Primary Ovarian Insufficiency_Premature Ovarian Failure

Gene: AXL

Red List (low evidence)

None of the variants have convincing evidence of pathogenicity.

Created: 1 Nov 2023, 3:49 a.m. | Last Modified: 1 Nov 2023, 3:49 a.m.

Panel Version: 0.321

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

I don't know

Axl null mice had delayed first oestrus and persistently abnormal oestrous cyclicality compared with wild-type controls. Only a single study reported screening human cases. In a screen of 104 probands with KS or nIHH, four heterozygous AXL mutations were identified in two KS and two nIHH unrelated subjects (two males and two females). Three of the variants appear to be too common in gnomAD v2.1 given the reported prevalence of KS reported in GeneReviews (1:30,000 in males and 1:125,000 in females): c.587-6C>T (normal splicing in RNA studies, NFE AF 0.0001472), p.Q361P (NFE 0.002560), p.L50F (AJ 0.004405). The other variant p.S202C (4 hets, 1 female in gnomAD v2.1) is rare enough in gnomAD for a dominant disorder. In vitro functional assays were conducted and p.S202C had an significant effect on function, but so did the more common variant p.Q361P.

Created: 25 Jun 2020, 5:41 a.m. | Last Modified: 25 Jun 2020, 5:41 a.m.

Panel Version: 0.8

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Kallman syndrome; normosmic idiopathic hypogonadotropic hypogonadism

Publications

• 18787040
• 24476074