Renal tubulopathies
Gene: EHHADHEnsemblGeneIds (GRCh38): ENSG00000113790
EnsemblGeneIds (GRCh37): ENSG00000113790
OMIM: 607037, Gene2Phenotype
EHHADH is in 3 panels
4 reviews
Anna de Burca (Oxford University Hospitals NHS Foundation Trust)
Comment on list classification: Single family reported with additional functional data. Gene demoted to amber pending further evidence for re-evaluation.Created: 27 Mar 2019, 12:42 p.m.
Eleanor Williams (Genomics England Curator)
Comment on list classification: 1 family plus functional data which is sufficient evidence to leave amber.Created: 4 Sep 2019, 3:37 p.m. | Last Modified: 4 Sep 2019, 3:37 p.m.
Panel Version: 1.84
PMID: 24401050 (Klootwijk et al 2014) - five-generation black family with isolated autosomal dominant Fanconi's syndrome. They found a heterozygous missense (p.E3K) mutation in EHHADH segregated with the disease. It results in a new mitochondrial targeting motif in the N-terminal portion of EHHADH. Functional studies of proximal tubular cells revealed impaired mitochondrial oxidative phosphorylation and defects in the transport of fluids and a glucose analogue across the epithelium. Further functional studies on the variant in PMID: 27160910 (Assmann et al 2016)
No other reports listed in OMIMCreated: 12 Feb 2019, 4:55 p.m.
This gene was part of an initial gene list collated by Emma Ashton (NE Thames Regional Genetics laboratory, GOSH NHS Foundation Trust) January 2019 on behalf of the GMS Renal Specialist Test Group; Gene Symbol submitted: EHHADH; Suggested initial gene rating: red; Evidence for inclusion: Klootwijk et al New Eng. J. Med. 370: 129-138, 2014. PubMed: 24401050, 1 large family, functional work; Evidence for exclusion: none provided; Technical notes (e.g. non-coding/CNV mutations requiring coverage?): none providedCreated: 3 Feb 2019, 11:32 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
?Fanconi renotubular syndrome 3 MIM 605615
Publications
- Klootwijk et al New Eng. J. Med. 370: 129-138, 2014. PubMed: 24401050
Variants in this GENE are reported as part of current diagnostic practice
Damian Smedley (Genomics England Curator)
Comment when marking as ready: Known expert and OMIM evidenceCreated: 10 May 2016, 10:52 a.m.
Fiona Karet (Universit y of Cambridge)
Mechanism involves mistargeting of mutant protein within cellCreated: 1 Nov 2015, 7:03 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
metabolic acidosis, glucosuria, phosphaturia, aminoaciduria, and proteinuria
Mode of pathogenicity
Other
Details
- Mode of Inheritance
- MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
- Sources
-
- Expert Review Amber
- NHS GMS
- Expert
- Phenotypes
-
- ?Fanconi renotubular syndrome 3, OMIM:615605
- L-bifunctional protein deficiency
- Metabolic acidosis
- Increased amino acids in urine
- OMIM
- 607037
- Clinvar variants
- Variants in EHHADH
- Penetrance
- Complete
- Publications
- Mode of Pathogenicity
- Other - please provide details in the comments
- Panels with this gene
History Filter Activity
Set Phenotypes
Arina Puzriakova (Genomics England Curator)Phenotypes for gene: EHHADH were changed from metabolic acidosis, glucosuria, phosphaturia, aminoaciduria, and proteinuria; ?Fanconi renotubular syndrome 3, 605615 to ?Fanconi renotubular syndrome 3, OMIM:615605; L-bifunctional protein deficiency; Metabolic acidosis; Increased amino acids in urine
Entity classified by Genomics England curator
Eleanor Williams (Genomics England Curator)Gene: ehhadh has been classified as Amber List (Moderate Evidence).
Set Phenotypes
Eleanor Williams (Genomics England Curator)Phenotypes for gene: EHHADH were changed from metabolic acidosis, glucosuria, phosphaturia, aminoaciduria, and proteinuria to metabolic acidosis, glucosuria, phosphaturia, aminoaciduria, and proteinuria; ?Fanconi renotubular syndrome 3, 605615
Entity classified by Genomics England curator
Anna de Burca (Oxford University Hospitals NHS Foundation Trust)Gene: ehhadh has been classified as Amber List (Moderate Evidence).
Set publications
Eleanor Williams (Genomics England Curator)Publications for gene: EHHADH were set to 24401050
Set publications
Eleanor Williams (Genomics England Curator)Publications for gene: EHHADH were set to
Added New Source, Status Update
Eleanor Williams (Genomics England Curator)Source NHS GMS was added to EHHADH. Rating Changed from Green List (high evidence) to Green List (high evidence)
Gene classified by Genomics England curator
Damian Smedley (Genomics England Curator)This gene has been classified as Green List (High Evidence).
Set Phenotypes
Damian Smedley (Genomics England Curator)Phenotypes for EHHADH were set to metabolic acidosis, glucosuria, phosphaturia, aminoaciduria, and proteinuria
Set mode of pathogenicity
Damian Smedley (Genomics England Curator)Mode of pathogenicity for EHHADH was changed to Other - please provide details in the comments
Set Mode of Inheritance
Damian Smedley (Genomics England Curator)Mode of inheritance for EHHADH was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Set Mode of Inheritance
Damian Smedley (Genomics England Curator)Mode of inheritance for EHHADH was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Gene classified by Genomics England curator
Damian Smedley (Genomics England Curator)This gene has been classified as Green List (High Evidence).
Added New Source
Eik Haraldsdottir (Genomics England)EHHADH was added to Renal tubular acidosispanel. Sources: Expert