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ALDH5A1 aldehyde dehydrogenase 5 family member A1 [ Homo sapiens (human) ]

Gene ID: 7915, updated on 2-Nov-2024

Summary

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Official Symbol
ALDH5A1provided by HGNC
Official Full Name
aldehyde dehydrogenase 5 family member A1provided by HGNC
Primary source
HGNC:HGNC:408
See related
Ensembl:ENSG00000112294 MIM:610045; AllianceGenome:HGNC:408
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
SSDH; SSADH
Summary
This protein belongs to the aldehyde dehydrogenase family of proteins. This gene encodes a mitochondrial NAD(+)-dependent succinic semialdehyde dehydrogenase. A deficiency of this enzyme, known as 4-hydroxybutyricaciduria, is a rare inborn error in the metabolism of the neurotransmitter 4-aminobutyric acid (GABA). In response to the defect, physiologic fluids from patients accumulate GHB, a compound with numerous neuromodulatory properties. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in liver (RPKM 26.0), brain (RPKM 18.3) and 23 other tissues See more
Orthologs
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Genomic context

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See ALDH5A1 in Genome Data Viewer
Location:
6p22.3
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (24494969..24537207)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (24364950..24407166)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (24495197..24537435)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene doublecortin domain containing 2 Neighboring gene RNA, U6 small nuclear 391, pseudogene Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:24400121-24400856 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:24400857-24401592 Neighboring gene Sharpr-MPRA regulatory region 326 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr6:24403801-24404535 Neighboring gene magnesium transporter MRS2 Neighboring gene MPRA-validated peak5733 silencer Neighboring gene glycosylphosphatidylinositol specific phospholipase D1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16989 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16990 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24152 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24153 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16991 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16992 Neighboring gene uncharacterized LOC124901277 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr6:24538795-24539994 Neighboring gene NANOG hESC enhancer GRCh37_chr6:24547459-24547981 Neighboring gene KIAA0319 Neighboring gene MPRA-validated peak5735 silencer Neighboring gene keratin 8 pseudogene 43 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16993 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:24666173-24666845 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:24666846-24667517 Neighboring gene tyrosyl-DNA phosphodiesterase 2

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. Clinical diagnosis and mutation analysis of four Chinese families with succinic semialdehyde dehydrogenase deficiency. Wang P, et al. BMC Med Genet, 2019 May 22. PMID 31117962, Free PMC Article
  2. Novel ALDH5A1 variants and genotype: Phenotype correlation in SSADH deficiency. DiBacco ML, et al. Neurology, 2020 Nov 10. PMID 32887777, Free PMC Article
  3. ALDH5A1 acts as a tumour promoter and has a prognostic impact in papillary thyroid carcinoma. Deng XY, et al. Cell Biochem Funct, 2021 Mar. PMID 32881051
  4. Redox-switch modulation of human SSADH by dynamic catalytic loop. Kim YG, et al. EMBO J, 2009 Apr 8. PMID 19300440, Free PMC Article
  5. Decreased GABA-A binding on FMZ-PET in succinic semialdehyde dehydrogenase deficiency. Pearl PL, et al. Neurology, 2009 Aug 11. PMID 19667317, Free PMC Article

See all (100) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Clinical features and ALDH5A1 gene findings in 13 Chinese cases with succinic semialdehyde dehydrogenase deficiency.
    Title: Clinical features and ALDH5A1 gene findings in 13 Chinese cases with succinic semialdehyde dehydrogenase deficiency.
  2. Functional Characterization of a Spectrum of Genetic Variants in a Family with Succinic Semialdehyde Dehydrogenase Deficiency.
    Title: Functional Characterization of a Spectrum of Genetic Variants in a Family with Succinic Semialdehyde Dehydrogenase Deficiency.
  3. Clinical and molecular outcomes from the 5-Year natural history study of SSADH Deficiency, a model metabolic neurodevelopmental disorder.
    Title: Clinical and molecular outcomes from the 5-Year natural history study of SSADH Deficiency, a model metabolic neurodevelopmental disorder.
  4. ALDH5A1-deficient iPSC-derived excitatory and inhibitory neurons display cell type specific alterations.
    Title: ALDH5A1-deficient iPSC-derived excitatory and inhibitory neurons display cell type specific alterations.
  5. Phenotypic correlates of structural and functional protein impairments resultant from ALDH5A1 variants.
    Title: Phenotypic correlates of structural and functional protein impairments resultant from ALDH5A1 variants.
  6. Glioma Cells Expressing High Levels of ALDH5A1 Exhibit Enhanced Migration Transcriptional Signature in Patient Tumors.
    Title: Glioma Cells Expressing High Levels of ALDH5A1 Exhibit Enhanced Migration Transcriptional Signature in Patient Tumors.
  7. Assessing Prevalence and Carrier Frequency of Succinic Semialdehyde Dehydrogenase Deficiency.
    Title: Assessing Prevalence and Carrier Frequency of Succinic Semialdehyde Dehydrogenase Deficiency.
  8. ALDH5A1 acts as a tumour promoter and has a prognostic impact in papillary thyroid carcinoma.
    Title: ALDH5A1 acts as a tumour promoter and has a prognostic impact in papillary thyroid carcinoma.
  9. Novel mutations in a Chinese family with two patients with succinic semialdehyde dehydrogenase deficiency.
    Title: Novel mutations in a Chinese family with two patients with succinic semialdehyde dehydrogenase deficiency.
  10. Gene expression analysis in epileptic hippocampi reveals a promoter haplotype conferring reduced aldehyde dehydrogenase 5a1 expression and responsiveness.
    Title: Gene expression analysis in epileptic hippocampi reveals a promoter haplotype conferring reduced aldehyde dehydrogenase 5a1 expression and responsiveness.
Submit: New GeneRIF Correction See all GeneRIFs (42)

