Hypogonadotropic hypogonadism (GMS)
Gene: PLXNA3The rating of this gene has been updated to GREEN and the mode of inheritance set to X-LINKED: hemizygous mutation in males, biallelic mutations in females 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: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with any phenotypes in OMIM or Gene2Phenotype. Based on the expert review there is sufficient evidence to support a gene-disease association. This gene should be rated Green at the next review.Created: 29 Jul 2022, 10:51 a.m. | Last Modified: 29 Jul 2022, 10:51 a.m.
Panel Version: 1.54
Screened 216 patients with Idiopathic hypogonadotropic hypogonadism by exome sequencing. Identified 7 individuals from 5 families with hemizygous PLXNA3 missense variants.
In 2 of the kindreds, there was at least one more gene known to be associated with IHH (oligogenecity). Data provided with evidence that PLXNA3, a key component of the SEMA3F holoreceptor complex,31 is expressed by the human GnRH and olfactory/vomeronasal systems. S646P variant showed PLXNA3 localization exclusively in the ER, indicating that the variant S646P disrupts cell surface localization of PLXNA3.
Sources: LiteratureCreated: 8 Jul 2021, 7:58 a.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
Hypogonadotropic hypogonadism
Publications
Tag gene-checked tag was added to gene: PLXNA3.
Tag Q3_22_rating was removed from gene: PLXNA3.
Source Expert Review Green was added to PLXNA3. Source NHS GMS was added to PLXNA3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q3_22_rating tag was added to gene: PLXNA3.
Gene: plxna3 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: PLXNA3 were changed from Hypogonadotropic hypogonadism to Hypogonadotropic hypogonadism, MONDO:0018555
gene: PLXNA3 was added gene: PLXNA3 was added to Hypogonadotropic hypogonadism idiopathic. Sources: Literature Mode of inheritance for gene: PLXNA3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: PLXNA3 were set to 33495532 Phenotypes for gene: PLXNA3 were set to Hypogonadotropic hypogonadism Review for gene: PLXNA3 was set to GREEN