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

Gene ID: 5832, updated on 8-Jul-2018
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; Vega:OTTHUMG00000018815
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
See ALDH18A1 in Genome Data Viewer
Location:
10q24.1
Exon count:
19
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 10 NC_000010.11 (95605929..95656901, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (97365686..97416759, complement)

Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene sorbin and SH3 domain containing 1 Neighboring gene VISTA enhancer hs2353 Neighboring gene ribosomal protein S3a pseudogene 36 Neighboring gene tectonic family member 3 Neighboring gene ectonucleoside triphosphate diphosphohydrolase 1 Neighboring gene ENTPD1 antisense RNA 1

  • 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 Jun 15 11:32:44 2016

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Associated conditions

Description Tests
Cutis laxa, autosomal dominant 3
MedGen: C4225268 OMIM: 616603 GeneReviews: Not available
Compare labs
Cutis laxa-corneal clouding-oligophrenia syndrome
MedGen: C0268354 OMIM: 219150 GeneReviews: Not available
Compare labs
Spastic paraplegia 9
MedGen: C1832669 OMIM: 601162 GeneReviews: Not available
Compare labs
Spastic paraplegia 9b, autosomal recessive
MedGen: C4225272 OMIM: 616586 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
An atlas of genetic influences on human blood metabolites.
NHGRI GWA Catalog

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

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • MGC117316

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
RNA binding HDA PubMed 
delta1-pyrroline-5-carboxylate synthetase activity EXP
Inferred from Experiment
more info
PubMed 
glutamate 5-kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
glutamate 5-kinase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
glutamate-5-semialdehyde dehydrogenase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
glutamate-5-semialdehyde dehydrogenase activity IDA
Inferred from Direct Assay
more info
PubMed 
glutamate-5-semialdehyde dehydrogenase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
identical protein binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
L-proline biosynthetic process IEA
Inferred from Electronic Annotation
more info
 
cellular amino acid biosynthetic process TAS
Traceable Author Statement
more info
 
citrulline biosynthetic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
glutamate metabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
ornithine biosynthetic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
oxidation-reduction process IEA
Inferred from Electronic Annotation
more info
 
phosphorylation IEA
Inferred from Electronic Annotation
more info
 
proline biosynthetic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
cytosol IDA
Inferred from Direct Assay
more info
 
mitochondrial inner membrane TAS
Traceable Author Statement
more info
 
mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
mitochondrion IDA
Inferred from Direct Assay
more info
PubMed 
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
XP_024303862.1
XP_024303863.1
XP_024303864.1
XP_024303865.1

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
    5001..55882
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001017423.1NP_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, OTTHUMP00000020160, ENST00000371221.3, OTTHUMT00000049553
    Conserved Domains (1) summary
    TIGR01092
    Location:64792
    P5CS; delta l-pyrroline-5-carboxylate synthetase
  2. NM_001323412.1NP_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 (3) summary
    TIGR01092
    Location:1683
    P5CS; delta l-pyrroline-5-carboxylate synthetase
    cd07079
    Location:253655
    ALDH_F18-19_ProA-GPR; Gamma-glutamyl phosphate reductase (GPR), aldehyde dehydrogenase families 18 and 19
    cd04256
    Location:1243
    AAK_P5CS_ProBA; AAK_P5CS_ProBA: Glutamate-5-kinase (G5K) domain of the bifunctional delta 1-pyrroline-5-carboxylate synthetase (P5CS), composed of an N-terminal G5K (ProB) and a C-terminal glutamyl 5- phosphate reductase (G5PR, ProA), the first and second enzyme ...
  3. NM_001323413.1NP_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
    P54886
    Conserved Domains (1) summary
    TIGR01092
    Location:64794
    P5CS; delta l-pyrroline-5-carboxylate synthetase
  4. NM_001323414.1NP_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
    P54886
    Conserved Domains (1) summary
    TIGR01092
    Location:64794
    P5CS; delta l-pyrroline-5-carboxylate synthetase
  5. NM_001323415.1NP_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_001323416.1NP_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 (3) summary
    TIGR01092
    Location:1683
    P5CS; delta l-pyrroline-5-carboxylate synthetase
    cd07079
    Location:253655
    ALDH_F18-19_ProA-GPR; Gamma-glutamyl phosphate reductase (GPR), aldehyde dehydrogenase families 18 and 19
    cd04256
    Location:1243
    AAK_P5CS_ProBA; AAK_P5CS_ProBA: Glutamate-5-kinase (G5K) domain of the bifunctional delta 1-pyrroline-5-carboxylate synthetase (P5CS), composed of an N-terminal G5K (ProB) and a C-terminal glutamyl 5- phosphate reductase (G5PR, ProA), the first and second enzyme ...
  7. NM_001323417.1NP_001310346.1  delta-1-pyrroline-5-carboxylate synthase isoform 4

    Status: REVIEWED

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

    Status: REVIEWED

    Source sequence(s)
    AL356632
  9. NM_001323419.1NP_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_002860.3NP_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
    P54886
    Related
    ENSP00000360268.2, OTTHUMP00000020159, ENST00000371224.6, OTTHUMT00000049552
    Conserved Domains (1) summary
    TIGR01092
    Location:64794
    P5CS; delta l-pyrroline-5-carboxylate synthetase

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000010.11 Reference GRCh38.p12 Primary Assembly

    Range
    95605929..95656901 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_024448096.1XP_024303864.1  delta-1-pyrroline-5-carboxylate synthase isoform X2

    Conserved Domains (1) summary
    cl25378
    Location:64826
    ProB; Glutamate 5-kinase [Amino acid transport and metabolism]
  2. XM_024448094.1XP_024303862.1  delta-1-pyrroline-5-carboxylate synthase isoform X1

    Conserved Domains (1) summary
    cl25378
    Location:64828
    ProB; Glutamate 5-kinase [Amino acid transport and metabolism]
  3. XM_024448097.1XP_024303865.1  delta-1-pyrroline-5-carboxylate synthase isoform X3

    Conserved Domains (1) summary
    cl25378
    Location:1717
    ProB; Glutamate 5-kinase [Amino acid transport and metabolism]
  4. XM_024448095.1XP_024303863.1  delta-1-pyrroline-5-carboxylate synthase isoform X1

    Conserved Domains (1) summary
    cl25378
    Location:64828
    ProB; Glutamate 5-kinase [Amino acid transport and metabolism]
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