Proteinuric renal disease

Gene: DLC1

Green List (high evidence)

DLC1 (DLC1 Rho GTPase activating protein)
EnsemblGeneIds (GRCh38): ENSG00000164741
EnsemblGeneIds (GRCh37): ENSG00000164741
OMIM: 604258, Gene2Phenotype
DLC1 is in 3 panels

1 review

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Plausible disease causing variants found in more than 3 cases.
Created: 3 Jul 2019, 4:36 a.m. | Last Modified: 3 Jul 2019, 4:36 a.m.
Panel Version: 1.216
Comment on list classification: Plausible disease causing variants found in more than 3 cases.
Created: 30 Mar 2019, 4:11 p.m.
In OMIM this gene is only associated with Colorectal cancer, somatic, not a relevant phenotype.

PMID: 29773874 -performed homozygosity mapping combined with whole exome sequencing in multiple families with Nephrotic Syndrome. Also performed high-throughput exon sequencing in a worldwide cohort of ~1000 additional families with NS, examining specific candidate genes for NS based on genetic mouse models of NS. We identified recessive mutations of DLC1 in 4 families with NS. 6 different variants. Two individuals were compound heterozygous, two were homozygous. Families of different ethnicities. Some functional data showing DLC1 is expressed at focal and fibrillar adhesions in podocytes, consistent with the role of focal adhesions in podocyte migration26 and the pathogenesis of NS2. Knockdown of DLC1 in both IMCD3 cells and human podocytes also show a reduction in cell migration. This effect is found to be reversed when WT human DLC1 is transfected to IMCD3 cells. In contrast, four out of six DLC1 mutants (Trp10*, Ala456Val, Ala1352Val, and Lys1358Thr), detected in pTSNS, failed to fully rescue this decreased migratory phenotype.
Created: 30 Mar 2019, 3:59 p.m.
This gene was part of an initial gene list collated by Elizabeth Watson, North Bristol NHS Trust, February 2019 on behalf of the GMS Renal Specialist Test Group. Gene Symbol submitted: DLC1; Suggested initial gene rating: green; Evidence for inclusion: PMID: 29773874; Other comments: Only one publication, but includes 4 unrelated patients with SSNS/SRNS and rare homozygous or compound het variants in DLC1
Created: 4 Feb 2019, 10:41 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Childhood and adult SSNS and SRNS

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • NHS GMS
Phenotypes
  • Childhood and adult SSNS and SRNS
OMIM
604258
Clinvar variants
Variants in DLC1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

3 Jul 2019, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: dlc1 has been classified as Green List (High Evidence).

30 Mar 2019, Gel status: 1

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: DLC1 were changed from to Childhood and adult SSNS and SRNS

30 Mar 2019, Gel status: 1

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: DLC1 were set to

30 Mar 2019, Gel status: 1

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: DLC1 was changed from to BIALLELIC, autosomal or pseudoautosomal

30 Mar 2019, Gel status: 1

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: dlc1 has been classified as Red List (Low Evidence).

4 Feb 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Eleanor Williams (Genomics England Curator)

gene: DLC1 was added gene: DLC1 was added to Proteinuric renal disease. Sources: NHS GMS Mode of inheritance for gene: DLC1 was set to