Hypogonadotropic hypogonadism idiopathic

Gene: CCDC141

Amber List (moderate evidence)

CCDC141 (coiled-coil domain containing 141)
EnsemblGeneIds (GRCh38): ENSG00000163492
EnsemblGeneIds (GRCh37): ENSG00000163492
OMIM: 616031, Gene2Phenotype
CCDC141 is in 2 panels

2 reviews

Ivone Leong (Genomics England Curator)

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype.

PMID: 251920460 describes 2 affected siblings from a consanguineous family with anosmic HH, who had homozygous variant in FEZF1 (Amber gene on this panel) and also homozyous for variant in CCDC141.

PMID: 28324054 describes the above case and also 3 new cases (all had normal sense of smell and HH). Family 2: compound het for CCDC141 and heterozygous for DMXL2 variant. Family 3: heterozygous for CCDC141 variant and heterozygous for variants in 3 other genes (NR5A2, FSHB - Green on HH panel, IGSF10). Family 4: affected patient was heterozygous for CCDC141 variant, which the father also carried but father was unaffected.

PMID: 32520725 describes a large Chinese cohort with congenital HH looking at the contribution of CCDC141 to the disease. 12 probands had variants CCDC141 and 9 of these probands had variants in other HH-related genes (inluding PCSK1, ANOS1, PROKR2, AXL, SOX10, HS6ST1, PNPLA6 and FGFR1). The authors concluded that CCDC141 variants alone is not sufficient to cause HH.

PMID: 27014940 talks about a ccdc141 knockdown mouse model reduces GnRH neuronal migration.

After discussing with the Genomics England Clinical Team, it was decided that this gene should have an Amber rating as variants. Helen Brittain (Genomics England):
"...variants in this gene may be seen as a risk allele (either with other known contributory genetic factors, or unexplained variable penetrance)."
Created: 23 Mar 2021, 9:07 a.m. | Last Modified: 23 Mar 2021, 9:07 a.m.
Panel Version: 1.15

Zornitza Stark (Australian Genomics)

I don't know

A consanguineous family had a homozygous nonsense variant, but also had a homozygous missense in FEZF1. 3 other families reported with heterozygous variants, but other variants in other genes present. In an olfactory mouse model, Ccdc141 is expressed in GnRH neurons and olfactory fibers and that knockdown of Ccdc141 reduces GnRH neuronal migration.
Sources: Literature
Created: 7 Jan 2021, 8:23 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Anosmic hypogonadotropic hypogonadism

Publications

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Anosmic hypogonadotropic hypogonadism
  • congenital hypogonadotropic hypogonadism, MONDO:0015770
Tags
Q2_21_expert_review
OMIM
616031
Clinvar variants
Variants in CCDC141
Penetrance
None
Publications
Panels with this gene

History Filter Activity

23 Mar 2021, Gel status: 2

Added Tag

Ivone Leong (Genomics England Curator)

Tag Q2_21_expert_review tag was added to gene: CCDC141.

23 Mar 2021, Gel status: 2

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

Gene: ccdc141 has been classified as Amber List (Moderate Evidence).

23 Mar 2021, Gel status: 0

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: CCDC141 were changed from Anosmic hypogonadotropic hypogonadism to Anosmic hypogonadotropic hypogonadism; congenital hypogonadotropic hypogonadism, MONDO:0015770

23 Mar 2021, Gel status: 0

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: CCDC141 were set to 27014940; 28324054; 25192046

7 Jan 2021, Gel status: 0

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

Zornitza Stark (Australian Genomics)

gene: CCDC141 was added gene: CCDC141 was added to Hypogonadotropic hypogonadism idiopathic. Sources: Literature Mode of inheritance for gene: CCDC141 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: CCDC141 were set to 27014940; 28324054; 25192046 Phenotypes for gene: CCDC141 were set to Anosmic hypogonadotropic hypogonadism Review for gene: CCDC141 was set to AMBER