Pulmonary arterial hypertension

Gene: KDR

Amber List (moderate evidence)

KDR (kinase insert domain receptor)
EnsemblGeneIds (GRCh38): ENSG00000128052
EnsemblGeneIds (GRCh37): ENSG00000128052
OMIM: 191306, Gene2Phenotype
KDR is in 4 panels

4 reviews

Stefan Graf (Department of Medicine, University of Cambridge)

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

Nicholas Morrell (University of Cambridge)

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

Ivone Leong (Genomics England Curator)

Green List (high evidence)

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

Zornitza Stark (Australian Genomics)

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
Phenotypes
  • Heritable pulmonary arterial hypertension, MONDO:0017148
Tags
Q2_21_rating
OMIM
191306
Clinvar variants
Variants in KDR
Penetrance
None
Publications
Panels with this gene

History Filter Activity

16 Apr 2021, Gel status: 2

Removed Tag, Added Tag

Ivone Leong (Genomics England Curator)

Tag watchlist was removed from gene: KDR. Tag Q2_21_rating tag was added to gene: KDR.

16 Apr 2021, Gel status: 2

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: KDR were set to 31980491; 32880713; 33320693

16 Apr 2021, Gel status: 2

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: KDR were changed from Pulmonary hypertension to Heritable pulmonary arterial hypertension, MONDO:0017148

16 Apr 2021, Gel status: 2

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: KDR were set to 31980491; 32880713

3 Dec 2020, Gel status: 2

Added Tag

Ivone Leong (Genomics England Curator)

Tag watchlist tag was added to gene: KDR.

3 Dec 2020, Gel status: 2

Entity classified by Genomics England curator

Ivone Leong (Genomics England Curator)

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

3 Dec 2020, Gel status: 0

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: KDR were set to 31980491

27 Jul 2020, Gel status: 0

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

Zornitza Stark (Australian Genomics)

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