The BIN3 protein contains a BAR domain that mediates membrane curvature sensing and induction, and is involved in cytokinesis and F-actin localization. Mutations cause autosomal recessive centronuclear myopathy with onset in infancy or early childhood, characterized by muscle weakness and distinctive centrally located nuclei in muscle fibers. The gene is not highly constrained against loss-of-function variation.

Summary from RefSeq, UniProt
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0
Active trials
3
Pubs (1 yr)
0
P/LP submissions
P/LP missense
1.60
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryBIN3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — 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
1.60LOEUF
pLI 0.000
Z-score -0.31
OE 1.08 (0.751.60)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.30Z-score
OE missense 1.07 (0.941.21)
166 obs / 155.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.08 (0.751.60)
00.351.4
Missense OE1.07 (0.941.21)
00.61.4
Synonymous OE1.45
01.21.6
LoF obs/exp: 18 / 16.6Missense obs/exp: 166 / 155.6Syn Z: -2.78
DN
0.7132th %ile
GOF
0.6444th %ile
LOF
0.3358th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

BIN3 · protein map & ClinVar variants

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

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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