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    ALDH18A1 aldehyde dehydrogenase 18 family member A1 [ Homo sapiens (human) ]

    Gene ID: 5832, updated on 7-Jan-2024

    Summary

    Official Symbol
    ALDH18A1provided by HGNC
    Official Full Name
    aldehyde dehydrogenase 18 family member A1provided by HGNC
    Primary source
    HGNC:HGNC:9722
    See related
    Ensembl:ENSG00000059573 MIM:138250; AllianceGenome:HGNC:9722
    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
    GSAS; P5CS; PYCS; SPG9; ADCL3; SPG9A; SPG9B; ARCL3A
    Summary
    This gene is a member of the aldehyde dehydrogenase family and encodes a bifunctional ATP- and NADPH-dependent mitochondrial enzyme with both gamma-glutamyl kinase and gamma-glutamyl phosphate reductase activities. The encoded protein catalyzes the reduction of glutamate to delta1-pyrroline-5-carboxylate, a critical step in the de novo biosynthesis of proline, ornithine and arginine. Mutations in this gene lead to hyperammonemia, hypoornithinemia, hypocitrullinemia, hypoargininemia and hypoprolinemia and may be associated with neurodegeneration, cataracts and connective tissue diseases. Alternatively spliced transcript variants, encoding different isoforms, have been described for this gene. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in duodenum (RPKM 41.4), small intestine (RPKM 34.7) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See ALDH18A1 in Genome Data Viewer
    Location:
    10q24.1
    Exon count:
    18
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 10 NC_000010.11 (95605941..95656711, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 10 NC_060934.1 (96485079..96535811, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (97365698..97416468, complement)

    Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene Sharpr-MPRA regulatory region 12220 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:97106670-97107322 Neighboring gene sorbin and SH3 domain containing 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2645 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2646 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3800 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:97190228-97190728 Neighboring gene Sharpr-MPRA regulatory region 10569 Neighboring gene VISTA enhancer hs2353 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr10:97291131-97291878 Neighboring gene NANOG hESC enhancer GRCh37_chr10:97299485-97299986 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:97311480-97312414 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr10:97320711-97321473 Neighboring gene Sharpr-MPRA regulatory region 13709 Neighboring gene Sharpr-MPRA regulatory region 3716 Neighboring gene RPS3A pseudogene 36 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2649 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3801 Neighboring gene H3K27ac hESC enhancer GRCh37_chr10:97454143-97454644 Neighboring gene MPRA-validated peak1056 silencer Neighboring gene tectonic family member 3 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3802 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3803 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3804 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2650 Neighboring gene ectonucleoside triphosphate diphosphohydrolase 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3805 Neighboring gene ENTPD1 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 2651 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3806 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3807 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3808 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3809 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3810 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 3811 Neighboring gene Sharpr-MPRA regulatory region 13404

    Genomic regions, transcripts, and products

    Expression

    • 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

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    ALDH18A1-related de Barsy syndrome
    MedGen: C5234852 OMIM: 219150 GeneReviews: Not available
    Compare labs
    Autosomal recessive complex spastic paraplegia type 9B
    MedGen: C5568980 OMIM: 616586 GeneReviews: Not available
    Compare labs
    Cutis laxa, autosomal dominant 3
    MedGen: C4225268 OMIM: 616603 GeneReviews: Not available
    Compare labs
    Hereditary spastic paraplegia 9A
    MedGen: C5568978 OMIM: 601162 GeneReviews: Not available
    Compare labs

    EBI GWAS Catalog

    Description
    An atlas of genetic influences on human blood metabolites.
    EBI GWAS Catalog

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Tandem affinity purification and mass spectrometry analysis identify aldehyde dehydrogenase 18 family member A1 (ALDH18A1), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Gag-Pol gag-pol Tandem affinity purification and mass spectrometry analysis identify aldehyde dehydrogenase 18 family member A1 (ALDH18A1), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Nef nef Tandem affinity purification and mass spectrometry analysis identify aldehyde dehydrogenase 18 family member A1 (ALDH18A1), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
    Pr55(Gag) gag Tandem affinity purification and mass spectrometry analysis identify aldehyde dehydrogenase 18 family member A1 (ALDH18A1), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • MGC117316

    Gene Ontology Provided by GOA

    Process Evidence Code Pubs
    involved_in L-proline biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in citrulline biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in glutamate metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in ornithine biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in phosphorylation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in proline biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in response to temperature stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    located_in mitochondrial inner membrane TAS
    Traceable Author Statement
    more info
     
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    delta-1-pyrroline-5-carboxylate synthase
    Names
    Spastic paraplegia-9 (spastic paraparesis with amyotrophy, cataracts and gastroesophageal reflux)
    aldehyde dehydrogenase family 18 member A1
    delta-1-pyrroline-5-carboxylate synthetase
    delta1-pyrroline-5-carboxlate synthetase
    pyrroline-5-carboxylate synthetase (glutamate gamma-semialdehyde synthetase)
    spastic paraplegia 9 (autosomal dominant)
    NP_001017423.1
    NP_001310341.1
    NP_001310342.1
    NP_001310343.1
    NP_001310344.1
    NP_001310345.1
    NP_001310346.1
    NP_001310347.1
    NP_001310348.1
    NP_002851.2

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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_012258.1 RefSeqGene

      Range
      5100..55870
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001017423.2NP_001017423.1  delta-1-pyrroline-5-carboxylate synthase isoform 2

