Chromosome 5 Open Reading Frame 42

Alternative Names

  • C5orf42
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OMIM Number

614571

Gene Map Locus
5p13.2

Description

C5orf42 is a highly conserved gene that encodes a protein with a coiled coil domain.  Based on its role in lower species, the protein is thought to be involved in cilium assembly, cerebellum development, establishment of planar polarity, palate development and embryonic digit morphogenesis.

 

Mutations in C5orf42 are associated with Joubert Syndrome 17 (JBTS17), a disorder characterized by brain anomalies such as cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa.  C5orf42 mutations can also result in Orofaciodigital Syndrome VI (OFD6). This rare disease also presents with brain anomalies such as in JBTS17, but is accompanied by malformations of the oral cavity, face and metacarpals with central polydactyly. 

Molecular Genetics

The C5orf42 gene, located on the short arm of chromosome 5, is about 184 kb long.  Its coding sequence comprises of 59 exons.  The protein encoded by the gene is made up of 3197 amino acids and is approximately 361 kDa.  Two isoforms of the protein exist due to alternative splicing.  Compound heterozygous mutations in the C5orf42 gene are associated with JBTS17 while both homozygous and compound heterozygous mutations are associated with OFD6. 

Epidemiology in the Arab World

View Map
Variant NameCountryGenomic LocationClinvar Clinical SignificanceCTGA Clinical Significance Condition(s)HGVS ExpressionsdbSNPClinvar
NM_001384732.1:c.8140C>TSaudi ArabiaNC_000005.10:g.37153973G>APathogenicLikely PathogenicJoubert Syndrome 17NG_032772.3:g.100403C>T; NM_001384732.1:c.8140C>T; NP_001371661.1:p.Arg2714Ter147416429217566
NM_001384732.1:c.8150_8151delSaudi ArabiaNC_000005.10:g.37153962_37153963delPathogenicLikely PathogenicJoubert Syndrome 17NG_032772.3:g.100413_100414del; NM_001384732.1:c.8150_8151del; NP_001371661.1:p.Gly2717AlafsTer40730882217183307

Other Reports

Saudi Arabia

Shaheen et al. (2013) identified the genes associated with Meckel-Gruber syndrome (MKS) syndrome by studying 18 consanguineous Saudi families.  Members of these families were diagnosed with MKS based on the presence of occipital encephalocele as well as any combination of liver fibrosis, cleft palate, dysplastic kidneys, polydactyly and early lethality.  DNA from both affected and healthy members was obtained and an autozygome guided mutation analysis of known MKS genes was carried out.  When this did not uncover any mutations in some of the families, an exome sequencing was performed.  Exomes were then searched for compound heterozygous mutations in known MKS genes.  Failing that, all detected variants were filtered for homozygous novel changes within the autozygome.  This resulted in the detection of a c.7988_7989delGA (p.G2663Afs40) mutation in the C5orf42 gene in one of the affected families.  

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