ALDH5A1

Protein identityUniProt · HPA

UniProt accession

P51649

Gene

ALDH5A1

Ensembl

ENSG00000112294

Chromosome

6

Canonical length

535 aa

Protein class

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

Subcellular location

Mitochondria

Quaternary structure

Homotetramer

OverviewNCBI Gene

This protein belongs to the aldehyde dehydrogenase family of proteins. This gene encodes a mitochondrial NAD(+)-dependent succinic semialdehyde dehydrogenase. A deficiency of this enzyme, known as 4-hydroxybutyricaciduria, is a rare inborn error in the metabolism of the neurotransmitter 4-aminobutyric acid (GABA). In response to the defect, physiologic fluids from patients accumulate GHB, a compound with numerous neuromodulatory properties. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

535 residues, UniProt reviewed canonical sequence.

>P51649|ALDH5A1
     1  MATCIWLRSC GARRLGSTFP GCRLRPRAGG LVPASGPAPG PAQLRCYAGR LAGLSAALLR
    61  TDSFVGGRWL PAAATFPVQD PASGAALGMV ADCGVREARA AVRAAYEAFC RWREVSAKER
   121  SSLLRKWYNL MIQNKDDLAR IITAESGKPL KEAHGEILYS AFFLEWFSEE ARRVYGDIIH
   181  TPAKDRRALV LKQPIGVAAV ITPWNFPSAM ITRKVGAALA AGCTVVVKPA EDTPFSALAL
   241  AELASQAGIP SGVYNVIPCS RKNAKEVGEA ICTDPLVSKI SFTGSTTTGK ILLHHAANSV
   301  KRVSMELGGL APFIVFDSAN VDQAVAGAMA SKFRNTGQTC VCSNQFLVQR GIHDAFVKAF
   361  AEAMKKNLRV GNGFEEGTTQ GPLINEKAVE KVEKQVNDAV SKGATVVTGG KRHQLGKNFF
   421  EPTLLCNVTQ DMLCTHEETF GPLAPVIKFD TEEEAIAIAN AADVGLAGYF YSQDPAQIWR
   481  VAEQLEVGMV GVNEGLISSV ECPFGGVKQS GLGREGSKYG IDEYLELKYV CYGGL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ALDH5A1 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)

0.25

Highest tissue expression

92 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ALDH5A1.

Disease | AllUniProt

Conditions ALDH5A1 is implicated in, by any mechanism.

• Succinic semialdehyde dehydrogenase deficiency (SSADHD) MIM:271980

Disease | GeneticClinVar

150 pathogenic / likely-pathogenic of 904 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Succinate-semialdehyde dehydrogenase deficiency
• Inborn genetic diseases
• ALDH5A1-related disorder
• Likely inborn error of metabolism
• Arthrogryposis multiplex congenita

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)

0.94

gnomAD pLI

0

gnomAD missense Z

0.73

DepMap mean gene effect

-0.05

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• central nervous system development
• gamma-aminobutyric acid catabolic process
• glutamate metabolic process
• post-embryonic development
• succinate metabolic process
• synaptic transmission, GABAergic

Molecular functions

• identical protein binding
• succinate-semialdehyde dehydrogenase (NAD+) activity

Cellular components

• mitochondrial matrix
• mitochondrion
• synapse

Protein domainsUniProt · Pfam · InterPro

• Aldehyde dehydrogenase domain
• Aldehyde dehydrogenase, cysteine active site
• Aldehyde/histidinol dehydrogenase
• Aldehyde dehydrogenase, N-terminal
• Aldehyde dehydrogenase, C-terminal
• Aldehyde dehydrogenase, glutamic acid active site
• Aldehyde dehydrogenase family
• Succinate semialdehyde dehydrogenase
• Aldehyde Dehydrogenase Superfamily

KeywordsUniProt

• Acetylation
• Disulfide bond
• Mitochondrion
• NAD
• Oxidoreductase
• Phosphoprotein
• Transit peptide