Primary Ovarian Insufficiency_Premature Ovarian Failure

Gene: AXL

Red List (low evidence)

AXL (AXL receptor tyrosine kinase)
EnsemblGeneIds (GRCh38): ENSG00000167601
EnsemblGeneIds (GRCh37): ENSG00000167601
OMIM: 109135, Gene2Phenotype
AXL is in 5 panels

2 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

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

Bryony Thompson (Royal Melbourne Hospital)

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Royal Melbourne Hospital
Phenotypes
  • Kallman syndrome
  • normosmic idiopathic hypogonadotropic hypogonadism
OMIM
109135
Clinvar variants
Variants in AXL
Penetrance
None
Publications
Panels with this gene

History Filter Activity

1 Nov 2023, Gel status: 1

Set mode of inheritance

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Mode of inheritance for gene: AXL was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

1 Nov 2023, Gel status: 1

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: axl has been classified as Red List (Low Evidence).

25 Jun 2020, Gel status: 2

Set Phenotypes

Bryony Thompson (Royal Melbourne Hospital)

Phenotypes for gene: AXL were changed from to Kallman syndrome; normosmic idiopathic hypogonadotropic hypogonadism

25 Jun 2020, Gel status: 2

Set publications

Bryony Thompson (Royal Melbourne Hospital)

Publications for gene: AXL were set to

25 Jun 2020, Gel status: 2

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: axl has been classified as Amber List (Moderate Evidence).

25 Jun 2020, Gel status: 2

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: axl has been classified as Amber List (Moderate Evidence).

24 Jun 2020, Gel status: 3

Created, Added New Source, Set mode of inheritance

Bryony Thompson (Royal Melbourne Hospital)

gene: AXL was added gene: AXL was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital Mode of inheritance for gene: AXL was set to