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PRODH proline dehydrogenase 1 [ Homo sapiens (human) ]

Gene ID: 5625, updated on 3-Apr-2024

Summary

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Official Symbol
PRODHprovided by HGNC
Official Full Name
proline dehydrogenase 1provided by HGNC
Primary source
HGNC:HGNC:9453
See related
Ensembl:ENSG00000100033 MIM:606810; AllianceGenome:HGNC:9453
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
POX; PIG6; HSPOX2; PRODH1; PRODH2; TP53I6
Summary
This gene encodes a mitochondrial protein that catalyzes the first step in proline degradation. Mutations in this gene are associated with hyperprolinemia type 1 and susceptibility to schizophrenia 4 (SCZD4). This gene is located on chromosome 22q11.21, a region which has also been associated with the contiguous gene deletion syndromes, DiGeorge and CATCH22. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2010]
Expression
Biased expression in small intestine (RPKM 24.9), skin (RPKM 13.7) and 11 other tissues See more
Orthologs
mouse all
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Genomic context

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Location:
22q11.21
Exon count:
15
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 22 NC_000022.11 (18912781..18936553, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 22 NC_060946.1 (19288173..19311947, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (18900294..18924066, complement)

Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene family with sequence similarity 230 member F Neighboring gene OCT4 hESC enhancer GRCh37_chr22:18883553-18884054 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:18890927-18891786 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:18891787-18892644 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:18892762-18893300 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:18893301-18893838 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:18893839-18894376 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:18895933-18896636 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:18896637-18897339 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:18897340-18898042 Neighboring gene DiGeorge syndrome critical region gene 6 Neighboring gene uncharacterized LOC122455341 Neighboring gene human-specific endogenous retroviral insert PRODH enhancer Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:18934751-18935496 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr22:18945292-18945809 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:18957062-18957893 Neighboring gene DiGeorge syndrome critical region gene 5 Neighboring gene ReSE screen-validated silencer GRCh37_chr22:18985578-18985746 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:19005353-19005854 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr22:19007165-19007664 Neighboring gene family with sequence similarity 246 member C (gene/pseudogene)

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Metformin Treatment or PRODH/POX-Knock out Similarly Induces Apoptosis by Reprograming of Amino Acid Metabolism, TCA, Urea Cycle and Pentose Phosphate Pathway in MCF-7 Breast Cancer Cells. Huynh TYL, et al. Biomolecules, 2021 Dec 15. PMID 34944532, Free PMC Article
  2. Understanding the role of key amino acids in regulation of proline dehydrogenase/proline oxidase (prodh/pox)-dependent apoptosis/autophagy as an approach to targeted cancer therapy. Huynh TYL, et al. Mol Cell Biochem, 2020 Mar. PMID 31933109, Free PMC Article
  3. Exercise Reveals Proline Dehydrogenase as a Potential Target in Heart Failure. Moreira JBN, et al. Prog Cardiovasc Dis, 2019 Mar-Apr. PMID 30867130
  4. Functional Consequences of Intracellular Proline Levels Manipulation Affecting PRODH/POX-Dependent Pro-Apoptotic Pathways in a Novel in Vitro Cell Culture Model. Zareba I, et al. Cell Physiol Biochem, 2017. PMID 28942439
  5. Proline dehydrogenase promotes senescence through the generation of reactive oxygen species. Nagano T, et al. J Cell Sci, 2017 Apr 15. PMID 28264926

