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Aliases for ALDH4A1 Gene

Aliases for ALDH4A1 Gene

  • Aldehyde Dehydrogenase 4 Family Member A1 2 3 5
  • L-Glutamate Gamma-Semialdehyde Dehydrogenase 3 4
  • Aldehyde Dehydrogenase Family 4 Member A1 3 4
  • P5C Dehydrogenase 3 4
  • ALDH4 3 4
  • P5CDh 3 4
  • Delta-1-Pyrroline-5-Carboxylate Dehydrogenase, Mitochondrial 3
  • Mitochondrial Delta-1-Pyrroline 5-Carboxylate Dehydrogenase 3
  • Aldehyde Dehydrogenase 4 Family, Member A1 2
  • EC 58
  • EC 4
  • P5CD 3

External Ids for ALDH4A1 Gene

Previous HGNC Symbols for ALDH4A1 Gene

  • ALDH4

Previous GeneCards Identifiers for ALDH4A1 Gene

  • GC01U990216
  • GC01M018343
  • GC01M018667
  • GC01M018943
  • GC01M019070
  • GC01M019181
  • GC01M017442
  • GC01M019197

Summaries for ALDH4A1 Gene

Entrez Gene Summary for ALDH4A1 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]

GeneCards Summary for ALDH4A1 Gene

ALDH4A1 (Aldehyde Dehydrogenase 4 Family Member A1) is a Protein Coding gene. Diseases associated with ALDH4A1 include Hyperprolinemia, Type Ii and Hyperprolinemia. Among its related pathways are Arginine and proline metabolism and Metabolism. GO annotations related to this gene include identical protein binding and electron carrier activity.

UniProtKB/Swiss-Prot for ALDH4A1 Gene

  • Irreversible conversion of delta-1-pyrroline-5-carboxylate (P5C), derived either from proline or ornithine, to glutamate. This is a necessary step in the pathway interconnecting the urea and tricarboxylic acid cycles. The preferred substrate is glutamic gamma-semialdehyde, other substrates include succinic, glutaric and adipic semialdehydes.

Gene Wiki entry for ALDH4A1 Gene

Additional gene information for ALDH4A1 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ALDH4A1 Gene

Genomics for ALDH4A1 Gene

Regulatory Elements for ALDH4A1 Gene

Enhancers for ALDH4A1 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH01H018906 1.5 Ensembl ENCODE dbSUPER 9.3 -5.5 -5470 2.8 HDGF PKNOX1 ATF1 ARNT TCF12 ZNF766 CBX5 GATA2 ELK1 ZNF143 ALDH4A1 ENSG00000255275
GH01H018901 1.4 ENCODE dbSUPER 9.9 -0.1 -54 3.6 HDGF PKNOX1 FOXA2 MLX ARNT ARID4B SIN3A DMAP1 ZNF2 YY1 UBR4 IFFO2 ALDH4A1 ENSG00000255275
GH01H018946 2 FANTOM5 Ensembl ENCODE dbSUPER 6.6 -49.4 -49382 10.9 PKNOX1 FOXA2 MLX ZFP64 ARID4B SIN3A DMAP1 ZNF2 YY1 SLC30A9 IFFO2 EMC1 ALDH4A1 AKR7A3 UBR4 AKR7A2 ENSG00000255275
GH01H018912 1.4 Ensembl ENCODE dbSUPER 7.8 -10.5 -10532 1.3 RB1 ARID4B KLF17 RAD21 GLIS2 ZNF143 ATF7 RUNX3 SMARCA5 ZNF654 ALDH4A1 IFFO2 ENSG00000255275
GH01H019045 0.9 ENCODE 11.1 -143.0 -142955 0.7 ELF3 FOXA2 RAD21 RARA YY1 SCRT2 ATF7 THAP11 HMG20B REST MIR1290 ALDH4A1 EMC1 LOC105376815 GC01P019027
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around ALDH4A1 on UCSC Golden Path with GeneCards custom track

Promoters for ALDH4A1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000002367 199 1601 HDGF PKNOX1 ARNT ARID4B SIN3A DMAP1 ZNF2 YY1 ZNF766 ZNF143

Genomic Locations for ALDH4A1 Gene

Genomic Locations for ALDH4A1 Gene
31,370 bases
Minus strand

Genomic View for ALDH4A1 Gene

Genes around ALDH4A1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ALDH4A1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ALDH4A1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ALDH4A1 Gene

Proteins for ALDH4A1 Gene

  • Protein details for ALDH4A1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial
    Protein Accession:
    Secondary Accessions:
    • A8K1Q7
    • B4DGE4
    • D2D4A3
    • Q16882
    • Q53HU4
    • Q5JNV6
    • Q8IZ38
    • Q96IF0
    • Q9UDI6

    Protein attributes for ALDH4A1 Gene

    563 amino acids
    Molecular mass:
    61719 Da
    Quaternary structure:
    • Homodimer.

