Pulmonary arterial hypertension

Gene: KDR

Green List (high evidence)

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

• PMID: 33320693
• 31980491

Green List (high evidence)

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

• PMID: 33320693
• PMID: 31980491

Green List (high evidence)

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

I don't know

Two unrelated individuals with PAH and LoF variants reported; segregation evidence in one family.
Sources: Expert list

Created: 27 Jul 2020, 12:57 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Pulmonary hypertension

Publications

• 31980491