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WDR4

Chr 21q22.3

WDR4 tRNA N7-guanosine methyltransferase non-catalytic subunit

Aliases:
TRM82, TRMT82, Wuho
MANE:
ENST00000398208.3

Annotations refreshed 9 hours ago.

Predicted protein structure

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

  • Fetal anomalies

    BIALLELIC, autosomal or pseudoautosomal
  • Intellectual disability

    BIALLELIC, autosomal or pseudoautosomal
  • Severe microcephaly

    BIALLELIC, autosomal or pseudoautosomal
  • DDG2P

    BIALLELIC, autosomal or pseudoautosomal
  • Proteinuric renal disease

    BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

  • Galloway-Mowat syndrome

    0.72
  • microcephaly, growth deficiency, seizures, and brain malformations

    0.68
  • hereditary disease

    0.42
  • placental retention

    0.33
  • placental abruption

    0.28
  • hepatocellular carcinoma

    0.10
  • breast cancer

    0.09
  • cancer

    0.09
  • prostate cancer

    0.08
  • Familial prostate cancer

    0.08

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

tRNA (guanine-N(7)-)-methyltransferase non-catalytic subunit WDR4

Non-catalytic component of the METTL1-WDR4 methyltransferase complex required for the formation of N(7)-methylguanine in a subset of RNA species, such as tRNAs, mRNAs and microRNAs (miRNAs) (PubMed:12403464, PubMed:31031083, PubMed:31031084, PubMed:36599982, PubMed:36599985, PubMed:37369656). In the METTL1-WDR4 methyltransferase complex, WDR4 acts as a scaffold for tRNA-binding (PubMed:36599982, PubMed:36599985, PubMed:37369656). Required for the formation of N(7)-methylguanine at position 46 (m7G46) in a large subset of tRNAs that contain the 5'-RAGGU-3' motif within the variable loop (PubMed:12403464, PubMed:34352206, PubMed:34352207, PubMed:36599982, PubMed:36599985, PubMed:37369656). M7G46 interacts with C13-G22 in the D-loop to stabilize tRNA tertiary structure and protect tRNAs from decay (PubMed:36599982, PubMed:36599985). Also required for the formation of N(7)-methylguanine at internal sites in a subset of mRNAs (PubMed:31031084, PubMed:37379838). Also required for methylation of a specific subset of miRNAs, such as let-7 (PubMed:31031083). Independently of METTL1, also plays a role in genome stability: localizes at the DNA replication site and regulates endonucleolytic activities of FEN1 (PubMed:26751069)

Data sources: HGNC (CC BY 4.0), AlphaFold (CC BY 4.0, Jumper et al. Nature 2021), Genomics England PanelApp (CC BY 4.0), ClinGen, Open Targets (CC0), UniProt.

Not for sole clinical decision-making. Always verify against primary sources.