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CEP164 – Ciliopathy

CEP164 has been recently associated with a motile ciliopathy phenotype in a patient presenting with bronchiectasis, infertility, and hydrocephalus who harboured compound heterozygous loss-of-function variants in CEP164. The autosomal recessive inheritance is supported by two truncating changes (c.4228C>T (p.Arg576Ter)) (PMID:36273371) lacking segregation data but consistent with a loss-of-function mechanism in primary ciliogenesis.

Functional assays demonstrate that CEP164 binding to TTBK2 is essential for CP110 removal and ciliogenesis in human cells, with loss of interaction impairing ciliary assembly and mirroring patient phenotypes (PMID:25297623). This evidence supports CEP164 haploinsufficiency as the likely pathogenic mechanism in both primary and motile ciliopathy syndromes. CEP164 should be included in genetic testing panels for suspected ciliopathy patients.

References

  • Clinical genetics • 2023 • Biallelic variants in CEP164 cause a motile ciliopathy-like syndrome. PMID:36273371
  • Genes to cells • 2014 • Binding to Cep164, but not EB1, is essential for centriolar localization of TTBK2 and its function in ciliogenesis. PMID:25297623

Evidence Based Scoring (AI generated)

Gene–Disease Association

Limited

One proband with compound heterozygous loss-of-function CEP164 variants (AR inheritance), no segregation data, preliminary functional concordance

Genetic Evidence

Limited

One reported proband with biallelic predicted loss-of-function variants: c.4228C>T (p.Arg576Ter) ([PMID:36273371]) under autosomal recessive inheritance

Functional Evidence

Moderate

Cellular assays demonstrate CEP164 binding to TTBK2 is essential for ciliogenesis; loss-of-function consistent with patient phenotype ([PMID:25297623])