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Features include always present findings: Gonadal dysgenesis; and common findings: Sex reversal. 9 total HPO annotations.
MAP3K1 encodes mitogen-activated protein kinase kinase kinase 1 (1,512 aa). Component of a protein kinase signal transduction cascade. Activates the ERK and JNK kinase pathways by phosphorylation of MAP2K1 and MAP2K4. May phosphorylate the MAPK8/JNK1 kinase. Highest expression in Skin Not Sun Exposed Suprapubic (37.2 TPM) and Skin Sun Exposed Lower leg (36.7 TPM).
46,XY sex reversal 6 is associated with mutations in the MAP3K1 gene on chromosome 5.
The MAP3K1 protein participates in Interaction of MEKK1 with TRAF6 pathway.
MAP3K1 is classified as a druggable target (Clinically Actionable, Druggable Genome, Enzyme, Kinase, and Serine Threonine Kinase categories) with score 2.9.
Genetic testing for MAP3K1 is available. Testing is considered confirmatory for diagnosis.
Phenotype severity distribution: 1 always present feature, 1 common feature.
No clinical trials have been registered for 46,XY sex reversal 6.
8 publications have been identified in PubMed for 46,XY sex reversal 6. Research spans Case Report / Case Series (50%), Review / Meta-Analysis (38%), and Basic Science / Preclinical (13%).
Pachapure SS (2026). [PMID: 41847829](https://pubmed.ncbi.nlm.nih.gov/41847829/). *J Pediatr Endocrinol Metab*. [Case Report / Case Series]
Singh S (2026). [PMID: 31194363](https://pubmed.ncbi.nlm.nih.gov/31194363/). *Unknown Journal*. [Review / Meta-Analysis]
Petrillo T (2025). [PMID: 40747867](https://pubmed.ncbi.nlm.nih.gov/40747867/). *J Obstet Gynaecol Res*. [Case Report / Case Series]
Lu Y (2025). [PMID: 40476564](https://pubmed.ncbi.nlm.nih.gov/40476564/). *Mol Med Rep*. [Basic Science / Preclinical]
Turk Yilmaz RS (2025). [PMID: 39726663](https://pubmed.ncbi.nlm.nih.gov/39726663/). *JCEM Case Rep*. [Case Report / Case Series]
Data assembled from 5 of 12 sources · Last updated Sep 19, 2026, 4:16 PM UTC
Online Mendelian Inheritance in Man
Genetic and Rare Diseases Info Center
Common questions about 46,XY sex reversal 6
Kırkgöz T (2024). [PMID: 38650427](https://pubmed.ncbi.nlm.nih.gov/38650427/). *J Pediatr Endocrinol Metab*. [Case Report / Case Series]
Luppino G (2024). [PMID: 38785542](https://pubmed.ncbi.nlm.nih.gov/38785542/). *Curr Issues Mol Biol*. [Review / Meta-Analysis]
AI-curated news mentioning 46,XY sex reversal 6
Updated Jul 8, 2026
A new treatment for children aged 2 or older with sickle cell disease has been approved by the U.S. Food & Drug Administration. In a press release on Wednesday, the FDA announced it had approved Casgevy, the first gene therapy for children with sickle cell disease. (NewsNation) — A new treatment for children aged 2 or older with sickle cell disease has been approved by the Food & Drug Administration (FDA). In a Wednesday news release, the FDA announced it had approved Casgevy, the first gene therapy for children with the disease. “Casgevy is a gene therapy consisting of the patient’s own (autologous) hematopoietic (blood) stem cells, administered as a one-time single dose for intravenous infusion,” the release noted. “Pediatric patients as young as 2 years of age can now access a critical additional treatment option to treat these debilitating, life-threatening diseases,” Karim Mikhail, the acting director of the Center for Biologics Evaluation and Research, wrote. “These disorders carry a heavy burden for children and their families, affecting growth, development, and long-term health in profound ways,” Megha Kaushal, acting deputy director of the Office of Therapeutic Products in CBER, said in the release.