BHLHE23

Chr 20

basic helix-loop-helix family member e23

Also known as: BETA4, BHLHB4, Beta3b, bA305P22.3

This gene encodes a basic helix-loop-helix transcription factor that functions as a transcriptional repressor and modulates gene expression required for pancreatic and neuronal cell differentiation and maintenance, with particular importance for rod bipolar cell maturation in the retina. Mutations cause autosomal recessive retinal dystrophy with early childhood onset, affecting primarily the visual system. The gene shows moderate tolerance to loss-of-function variants, consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.55
Clinical SummaryBHLHE23
Population Constraint (gnomAD)
Low constraint (pLI 0.20) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.55LOEUF
pLI 0.196
Z-score 0.97
OE 0.37 (0.131.55)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.13Z-score
OE missense 1.04 (0.871.24)
86 obs / 82.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.37 (0.131.55)
00.351.4
Missense OE1.04 (0.871.24)
00.61.4
Synonymous OE1.28
01.21.6
LoF obs/exp: 1 / 2.7Missense obs/exp: 86 / 82.7Syn Z: -1.40
DN
0.6261th %ile
GOF
0.4184th %ile
LOF
0.59top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

BHLHE23 · 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

No active trials found for this gene.

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Clinical Literature
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