WDR4
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. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq]
Full Name
WD repeat domain 4
Function
Non-catalytic component of a methyltransferase complex required for the formation of N7-methylguanine in a subset of RNA species, such as tRNAs, mRNAs and microRNAs (miRNAs) (PubMed:12403464, PubMed:31031084, PubMed:31031083).
In the methyltransferase complex, it is required to stabilize and induce conformational changes of the catalytic subunit (PubMed:12403464).
Required for the formation of N7-methylguanine at position 46 (m7G46) in tRNA (PubMed:12403464, PubMed:31031084).
Also required for the formation of N7-methylguanine at internal sites in a subset of mRNAs (PubMed:31031084).
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).
Biological Process
Biological Process cellular response to DNA damage stimulus Source:UniProtKB-KW
Biological Process tRNA (guanine-N7)-methylation Source:GOC
Biological Process tRNA modification Source:UniProtKB1 Publication
Cellular Location
Nucleus
Chromosome
Localizes at the site of nascent DNA synthesis.
Involvement in disease
Galloway-Mowat syndrome 6 (GAMOS6):
A form of Galloway-Mowat syndrome, a severe renal-neurological disease characterized by early-onset nephrotic syndrome associated with microcephaly, central nervous system abnormalities, developmental delays, and a propensity for seizures. Brain anomalies include gyration defects ranging from lissencephaly to pachygyria and polymicrogyria, and cerebellar hypoplasia. Most patients show facial dysmorphism characterized by a small, narrow forehead, large/floppy ears, deep-set eyes, hypertelorism and micrognathia. Additional variable features are visual impairment and arachnodactyly. Most patients die in early childhood. GAMOS6 is an autosomal recessive form with onset in infancy or early childhood. Affected individuals manifest microcephaly, global developmental delay, variable degrees of intellectual disability, and growth deficiency. Renal impairment may be age-dependent or may not be present.
Microcephaly, growth deficiency, seizures, and brain malformations (MIGSB):
An autosomal recessive disorder characterized by intrauterine growth retardation, postnatal growth deficiency, microcephaly, facial dysmorphism, early-onset seizures, brain malformations such as partial agenesis of the corpus callosum and simplified gyration, and poor or absent psychomotor development.