EHHADH

enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase, the group of MicroRNA protein coding host genes

Basic information

Region (hg38): 3:185190624-185281990

Previous symbols: [ "ECHD" ]

Links

ENSG00000113790 ∙ NCBI:1962 ∙ OMIM:607037 ∙ HGNC:3247 ∙ Uniprot:Q08426 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• primary Fanconi syndrome (Supportive), mode of inheritance: AD
• Fanconi renotubular syndrome 3 (Limited), mode of inheritance: AD
• Fanconi renotubular syndrome 3 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fanconi renotubular syndrome 3	AD	Renal	Manifestations in the described individuals can include severe rickets, and early knowledge may allow medical/dietary interventions (eg, with calcitriol, and phosphate supplementation) to prevent (and treat) this complication	Renal	1627757; 24401050

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EHHADH gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EHHADH gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			10	21	2	33
missense			76	12	14	102
nonsense			6	1		7
start loss						0
frameshift			6			6
inframe indel			2			2
splice donor/acceptor (+/-2bp)						0
splice region			2	1	1	4
non coding			1	2	16	19
Total	0	0	101	36	32

Variants in EHHADH

This is a list of pathogenic ClinVar variants found in the EHHADH region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-185192216-G-A		EHHADH-related disorder	Likely benign (Apr 24, 2023)
3-185192218-A-G			Uncertain significance (Aug 30, 2018)
3-185192237-T-C		not specified • EHHADH-related disorder	Likely benign (May 09, 2017)
3-185192245-G-A		not specified	Uncertain significance (Oct 03, 2022)
3-185192254-A-G			Benign (May 04, 2021)
3-185192256-G-T		not specified	Uncertain significance (Dec 04, 2023)
3-185192278-G-A		EHHADH-related disorder	Uncertain significance (Aug 22, 2024)
3-185192281-T-A		not specified	Benign (Sep 01, 2022)
3-185192284-C-T		not specified	Uncertain significance (Jun 11, 2021)
3-185192290-G-A		Chronic kidney disease	Conflicting classifications of pathogenicity (Jun 01, 2024)
3-185192297-G-GT		not specified	Uncertain significance (Sep 18, 2023)
3-185192300-T-G		not specified	Uncertain significance (Oct 26, 2022)
3-185192304-T-C		EHHADH-related disorder	Uncertain significance (Feb 02, 2017)
3-185192317-G-A		EHHADH-related disorder • not specified	Uncertain significance (Aug 15, 2023)
3-185192320-T-C		EHHADH-related disorder	Uncertain significance (Mar 27, 2018)
3-185192323-A-T			Uncertain significance (Sep 16, 2018)
3-185192326-TGGG-T			Uncertain significance (Mar 21, 2017)
3-185192332-A-G			Benign (Dec 31, 2019)
3-185192339-G-T		not specified	Uncertain significance (Jun 02, 2024)
3-185192345-G-T			Benign (Aug 20, 2019)
3-185192346-CCTGTA-AT		EHHADH-related disorder	Uncertain significance (Feb 29, 2024)
3-185192348-T-C			Benign (Dec 31, 2019)
3-185192355-T-G			Uncertain significance (Jun 21, 2018)
3-185192372-G-T		not specified	Uncertain significance (May 16, 2024)
3-185192375-C-T			Uncertain significance (Apr 03, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EHHADH	protein_coding	protein_coding	ENST00000231887	7	91367

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.24e-10	0.831	125497	2	248	125747	0.000995

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0259	394	393	1.00	0.0000204	4636
Missense in Polyphen		139	137.71	1.0094		1666
Synonymous	0.688	139	150	0.928	0.00000765	1492
Loss of Function	1.68	19	28.7	0.662	0.00000156	366

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00134	0.00126
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.000139	0.000139
European (Non-Finnish)	0.00104	0.00104
Middle Eastern	0.000272	0.000272
South Asian	0.00308	0.00301
Other	0.000491	0.000489

dbNSFP

Source: dbNSFP

• Disease: DISEASE: Fanconi renotubular syndrome 3 (FRTS3) [MIM:615605]: A disease due to a generalized dysfunction of the proximal kidney tubule resulting in decreased solute and water reabsorption. Patients have polydipsia and polyuria with phosphaturia, glycosuria and aminoaciduria. They may develop hypophosphatemic rickets or osteomalacia, acidosis and a tendency toward dehydration. Some eventually develop renal insufficiency. {ECO:0000269|PubMed:24401050}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Tryptophan metabolism - Homo sapiens (human);Butanoate metabolism - Homo sapiens (human);beta-Alanine metabolism - Homo sapiens (human);Lysine degradation - Homo sapiens (human);Propanoate metabolism - Homo sapiens (human);Peroxisome - Homo sapiens (human);Fatty acid degradation - Homo sapiens (human);PPAR signaling pathway - Homo sapiens (human);Valine, leucine and isoleucine degradation - Homo sapiens (human);Valproic Acid Metabolism Pathway;Constitutive Androstane Receptor Pathway;PPAR Alpha Pathway;Nuclear Receptors Meta-Pathway;Mitochondrial LC-Fatty Acid Beta-Oxidation;Valproic acid pathway;Amino Acid metabolism;PPAR signaling pathway;Liver steatosis AOP;mechanism of gene regulation by peroxisome proliferators via ppara;Butanoate metabolism;fatty acid β-oxidation (unsaturated, odd number);Metabolism of lipids;Metabolism of proteins;Tyrosine metabolism;3-oxo-10R-octadecatrienoate beta-oxidation;Leukotriene metabolism;Omega-3 fatty acid metabolism;Saturated fatty acids beta-oxidation;Trihydroxycoprostanoyl-CoA beta-oxidation;Beta-oxidation of very long chain fatty acids;Peroxisomal lipid metabolism;Metabolism;Lysine degradation;Peroxisomal protein import;Fatty acid metabolism;inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages;Propanoate metabolism;Mono-unsaturated fatty acid beta-oxidation;Omega-6 fatty acid metabolism;Valine, leucine and isoleucine degradation;Butanoate metabolism;Propanoate metabolism;Bile acid biosynthesis;Dimethyl-branched-chain fatty acid mitochondrial beta-oxidation;Di-unsaturated fatty acid beta-oxidation;Phytanic acid peroxisomal oxidation;Vitamin E metabolism;fatty acid β-oxidation (peroxisome);fatty acid β-oxidation;Tryptophan degradation;Valine Leucine Isoleucine degradation (Consensus)

Recessive Scores

• pRec: 0.408

Intolerance Scores

• loftool: 0.325
• rvis_EVS: 2.27
• rvis_percentile_EVS: 98.24

Haploinsufficiency Scores

• pHI: 0.0627
• hipred: N
• hipred_score: 0.230

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.224

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ehhadh
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype

Gene ontology

• Biological process: internal protein amino acid acetylation;protein targeting to peroxisome;fatty acid beta-oxidation;fatty acid beta-oxidation using acyl-CoA oxidase
• Cellular component: peroxisome;peroxisomal matrix;cytosol
• Molecular function: 3-hydroxyacyl-CoA dehydrogenase activity;dodecenoyl-CoA delta-isomerase activity;enoyl-CoA hydratase activity;signaling receptor binding;protein binding;long-chain-enoyl-CoA hydratase activity;enzyme binding