    Three dimensional structures from OCA and Proteopedia for ALDH4A1 Gene

    Alternative splice isoforms for ALDH4A1 Gene


neXtProt entry for ALDH4A1 Gene

Selected DME Specific Peptides for ALDH4A1 Gene


Post-translational modifications for ALDH4A1 Gene

  • Ubiquitination at posLast=495495
  • Modification sites at PhosphoSitePlus

Other Protein References for ALDH4A1 Gene

Domains & Families for ALDH4A1 Gene

Gene Families for ALDH4A1 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Plasma proteins
  • Potential drug targets
  • Predicted intracellular proteins

Graphical View of Domain Structure for InterPro Entry



  • Belongs to the aldehyde dehydrogenase family.
  • Belongs to the aldehyde dehydrogenase family.
genes like me logo Genes that share domains with ALDH4A1: view

Function for ALDH4A1 Gene

Molecular function for ALDH4A1 Gene

UniProtKB/Swiss-Prot BiophysicochemicalProperties:
Kinetic parameters: KM=100 uM for NAD {ECO:0000269 PubMed:22516612}; KM=32 uM for L-pyrroline-5-carboxylate {ECO:0000269 PubMed:22516612};
UniProtKB/Swiss-Prot CatalyticActivity:
L-glutamate 5-semialdehyde + NAD(+) + H(2)O = L-glutamate + NADH.
UniProtKB/Swiss-Prot Function:
Irreversible conversion of delta-1-pyrroline-5-carboxylate (P5C), derived either from proline or ornithine, to glutamate. This is a necessary step in the pathway interconnecting the urea and tricarboxylic acid cycles. The preferred substrate is glutamic gamma-semialdehyde, other substrates include succinic, glutaric and adipic semialdehydes.

Enzyme Numbers (IUBMB) for ALDH4A1 Gene

Phenotypes From GWAS Catalog for ALDH4A1 Gene

Gene Ontology (GO) - Molecular Function for ALDH4A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003842 1-pyrroline-5-carboxylate dehydrogenase activity EXP 8621661
GO:0004029 aldehyde dehydrogenase (NAD) activity IDA 4015840
GO:0009055 electron carrier activity TAS 8621661
GO:0016491 oxidoreductase activity IEA --
GO:0042802 identical protein binding IPI 22516612
genes like me logo Genes that share ontologies with ALDH4A1: view
genes like me logo Genes that share phenotypes with ALDH4A1: view

Human Phenotype Ontology for ALDH4A1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

miRNA for ALDH4A1 Gene

miRTarBase miRNAs that target ALDH4A1

Clone Products

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for ALDH4A1 Gene

Localization for ALDH4A1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ALDH4A1 Gene

Mitochondrion matrix.

Subcellular locations from

Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ALDH4A1 gene
Compartment Confidence
mitochondrion 5
cytosol 4

Gene Ontology (GO) - Cellular Components for ALDH4A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005739 mitochondrion IEA --
GO:0005759 mitochondrial matrix TAS --
genes like me logo Genes that share ontologies with ALDH4A1: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for ALDH4A1 Gene

Pathways & Interactions for ALDH4A1 Gene

genes like me logo Genes that share pathways with ALDH4A1: view

UniProtKB/Swiss-Prot P30038-AL4A1_HUMAN

  • Pathway: Amino-acid degradation; L-proline degradation into L-glutamate; L-glutamate from L-proline: step 2/2.

