ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

  • 12q24.13
  • GRCh37/hg19 chr12: 113,012,901-113,336,686
  • View: NCBI | Ensembl | UCSC
  • GRCh38/hg38 chr12: 112,575,097-112,898,881
  • View: NCBI | Ensembl | UCSC
Select assembly: (NC_000012.11) (NC_000012.12)
  • Haploinsufficiency score: 1
  • Strength of Evidence (disclaimer): Little evidence for dosage pathogenicity
Evidence for haploinsufficiency phenotype
PubMed ID Description
28263302 Yuen et al. 2017 - WGS study of families with autism identified 1 instance of a de novo nonsense mutation.
22083728 Kirov et al. 2012 - study of copy number variants in patients with schizophrenia which found a patient with a likely loss of function de novo deletion of 3 exons in RPH3A.

Haploinsufficiency phenotype comments:

Two separate reports of loss of function mutations, but in patients with varying phenotypes. Missense mutations have been reported in patients with cognitive and/or behavioral phenotypes as well. Bowling et al. 2017 (PMID 28554332) found a de novo VUS in RPH3A in a patient with intellectual disability, speech delay, hypotonia and seizures. Iossifov et al. 2014 (PMID 25363768) identified a missense mutation in RPH3A in a patient with autism. In addition, potential biallelic loss of function mutations in RPH3A were identified by Maselli et al. 2018 (PMID 29441694) in a patient with learning disabilities, tremors, ataxia, transient hyperglycemia and muscle fatigability. Parents were apparently unaffected.

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