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 identifies loci influencing concentrations of liver enzymes in plasma.
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)

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

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables succinate-semialdehyde dehydrogenase (NAD+) activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables succinate-semialdehyde dehydrogenase (NAD+) activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables succinate-semialdehyde dehydrogenase (NAD+) activity ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
Process Evidence Code Pubs
involved_in central nervous system development IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in gamma-aminobutyric acid catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in gamma-aminobutyric acid catabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in gamma-aminobutyric acid catabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in gamma-aminobutyric acid catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in glutamate metabolic process ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in post-embryonic development IEA
Inferred from Electronic Annotation
more info
  
involved_in succinate metabolic process ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in synaptic transmission, GABAergic IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
  
located_in mitochondrion HDA PubMed 
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 mitochondrion ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in synapse IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
succinate-semialdehyde dehydrogenase, mitochondrial
Names
NAD(+)-dependent succinic semialdehyde dehydrogenase
mitochondrial succinate semialdehyde dehydrogenase
NP_001071.1
NP_001355883.1
NP_733936.1

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_008161.1 RefSeqGene

    Range
    5001..47239
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001080.3 → NP_001071.1  succinate-semialdehyde dehydrogenase, mitochondrial isoform 2 precursor

    See identical proteins and their annotated locations for NP_001071.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an in-frame segment of the coding region, compared to variant 1. It encodes a shorter isoform (2), that is missing an internal segment compared to isoform 1.
    Source sequence(s)
    AL031230
    Consensus CDS
    CCDS4555.1
    UniProtKB/Swiss-Prot
    B2RD26, G5E949, P51649, Q546H9, Q8N3W6
    UniProtKB/TrEMBL
    A8K435, X5D8T4, X5DQN2
    Related
    ENSP00000350191.3, ENST00000357578.8
    Conserved Domains (1) summary
    TIGR01780
    Location:78 → 528
    SSADH; succinate-semialdehyde dehydrogenase

  2. NM_001368954.1 → NP_001355883.1  succinate-semialdehyde dehydrogenase, mitochondrial isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks two consecutive, in-frame, alternate exons, compared to variant 1. It encodes isoform 3, which is shorter than isoform 1.
    Source sequence(s)
    AL031230
    UniProtKB/TrEMBL
    A8K435, X5D8T4
    Related
    ENSP00000500876.1, ENST00000672352.1
    Conserved Domains (1) summary
    cl11961
    Location:78 → 480
    ALDH-SF; NAD(P)+-dependent aldehyde dehydrogenase superfamily

  3. NM_170740.1 → NP_733936.1  succinate-semialdehyde dehydrogenase, mitochondrial isoform 1 precursor

    See identical proteins and their annotated locations for NP_733936.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript, and encodes the longer isoform (1).
    Source sequence(s)
    AL031230
    Consensus CDS
    CCDS4556.1
    UniProtKB/TrEMBL
    A8K435, X5D299, X5D8T4
    Related
    ENSP00000314649.3, ENST00000348925.2
    Conserved Domains (1) summary
    TIGR01780
    Location:78 → 541
    SSADH; succinate-semialdehyde dehydrogenase

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_000006.12 Reference GRCh38.p14 Primary Assembly

    Range
    24494969..24537207
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060930.1 Alternate T2T-CHM13v2.0

    Range
    24364950..24407166
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P51649.2 GenPept UniProtKB/Swiss-Prot:P51649

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