Gene Ontology (GO) - Biological Process for ALDH4A1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006560 proline metabolic process TAS 8621661
GO:0006562 proline catabolic process TAS --
GO:0008152 metabolic process IEA --
GO:0010133 proline catabolic process to glutamate IEA --
GO:0019470 4-hydroxyproline catabolic process TAS 21998747
genes like me logo Genes that share ontologies with ALDH4A1: view

No data available for SIGNOR curated interactions for ALDH4A1 Gene

Drugs & Compounds for ALDH4A1 Gene

(7) Drugs for ALDH4A1 Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Famotidine Approved Pharma Histamine H2-receptor antagonist 62
Water Approved Pharma 0
Glutamic Acid Approved Nutra Full agonist, Agonist 236
NADH Nutra Target 0
NAD Pharma Full agonist, Agonist 0

(10) Additional Compounds for ALDH4A1 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
1-Pyrroline-5-carboxylic acid
  • (S)-1-pyrroline-5-carboxylate
  • 1-Pyrroline-5-carboxylate
  • 1-Pyrroline-5-carboxylic acid
  • 3,4-Dihydro-2h-pyrrole-2-carboxylate
  • 3,4-Dihydro-2h-pyrrole-2-carboxylic acid
4-Hydroxy-L-glutamic acid
  • (2S)-2-amino-4-hydroxypentanedioate
  • (2S)-2-amino-4-hydroxypentanedioic acid
  • 4-Hydroxy-L-glutamate
  • 4-Hydroxy-L-glutamic acid
  • Erythro-4-hydroxyglutamate
Hydrogen Ion
  • Hydrogen cation
  • Hydron
  • Proton
L-4-Hydroxyglutamate semialdehyde
L-Glutamic gamma-semialdehyde
  • Glutamate-semialdehyde
  • Glutamic gamma-semialdehyde
  • L-Glutamate 5-semialdehyde
  • L-Glutamate-5-semialdehyde
  • L-Glutamate-gamma-semialdehyde
genes like me logo Genes that share compounds with ALDH4A1: view

Transcripts for ALDH4A1 Gene

Unigene Clusters for ALDH4A1 Gene

Aldehyde dehydrogenase 4 family, member A1:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for ALDH4A1 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10a · 10b ^ 11 ^ 12a · 12b ^ 13 ^ 14 ^ 15 ^ 16
SP1: -
SP2: -

Relevant External Links for ALDH4A1 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for ALDH4A1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for ALDH4A1 Gene

mRNA differential expression in normal tissues according to GTEx for ALDH4A1 Gene

This gene is overexpressed in Liver (x13.9) and Kidney - Cortex (x8.9).

Protein differential expression in normal tissues from HIPED for ALDH4A1 Gene

This gene is overexpressed in Liver (23.2), Kidney (11.0), and Fetal Liver (6.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for ALDH4A1 Gene

Protein tissue co-expression partners for ALDH4A1 Gene

NURSA nuclear receptor signaling pathways regulating expression of ALDH4A1 Gene:


SOURCE GeneReport for Unigene cluster for ALDH4A1 Gene:


mRNA Expression by UniProt/SwissProt for ALDH4A1 Gene:

Tissue specificity: Highest expression is found in liver followed by skeletal muscle, kidney, heart, brain, placenta, lung and pancreas.

Evidence on tissue expression from TISSUES for ALDH4A1 Gene

  • Nervous system(4.9)
  • Kidney(4.8)
  • Liver(4.7)
  • Eye(4.3)
  • Lung(4.3)
  • Skin(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for ALDH4A1 Gene

Germ Layers:
  • ectoderm
  • mesoderm
  • nervous
  • urinary
Head and neck:
  • brain
  • head
  • kidney
genes like me logo Genes that share expression patterns with ALDH4A1: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery for ALDH4A1 Gene

Orthologs for ALDH4A1 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for ALDH4A1 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia ALDH4A1 34 33
  • 99.35 (n)
(Canis familiaris)
Mammalia ALDH4A1 33
  • 90.29 (n)
TAS1R2 34
  • 34 (a)
(Bos Taurus)
Mammalia ALDH4A1 33 34
  • 88.34 (n)
(Rattus norvegicus)
Mammalia Aldh4a1 33
  • 87.19 (n)
(Mus musculus)
Mammalia Aldh4a1 33 16 34
  • 86.71 (n)
(Monodelphis domestica)
Mammalia ALDH4A1 34
  • 82 (a)
(Ornithorhynchus anatinus)
Mammalia ALDH4A1 34
  • 82 (a)
(Gallus gallus)
Aves ALDH4A1 33 34
  • 78.38 (n)
tropical clawed frog
(Silurana tropicalis)
Amphibia aldh4a1 33
  • 72.28 (n)
(Danio rerio)
Actinopterygii aldh4a1 33 34
  • 69.69 (n)
zgc63592 33
fruit fly
(Drosophila melanogaster)
Insecta P5CDh1 33 34
  • 64.4 (n)
CG7145 35
  • 61 (a)
P5CDh2 34
  • 42 (a)
CG6661 34
  • 16 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP004366 33
  • 63.4 (n)
(Caenorhabditis elegans)
Secernentea alh-6 33 34
  • 56.77 (n)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AAL071C 33
  • 55.39 (n)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0C10549g 33
  • 47.94 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes PUT2 33 34 36
  • 46.03 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 63 (a)
bread mold
(Neurospora crassa)
Ascomycetes NCU03076 33
  • 53.32 (n)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes SPBC24C6.04 33
  • 52.67 (n)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.1289 33
Species where no ortholog for ALDH4A1 was found in the sources mined by GeneCards:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for ALDH4A1 Gene

