CEP164 gene


Gene (OMIM No.)
Function of gene/protein
  • Protein: Centrosomal protein 164
  • Microtubule organization and maintenance for the formation of primary cilia
  • Mediates cell mitosis at the G2/M checkpoint and chromosomal segregation to maintain genomic stability
  • Involved in the excision repair pathway to remove UV-induced aberrant DNA structures
  • Loss of gene function results in the impairment of DNA damage response signaling
Clinical phenotype
(OMIM phenotype no.)
  • Autosomal recessive
Signs for LCA/EOSRD
  • Early onset visual impairment
  • Nystagmus
  • Vascular attenuation
  • Diffuse RPE atrophy
  • Hypermetropic discs
Visual function
  • Severe visual dysfunction in the 1st decade; some may be certified blind as early as 5 months old
Systemic features
  • Cystic kidney disease (nephrophthisis) leading to renal failure in childhood or adolescence
  • Neurological (cerebellar vermis hypoplasia, seizures)
  • Bronchiectasis
  • Obesity
  • Polydactyly
  • Developmental delays
  • Learning difficulties
Key investigations
  • ERG: absent responses
  • FAF and OCT to assess status of the outer retinal layers and RPE
  • Renal ultrasound
  • Systemic assessment with a paediatrican and other relevant specialists
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (retinal)
  • Whole exome sequencing
  • Whole genome sequencing
  • Multidisciplinary approach
Therapies under researchNone at present
Further information

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Additional information

A degree of genotype-phenotype relationship was suggested by Chaki et al whereby null mutations are associated with more severe ciliopathy phenotypes such as Meckel syndrome (nephronophthisis, occipital encephalocele and liver fibrosis) and Joubert syndrome (cerebellar vermis hypoplasia leading to ataxia, ocular apraxia, breathing difficulties and psychomotor delay; may be associated with LCA and/or nephronophthisis), while hypomorphic alleles are associated with milder phenotypes such as nephronophthisis and Senior-Loken syndrome (nephronophthisis with LCA).[6]

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  1.  Graser S, Stierhof YD, Lavoie SB, et al. Cep164, a novel centriole appendage protein required for primary cilium formation. J Cell Biol. 2007;179(2):321-330
  2.  Hoff S, Halbritter J, Epting D, et al. ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3. Nat Genet. 2013;45(8):951-956
  3.  Humbert MC, Weihbrecht K, Searby CC, et al. ARL13B, PDE6D, and CEP164 form a functional network for INPP5E ciliary targeting. Proc Natl Acad Sci U S A. 2012;109(48):19691-19696
  4.  Pan YR, Lee EY. UV-dependent interaction between Cep164 and XPA mediates localization of Cep164 at sites of DNA damage and UV sensitivity. Cell Cycle. 2009;8(4):655-664
  5.  Sivasubramaniam S, Sun X, Pan YR, Wang S, Lee EY. Cep164 is a mediator protein required for the maintenance of genomic stability through modulation of MDC1, RPA, and CHK1. Genes Dev. 2008;22(5):587-600
  6.  Chaki M, Airik R, Ghosh AK, et al. Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling. Cell. 2012;150(3):533-548

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Updated on November 30, 2020
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