See all (91) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Proline Dehydrogenase (PRODH) Is Expressed in Lung Adenocarcinoma and Modulates Cell Survival and 3D Growth by Inducing Cellular Senescence.
    Title: Proline Dehydrogenase (PRODH) Is Expressed in Lung Adenocarcinoma and Modulates Cell Survival and 3D Growth by Inducing Cellular Senescence.
  2. Prognostic and immunomodulatory roles of schizophrenia-associated genes HTR2A, COMT, and PRODH in pan-cancer analysis and glioma survival prediction model.
    Title: Prognostic and immunomodulatory roles of schizophrenia-associated genes HTR2A, COMT, and PRODH in pan-cancer analysis and glioma survival prediction model.
  3. Impact of COMT, PRODH and DISC1 Genetic Variants on Cognitive Performance of Patients with Schizophrenia.
    Title: Impact of COMT, PRODH and DISC1 Genetic Variants on Cognitive Performance of Patients with Schizophrenia.
  4. Metformin Treatment or PRODH/POX-Knock out Similarly Induces Apoptosis by Reprograming of Amino Acid Metabolism, TCA, Urea Cycle and Pentose Phosphate Pathway in MCF-7 Breast Cancer Cells.
    Title: Metformin Treatment or PRODH/POX-Knock out Similarly Induces Apoptosis by Reprograming of Amino Acid Metabolism, TCA, Urea Cycle and Pentose Phosphate Pathway in MCF-7 Breast Cancer Cells.
  5. Understanding the role of key amino acids in regulation of proline dehydrogenase/proline oxidase (prodh/pox)-dependent apoptosis/autophagy as an approach to targeted cancer therapy.
    Title: Understanding the role of key amino acids in regulation of proline dehydrogenase/proline oxidase (prodh/pox)-dependent apoptosis/autophagy as an approach to targeted cancer therapy.
  6. Proline Dehydrogenase (PRODH) expression is reduced in human with Heart Failure. PRODH appears to be crucial to sustain normal mitochondrial function and maintenance of ATP levels in human cardiomyocytes in a hypoxic environment, as well as for redox homeostasis in both normoxic and hypoxic conditions.
    Title: Exercise Reveals Proline Dehydrogenase as a Potential Target in Heart Failure.
  7. PRODH1-mediated proline metabolism promotes pancreatic ductal adenocarcinoma growth.
    Title: Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions.
  8. Here, we show that Prodh-deficient mice with elevated CNS L-proline display specific deficits in high-frequency GABA-ergic transmission and gamma-band oscillations. We find that L-proline is a GABA-mimetic and can act at multiple GABA-ergic targets
    Title: Cytosolic Accumulation of L-Proline Disrupts GABA-Ergic Transmission through GAD Blockade.
  9. PRODH/POX knockdown decreased DNA and collagen biosynthesis, whereas increased prolidase activity and intracellular proline level in MCF-7shPRODH/POX cells.
    Title: Functional Consequences of Intracellular Proline Levels Manipulation Affecting PRODH/POX-Dependent Pro-Apoptotic Pathways in a Novel in Vitro Cell Culture Model.
  10. this study shows that PRODH plays a causative role in DNA damage-induced senescence through the enzymatic generation of reactive oxygen species
    Title: Proline dehydrogenase promotes senescence through the generation of reactive oxygen species.
Submit: New GeneRIF Correction See all GeneRIFs (56)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Proline dehydrogenase deficiency
MedGen: C0268529 OMIM: 239500 GeneReviews: Not available
Compare labs
Schizophrenia 4
MedGen: C1833247 OMIM: 600850 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
An atlas of genetic influences on human blood metabolites.
EBI GWAS Catalog
Human metabolic individuality in biomedical and pharmaceutical research.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 Env gp120 upregulates the mitochondrial redox enzyme PRODH (POX) PubMed
env HIV-1 Env gp120 induces PRODH (POX) that elicits reactive oxygen species (ROS)-mediated neuronal autophagy PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ10497, FLJ33744, MGC148078, MGC148079

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables FAD binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables FAD binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables proline dehydrogenase activity EXP
Inferred from Experiment
more info
 PubMed 
enables proline dehydrogenase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables proline dehydrogenase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in 4-hydroxyproline catabolic process TAS
Traceable Author Statement
more info
 PubMed 
involved_in intrinsic apoptotic signaling pathway in response to oxidative stress NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in proline catabolic process TAS
Traceable Author Statement
more info
  
involved_in proline catabolic process to glutamate IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in proline catabolic process to glutamate IEA
Inferred from Electronic Annotation
more info
  
involved_in proline metabolic process TAS
Traceable Author Statement
more info
 PubMed 
involved_in regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
  
located_in mitochondrial inner membrane TAS
Traceable Author Statement
more info
  
located_in mitochondrial matrix IEA
Inferred from Electronic Annotation
more info
  
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
proline dehydrogenase 1, mitochondrial
Names
p53 Inducible gene 6
p53-induced gene 6 protein
proline dehydrogenase (oxidase) 1
proline oxidase 2
proline oxidase, mitochondrial
tumor protein p53 inducible protein 6
NP_001182155.2
NP_001355179.2
NP_057419.5

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008226.3 RefSeqGene

    Range
    5261..28773
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001195226.2 → NP_001182155.2  proline dehydrogenase 1, mitochondrial isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) is missing an internal exon at the 5' end compared to variant 1, resulting in translation initiation from an in-frame downstream AUG and an isoform (2) with a shorter N-terminus compared to isoform 1.
    Source sequence(s)
    AC007326
    Consensus CDS
    CCDS56223.1
    UniProtKB/Swiss-Prot
    A6NF53, O14680, O43272, Q0P507, Q147W8, Q504W1, Q59FI8, Q6NV86, Q9UF13
    UniProtKB/TrEMBL
    E7EQL6, X5D7N2
    Related
    ENSP00000334726.2, ENST00000334029.6

  2. NM_001368250.2 → NP_001355179.2  proline dehydrogenase 1, mitochondrial isoform 2

    Status: REVIEWED

    Source sequence(s)
    AC007326
    UniProtKB/TrEMBL
    E7EQL6
    Related
    ENSP00000410805.1, ENST00000420436.5

  3. NM_016335.6 → NP_057419.5  proline dehydrogenase 1, mitochondrial isoform 1 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longer isoform (1).
    Source sequence(s)
    AC007326
    Consensus CDS
    CCDS13754.1
    UniProtKB/Swiss-Prot
    A6NF53, O14680, O43272, Q0P507, Q147W8, Q504W1, Q59FI8, Q6NV86, Q9UF13
    UniProtKB/TrEMBL
    A0A087WWM6, X5D7N2
    Related
    ENSP00000349577.6, ENST00000357068.11

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000022.11 Reference GRCh38.p14 Primary Assembly

    Range
    18912781..18936553 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060946.1 Alternate T2T-CHM13v2.0

    Range
    19288173..19311947 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O43272.3 GenPept UniProtKB/Swiss-Prot:O43272

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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