Primary Ovarian Insufficiency_Premature Ovarian Failure

Gene: FLRT3

Red List (low evidence)

FLRT3 (fibronectin leucine rich transmembrane protein 3)
EnsemblGeneIds (GRCh38): ENSG00000125848
EnsemblGeneIds (GRCh37): ENSG00000125848
OMIM: 604808, Gene2Phenotype
FLRT3 is in 5 panels

2 reviews

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Red List (low evidence)

Insufficient evidence for FLRT3 as a monogenic cause of hypogonadotropic hypogonadism, although it is a candidate gene based on its involvement in the FGFR1 signaling pathway. Most individuals found to have variants in this gene also have variants in other genes in this signalling pathway. PMID: 23643382: three probands with Kallman syndrome identified with missense FLRT3 variants, however one also had a FGFR1 variant (the FLRT3 variant was also present in gnomAD (7 heterozygotes)) and one also had FGFR1, HS6ST1, and FGF17 variants (this individual had a homozygous missense FLRT3 variant and a heterozygous missense FLRT3 variant, both absent from gnomAD). No functional studies were performed on any of the variants. PMID: 31200363: one proband with normosmic congenital hypogonadotropic hypogonadism with a missense FLRT3 variant, however this missense variant is present in gnomAD (22 heterozygotes) and it was found along with a missense variant in POLR3A. No functional studies were performed on any of the variants.
Created: 3 Jul 2020, 3:06 a.m. | Last Modified: 3 Jul 2020, 3:06 a.m.
Panel Version: 0.3211

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hypogonadotropic hypogonadism 21 with anosmia (MIM# 615271)

Publications

Lauren Akesson (Royal Melbourne Hospital)

Red List (low evidence)

Insufficient evidence for FLRT3 as a monogenic cause of hypogonadotropic hypogonadism, although it is a candidate gene based on its involvement in the FGFR1 signaling pathway. Most individuals found to have variants in this gene also have variants in other genes in this signalling pathway.

PMID: 23643382: three probands with Kallman syndrome identified with missense FLRT3 variants, however one also had a FGFR1 variant (the FLRT3 variant was also present in gnomAD (7 heterozygotes)) and one also had FGFR1, HS6ST1, and FGF17 variants (this individual had a homozygous missense FLRT3 variant and a heterozygous missense FLRT3 variant, both absent from gnomAD). No functional studies were performed on any of the variants.

PMID: 31200363: one proband with normosmic congenital hypogonadotropic hypogonadism with a missense FLRT3 variant, however this missense variant is present in gnomAD (22 heterozygotes) and it was found along with a missense variant in POLR3A. No functional studies were performed on any of the variants.
Created: 2 Jul 2020, 11:34 p.m. | Last Modified: 2 Jul 2020, 11:34 p.m.
Panel Version: 0.31

Mode of inheritance
Unknown

Phenotypes
Hypogonadotropic hypogonadism 21 with anosmia (MIM# 615271)

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Expert Review Red
  • Royal Melbourne Hospital
  • Victorian Clinical Genetics Services
Phenotypes
  • Hypogonadotropic hypogonadism 21 with anosmia 615271
OMIM
604808
Clinvar variants
Variants in FLRT3
Penetrance
None
Publications
Panels with this gene

History Filter Activity

9 Jul 2020, Gel status: 1

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: flrt3 has been classified as Red List (Low Evidence).

9 Jul 2020, Gel status: 1

Set publications

Bryony Thompson (Royal Melbourne Hospital)

Publications for gene: FLRT3 were set to

9 Jul 2020, Gel status: 1

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: flrt3 has been classified as Red List (Low Evidence).

24 Jun 2020, Gel status: 3

Created, Added New Source, Set mode of inheritance, Set Phenotypes

Bryony Thompson (Royal Melbourne Hospital)

gene: FLRT3 was added gene: FLRT3 was added to Amenorrhoea. Sources: Expert Review Green,Royal Melbourne Hospital Mode of inheritance for gene: FLRT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: FLRT3 were set to Hypogonadotropic hypogonadism 21 with anosmia 615271