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

    Gene ID: 7915, updated on 10-Dec-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
    • 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

    Associated conditions

    Description Tests
    Succinate-semialdehyde dehydrogenase deficiency
    MedGen: C0268631 OMIM: 271980 GeneReviews: Succinic Semialdehyde Dehydrogenase Deficiency
    		not available

    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

      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

      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

    Gene LinkOut

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