Details for: PRODH2

Gene ID: 58510

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PRODH2

Ensembl ID: ENSG00000250799

Description: proline dehydrogenase 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • enteroendocrine cell CL0000164
    CSI 5.25
    rCSI 7.17%
    PRS 98.59
  • epithelial cell of proximal tubule CL0002306
    CSI 4
    rCSI 9.77%
    PRS 97.79
  • hepatocyte CL0000182
    CSI 3.34
    rCSI 5.98%
    PRS 98.57
  • periportal region hepatocyte CL0019026
    CSI 3.15
    rCSI 12.25%
    PRS 98.4
  • centrilobular region hepatocyte CL0019029
    CSI 2.68
    rCSI 7%
    PRS 98.13
  • parietal epithelial cell CL1000452
    CSI 1.53
    rCSI 4.08%
    PRS 98.75
  • epithelial cell of proximal tubule segment 3 CL4030011
    CSI 1.5
    rCSI 11.93%
    PRS 98.27
  • podocyte CL0000653
    CSI 1.47
    rCSI 6.51%
    PRS 99.17
  • kidney proximal convoluted tubule epithelial cell CL1000838
    CSI 1.37
    rCSI 14.58%
    PRS 98.85

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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  • Node Color (Target Cell CSI, relative to current network):
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  • Node Size: Proportional to Target Cell CSI magnitude
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  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PRODH2](/details-gene/58510) (proline dehydrogenase 2) encodes a mitochondrial enzyme that plays a crucial role in amino acid catabolism. Localized to the inner mitochondrial membrane, this FAD-dependent oxidoreductase primarily catalyzes the degradation of proline. Recent research has also identified it as a hydroxyproline dehydrogenase, implicating it in the metabolic pathway that can lead to oxalate production ([Link](https://doi.org/10.1042/bj20141159)). **Overall**, expression data reveals that [PRODH2](/details-gene/58510) is a significant gene in metabolically active tissues, showing the highest significance scores in [enteroendocrine cells](/details-cell/CL0000164) of the gut, various epithelial cells of the kidney proximal tubule, and [hepatocytes](/details-cell/CL0000182) in the liver. This expression pattern aligns with its function in amino acid metabolism and its emerging role in metabolic disorders such as primary hyperoxaluria. ## Cellular Roles and Expression Landscape The expression profile of [PRODH2](/details-gene/58510) highlights its specialization in tissues central to metabolic homeostasis. The gene's highest significance is observed in intestinal [enteroendocrine cells](/details-cell/CL0000164) (CSI: 5.25), suggesting a potential role in coupling nutrient sensing to hormonal signaling. A prominent role for [PRODH2](/details-gene/58510) is evident in the kidney, where it is highly significant in multiple cell types responsible for reabsorption and metabolism. These include [epithelial cells of the proximal tubule](/details-cell/CL0002306) (CSI: 4.00), [parietal epithelial cells](/details-cell/CL1000452) (CSI: 1.53), and [podocytes](/details-cell/CL0000653) (CSI: 1.47). This renal-specific expression pattern is consistent with the kidney's function in filtering and processing metabolites from the blood, including amino acids like proline and hydroxyproline. Similarly, [PRODH2](/details-gene/58510) is a key gene in the liver, with high significance in [hepatocytes](/details-cell/CL0000182) (CSI: 3.34), including those in both the [periportal](/details-cell/CL0019026) and [centrilobular regions](/details-cell/CL0019029). This underscores its contribution to the liver's extensive metabolic functions, particularly amino acid degradation. The collective expression data paints a clear picture of [PRODH2](/details-gene/58510) as a specialized metabolic enzyme operating primarily within the gut, kidney, and liver. ## Pathways and Molecular Function Functionally, [PRODH2](/details-gene/58510) is an oxidoreductase localized to the [mitochondrion](/https://www.ebi.ac.uk/QuickGO/term/GO:0005739), specifically the [mitochondrial inner membrane](/https://www.ebi.ac.uk/QuickGO/term/GO:0005743). Its primary molecular function is [proline dehydrogenase activity](/https://www.ebi.ac.uk/QuickGO/term/GO:0004657), a key step in the [proline catabolic process](/https://www.ebi.ac.uk/QuickGO/term/GO:0006562). This role is well-defined within the Reactome pathway for [Proline catabolism](/https://reactome.org/content/detail/R-HSA-70688), which is part of the broader [Metabolism of amino acids and derivatives](/https://reactome.org/content/detail/R-HSA-71291). Crucially, research has expanded the known function of [PRODH2](/details-gene/58510) to include the degradation of hydroxyproline ([Link](https://doi.org/10.1042/bj20141159)). This activity connects it to [Glyoxylate metabolism and glycine degradation](/https://reactome.org/content/detail/R-HSA-389661), as hydroxyproline breakdown yields glyoxylate, a direct precursor to oxalate. This dual specificity for both proline and hydroxyproline catabolism is central to its physiological role and its implication in pathology. ## Research Directions The established role of [PRODH2](/details-gene/58510) in hydroxyproline metabolism and its link to primary hyperoxaluria present clear avenues for investigation. The gene's high expression in the specific cell types affected by this disease, namely [hepatocytes](/details-cell/CL0000182) and [renal proximal tubule cells](/details-cell/CL0002306), strengthens this connection. Based on the available data, several testable hypotheses can be proposed: 1. Inhibition of [PRODH2](/details-gene/58510) enzymatic activity in [hepatocytes](/details-cell/CL0000182) will reduce the metabolic flux from hydroxyproline to glyoxylate, thereby lowering systemic oxalate levels and preventing kidney stone formation in models of primary hyperoxaluria. 2. The high significance of [PRODH2](/details-gene/58510) in [enteroendocrine cells](/details-cell/CL0000164) suggests that proline/hydroxyproline catabolism in these cells acts as a metabolic sensor, linking dietary amino acid intake to the secretion of gut hormones like GLP-1 or PYY, thereby influencing glucose homeostasis and satiety. To test the first and most clinically relevant hypothesis, a key experiment could be designed. A liver-specific and/or kidney-specific knockout of the `Prodh2` gene could be generated in a mouse model of primary hyperoxaluria (e.g., `Agxt` knockout mice). The therapeutic efficacy of this genetic ablation would be assessed by quantifying urinary oxalate and glyoxylate excretion, alongside histological analysis of renal calcium oxalate crystal deposition. This would provide direct evidence for the contribution of [PRODH2](/details-gene/58510) to the disease phenotype in the most relevant organs. Given that its enzymatic activity contributes directly to the production of a toxic metabolite, [PRODH2](/details-gene/58510) is a compelling candidate for therapeutic inhibition. The development of a specific small molecule inhibitor targeting the active site of [PRODH2](/details-gene/58510) represents a promising strategy for treating primary hyperoxaluria, as suggested by previous work ([Link](https://doi.org/10.1042/bj20141159)). Such a drug would aim to reduce the metabolic burden of oxalate, offering a targeted therapy for this debilitating disease.