Gene Tree for ALDH4A1 (if available)
Gene Tree for ALDH4A1 (if available)

Paralogs for ALDH4A1 Gene

No data available for Paralogs for ALDH4A1 Gene

Variants for ALDH4A1 Gene

Sequence variations from dbSNP and Humsavar for ALDH4A1 Gene

SNP ID Clin Chr 01 pos Sequence Context AA Info Type
rs137852937 Pathogenic, Hyperprolinemia 2 (HYRPRO2) [MIM:239510] 18,877,498(-) GTGCT(C/G/T)GCGTC nc-transcript-variant, reference, missense
rs387906314 Pathogenic 18,902,503(-) CCCGC(-/G)CTCCG nc-transcript-variant, reference, frameshift-variant
rs779536510 Pathogenic 18,874,481(+) CCCCC(-/A)AAAGG nc-transcript-variant, reference, frameshift-variant
rs11311839 Likely benign 18,872,188(+) AGCGG(-/C)CCCCC intron-variant, nc-transcript-variant, utr-variant-3-prime
rs1138267 Likely benign 18,872,082(-) TCCCT(C/G/T)TGATC intron-variant, nc-transcript-variant, utr-variant-3-prime

Structural Variations from Database of Genomic Variants (DGV) for ALDH4A1 Gene

Variant ID Type Subtype PubMed ID
nsv545719 CNV loss 21841781
nsv479029 CNV novel sequence insertion 20440878
nsv1075672 CNV deletion 25765185

Variation tolerance for ALDH4A1 Gene

Residual Variation Intolerance Score: 74.1% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 6.37; 76.94% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for ALDH4A1 Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ALDH4A1 Gene

Disorders for ALDH4A1 Gene

MalaCards: The human disease database

(5) MalaCards diseases for ALDH4A1 Gene - From: HGMD, OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
hyperprolinemia, type ii
  • hyperprolinemia type 2
  • hyperprolinemia type 1
succinic semialdehyde dehydrogenase deficiency
  • 4-hydroxybutyric aciduria
hypophosphatasia, infantile
  • infantile hypophosphatasia
gamma-amino butyric acid metabolism disorder
- elite association - COSMIC cancer census association via MalaCards


  • Hyperprolinemia 2 (HYRPRO2) [MIM:239510]: An inborn error of proline metabolism resulting in elevated plasma levels of proline and delta-1-pyrroline-5-carboxylate (P5C). The condition is considered to be benign, but affected individuals can exhibit neurological manifestations that vary in severity. Clinical signs include seizures, intellectual deficit and mild developmental delay. {ECO:0000269 PubMed:22516612, ECO:0000269 PubMed:9700195}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for ALDH4A1

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
genes like me logo Genes that share disorders with ALDH4A1: view

No data available for Genatlas for ALDH4A1 Gene

Publications for ALDH4A1 Gene

  1. Cloning, characterization, and expression of cDNAs encoding human delta 1-pyrroline-5-carboxylate dehydrogenase. (PMID: 8621661) Hu CA … Valle D (The Journal of biological chemistry 1996) 2 3 4 22 60
  2. The three-dimensional structural basis of type II hyperprolinemia. (PMID: 22516612) Srivastava D … Tanner JJ (Journal of molecular biology 2012) 3 4 60
  3. A Large-scale genetic association study of esophageal adenocarcinoma risk. (PMID: 20453000) Liu CY … Christiani DC (Carcinogenesis 2010) 3 45 60
  4. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson SL … O'Brien SJ (PloS one 2010) 3 45 60
  5. Genetic variants in TPMT and COMT are associated with hearing loss in children receiving cisplatin chemotherapy. (PMID: 19898482) Ross CJ … CPNDS Consortium (Nature genetics 2009) 3 45 60

Products for ALDH4A1 Gene

Sources for ALDH4A1 Gene

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