ClinGen Dosage Sensitivity Curation Page

MAP3K1

  • Curation Status: Complete

Location Information

Select assembly: (NC_000005.9) (NC_000005.10)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

Mutations in MAP3K1 have been associated with 46,XY disorders of sex development. Pearlman et al. 2010: 3 coding missense mutations and one variant in the polypyrimidine track of the splice-acceptor site in intron 2 (c.634-8T>A) in MAP3K1 are described in two unrelated families with 46, XY disorders of sex development (DSD) and two of 11 sporadic cases of 46,XY DSD. The intron 2 variant resulted in both wild-type and aberrant splice variants. In cultured primary lymphoblastoid cells from three of the cases, these mutations altered the phosphorylation of the downstream targets, p38 and/or ERK1/2, and enhanced binding of RHOA to the MAP3K1 complex. (PMID:21129722). At this time, there is no evidence to support the idea that haploinsufficiency of MAP3K1 results in a demonstrable human phenotype.

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