BHLHA15

Chr 7

basic helix-loop-helix family member a15

Also known as: BHLHB8, MIST1

NCBI Gene: 168620ENSG00000180535UniProt: Q7RTS1

Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in several processes, including cellular response to glucose starvation; endoplasmic reticulum unfolded protein response; and negative regulation of myotube differentiation. Predicted to act upstream of or within several processes, including cell-cell adhesion mediated by cadherin; epithelial cell maturation; and intracellular distribution of mitochondria. Predicted to be located in chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

58
ClinVar variants
12
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— BHLHA15
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
12 Pathogenic / Likely Pathogenic· 43 VUS of 58 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.85LOEUF
pLI 0.007
Z-score 0.02
OE 0.99 (0.43–1.85)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.49Z-score
OE missense 0.87 (0.74–1.03)
96 obs / 110.5 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.0.99 (0.43–1.85)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.74–1.03)
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.1.11
0≤1.21.6
LoF obs/exp: 3 / 3.0Missense obs/exp: 96 / 110.5Syn Z: -0.65

ClinVar Variant Classifications

58 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
VUS43
Likely Benign3
12
Pathogenic
43
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
0
0
0
0
0
VUS
0
40
3
0
43
Likely Benign
0
2
1
0
3
Benign
0
0
0
0
0
Total04216058

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

View in ClinVar →

Protein Context — Lollipop Plot

BHLHA15 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Gasdermin B modulates intestinal epithelial homeostasis via regulating hyperactive unfolded protein response in Crohn's disease.
Gong W et al.·J Crohns Colitis
2025
A novel tsRNA, tRF-33-6978WPRLXN4V0O inhibits breast cancer development via regulating PTEN/AKT pathway in BHLHA15-mediated manner.
Dai J et al.·J Mol Med (Berl)
2025
Sex-specific alteration in human muscle transcriptome with age.
Gharpure M et al.·Geroscience
2023
Comprehensive analysis and validation of TP73 as a biomarker for calcium oxalate nephrolithiasis using machine learning and in vivo and in vitro experiments.
Zhou Z et al.·Urolithiasis
2024
Establishment of prognostic risk model and drug sensitivity based on prognostic related genes of esophageal cancer.
Dai J et al.·Sci Rep
2022Functional
Activation of protein kinase Cδ leads to increased pancreatic acinar cell dedifferentiation in the absence of MIST1.
Johnson CL et al.·J Pathol
2012
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