Pathogenic Variants in MAP3K1 Cause 46,XY Gonadal Dysgenesis: A Review

Research output: Contribution to journalReview articlepeer-review

Abstract

Pathogenic variants in the MAP3K1 gene are an important cause of 46,XY non-syndromic partial and complete gonadal dysgenesis, accounting for at least 4% of cases. Inheritance occurs in a sex-limited, autosomal dominant fashion with virtually complete penetrance in 46,XY individuals. 46,XX carriers appear to have normal fertility and no developmental abnormalities. Pathogenic variants occur almost exclusively within known domains of the MAP3K1 protein, facilitating annotation when identified. Where studied, these variants have been modeled to alter the local MAP3K1 folding and surface domains and have been shown to alter interactions with known binding partners. The net effect of these variants is to increase phosphorylation of downstream targets ERK1, ERK2, and p38, resulting in multiple gain-of-function effects interfering with testis determination and enabling ovarian determination.

Original languageEnglish (US)
JournalSexual Development
DOIs
StateAccepted/In press - 2022

Keywords

  • Gonadal dysgenesis
  • MAP kinases
  • Signal transduction

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Embryology
  • Developmental Biology

Fingerprint

Dive into the research topics of 'Pathogenic Variants in MAP3K1 Cause 46,XY Gonadal Dysgenesis: A Review'. Together they form a unique fingerprint.

Cite this