Hypogonadotropic hypogonadism (GMS)
Gene: KLBThe rating of this gene has been updated to GREEN following NHS Genomic Medicine Service approval.Created: 31 Jan 2023, 5:03 p.m. | Last Modified: 31 Jan 2023, 5:03 p.m.
Panel Version: 2.5
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
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
Tag gene-checked tag was added to gene: KLB.
Tag Q2_21_rating was removed from gene: KLB.
Source Expert Review Green was added to KLB. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: klb has been classified as Amber List (Moderate Evidence).
Tag Q2_21_rating tag was added to gene: KLB.
Publications for gene: KLB were set to
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