HADH hydroxyacyl-CoA dehydrogenase [Homo sapiens (human)] - Gene

Summary

Official Symbol: HADHprovided by HGNC
Official Full Name: hydroxyacyl-CoA dehydrogenaseprovided by HGNC
Primary source: HGNC:HGNC:4799
See related: Ensembl:ENSG00000138796 MIM:601609; AllianceGenome:HGNC:4799
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HAD; HCDH; HHF4; HADH1; SCHAD; HADHSC; MSCHAD
Summary: This gene is a member of the 3-hydroxyacyl-CoA dehydrogenase gene family. The encoded protein functions in the mitochondrial matrix to catalyze the oxidation of straight-chain 3-hydroxyacyl-CoAs as part of the beta-oxidation pathway. Its enzymatic activity is highest with medium-chain-length fatty acids. Mutations in this gene cause one form of familial hyperinsulinemic hypoglycemia. The human genome contains a related pseudogene of this gene on chromosome 15. [provided by RefSeq, May 2010]
Expression: Ubiquitous expression in fat (RPKM 86.5), kidney (RPKM 61.3) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 4q25

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (107989889..108035171)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (111292223..111337508)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (108911045..108956327)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Abnormal expression of HADH, an enzyme of fatty acid oxidation, affects tumor development and prognosis (Review).
Title: Abnormal expression of HADH, an enzyme of fatty acid oxidation, affects tumor development and prognosis (Review).
Differentially expressed genes PCCA, ECHS1, and HADH are potential prognostic biomarkers for gastric cancer.
Title: Differentially expressed genes PCCA, ECHS1, and HADH are potential prognostic biomarkers for gastric cancer.
Functional evaluation of 16 SCHAD missense variants: Only amino acid substitutions causing congenital hyperinsulinism of infancy lead to loss-of-function phenotypes in vitro.
Title: Functional evaluation of 16 SCHAD missense variants: Only amino acid substitutions causing congenital hyperinsulinism of infancy lead to loss-of-function phenotypes in vitro.
Genetic pathogenesis, diagnosis, and treatment of short-chain 3-hydroxyacyl-coenzyme A dehydrogenase hyperinsulinism.
Title: Genetic pathogenesis, diagnosis, and treatment of short-chain 3-hydroxyacyl-coenzyme A dehydrogenase hyperinsulinism.
The most frequently seen mutations in Turkish patients with congenital hyperinsulinism (CHI) were ATP binding cassette subfamily C member 8 (ABCC8) gene, followed by 3-hydroxyacyl CoA dehydrogenase (HADH) and kcnj11 channel (KCNJ11) genes.
Title: Current Status of Childhood Hyperinsulinemic Hypoglycemia in Turkey.
Paretic muscle in hemiparetic stroke survivors had lower HAD concentration.
Title: Skeletal muscle fiber characteristics and oxidative capacity in hemiparetic stroke survivors.
We present clinical and laboratory findings together with the long-term clinical course of a case with a deep intronic HADH splicing mutation (c.636+471G>T) causing neonatal-onset hyperinsulinemic hypoglycemia with mild progression
Title: A Deep Intronic HADH Splicing Mutation (c.636+471G>T) in a Congenital Hyperinsulinemic Hypoglycemia Case: Long Term Clinical Course.
in a cohort of hyperinsulinemic hypoglycemia patients from Isfahan, Iran, 78% were noted to have disease-causing mutations: 48% had HADH mutations and 26% had ABCC8 mutations.
Title: Genotype and phenotype correlations in Iranian patients with hyperinsulinaemic hypoglycaemia.
Next-generation sequencing reveals deep intronic cryptic ABCC8 and HADH splicing founder mutations causing hyperinsulinism by pseudoexon activation.
Title: Next-generation sequencing reveals deep intronic cryptic ABCC8 and HADH splicing founder mutations causing hyperinsulinism by pseudoexon activation.
Loss of function mutations in 3-Hydroxyacyl-CoA Dehydrogenase (HADH) cause leucine sensitive hyperinsulinaemic hypoglycaemia.
Title: Leucine-sensitive hyperinsulinaemic hypoglycaemia in patients with loss of function mutations in 3-Hydroxyacyl-CoA Dehydrogenase.

