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

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: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 10q24.1

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (95605941..95656711, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (96485079..96535811, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (97365698..97416468, complement)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

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

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Two novel homozygous variants of ATP6V0A2 and ALDH18A1 lead to autosomal recessive cutis laxa type 2 and 3 in two Pakistani families.
Title: Two novel homozygous variants of ATP6V0A2 and ALDH18A1 lead to autosomal recessive cutis laxa type 2 and 3 in two Pakistani families.
Functional assessment of homozygous ALDH18A1 variants reveals alterations in amino acid and antioxidant metabolism.
Title: Functional assessment of homozygous ALDH18A1 variants reveals alterations in amino acid and antioxidant metabolism.
Delta(1) -Pyrroline-5-carboxylate synthetase deficiency: An emergent multifaceted urea cycle-related disorder.
Title: Δ(1) -Pyrroline-5-carboxylate synthetase deficiency: An emergent multifaceted urea cycle-related disorder.
Inhibition of the ALDH18A1-MYCN positive feedback loop attenuates MYCN-amplified neuroblastoma growth.
Title: Inhibition of the ALDH18A1-MYCN positive feedback loop attenuates MYCN-amplified neuroblastoma growth.
SPG9A with the new occurrence of an ALDH18A1 mutation in a CMT1A family with PMP22 duplication: case report.
Title: SPG9A with the new occurrence of an ALDH18A1 mutation in a CMT1A family with PMP22 duplication: case report.
Novel mutations in the ALDH18A1 gene in complicated hereditary spastic paraplegia with cerebellar ataxia and cognitive impairment.
Title: Novel mutations in the ALDH18A1 gene in complicated hereditary spastic paraplegia with cerebellar ataxia and cognitive impairment.
This is the first report of an individual with ALDH18A1-ADCL due to a substitution at a residue other than p.Arg138. Knowledge of the complete spectrum of dominant-acting mutations that cause this rare syndrome will have implications for molecular diagnosis and genetic counselling of these families.
Title: Autosomal dominant cutis laxa with progeroid features due to a novel, de novo mutation in ALDH18A1.
ALDH18A1 gene during vertebrate and invertebrate evolution and a proposal for generating the bifunctional vertebrate and invertebrate ALDH18A1 gene from a bacterial operon (proBA) encoding glutamyl kinase and glutamyl phosphate reductase.
Title: Comparative and evolutionary studies of ALDH18A1 genes and proteins.
Recurrent De Novo Mutations Affecting Residue Arg138 of Pyrroline-5-Carboxylate Synthase Cause a Progeroid Form of Autosomal-Dominant Cutis Laxa.
Title: Recurrent De Novo Mutations Affecting Residue Arg138 of Pyrroline-5-Carboxylate Synthase Cause a Progeroid Form of Autosomal-Dominant Cutis Laxa.
autosomal recessive transmission of ALDH18A1 mutations, and predominant complex hereditary spastic paraplegia with marked cognitive impairment
Title: Alteration of ornithine metabolism leads to dominant and recessive hereditary spastic paraplegia.

Submit: New GeneRIF Correction See all GeneRIFs (18)

Phenotypes

Go to the top of the page Help

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
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 EBI GWAS CatalogPubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

Go to the top of the page Help

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

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

D8S2279 (e-PCR)
- UniSTS:473907

fc35a07.x1 (e-PCR)
- UniSTS:193620

D1S1423 (e-PCR)
- UniSTS:149619

D10S2402 (e-PCR)
- UniSTS:21907

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables RNA binding	HDA more info	PubMed
enables glutamate 5-kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables glutamate 5-kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables glutamate-5-semialdehyde dehydrogenase activity	IBA Inferred from Biological aspect of Ancestor more info
enables glutamate-5-semialdehyde dehydrogenase activity	IDA Inferred from Direct Assay more info	PubMed
enables glutamate-5-semialdehyde dehydrogenase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables identical protein binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

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 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 mitochondrial matrix	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	HTP more info	PubMed
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

Go to the top of the page Help

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

EC 1.2.1.41

EC 2.7.2.11

NP_001310341.1

EC 1.2.1.41

EC 2.7.2.11

NP_001310342.1

EC 1.2.1.41

EC 2.7.2.11

NP_001310343.1

EC 1.2.1.41

EC 2.7.2.11

NP_001310344.1

EC 1.2.1.41

EC 2.7.2.11

NP_001310345.1

EC 1.2.1.41

EC 2.7.2.11

NP_001310346.1

EC 1.2.1.41

EC 2.7.2.11

NP_001310347.1

EC 1.2.1.41

EC 2.7.2.11

NP_001310348.1

EC 1.2.1.41

EC 2.7.2.11

NP_002851.2

EC 1.2.1.41

EC 2.7.2.11

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

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

NG_012258.1 RefSeqGene

Range

5100..55870

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001017423.2 → NP_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:64 → 792

P5CS; delta l-pyrroline-5-carboxylate synthetase
NM_001323412.2 → NP_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:1 → 683

P5CS; delta l-pyrroline-5-carboxylate synthetase
NM_001323413.2 → NP_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:64 → 794

P5CS; delta l-pyrroline-5-carboxylate synthetase
NM_001323414.2 → NP_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:64 → 794

P5CS; delta l-pyrroline-5-carboxylate synthetase
NM_001323415.2 → NP_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:64 → 792

P5CS; delta l-pyrroline-5-carboxylate synthetase
NM_001323416.2 → NP_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:1 → 683

P5CS; delta l-pyrroline-5-carboxylate synthetase
NM_001323417.2 → NP_001310346.1 delta-1-pyrroline-5-carboxylate synthase isoform 4

Status: REVIEWED

Source sequence(s)

AL356632
NM_001323418.2 → NP_001310347.1 delta-1-pyrroline-5-carboxylate synthase isoform 5

Status: REVIEWED

Source sequence(s)

AL356632

Conserved Domains (1) summary

TIGR01092
Location:1 → 681

P5CS; delta l-pyrroline-5-carboxylate synthetase
NM_001323419.2 → NP_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:152 → 554

ALDH_F18-19_ProA-GPR; Gamma-glutamyl phosphate reductase (GPR), aldehyde dehydrogenase families 18 and 19

cl00452
Location:1 → 142

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 ...
NM_002860.4 → NP_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:64 → 794

P5CS; delta l-pyrroline-5-carboxylate synthetase