Pulmonary arterial hypertension
Gene: KDR
Recently reviewed current genetic and experimental evidence for this gene-disease association was judged as STRONG by the ClinGen Pulmonary Hypertension Gene Curation Expert Panel (https://search.clinicalgenome.org/kb/gene-validity/CGGV:assertion_07a11f06-0904-4a38-9fd3-0aec2bece699-2021-01-20T132509.404Z).Created: 11 May 2021, 10:52 a.m. | Last Modified: 11 May 2021, 10:52 a.m.
Panel Version: 2.13
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
pulmonary arterial hypertension; significantly reduced diffusing coefficient for carbon monoxide, late disease onset
Publications
Two publications independently confirming loss of function variants in KDR associated with PAH and reduced Kco. Familial segregation confirmed.Created: 1 Feb 2021, 4:13 p.m. | Last Modified: 1 Feb 2021, 4:13 p.m.
Panel Version: 2.9
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Pulmonary arterial hypertension; low diffusion coefficient for carbon monoxide
Publications
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 8 Mar 2022, 11:25 a.m. | Last Modified: 8 Mar 2022, 11:25 a.m.
Panel Version: 2.18
This gene is associated with a phenotype in OMIM but not in Gene2Phenotype. This gene is also identified as a novel PAH disease gene in PMID:29650961, which was found in 4 cases and 0 in controls. Clingen has curated this gene-disease association and given it a Strong rating. There is enough evidence to support a gene-disease association. This gene should be rated Green at the next review.Created: 16 Apr 2021, 12:22 p.m. | Last Modified: 16 Apr 2021, 12:22 p.m.
Panel Version: 2.13
Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is associated with a phenotype in OMIM. Based on the available evidence this gene has been given an Amber rating.Created: 3 Dec 2020, 9:48 a.m. | Last Modified: 3 Dec 2020, 9:48 a.m.
Panel Version: 2.7
Comment on publications: PMID: 32880713 describes a mouse model where Kdr was conditionally knocked out. Kdr knockout led to mild pulmonary hypertension under normoxia that worsened under hypoxia. Kdr knockout mice had significant increase in pulmonary arterial wall thickness, muscularization, and VEGFR-3+ endothelial cells obliterating the pulmonary artery vessel lumen.Created: 3 Dec 2020, 9 a.m. | Last Modified: 3 Dec 2020, 9 a.m.
Panel Version: 2.6
Two unrelated individuals with PAH and LoF variants reported; segregation evidence in one family.
Sources: Expert listCreated: 27 Jul 2020, 12:57 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Pulmonary hypertension
Publications
Tag Q2_21_rating was removed from gene: KDR.
Source Expert Review Green was added to KDR. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag watchlist was removed from gene: KDR. Tag Q2_21_rating tag was added to gene: KDR.
Publications for gene: KDR were set to 31980491; 32880713; 33320693
Phenotypes for gene: KDR were changed from Pulmonary hypertension to Heritable pulmonary arterial hypertension, MONDO:0017148
Publications for gene: KDR were set to 31980491; 32880713
Tag watchlist tag was added to gene: KDR.
Gene: kdr has been classified as Amber List (Moderate Evidence).
Publications for gene: KDR were set to 31980491
gene: KDR was added gene: KDR was added to Pulmonary arterial hypertension. Sources: Expert list Mode of inheritance for gene: KDR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KDR were set to 31980491 Phenotypes for gene: KDR were set to Pulmonary hypertension Review for gene: KDR was set to AMBER