WDR4

Chr 21

WDR4 tRNA N7-guanosine methyltransferase non-catalytic subunit

Also known as: GAMOS6, MIGSB, TRM82, TRMT82, Wuho, hWH

NCBI Gene: 10785 ENSG00000160193 UniProt: P57081

WDR4 encodes a non-catalytic component of the METTL1-WDR4 methyltransferase complex that acts as a scaffold for tRNA binding and is required for N(7)-methylguanine formation in tRNAs, mRNAs, and microRNAs. Mutations cause autosomal recessive Galloway-Mowat syndrome 6 and a distinct phenotype of microcephaly, growth deficiency, seizures, and brain malformations. The gene is highly constrained against loss-of-function variants (LOEUF 1.116), consistent with severe developmental phenotypes when disrupted.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene is excluded as a candidate for a form of nonsyndromic deafness (DFNB10), but is still a candidate for other disorders mapped to 21q22.3 as well as for the development of Down syndrome phenotypes. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, May 2012]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtGalloway-Mowat syndrome 6

UniProtMicrocephaly, growth deficiency, seizures, and brain malformations

Clinical highlights

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

1.12

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

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