PLEKHM3

Chr 2

pleckstrin homology domain containing M3

Also known as: DAPR, PLEKHM1L

NCBI Gene: 389072 ENSG00000178385 UniProt: Q6ZWE6 OMIM: 619186

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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable zinc ion binding activity. Predicted to be involved in myoblast differentiation. Predicted to be located in Golgi apparatus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOEUF 0.57

Clinical Summary— PLEKHM3

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

88 VUS of 99 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.57LOEUF

pLI 0.000

Z-score 3.68

OE 0.36 (0.24–0.57)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.45Z-score

OE missense 0.80 (0.73–0.88)

343 obs / 427.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.36 (0.24–0.57)

0≤0.351.4

Missense OE?0.80 (0.73–0.88)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 14 / 38.7Missense obs/exp: 343 / 427.5Syn Z: 1.06

ClinVar Variant Classifications

99 submitted variants in ClinVar

ClinVar

Classification Summary

VUS88

Likely Benign4

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	88	88
Likely Benign	4	4
Benign	0	0
Total	92	92

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

View in ClinVar →

26 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap PLEKHM3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →