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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 1.5.1.12 61
  • EC 1.2.1.88 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 Metabolism and Arginine and proline 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

No data available for 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
GH01F018972 0.7 Ensembl ENCODE 11.3 -70.2 -70202 1.2 CTCF CREB3L1 ZMYM3 RAD21 GTF3C2 GATA3 GATA2 ZNF366 SCRT2 SMC3 ALDH4A1 MIR1290 TAS1R2 EMC1 AKR7A3 IFFO2 GC01P019006
GH01F019045 1 Ensembl ENCODE 11.1 -142.9 -142864 0.9 ELF3 RAD21 RARA YY1 SCRT2 THAP11 HMG20B PPARG NR2F2 KLF16 ALDH4A1 MIR1290 EMC1 LOC105376815 GC01P019027
GH01F018989 0.4 ENCODE 10.4 -86.2 -86243 0.1 ELF3 HDAC1 MLX ARID4B NFXL1 ZBTB40 RAD21 RARA GATA4 ZNF143 IFFO2 ALDH4A1 MIR1290 GC01P019006
GH01F018901 0.6 ENCODE 9.9 -0.1 -54 3.6 HDGF PKNOX1 ARNT MLX WRNIP1 ARID4B SIN3A DMAP1 ZNF2 YY1 OTUD3 EMC1 TMCO4 IFFO2 ALDH4A1 ENSG00000255275
GH01F018899 0.5 Ensembl 9.4 +2.9 2899 0.2 ADNP ZMYM3 KDM1A ALDH4A1 MIR1290
- Elite enhancer/Elite enhancer-gene association Download Table
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
ENSR00001517931 299 1801 HDGF PKNOX1 ARNT WRNIP1 ARID4B SIN3A DMAP1 ZNF2 YY1 ZNF143

Genomic Location for ALDH4A1 Gene

Chromosome:
1
Start:
18,871,430 bp from pter
End:
18,902,799 bp from pter
Size:
31,370 bases
Orientation:
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:
    P30038-AL4A1_HUMAN
    Recommended name:
    Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial
    Protein Accession:
    P30038
    Secondary Accessions:
    • A8K1Q7
    • B4DGE4
    • D2D4A3
    • Q16882
    • Q53HU4
    • Q5JNV6
    • Q8IZ38
    • Q96IF0
    • Q9UDI6

    Protein attributes for ALDH4A1 Gene

    Size:
    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

    UniProtKB/Swiss-Prot:

neXtProt entry for ALDH4A1 Gene

Post-translational modifications for ALDH4A1 Gene

  • Ubiquitination at Lys 495
  • Modification sites at PhosphoSitePlus

Other Protein References for ALDH4A1 Gene

Domains & Families for ALDH4A1 Gene

Gene Families for ALDH4A1 Gene

Graphical View of Domain Structure for InterPro Entry

P30038

UniProtKB/Swiss-Prot:

AL4A1_HUMAN :
  • Belongs to the aldehyde dehydrogenase family.
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

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,TAS 4015840
GO:0009055 electron carrier activity TAS 8621661
GO:0016491 oxidoreductase activity IEA --
GO:0016620 oxidoreductase activity, acting on the aldehyde or oxo group of donors, NAD or NADP as acceptor IEA --
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

Animal Model Products

miRNA for ALDH4A1 Gene

miRTarBase miRNAs that target ALDH4A1

Inhibitory RNA Products

Flow Cytometry 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

COMPARTMENTS
Jensen Localization Image for ALDH4A1 Gene COMPARTMENTS Subcellular localization image for ALDH4A1 gene
Compartment Confidence
mitochondrion 5
cytosol 3

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

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:0006537 glutamate biosynthetic process IEA --
GO:0006560 proline metabolic process TAS 8621661
GO:0006561 proline biosynthetic process IEA --
GO:0006562 proline catabolic process TAS --
GO:0008152 metabolic process IEA --
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 59
Water Approved Pharma 0
NADH Nutra Target 0
NAD Pharma Full agonist, Agonist 0
L-Glutamic Acid Nutra 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
2906-39-0
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
2485-33-8
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
496-92-4
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:

Inhibitory RNA Products

Flow Cytometry 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: -
SP3:

