Proteinuric renal disease

Gene: EMP2

I don't know

The rating of this gene has been updated to Amber following NHS Genomic Medicine Service approval.

Created: 30 Jan 2023, 7:07 p.m. | Last Modified: 30 Jan 2023, 7:07 p.m.

Panel Version: 3.3

Red List (low evidence)

A single study from 2014 (PMID: 24814193) reports biallelic (1 x nonsense and 2 x missense) rare EMP2 variants in 4 individuals with steroid sensitive nephrotic syndrome from 3 (out of 1600) nephrotic syndrome cases studied and this finding has not been replicated in further studies of SSNS (PMID: 29058154) or knockout mice (PMID: 31508419). Subsequent data from GnomAD does not show evidence of depletion of LoF or missense variation in this gene and no signal has been reported in gene-based burden or variant testing of large cohorts. Therefore further evidence is needed for biallelic mutations in this gene to be clinically reportable.

Created: 7 Mar 2022, 9:29 a.m. | Last Modified: 7 Mar 2022, 9:29 a.m.

Panel Version: 2.64

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Proteinuric renal disease; Unexplained paediatric onset end-stage renal disease

Publications

• PMID: 31508419
• 24814193
• 29058154

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Comment on list classification: The rating of this gene has been left as green, but with a recommendation for demotion to amber following expert review of the evidence.

Created: 21 May 2022, 11:53 p.m. | Last Modified: 21 May 2022, 11:53 p.m.

Panel Version: 2.76

Comment on list classification: 3 families with variants in this gene which segregate with the condition, plus some functional data.

Created: 30 Mar 2019, 4:45 p.m.

Associated with Nephrotic syndrome, type 10 615861 in OMIM.

PMID 24814193 - Gee et al 2014 - performed homozygosity mapping, whole-exome sequencing, and multiplex PCR followed by next-generation sequencing. They found biallelic mutations in EMP2 (epithelial membrane protein 2) in four individuals from three unrelated families affected by SRNS or SSNS. Consanguineous Turkish family A1679 had a homozygous truncating variant (c.184C>T [p.Gln62∗]) in EMP2 which segregated in the condition. In another Turkish family (A150) the affected individual was compound heterozygous for 2 variants in EMP2 - 21C>G, p.Phe7Leu and
c.184C>T, p.Gln62∗. In a third African-American family (A4601) the proband was homozygous for a missense mutation c.28G>A, p.Ala10Thr. All mutations were absent from >190 ethnically matched healthy control individuals and from >8,600 European control individuals in the NHLBI EVS

Functional studies showed that EMP2 exclusively localized to glomeruli in the kidney. Knockdown of emp2 in zebrafish resulted in pericardial effusion, supporting the pathogenic role of mutated EMP2 in human NS. Knockdown of EMP2 in podocytes and endothelial cells resulted in an increased amount of CAVEOLIN-1 and decreased cell proliferation.

Created: 30 Mar 2019, 4:45 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: EMP2; Suggested initial gene rating: green; Evidence for inclusion: PMID24814193; Other comments: PMID 24814193 reports 4 individuals from 3 unrelated families with SRNS or SSNS and AR rare variants in this gene

Created: 4 Feb 2019, 10:41 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Nephrotic syndrome, type 10 #615861

Publications

• PMID24814193

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Sources: Literature

Created: 20 Sep 2018, 8:39 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
steroid sensitive nephrotic syndrome

Publications

• 24814193