MORC2 Gene
MORC Family CW-Type Zinc Finger 2
Gene Information Card
| Symbol | MORC2 |
|---|---|
| Full Name | MORC family CW-type zinc finger 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q12.2 |
| NCBI Gene ID | 22880 ncbi.nlm.nih.gov/gene/22880 |
| Ensembl ID | ENSG00000100219 |
| UniProt ID | Q9Y6X9 |
| OMIM ID | 616661 |
| HGNC ID | 23573 |
| Aliases | AC004542.4, ZCW3, ZCWCC3, MORC2A, KIAA0852 |
Description
MORC2 encodes a member of the MORC (microrehidia) family of CW-type zinc finger proteins. The protein functions as an ATP-dependent chromatin remodeler and transcriptional repressor. It is involved in DNA damage repair, cell cycle regulation, and adipocyte differentiation. Mutations in MORC2 are associated with Charcot-Marie-Tooth disease type 2Z (CMT2Z) and spinal muscular atrophy with lower extremity predominance (SMALED).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Charcot-Marie-Tooth disease type 2Z (CMT2Z) | Dominant-negative or gain-of-function mutations impair ATPase activity and chromatin remodeling, leading to axonal degeneration. | ClinVar, OMIM #616661 |
| Spinal muscular atrophy with lower extremity predominance (SMALED) | Loss-of-function mutations disrupt nuclear localization and transcriptional repression, causing motor neuron dysfunction. | ClinVar, OMIM #618291 |
| Hereditary motor and sensory neuropathy | Mutations in MORC2 cause peripheral neuropathy with variable severity. | NCBI Gene, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Spinal cord | 10.2 | Medium |
| Testis | 8.9 | Medium |
| Heart | 6.3 | Low |
| Skeletal muscle | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.3 | High expression |
| HeLa (cervical carcinoma) | 8.7 | Medium expression |
| HEK293 (embryonic kidney) | 6.2 | Low expression |
| HepG2 (hepatocellular carcinoma) | 4.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.754C>T (p.Arg252Trp) | Missense | Unknown | Dominant-negative; associated with CMT2Z |
| c.1490G>A (p.Arg497His) | Missense | Unknown | Gain-of-function; associated with CMT2Z |
| c.1018C>T (p.Arg340Cys) | Missense | Unknown | Loss-of-function; associated with SMALED |
| c.1321C>T (p.Arg441Trp) | Missense | Unknown | Dominant-negative; associated with CMT2Z |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Arg340Cys impair nuclear localization and transcriptional repression, leading to SMALED.
Gain of Function (GOF)
Mutations such as p.Arg497His enhance ATPase activity or alter chromatin binding, causing CMT2Z.
Dominant Negative (DN)
Mutations such as p.Arg252Trp disrupt ATPase activity and dimerization, interfering with wild-type MORC2 function in CMT2Z.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Chromatin remodeling (Reactome: R-HSA-5250913)
• DNA damage response (Reactome: R-HSA-73894)
• Transcriptional regulation by MORC2 (UniProt)
Protein Summary
MORC2 is a 1032-amino acid protein containing a CW-type zinc finger domain, a GHKL-type ATPase domain, and a coiled-coil region. It localizes to the nucleus and forms homodimers. The ATPase activity is essential for chromatin remodeling and transcriptional repression. Mutations in the ATPase domain are common in CMT2Z, while mutations in the nuclear localization signal region cause SMALED. The protein interacts with histone deacetylases (HDACs) and other chromatin modifiers.
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