Relevant External Links for ALDH4A1 Gene

GeneLoc Exon Structure for
ALDH4A1
ECgene alternative splicing isoforms for
ALDH4A1

Expression for ALDH4A1 Gene

mRNA expression in normal human tissues 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:

ALDH4A1

SOURCE GeneReport for Unigene cluster for ALDH4A1 Gene:

Hs.77448

mRNA Expression by UniProt/SwissProt for ALDH4A1 Gene:

P30038-AL4A1_HUMAN
Tissue specificity: Highest expression is found in liver followed by skeletal muscle, kidney, heart, brain, placenta, lung and pancreas.
genes like me logo Genes that share expression patterns with ALDH4A1: view

Primer Products

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
chimpanzee
(Pan troglodytes)
Mammalia ALDH4A1 34 35
  • 99.35 (n)
dog
(Canis familiaris)
Mammalia ALDH4A1 34
  • 90.29 (n)
TAS1R2 35
  • 34 (a)
OneToOne
cow
(Bos Taurus)
Mammalia ALDH4A1 34 35
  • 88.34 (n)
rat
(Rattus norvegicus)
Mammalia Aldh4a1 34
  • 87.19 (n)
mouse
(Mus musculus)
Mammalia Aldh4a1 34 16 35
  • 86.71 (n)
oppossum
(Monodelphis domestica)
Mammalia ALDH4A1 35
  • 82 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia ALDH4A1 35
  • 82 (a)
OneToOne
chicken
(Gallus gallus)
Aves ALDH4A1 34 35
  • 78.38 (n)
tropical clawed frog
(Silurana tropicalis)
Amphibia aldh4a1 34
  • 72.28 (n)
zebrafish
(Danio rerio)
Actinopterygii aldh4a1 34 35
  • 69.69 (n)
zgc63592 34
fruit fly
(Drosophila melanogaster)
Insecta P5CDh1 34 35
  • 64.4 (n)
CG7145 36
  • 61 (a)
P5CDh2 35
  • 42 (a)
OneToMany
CG6661 35
  • 16 (a)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP004366 34
  • 63.4 (n)
worm
(Caenorhabditis elegans)
Secernentea alh-6 34 35
  • 56.77 (n)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AAL071C 34
  • 55.39 (n)
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0C10549g 34
  • 47.94 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes PUT2 34 35 37
  • 46.03 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 63 (a)
OneToOne
bread mold
(Neurospora crassa)
Ascomycetes NCU03076 34
  • 53.32 (n)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes SPBC24C6.04 34
  • 52.67 (n)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.1289 34
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

ENSEMBL:
Gene Tree for ALDH4A1 (if available)
TreeFam:
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 Hyperprolinemia 2 (HYRPRO2) [MIM:239510], Pathogenic 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
rs1009971 -- 18,895,526(+) GTGGC(A/G)GGAGA intron-variant
rs1009972 -- 18,895,690(+) AGCTG(C/T)GGGCC intron-variant

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

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

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)
ALDH4A1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
ALDH4A1

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

Disorders for ALDH4A1 Gene

MalaCards: The human disease database

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

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

UniProtKB/Swiss-Prot

AL4A1_HUMAN
  • 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:9700195}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for ALDH4A1

Genetic Association Database (GAD)
ALDH4A1
Human Genome Epidemiology (HuGE) Navigator
ALDH4A1
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
ALDH4A1
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 C.-A. … Valle D. (J. Biol. Chem. 1996) 2 3 4 22 64
  2. The three-dimensional structural basis of type II hyperprolinemia. (PMID: 22516612) Srivastava D. … Tanner J.J. (J. Mol. Biol. 2012) 3 4 64
  3. A Large-scale genetic association study of esophageal adenocarcinoma risk. (PMID: 20453000) Liu C.Y. … Christiani D.C. (Carcinogenesis 2010) 3 46 64
  4. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson S.L. … O'Brien S.J. (PLoS ONE 2010) 3 46 64
  5. Genetic variants in TPMT and COMT are associated with hearing loss in children receiving cisplatin chemotherapy. (PMID: 19898482) Ross C.J. … Hayden M.R. (Nat. Genet. 2009) 3 46 64

Products for ALDH4A1 Gene

Sources for ALDH4A1 Gene

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