PRODH Gene - Proline Dehydrogenase 1
Genetic and Functional Insights into PRODH, a Key Enzyme in Proline Catabolism Associated with Metabolic and Neurodevelopmental Disorders
Gene Information Card
| Symbol | PRODH |
|---|---|
| Full Name | Proline Dehydrogenase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 22q11.21 |
| NCBI Gene ID | 5625 ncbi.nlm.nih.gov/gene/5625 |
| Ensembl ID | ENSG00000100100 |
| UniProt ID | O43272 |
| OMIM ID | 606810 |
| HGNC ID | 9453 |
| Aliases | PRODH1, PRODH2, PIG6, HSPOX2, PRODH1A |
Description
The PRODH gene encodes proline dehydrogenase 1 (also known as proline oxidase), a mitochondrial enzyme that catalyzes the first step in proline catabolism, converting proline to Δ1-pyrroline-5-carboxylate. This reaction is critical for cellular energy metabolism, redox balance, and neurotransmitter synthesis. Located on chromosome 22q11.21, PRODH is frequently deleted in DiGeorge/velocardiofacial syndrome and is associated with hyperprolinemia type I and increased risk for schizophrenia and other neuropsychiatric disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hyperprolinemia type I | Loss-of-function mutations in PRODH impair proline degradation, leading to accumulation of proline in plasma and urine. | ClinVar, OMIM |
| Schizophrenia | PRODH deletions and variants on 22q11.21 are associated with increased risk; altered proline metabolism may affect glutamatergic signaling. | OMIM, NCBI |
| DiGeorge syndrome / Velocardiofacial syndrome | PRODH is located in the 22q11.2 deletion region; haploinsufficiency contributes to metabolic and neurodevelopmental features. | OMIM, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 8.3 | Medium |
| Brain (cerebellum) | 6.1 | Low |
| Heart | 4.2 | Low |
| Lung | 2.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.2 | Hepatocellular carcinoma cell line |
| HEK 293 | 7.8 | Embryonic kidney cells |
| SH-SY5Y | 5.4 | Neuroblastoma cell line |
| A549 | 3.1 | Lung carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1279C>T (p.Arg427Ter) | Nonsense | Rare | Loss of function; associated with hyperprolinemia type I |
| c.425G>A (p.Arg142Gln) | Missense | Low | Reduced enzyme activity; reported in schizophrenia cohorts |
| c.1546G>A (p.Gly516Arg) | Missense | Very rare | Impaired proline oxidase activity |
| 22q11.2 deletion (including PRODH) | Copy number loss | Common in 22q11.2 deletion syndrome | Haploinsufficiency; contributes to metabolic and psychiatric phenotypes |
Mutation functional classification
Loss of Function (LOF)
Nonsense and missense mutations that reduce or abolish proline dehydrogenase activity lead to hyperprolinemia type I and may contribute to schizophrenia risk.
Gain of Function (GOF)
No gain-of-function mutations have been reported for PRODH.
Dominant Negative (DN)
No dominant-negative mechanisms have been described for PRODH.
View complete mutation data：
Gene Ontology (GO)
| • proline dehydrogenase activity | • FAD binding |
| • mitochondrion | • proline catabolic process |
| • cellular response to oxidative stress | • glutamate metabolic process |
Pathways
• Proline metabolism (Reactome: R-HSA-70614)
• Arginine and proline metabolism (KEGG: hsa00330)
• Metabolic pathways (KEGG: hsa01100)
Protein Summary
Proline dehydrogenase 1 (PRODH) is a 56 kDa mitochondrial flavoprotein that catalyzes the oxidation of proline to Δ1-pyrroline-5-carboxylate, using FAD as a cofactor. The enzyme is highly expressed in liver and kidney, with lower levels in brain. It plays a key role in proline homeostasis, energy production, and redox regulation. Mutations in PRODH cause hyperprolinemia type I and are implicated in neuropsychiatric disorders, particularly schizophrenia, due to altered glutamate and neurotransmitter metabolism.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PRODH Knockout HEK293 Cell Line | EDJ-KQ5543 | Human | 5625 | Details Get a Quote |
| PRODH2 Knockout HEK293 Cell Line | EDJ-KQ14160 | Human | 58510 | Details Get a Quote |
| PRODH Knockout HCT 116 Cell Line | EDJ-KQ28801 | Human | 5625 | Details Get a Quote |
| PRODH Knockout HeLa Cell Line | EDJ-KQ54223 | Human | 5625 | Details Get a Quote |
| PRODH2 Knockout HeLa Cell Line | EDJ-KQ56944 | Human | 58510 | Details Get a Quote |
| PRODH Knockout A-549 Cell Line | EDJ-KQ62717 | Human | 5625 | Details Get a Quote |
| PRODH2 Knockout A-549 Cell Line | EDJ-KQ65451 | Human | 58510 | Details Get a Quote |
| PRODH2 Knockout HCT 116 Cell Line | EDJ-KQ73887 | Human | 58510 | Details Get a Quote |
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