PYCR2 Gene - Pyrroline-5-Carboxylate Reductase 2
Genetic and Functional Insights into PYCR2, a Mitochondrial Enzyme Linked to Hypomyelinating Leukodystrophy
Gene Information Card
| Symbol | PYCR2 |
|---|---|
| Full Name | Pyrroline-5-Carboxylate Reductase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 1q42.12 |
| NCBI Gene ID | 29920 ncbi.nlm.nih.gov/gene/29920 |
| Ensembl ID | ENSG00000143845 |
| UniProt ID | Q96C36 |
| OMIM ID | 610875 |
| HGNC ID | 19962 |
| Aliases | P5CR2, PYC2, PROLINE oxidase 2 |
Description
PYCR2 encodes pyrroline-5-carboxylate reductase 2, a mitochondrial enzyme that catalyzes the NAD(P)H-dependent reduction of pyrroline-5-carboxylate to proline, a critical step in proline biosynthesis. This enzyme is essential for cellular redox balance and mitochondrial function. Mutations in PYCR2 are associated with hypomyelinating leukodystrophy type 10, a rare autosomal recessive neurological disorder characterized by developmental delay, intellectual disability, and brain white matter abnormalities.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypomyelinating leukodystrophy 10 | Loss-of-function mutations impair proline synthesis, leading to mitochondrial dysfunction and impaired myelination | ClinVar, OMIM |
| Developmental delay and intellectual disability | Pathogenic variants disrupt enzyme activity, affecting neuronal development | ClinVar, OMIM |
| Microcephaly | Reduced proline availability affects brain growth | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 10.2 | Medium |
| Brain | 8.7 | Low |
| Heart | 7.9 | Low |
| Skeletal Muscle | 6.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.3 | Liver cancer cell line, high expression |
| A549 | 9.8 | Lung carcinoma, moderate expression |
| HeLa | 7.2 | Cervical adenocarcinoma, low expression |
| K562 | 5.1 | Leukemia, low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.416C>T (p.Pro139Leu) | Missense | Rare | Loss of enzyme activity, associated with leukodystrophy |
| c.541G>A (p.Gly181Arg) | Missense | Rare | Impaired protein stability, reduced catalytic function |
| c.1A>G (p.Met1Val) | Start codon loss | Rare | Complete loss of protein, severe phenotype |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations are loss-of-function, reducing or abolishing enzyme activity, leading to proline deficiency and mitochondrial dysfunction.
Gain of Function (GOF)
No gain-of-function mutations reported for PYCR2.
Dominant Negative (DN)
No dominant-negative effects documented; inheritance is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
| • Pyrroline-5-carboxylate reductase activity | • NADPH binding |
| • Proline biosynthetic process | • Mitochondrion |
| • Oxidoreductase activity |
Pathways
• Proline biosynthesis
• Arginine and proline metabolism
• Metabolic pathways
Protein Summary
PYCR2 is a 320-amino acid mitochondrial protein that forms a homodimer and catalyzes the final step of proline synthesis. It is highly expressed in tissues with high metabolic demand. Defects in this enzyme lead to accumulation of pyrroline-5-carboxylate and depletion of proline, affecting cellular redox state and mitochondrial integrity. The protein is critical for normal brain development, particularly myelination.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PYCR2 Knockout HEK293 Cell Line | EDJ-KQ51244 | Human | 29920 | Details Get a Quote |
| PYCR2 Knockout HeLa Cell Line | EDJ-KQ56121 | Human | 29920 | Details Get a Quote |
| PYCR2 Knockout A-549 Cell Line | EDJ-KQ64607 | Human | 29920 | Details Get a Quote |
| PYCR2 Knockout HCT 116 Cell Line | EDJ-KQ73059 | Human | 29920 | Details Get a Quote |
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