PLEKHM3

Chr 2

pleckstrin homology domain containing M3

This protein enables zinc ion binding and acts as a scaffold protein for AKT1 during skeletal muscle differentiation, with predicted localization to the Golgi apparatus. Mutations cause autosomal recessive intermediate Charcot-Marie-Tooth disease type C, a hereditary peripheral neuropathy. The gene is highly constrained against loss-of-function variants, suggesting intolerance to protein-disrupting mutations.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.57
Clinical SummaryPLEKHM3
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

Moderate LoF intolerance
LoF Constraint
0.57LOEUF
pLI 0.000
Z-score 3.68
OE 0.36 (0.240.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.45Z-score
OE missense 0.80 (0.730.88)
343 obs / 427.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.36 (0.240.57)
00.351.4
Missense OE0.80 (0.730.88)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 14 / 38.7Missense obs/exp: 343 / 427.5Syn Z: 1.06

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PLEKHM3 · 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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