Hypogonadotropic hypogonadism idiopathic

Gene: KLB

Amber List (moderate evidence)

KLB (klotho beta)
EnsemblGeneIds (GRCh38): ENSG00000134962
EnsemblGeneIds (GRCh37): ENSG00000134962
OMIM: 611135, Gene2Phenotype
KLB is in 2 panels

3 reviews

Ivone Leong (Genomics England Curator)

Comment on list classification: Promoted from Red to Amber. This gene is not associated with a phenotype in OMIM or Gene2Phenotype. This gene is Green on the Hypogonadotropic hypogonadism (Version 1.29) panel and have the following review:

"Rachel Jones (GSTT)

Green List (high evidence)

Publication by Pitteloud et al:
"Genetic screening of 334 CHH patients identified seven heterozygous loss‐of‐function KLB mutations in 13 patients (4%). Most patients with KLB mutations (9/13) exhibited metabolic defects. In mice, lack of Klb led to delayed puberty, altered estrous cyclicity, and subfertility due to a hypothalamic defect associated with inability of GnRH neurons to release GnRH in response to FGF21."
They also included functional analysis and showed decreased activity in response to FGF21 and FGF8
KLB is an obligate coreceptor for FGF21 alongside FGFR1
Created: 10 Mar 2020, 10:55 a.m. | Last Modified: 10 Mar 2020, 10:55 a.m.
Panel Version: 1.27

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
hypogonadotrophic hypogonadism

Publications

PMID: 28754744

Created: 10 Mar 2020, 10:55 a.m.
Last Modified: 10 Mar 2020, 10:55 a.m.
Panel version: 1.27"

There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.
Created: 24 Mar 2021, 4:42 p.m. | Last Modified: 24 Mar 2021, 4:42 p.m.
Panel Version: 1.30

Zornitza Stark (Australian Genomics)

Green List (high evidence)

Seven heterozygous loss‐of‐function KLB mutations in 13 individuals reported. In mice, lack of Klb led to delayed puberty, altered estrous cyclicity, and subfertility due to a hypothalamic defect associated with inability of GnRH neurons to release GnRH in response to FGF21. Functional analysis showed decreased activity in response to FGF21 and FGF8. KLB is an obligate coreceptor for FGF21 alongside FGFR1.
Created: 18 Jul 2020, 8:18 a.m. | Last Modified: 18 Jul 2020, 8:18 a.m.
Panel Version: 1.8

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hypogonadotropic hypogonadism

Publications

Variants in this GENE are reported as part of current diagnostic practice

Simon Thomas (Wessex Regional Genetics Laboratory)

Red List (low evidence)

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • NHS GMS
  • Wessex and West Midlands GLH
Phenotypes
  • Congenital hypogonadotropic hypogonadism
Tags
Q2_21_rating
OMIM
611135
Clinvar variants
Variants in KLB
Penetrance
None
Publications
Panels with this gene

History Filter Activity

24 Mar 2021, Gel status: 2

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

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

24 Mar 2021, Gel status: 1

Added Tag

Ivone Leong (Genomics England Curator)

Tag Q2_21_rating tag was added to gene: KLB.

24 Mar 2021, Gel status: 1

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: KLB were set to

22 Mar 2019, Gel status: 1

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

Ivone Leong (Genomics England Curator)

gene: KLB was added gene: KLB was added to Hypogonadotropic hypogonadism idiopathic. Sources: Wessex and West Midlands GLH,NHS GMS,Expert Review Red Mode of inheritance for gene: KLB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: KLB were set to Congenital hypogonadotropic hypogonadism