      See identical proteins and their annotated locations for NP_001017423.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2), also known as P5Cs, uses an alternate in-frame splice site, compared to variant 1, resulting in a shorter isoform (2). Variants 2 and 6 both encode the same isoform (2).
      Source sequence(s)
      AW467503, BU170321, CD642171, U68758, X94453
      Consensus CDS
      CCDS31257.1
      UniProtKB/Swiss-Prot
      P54886
      Related
      ENSP00000360265.3, ENST00000371221.3
      Conserved Domains (1) summary
      TIGR01092
      Location:64792
      P5CS; delta l-pyrroline-5-carboxylate synthetase
    2. NM_001323412.2NP_001310341.1  delta-1-pyrroline-5-carboxylate synthase isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) and variant 7 both encode isoform 3.
      Source sequence(s)
      AL356632
      UniProtKB/Swiss-Prot
      P54886
      Conserved Domains (1) summary
      TIGR01092
      Location:1683
      P5CS; delta l-pyrroline-5-carboxylate synthetase
    3. NM_001323413.2NP_001310342.1  delta-1-pyrroline-5-carboxylate synthase isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) and variants 1 and 5 all encode isoform 1.
      Source sequence(s)
      AL356632
      Consensus CDS
      CCDS7443.1
      UniProtKB/Swiss-Prot
      B2R5Q4, B7Z350, B7Z5X8, B7ZLP1, D3DR44, O95952, P54886, Q3KQU2, Q5T566, Q5T567, Q9UM72
      Conserved Domains (1) summary
      TIGR01092
      Location:64794
      P5CS; delta l-pyrroline-5-carboxylate synthetase
    4. NM_001323414.2NP_001310343.1  delta-1-pyrroline-5-carboxylate synthase isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) and variants 1 and 4 all encode isoform 1.
      Source sequence(s)
      AL356632
      Consensus CDS
      CCDS7443.1
      UniProtKB/Swiss-Prot
      B2R5Q4, B7Z350, B7Z5X8, B7ZLP1, D3DR44, O95952, P54886, Q3KQU2, Q5T566, Q5T567, Q9UM72
      Conserved Domains (1) summary
      TIGR01092
      Location:64794
      P5CS; delta l-pyrroline-5-carboxylate synthetase
    5. NM_001323415.2NP_001310344.1  delta-1-pyrroline-5-carboxylate synthase isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) and variant 2 both encode isoform 2.
      Source sequence(s)
      AL356632
      Consensus CDS
      CCDS31257.1
      UniProtKB/Swiss-Prot
      P54886
      Conserved Domains (1) summary
      TIGR01092
      Location:64792
      P5CS; delta l-pyrroline-5-carboxylate synthetase
    6. NM_001323416.2NP_001310345.1  delta-1-pyrroline-5-carboxylate synthase isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) and variant 3 both encode isoform 3.
      Source sequence(s)
      AL356632
      UniProtKB/Swiss-Prot
      P54886
      Conserved Domains (1) summary
      TIGR01092
      Location:1683
      P5CS; delta l-pyrroline-5-carboxylate synthetase
    7. NM_001323417.2NP_001310346.1  delta-1-pyrroline-5-carboxylate synthase isoform 4

      Status: REVIEWED

      Source sequence(s)
      AL356632
    8. NM_001323418.2NP_001310347.1  delta-1-pyrroline-5-carboxylate synthase isoform 5

      Status: REVIEWED

      Source sequence(s)
      AL356632
      Conserved Domains (1) summary
      TIGR01092
      Location:1681
      P5CS; delta l-pyrroline-5-carboxylate synthetase
    9. NM_001323419.2NP_001310348.1  delta-1-pyrroline-5-carboxylate synthase isoform 6

      Status: REVIEWED

      Source sequence(s)
      AK299557, AL356632
      UniProtKB/Swiss-Prot
      P54886
      Conserved Domains (2) summary
      cd07079
      Location:152554
      ALDH_F18-19_ProA-GPR; Gamma-glutamyl phosphate reductase (GPR), aldehyde dehydrogenase families 18 and 19
      cl00452
      Location:1142
      AAK; Amino Acid Kinases (AAK) superfamily, catalytic domain; present in such enzymes like N-acetylglutamate kinase (NAGK), carbamate kinase (CK), aspartokinase (AK), glutamate-5-kinase (G5K) and UMP kinase (UMPK). The AAK superfamily includes kinases that ...
    10. NM_002860.4NP_002851.2  delta-1-pyrroline-5-carboxylate synthase isoform 1

      See identical proteins and their annotated locations for NP_002851.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1), also known as P5CSL, encodes the longest isoform (1). Variants 1, 4, and 5 all encode the same isoform (1).
      Source sequence(s)
      AW467503, BU170321, CD642171, U76542, X94453
      Consensus CDS
      CCDS7443.1
      UniProtKB/Swiss-Prot
      B2R5Q4, B7Z350, B7Z5X8, B7ZLP1, D3DR44, O95952, P54886, Q3KQU2, Q5T566, Q5T567, Q9UM72
      Related
      ENSP00000360268.2, ENST00000371224.7
      Conserved Domains (1) summary
      TIGR01092
      Location:64794
      P5CS; delta l-pyrroline-5-carboxylate synthetase

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000010.11 Reference GRCh38.p14 Primary Assembly

      Range
      95605941..95656711 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060934.1 Alternate T2T-CHM13v2.0

      Range
      96485079..96535811 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)