MORC2

MORC family CW-type zinc finger 2

Gene Function

ATP-dependent chromatin remodeler essential for epigenetic silencing by the HUSH (human silencing hub) complex. Recruited by HUSH to target site in heterochromatin, the ATPase activity and homodimerization are critical for HUSH-mediated silencing. Represses germ cell-related genes and L1 retrotransposons in collaboration with SETDB1 and the HUSH complex, the silencing is dependent of repressive epigenetic modifications, such as H3K9me3 mark. Silencing events often occur within introns of transcriptionally active genes, and lead to the down-regulation of host gene expression. During DNA damage response, regulates chromatin remodeling through ATP hydrolysis. Upon DNA damage, is phosphorylated by PAK1, both colocalize to chromatin and induce H2AX expression. ATPase activity is required and dependent of phosphorylation by PAK1 and presence of DNA. Recruits histone deacetylases, such as HDAC4, to promoter regions, causing local histone H3 deacetylation and transcriptional repression of genes such as CA9. Exhibits a cytosolic function in lipogenesis, adipogenic differentiation, and lipid homeostasis by increasing the activity of ACLY, possibly preventing its dephosphorylation. Together with MPHOSPH8, mediates silencing of protocadherin genes in the nervous system (By similarity) Source: UniProt

Relationship to CMT

CMT2 AD
1 subtype
22q12.2
First described 2016

Subtype Inheritance Class OMIM Sentinel Publication
SubtypeCMT2Z Inheritanceautosomal dominant ClassCMT2 OMIM616688 Sentinel Publication

2016 · 10.1002/ana.24575

Stored Identifiers

HGNC Aliases: ZCW3, KIAA0852, AC004542.C22.1
hgnc_idHGNC:23573
ensembl_gene_idENSG00000133422
coords_grch38chr22:30925130-30969662
coords_grch37chr22:31321117-31364284
entrez_id22880
omim_gene616661
uniprot_idsQ9Y6X9
refseq_accessionNM_014941
mane_refseqNM_001303256.3
mane_ensemblENST00000397641.8

ClinVar Variants

Pathogenic and likely pathogenic variants in MORC2, as classified in ClinVar, are read live from NCBI. Only aggregate germline records are shown. Uncertain and conflicting classifications are not. Experts in CMT makes no claim to the accuracy of ClinVar data. This index is provided for informational purposes only.

Review stars are ClinVar’s measure of how well a classification is supported: four for a practice guideline, three for an expert panel review, two for agreement among multiple submitters, one for a single submitter with criteria provided, and none where no criteria were provided.

Reported in CMT
Reported in Other Diseases

Reported in a disease other than CMT. Listed apart rather than counted as CMT variants.

Variants w/o a Recorded Disease

Pathogenic or likely pathogenic in ClinVar, submitted without a disease recorded.

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