Seroatlas · Human Serome Atlas

ALDH4A1

Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial

Also known as: AL4A1_HUMAN, ALDH4, P5CDh

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P30038
Gene
ALDH4A1
Ensembl
ENSG00000159423
Chromosome
1
Canonical length
563 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 protein belongs to the aldehyde dehydrogenase family of proteins. This enzyme is a mitochondrial matrix NAD-dependent dehydrogenase which catalyzes the second step of the proline degradation pathway, converting pyrroline-5-carboxylate to glutamate. Deficiency of this enzyme is associated with type II hyperprolinemia, an autosomal recessive disorder characterized by accumulation of delta-1-pyrroline-5-carboxylate (P5C) and proline. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jun 2009]

Canonical amino-acid sequenceUniProt

563 residues, UniProt reviewed canonical sequence.

>P30038|ALDH4A1
     1  MLLPAPALRR ALLSRPWTGA GLRWKHTSSL KVANEPVLAF TQGSPERDAL QKALKDLKGR
    61  MEAIPCVVGD EEVWTSDVQY QVSPFNHGHK VAKFCYADKS LLNKAIEAAL AARKEWDLKP
   121  IADRAQIFLK AADMLSGPRR AEILAKTMVG QGKTVIQAEI DAAAELIDFF RFNAKYAVEL
   181  EGQQPISVPP STNSTVYRGL EGFVAAISPF NFTAIGGNLA GAPALMGNVV LWKPSDTAML
   241  ASYAVYRILR EAGLPPNIIQ FVPADGPLFG DTVTSSEHLC GINFTGSVPT FKHLWKQVAQ
   301  NLDRFHTFPR LAGECGGKNF HFVHRSADVE SVVSGTLRSA FEYGGQKCSA CSRLYVPHSL
   361  WPQIKGRLLE EHSRIKVGDP AEDFGTFFSA VIDAKSFARI KKWLEHARSS PSLTILAGGK
   421  CDDSVGYFVE PCIVESKDPQ EPIMKEEIFG PVLSVYVYPD DKYKETLQLV DSTTSYGLTG
   481  AVFSQDKDVV QEATKVLRNA AGNFYINDKS TGSIVGQQPF GGARASGTND KPGGPHYILR
   541  WTSPQVIKET HKPLGDWSYA YMQ

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ALDH4A1 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)
0.23
Highest tissue expression
439 nTPM

Expression across tissuesHPA

Tissue

  • liver: 439 nTPM
  • kidney: 204 nTPM
  • choroid plexus: 122 nTPM
  • basal ganglia: 86 nTPM
  • midbrain: 74 nTPM
  • tongue: 70 nTPM

Single-cell type

  • hepatocytes: 449 nCPM
  • syncytiotrophoblasts: 112 nCPM
  • cytotrophoblasts: 109 nCPM
  • esophageal basal cells: 68 nCPM
  • retinal pigment epithelial cells: 68 nCPM
  • migrating cytotrophoblasts: 60 nCPM

Immune cell

  • myeloid DC: 4.5 nTPM
  • intermediate monocyte: 3.6 nTPM
  • classical monocyte: 2.7 nTPM
  • non-classical monocyte: 2 nTPM
  • eosinophil: 1.6 nTPM
  • plasmacytoid DC: 1.5 nTPM

Brain region

  • choroid plexus: 126 nTPM
  • thalamus: 98 nTPM
  • basal ganglia: 88 nTPM
  • midbrain: 77 nTPM
  • hypothalamus: 57 nTPM
  • cerebellum: 57 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ALDH4A1.

Disease | AllUniProt

Conditions ALDH4A1 is implicated in, by any mechanism.

Disease | GeneticClinVar

25 pathogenic / likely-pathogenic of 403 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • Hyperprolinemia type 2
  • See cases

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)
0.71
gnomAD pLI
0
gnomAD missense Z
-0.05
DepMap mean gene effect
-0.02
DepMap dependency class
none

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

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads ALDH4A1 as an antibody target. Whether an autoantibody or antibody against ALDH4A1 could matter depends on whether native ALDH4A1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ALDH4A1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label ALDH4A1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/ALDH4A1. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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