Genular Protein ID: 3405147302

Symbol: HYPDH_HUMAN

Name: Kidney and liver proline oxidase 1

UniProtKB Accession Codes:

Q9UF12 A0A590UKC3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioCyc 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 11 ChEMBL 1 DMDM 1 DNASU 1 DisGeNET 1 EC 2 EMBL 3 Ensembl 2 ExpressionAtlas 1 GO 7 Gene3D 1 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 2 RefSeq 2 Rhea 2 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

PubMed ID: 25697095

Title: Proline dehydrogenase 2 (PRODH2) is a hydroxyproline dehydrogenase (HYPDH) and molecular target for treating primary hyperoxaluria.

PubMed ID: 25697095

DOI: 10.1042/bj20141159

Sequence Information:

  • Length: 460
  • Mass: 50898
  • Checksum: 1CE20EC9778D86E3
  • Sequence:
    • MLRTCYVLCS QAGPPSRGWQ SLSFDGGAFH LKGTGELTRA LLVLRLCAWP PLVTHGLLLQ 
AWSRRLLGSR LSGAFLRASV YGQFVAGETA EEVKGCVQQL RTLSLRPLLA VPTEEEPDSA 
AKSGEAWYEG NLGAMLRCVD LSRGLLEPPS LAEASLMQLK VTALTSTRLC KELASWVRRP 
GASLELSPER LAEAMDSGQN LQVSCLNAEQ NQHLRASLSR LHRVAQYARA QHVRLLVDAE 
YTSLNPALSL LVAALAVRWN SPGEGGPWVW NTYQACLKDT FERLGRDAEA AHRAGLAFGV 
KLVRGAYLDK ERAVAQLHGM EDPTQPDYEA TSQSYSRCLE LMLTHVARHG PMCHLMVASH 
NEESVRQATK RMWELGIPLD GTVCFGQLLG MCDHVSLALG QAGYVVYKSI PYGSLEEVIP 
YLIRRAQENR SVLQGARREQ ELLSQELWRR LLPGCRRIPH