Pulmonary arterial hypertension

Gene: SMAD4

Red List (low evidence)

SMAD4 (SMAD family member 4)
EnsemblGeneIds (GRCh38): ENSG00000141646
EnsemblGeneIds (GRCh37): ENSG00000141646
OMIM: 600993, Gene2Phenotype
SMAD4 is in 27 panels

2 reviews

Louise Daugherty (Genomics England Curator)

Red List (low evidence)

Comment on phenotypes: added PAH
Created: 1 Oct 2018, 1:38 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.
PMID: 26387786 Mutations in the genes encoding the downstream signalling intermediaries for bone morphogenetic protein receptors, the Smad proteins have been reported in some patients with PAH. Of these, the SMAD1 and SMAD4 defects have been described as variants of unknown significance (VUS) due to in vitro luciferase SMAD responsive elements reporter assays demonstrating an unclear impact on the canonical pathways (PMID:21898662). However, these analyses did not investigate SMAD-independent pathways, implicated in disease pathogenesis, leaving open the possibility that the identified variants may deleteriously affect other BMP related systems. PAH associations are based on one paper 21898662 (2011) a patient was identified with a putative splice site mutation in SMAD4 which resulted in moderate transcript loss due to compromised splicing efficiency.
Created: 21 Jun 2017, 11:12 a.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

Publications

History Filter Activity

1 Oct 2018, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: SMAD4 were changed from Idiopathic pulmonary arterial hypertension; IPAH; Heritable pulmonary arterial hypertension; HPAH; Pulmonary arterial hypertension; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050, PAH to Idiopathic pulmonary arterial hypertension; IPAH; Heritable pulmonary arterial hypertension; HPAH; Pulmonary arterial hypertension; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050

1 Oct 2018, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: SMAD4 were changed from Idiopathic pulmonary arterial hypertension; IPAH; Heritable pulmonary arterial hypertension; HPAH; Pulmonary arterial hypertension; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050 to Idiopathic pulmonary arterial hypertension; IPAH; Heritable pulmonary arterial hypertension; HPAH; Pulmonary arterial hypertension; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050, PAH

16 Apr 2018, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for SMAD4 were set to 21898662; 24355637; 26387786; 29650961

22 Jun 2017, Gel status: 0

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: 0

Upload gene information

Louise Daugherty (Genomics England Curator)

SMAD4 was added to Pulmonary arterial hypertensionpanel. Sources: Expert list

19 Jun 2017, Gel status: 0

Set publications

Louise Daugherty (Genomics England Curator)

Publications for SMAD4 were set to 21898662; 24355637; 26387786

19 Jun 2017, Gel status: 0

Set publications

Louise Daugherty (Genomics England Curator)

Publications for SMAD4 were set to 21898662; 24355637; 263877862;26387786

14 Jun 2017, Gel status: 0

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for SMAD4 were set to Idiopathic pulmonary arterial hypertension; IPAH; Heritable pulmonary arterial hypertension; HPAH; Pulmonary arterial hypertension; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050

14 Jun 2017, Gel status: 0

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for SMAD4 were set to diopathic pulmonary arterial hypertension; IPAH; Heritable pulmonary arterial hypertension; HPAH; Pulmonary arterial hypertension;Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, 175050

9 Jun 2017, Gel status: 0

Added New Source

Louise Daugherty (Genomics England Curator)

SMAD4 was added to Pulmonary arterial hypertensionpanel. Sources: Literature

9 Jun 2017, Gel status: 0

Created

Louise Daugherty (Genomics England Curator)

SMAD4 was created by LouiseD