ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000009.11) (NC_000009.12)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

Some evidence has been presented in the medical literature suggesting that KANK1 deletion is associated with a clinical phenotype. PMID:16301218 described a 225Kb pure deletion of KANK1 that was associated with cerebral palsy and mental retardation in children of male carriers in a four generation family. The pattern was suggestive of maternal imprinting. Repression of expression of the KANK1 protein, ANKRD15, appeared to be linked to the methylation status of CpG islands near DMRT1, a gene centromeric to KANK1. In a later report (PMID 23454270), a familial, inherited deletion of KANK1 was described in which the proband had several phenotypic features in common with the previously reported deletion family. However, the family included an unaffected individual with a paternally inherited deletion. Indirect evidence was presented that suggested deletion involving the A isoform (short form, centromeric side) might be more clinically relevant than deletions affecting the B isoform alone. The authors suggested that the mechanism of inheritance for KANK1 associated mental retardation needs further study. A 2016 paper (PMID: 26656975) proposed that KANK1 as well as the neighbouring gene, DOCK8 may be subject to genetic and/or epigenetic modifiers and random, monoallelic gene expression as an explanation for lack of consistency in inheritance patterns and clinical phenotypes.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity