Pulmonary arterial hypertension

Gene: CAV1

Amber List (moderate evidence)

CAV1 (caveolin 1)
EnsemblGeneIds (GRCh38): ENSG00000105974
EnsemblGeneIds (GRCh37): ENSG00000105974
OMIM: 601047, Gene2Phenotype
CAV1 is in 8 panels

2 reviews

Louise Daugherty (Genomics England Curator)

I don't know

From GMS Respiratory Specialist Test Group webex call 18th Jan 2019 : agreed that LCCNS unlikely to present as non-syndromic PPHT so should remain amber
Created: 21 Jan 2019, 5:41 p.m.
Initial gene list and info collated by Ian Berry Leeds Genetics Laboratory November 2018 on behalf of the GMS Respiratory specialist test group. Gene Symbol submitted: CAV1; Suggested initial gene rating: Green; Evidence for inclusion: OMIM PPH gene; Evidence for exclusion: Severe infantile syndrome, PAH unlikely to be presenting feature; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none given
Created: 6 Dec 2018, 2:01 p.m.
PMID: 29650961 (2018) further question the validity of CAV1, SMAD1 and SMAD4 causing PAH. No pathogenic coding variants in CAV1, SMAD1 or SMAD4 were identified. However it was noted that the participants with causative variants reported in these genes might represent private mutations in in very rare families.
Created: 16 Apr 2018, 11:59 a.m.
Comment on publications: added publication suggested by A.Tucci PMID:27717241, which describes a mutation causing PAH and lipodystrophy, but recommenced by clinical team it is still not enough evidence to make this gene Green, so keep Amber for now.
Created: 22 Jun 2017, 8:14 a.m.
Two unrelated cases PMID:22474227 genetic analysis of an additional patient in the family supported the conclusion that a rare mutation in the CAV1 gene was of pertinence to disease since the observed mutation in exon 3 (c.474delA; p.L159Sfs*22), impacts a highly conserved region and predicts deleterious functional consequences. PMID:25917481 (2015) notes "The SMAD9 and CAV1 were reported as rare nucleotide changes in the exome sequencing project and could thus be regarded as likely non-pathogenic variants" (author statement only). However, it there are Cav1 knockout mice that develop pulmonary hypertension (PMID:12177436, 19419974), supporting the pathogenicity of the variants identified by Austin et al. (2012). PMID: 20301658 notes that most heritable PAH (75%) is caused by a pathogenic variant in BMPR2; pathogenic variants in other genes (i.e., ACVRL1, KCNK3, CAV1, SMAD9, BMPR1B,) are considerably less common (1-3%).
Created: 9 Jun 2017, 2:03 p.m.

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Idiopathic pulmonary arterial hypertension; IPAH; Heritable pulmonary arterial hypertension; HPAH; Pulmonary arterial hypertension

Publications

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • NHS GMS
  • Expert list
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • Expert Review Amber
  • Literature
Phenotypes
  • Pulmonary hypertension, primary, 3, 615343
  • Heritable pulmonary arterial hypertension
  • HPAH
  • Pulmonary arterial hypertension
OMIM
601047
Clinvar variants
Variants in CAV1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

6 Dec 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to CAV1.

16 Apr 2018, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for CAV1 were set to 25917481; 11498544; 12177436; 19487814; 20301658; 22474227; 26387786; 27717241; 29650961

22 Jun 2017, Gel status: 2

panel promoted to version 1

Louise Daugherty (Genomics England Curator)

Panel reviews were assessed, and panel was revised according to reviews and further in-house curation.

22 Jun 2017, Gel status: 2

Upload gene information

Louise Daugherty (Genomics England Curator)

CAV1 was added to Pulmonary arterial hypertensionpanel. Sources: Expert list

22 Jun 2017, Gel status: 2

Upload gene information

Louise Daugherty (Genomics England Curator)

CAV1 was added to Pulmonary arterial hypertensionpanel. Sources: Expert list

22 Jun 2017, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for CAV1 were set to 25917481; 11498544; 12177436; 19487814; 20301658; 22474227; 26387786;27717241

14 Jun 2017, Gel status: 2

Set publications

Louise Daugherty (Genomics England Curator)

Publications for CAV1 were set to 25917481; 11498544; 12177436; 19487814; 20301658; 22474227;26387786

9 Jun 2017, Gel status: 2

Upload gene information

Louise Daugherty (Genomics England Curator)

CAV1 was added to Pulmonary arterial hypertensionpanel. Sources: Radboud University Medical Center, Nijmegen,Emory Genetics Laboratory

9 Jun 2017, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

9 Jun 2017, Gel status: 0

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for CAV1 were set to Pulmonary hypertension, primary, 3, 615343;Heritable pulmonary arterial hypertension; HPAH; Pulmonary arterial hypertension

9 Jun 2017, Gel status: 0

Added New Source

Louise Daugherty (Genomics England Curator)

CAV1 was added to Pulmonary arterial hypertensionpanel. Sources: Literature

9 Jun 2017, Gel status: 0

Created

Louise Daugherty (Genomics England Curator)

CAV1 was created by LouiseD