ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000012.11) (NC_000012.12)
  • Haploinsufficiency score: Gene associated with autosomal recessive phenotype
  • Strength of Evidence (disclaimer): Gene associated with autosomal recessive phenotype
  • Haploinsufficiency Phenotype: FRASER SYNDROME 1; FRASRS1

Haploinsufficiency phenotype comments:

Of note, Mejias et al (2011) sequenced GRIP1 in autism and matched control cohorts and identified 5 rare missense variants only in the autism cohort. Each variant was found in a single family. In 4 of 4 families tested, the variant was inherited from an unaffected parent. In vitro studies suggest the missense variants are gain-of-function. The authors conclude: "Together, these results suggest that GRIP1 variants may modify the severity of the deficits in social interactions and cognitive function in autistic patients, but are not sufficient by themselves to cause autism" (PMID: 21383172). More recently, Vogel et al (PMID: 22510445) reported an association of recessive-type defects in the GRIP1 gene with Fraser syndrome, an autosomal recessive malformation syndrome characterised by cryptophthalmos, syndactyly and urogenital defects. Homozygous loss of function mutations were shown to segregate with the disease in three unrelated families with parental consanguinity.

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