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Mendeliome v2.332 PLEKHA6 Sangavi Sivagnanasundram Classified gene: PLEKHA6 as Amber List (moderate evidence)
Mendeliome v2.332 PLEKHA6 Sangavi Sivagnanasundram Gene: plekha6 has been classified as Amber List (Moderate Evidence).
Mendeliome v2.315 PLEKHA6 Sangavi Sivagnanasundram gene: PLEKHA6 was added
gene: PLEKHA6 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: PLEKHA6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PLEKHA6 were set to 10.64898/2026.04.10.26349358
Phenotypes for gene: PLEKHA6 were set to idiopathic hypogonadotropic hypogonadism MONDO:0018555
Review for gene: PLEKHA6 was set to AMBER
Added comment: Preprint publication Topaloglu et al 2026

The publication reports > 5 unrelated families with missense PLEKHA6 variants presenting with idiopathic hypogonadotropic hypogonadism (IHH).
Some of the reported missense variants are present in gnomAD with a high AF for AD GDA however there are rare variants reported as well.
The authors report one homozygous proband which appears to segregate in the family as homozygous as well however there is no pedigree available or mention of consanguinity. There are no other reports of AR association for this gene.

There are no pathogenic variants reported in ClinVar and the gene is not constrained for missense either.
Sources: Literature