Submit: New GeneRIF Correction See all GeneRIFs (19)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Deficiency of 3-hydroxyacyl-CoA dehydrogenase MedGen: C1291230 OMIM: 231530 GeneReviews: Not available	not available
Hyperinsulinemic hypoglycemia, familial, 4 MedGen: C1864948 OMIM: 609975 GeneReviews: Nonsyndromic Genetic Hyperinsulinism Overview	not available

EBI GWAS Catalog

Description
Genome-wide association study combining pathway analysis for typical sporadic amyotrophic lateral sclerosis in Chinese Han populations. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Vpr	vpr	HIV-1 Vpr regulates mitochondrial respiration and enhances the activity of hydroxyacyl-CoA dehydrogenase (HADH) through PPARbeta/delta	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-18759 (e-PCR)
- UniSTS:47112

SHGC-18755 (e-PCR)
- UniSTS:13097

D4S2516E (e-PCR)
- UniSTS:43333

D4S1008 (e-PCR)
- UniSTS:41817

D4S2795 (e-PCR)
- UniSTS:83290

SHGC-51987 (e-PCR)
- UniSTS:18805

SHGC-59812 (e-PCR)
- UniSTS:60798

SHGC-83599 (e-PCR)
- UniSTS:95893

RH18323 (e-PCR)
- UniSTS:62620

SHGC-57594 (e-PCR)
- UniSTS:51149

SHGC-67734 (e-PCR)
- UniSTS:1512

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 3-hydroxyacyl-CoA dehydrogenase activity	IBA Inferred from Biological aspect of Ancestor more info
enables 3-hydroxyacyl-CoA dehydrogenase activity	IDA Inferred from Direct Assay more info	PubMed
enables NAD+ binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IDA Inferred from Direct Assay more info	PubMed
enables transferase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in fatty acid beta-oxidation	IBA Inferred from Biological aspect of Ancestor more info
involved_in fatty acid beta-oxidation	IDA Inferred from Direct Assay more info	PubMed
involved_in fatty acid beta-oxidation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of insulin secretion	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cold-induced thermogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in regulation of insulin secretion	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to activity	IEA Inferred from Electronic Annotation more info
involved_in response to insulin	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in spermatogenesis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info
located_in mitochondrial matrix	TAS Traceable Author Statement more info
located_in mitochondrion	HTP more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: hydroxyacyl-coenzyme A dehydrogenase, mitochondrial

Names: L-3-hydroxyacyl-Coenzyme A dehydrogenase, short chain; medium and short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase; short-chain 3-hydroxyacyl-CoA dehydrogenase; testis secretory sperm-binding protein Li 203a

NP_001171634.3

EC 1.1.1.35

NP_001317956.2

EC 1.1.1.35

NP_005318.6

EC 1.1.1.35

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008156.3 RefSeqGene

Range

5002..50284

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001184705.4 → NP_001171634.3 hydroxyacyl-coenzyme A dehydrogenase, mitochondrial isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC114733, AC118062

Consensus CDS

CCDS54790.1

UniProtKB/TrEMBL

A0A0A0MSE2

Related

ENSP00000474560.1, ENST00000603302.5

Conserved Domains (1) summary

COG1250
Location:27 → 330

FadB; 3-hydroxyacyl-CoA dehydrogenase [Lipid transport and metabolism]
NM_001331027.2 → NP_001317956.2 hydroxyacyl-coenzyme A dehydrogenase, mitochondrial isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate 5' terminal exon and lacks an alternate in-frame exon in the 3' coding region, compared to variant 1. These differences cause translation initiation at an alternate start codon and result in isoform (3), with a distinct N-terminus and a missing internal segment, compared to isoform 1.

Source sequence(s)

AC118062

Consensus CDS

CCDS82943.1

UniProtKB/TrEMBL

A0A0D9SFP2, B3KTT6

Related

ENSP00000486771.1, ENST00000626637.2

Conserved Domains (1) summary

COG1250
Location:48 → 317

FadB; 3-hydroxyacyl-CoA dehydrogenase [Lipid transport and metabolism]
NM_005327.7 → NP_005318.6 hydroxyacyl-coenzyme A dehydrogenase, mitochondrial isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame exon in the coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.

Source sequence(s)

AC114733, AC118062

Consensus CDS

CCDS3678.1

UniProtKB/Swiss-Prot

J3KQ17, O00324, O00397, O00753, Q16836, Q4W5B4

UniProtKB/TrEMBL

A0A140VK76, B2RB06

Related

ENSP00000312288.4, ENST00000309522.8

Conserved Domains (1) summary

COG1250
Location:27 → 313

FadB; 3-hydroxyacyl-CoA dehydrogenase [Lipid transport and metabolism]