polydactyly.
Khan F et al.·Eur J Med Genet
2019
SHFLD3 phenotypes caused by 17p13.3 triplication/ duplication encompassing Fingerin (BHLHA9) invariably.
Bukowska-Olech E et al.·Orphanet J Rare Dis
2022Case report
Whole exome sequencing identified a novel frameshift variant in the BHLHA9 in an Iranian family with mesoaxial synostotic syndactyly.
Sedighzadeh SS et al.·Congenit Anom (Kyoto)
2021
A novel insertion and deletion mutation in the BHLHA9 underlies polydactyly and mesoaxial synostotic syndactyly with phalangeal reduction.
Ullah A et al.·Eur J Med Genet
2019Case report
First case of compound heterozygous BHLHA9 variants in mesoaxial synostotic syndactyly with phalangeal reduction.
Díaz-González F et al.·Am J Med Genet A
2020Case report
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients