P5CS, D1-pyrroline-5-carboxylate synthetase ALDH18A1 (10q24.19

https://www.ncbi.nlm.nih.gov/gene

Official Symbol

ALDH18A1

Official Full Name

aldehyde dehydrogenase 18 family member A1

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

 

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

Related articles in PubMed

1. Novel mutations in the ALDH18A1 gene in complicated hereditary spastic paraplegia with cerebellar ataxia and cognitive impairment. Koh K, et al. J Hum Genet, 2018 Sep. PMID 29915212
2. Autosomal dominant cutis laxa with progeroid features due to a novel, de novo mutation in ALDH18A1. Bhola PT, et al. J Hum Genet, 2017 Jun. PMID 28228640
3. Comparative and evolutionary studies of ALDH18A1 genes and proteins. Holmes RS. Chem Biol Interact, 2017 Oct 1. PMID 27989597
4. Further expansion of the phenotypic spectrum associated with mutations in ALDH18A1, encoding Δ¹-pyrroline-5-carboxylate synthase (P5CS). Skidmore DL, et al. Am J Med Genet A, 2011 Aug. PMID 21739576
5. Human Delta1-pyrroline-5-carboxylate synthase: function and regulation. Hu CA, et al. Amino Acids, 2008 Nov. PMID 18401542, Free PMC Article

See all (67) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

1. Novel mutations in the ALDH18A1 gene in complicated hereditary spastic paraplegia with cerebellar ataxia and cognitive impairment.
2. 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.
3. 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.
4. Recurrent De Novo Mutations Affecting Residue Arg138 of Pyrroline-5-Carboxylate Synthase Cause a Progeroid Form of Autosomal-Dominant Cutis Laxa.
5. autosomal recessive transmission of ALDH18A1 mutations, and predominant complex hereditary spastic paraplegia with marked cognitive impairment
6. A frameshift deletion of one nucleotide and a microdeletion affecting the ALDH18A1 gene, respectively, in a homozygous state in both patients, was identified.
7. expansion of the phenotypic spectrum associated with mutations in ALDH18A1
8. ALDH18A1 genetic variants are associated with Down syndrome in subjects with dementia of Alzheimer's disease.
9. Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
10. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)

Submit: New GeneRIF Correction See all GeneRIFs (13)