MORC2

Chr 22

MORC family CW-type zinc finger 2

Also known as: CMT2Z, DIGFAN, ZCW3, ZCWCC1

NCBI Gene: 22880 ENSG00000133422 UniProt: Q9Y6X9

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.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the Microrchidia (MORC) protein superfamily. The encoded protein is known to regulate the condensation of heterochromatin in response to DNA damage and play a role in repressing transcription. The protein has been found to regulate the activity of ATP citrate lyase via specific interaction with this enzyme in the cytosol of lipogenic breast cancer cells. The protein also plays a role in lipogenesis and adipocyte differentiation. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2016]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtCharcot-Marie-Tooth disease, axonal, type 2Z

UniProtDevelopmental delay, impaired growth, dysmorphic facies, and axonal neuropathy

Clinical highlights

Gene-disease validity (ClinGen)

Leigh syndrome · ADLimitednot for standalone diagnostic reporting2 gene-disease associations curated in total

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.20

LOEUF· LoF intol.

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

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