MORC2
Chr 22ADMORC family CW-type zinc finger 2
Also known as: CMT2Z, DIGFAN, ZCW3, ZCWCC1
This gene encodes an ATP-dependent chromatin remodeler that regulates heterochromatin condensation, epigenetic gene silencing, and DNA damage response, with additional cytosolic functions in lipid metabolism. Mutations cause autosomal dominant Charcot-Marie-Tooth disease type 2Z (axonal neuropathy) and a neurodevelopmental disorder characterized by developmental delay, impaired growth, dysmorphic features, and axonal neuropathy. The gene is highly constrained against loss-of-function variants (pLI=1.0, LOEUF=0.21), indicating that haploinsufficiency is likely not tolerated in the general population.
Limited evidence — not for standalone diagnostic reporting
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
MORC2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools