ZC4H2

Chr X

zinc finger C4H2-type containing

Also known as: HCA127, KIAA1166, MCS, MRXS4, WRWF, WRWFFR, WWS

NCBI Gene: 55906 ENSG00000126970 UniProt: Q9NQZ6

This gene encodes a zinc finger protein that regulates interneuron differentiation and neuromuscular junction formation during neuronal development. Mutations cause Wieacker-Wolff syndrome, characterized by intellectual disability and neuromuscular abnormalities, with X-linked inheritance that can affect both males and females. The gene is highly constrained against loss-of-function variants (pLI 0.91, LOEUF 0.39), indicating that functional copies are essential for normal development.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the zinc finger domain-containing protein family. This family member has a C-terminal zinc finger domain that is characterized by four cysteine residues and two histidine residues, and it also includes a coiled-coil region. This protein has been detected as an autoantigen in hepatocellular carcinoma patients. This gene has been identified as a potential candidate for X-linked cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtWieacker-Wolf syndrome

UniProtWieacker-Wolff syndrome, female-restricted

Clinical highlights

Gene-disease validity (ClinGen)

X-linked syndromic intellectual disability · XLDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.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

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LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (2)

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