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Mendeliome v1.4262 MAP2K4 Sangavi Sivagnanasundram Classified gene: MAP2K4 as Green List (high evidence)
Mendeliome v1.4262 MAP2K4 Sangavi Sivagnanasundram Gene: map2k4 has been classified as Green List (High Evidence).
Mendeliome v1.4261 MAP2K4 Sangavi Sivagnanasundram gene: MAP2K4 was added
gene: MAP2K4 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: MAP2K4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MAP2K4 were set to 41480045
Phenotypes for gene: MAP2K4 were set to Neurodevelopmental disorder, MONDO:0700092
Mode of pathogenicity for gene: MAP2K4 was set to Other
Review for gene: MAP2K4 was set to GREEN
Added comment: PMID 41480045 reports ten individuals from ten unrelated families with heterozygous de novo loss-of-function or missense MAP2K4 variants presenting with a syndromic neurodevelopmental disorder characterized by developmental delay/intellectual disability, epilepsy, and genitourinary and musculoskeletal congenital anomalies. All the reported variants were absent in gnomAD v4.1.

DD, ID - present in the majority of the reported individuals
CAKUT-like phenotypes reported in 5 individuals
Reports of hypotonia in three individuals
Epilepsy was reported in 4 individuals

A functional study using CRISPR-edited iPSC-derived neurons demonstrates reduced MP2K4 protein and impaired JNK signalling however, more evidence is required to confirm loss of function as the mechanism of disease. There are no pathogenic variants reported in ClinVar in this gene in the germline context.
Sources: Literature