ALDH18A1

Protein identityUniProt · HPA

UniProt accession

P54886

Gene

ALDH18A1

Ensembl

ENSG00000059573

Chromosome

10

Canonical length

795 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Mitochondria

Quaternary structure

Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

795 residues, UniProt reviewed canonical sequence.

>P54886|ALDH18A1
     1  MLSQVYRCGF QPFNQHLLPW VKCTTVFRSH CIQPSVIRHV RSWSNIPFIT VPLSRTHGKS
    61  FAHRSELKHA KRIVVKLGSA VVTRGDECGL ALGRLASIVE QVSVLQNQGR EMMLVTSGAV
   121  AFGKQRLRHE ILLSQSVRQA LHSGQNQLKE MAIPVLEARA CAAAGQSGLM ALYEAMFTQY
   181  SICAAQILVT NLDFHDEQKR RNLNGTLHEL LRMNIVPIVN TNDAVVPPAE PNSDLQGVNV
   241  ISVKDNDSLA ARLAVEMKTD LLIVLSDVEG LFDSPPGSDD AKLIDIFYPG DQQSVTFGTK
   301  SRVGMGGMEA KVKAALWALQ GGTSVVIANG THPKVSGHVI TDIVEGKKVG TFFSEVKPAG
   361  PTVEQQGEMA RSGGRMLATL EPEQRAEIIH HLADLLTDQR DEILLANKKD LEEAEGRLAA
   421  PLLKRLSLST SKLNSLAIGL RQIAASSQDS VGRVLRRTRI AKNLELEQVT VPIGVLLVIF
   481  ESRPDCLPQV AALAIASGNG LLLKGGKEAA HSNRILHLLT QEALSIHGVK EAVQLVNTRE
   541  EVEDLCRLDK MIDLIIPRGS SQLVRDIQKA AKGIPVMGHS EGICHMYVDS EASVDKVTRL
   601  VRDSKCEYPA ACNALETLLI HRDLLRTPLF DQIIDMLRVE QVKIHAGPKF ASYLTFSPSE
   661  VKSLRTEYGD LELCIEVVDN VQDAIDHIHK YGSSHTDVIV TEDENTAEFF LQHVDSACVF
   721  WNASTRFSDG YRFGLGAEVG ISTSRIHARG PVGLEGLLTT KWLLRGKDHV VSDFSEHGSL
   781  KYLHENLPIP QRNTN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ALDH18A1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.29

Highest tissue expression

113 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ALDH18A1.

Disease | AllUniProt

Conditions ALDH18A1 is implicated in, by any mechanism.

• Cutis laxa, autosomal recessive, 3A (ARCL3A) MIM:219150
• Cutis laxa, autosomal dominant, 3 (ADCL3) MIM:616603
• Spastic paraplegia 9A, autosomal dominant (SPG9A) MIM:601162
• Spastic paraplegia 9B, autosomal recessive (SPG9B) MIM:616586

Disease | GeneticClinVar

61 pathogenic / likely-pathogenic of 891 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Cutis laxa, autosomal dominant 3
• Autosomal dominant spastic paraplegia type 9
• de Barsy syndrome
• ALDH18A1-related de Barsy syndrome
• Autosomal recessive complex spastic paraplegia type 9B

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.52

gnomAD pLI

0

gnomAD missense Z

1.97

DepMap mean gene effect

-0.08

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• citrulline biosynthetic process
• glutamate metabolic process
• L-proline biosynthetic process
• response to temperature stimulus
• ornithine biosynthetic process

Molecular functions

• ATP binding
• identical protein binding
• RNA binding
• glutamate 5-kinase activity
• glutamate-5-semialdehyde dehydrogenase activity

Cellular components

• mitochondrial inner membrane
• mitochondrial matrix
• mitochondrion

Protein domainsUniProt · Pfam · InterPro

• Aspartate/glutamate/uridylate kinase
• Aldehyde dehydrogenase domain
• Aldehyde/histidinol dehydrogenase
• Aldehyde dehydrogenase, N-terminal
• Aldehyde dehydrogenase, C-terminal
• Acetylglutamate kinase-like superfamily
• Aldehyde dehydrogenase family
• Amino acid kinase family
• GPR domain
• Glutamate/acetylglutamate kinase
• Glutamate 5-kinase/delta-1-pyrroline-5-carboxylate synthase
• Delta l-pyrroline-5-carboxylate synthetase
• Glutamate 5-kinase, conserved site
• Gamma-glutamyl phosphate reductase GPR, conserved site
• Bifunctional delta 1-pyrroline-5-carboxylate synthetase, glutamate-5-kinase domain

KeywordsUniProt

• Amino-acid biosynthesis
• ATP-binding
• Hereditary spastic paraplegia
• Intellectual disability
• Kinase
• Mitochondrion
• Multifunctional enzyme
• NADP
• Neurodegeneration
• Nucleotide-binding
• Oxidoreductase
• Proline biosynthesis
• Transferase