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

Gene ID: 3033, updated on 3-Nov-2024

Summary

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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
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Genomic context

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See HADH in Genome Data Viewer
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_000004.12Genomic Context describing neighboring genes Neighboring gene CYP2U1 and SGMS2 antisense RNA 1 Neighboring gene uncharacterized LOC107986298 Neighboring gene uncharacterized LOC124900751 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:108852075-108852582 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21791 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21792 Neighboring gene uncharacterized LOC107986299 Neighboring gene cytochrome P450 family 2 subfamily U member 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15614 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:108977631-108978132 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21793 Neighboring gene lymphoid enhancer binding factor 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21794 Neighboring gene NANOG hESC enhancer GRCh37_chr4:109038529-109039038 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15615 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21795 Neighboring gene OCT4-NANOG-H3K4me1 hESC enhancer GRCh37_chr4:109056573-109057124 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:109088159-109088660 Neighboring gene uncharacterized LOC124900752 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 21796 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15617 Neighboring gene NANOG hESC enhancer GRCh37_chr4:109091848-109092478 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15618 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 15619 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:109107455-109107956 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr4:109107957-109108456 Neighboring gene LEF1 antisense RNA 1 Neighboring gene VISTA enhancer hs1545 Neighboring gene uncharacterized LOC124900753

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues 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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Related articles in PubMed

  1. A preliminary analysis of the segregation of human hydroxyacyl coenzyme A dehydrogenase in human-mouse somatic cell hybrids. Craig I, et al. Cytogenet Cell Genet, 1976. PMID 975867
  2. A Deep Intronic HADH Splicing Mutation (c.636+471G>T) in a Congenital Hyperinsulinemic Hypoglycemia Case: Long Term Clinical Course. Çamtosun E, et al. J Clin Res Pediatr Endocrinol, 2015 Jun. PMID 26316438, Free PMC Article
  3. Leucine-sensitive hyperinsulinaemic hypoglycaemia in patients with loss of function mutations in 3-Hydroxyacyl-CoA Dehydrogenase. Heslegrave AJ, et al. Orphanet J Rare Dis, 2012 May 14. PMID 22583614, Free PMC Article
  4. Functional evaluation of 16 SCHAD missense variants: Only amino acid substitutions causing congenital hyperinsulinism of infancy lead to loss-of-function phenotypes in vitro. Velasco K, et al. J Inherit Metab Dis, 2021 Jan. PMID 32876354
  5. Short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: the clinical relevance of an early diagnosis and report of four new cases. Martins E, et al. J Inherit Metab Dis, 2011 Jun. PMID 21347589

See all (91) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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).
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. Paretic muscle in hemiparetic stroke survivors had lower HAD concentration.
    Title: Skeletal muscle fiber characteristics and oxidative capacity in hemiparetic stroke survivors.
  7. 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.
  8. 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.
  9. 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.
  10. 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

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

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

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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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

Homology

Clone Names

  • MGC8392

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 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
NP_001317956.2
NP_005318.6

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

  1. NG_008156.3 RefSeqGene

    Range
    5002..50284
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. 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]

  2. 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]

  3. 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]

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000004.12 Reference GRCh38.p14 Primary Assembly

    Range
    107989889..108035171
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

RNA

  1. XR_007096395.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060928.1 Alternate T2T-CHM13v2.0

    Range
    111292223..111337508
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

RNA

  1. XR_008486973.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q16836.3 GenPept UniProtKB/Swiss-Prot:Q16836

Gene LinkOut

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