PYCR3
protein-codingpyrroline-5-carboxylate reductase 3
Gene summary
This gene encodes a protein that belongs to the pyrroline-5-carboxylate reductase family of enzymes. Members of this family catalyze the final step in proline biosynthesis, converting pyrroline-5-carboxylate to proline. Glutamate and ornithine are precursors in the synthesis of proline. The protein encoded by this gene is a cytoplasmic enzyme involved in the biosynthesis of proline from ornithine. [provided by RefSeq, Aug 2016]
- PYCRL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PYCR3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_023078.6. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 63 | 2 | 65 | |||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 69 | 3 | 0 | 72 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_075566.3 | 6 | MANE Select | |
| Ensembl | ENSP00000480945.1 | 6 | MANE Select | |
| RefSeq | NP_001316795.2 | 6 | Standard | |
| Ensembl | ENSP00000220966.6 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| pycr3 | Danio rerio | Structure: post-vent region Quality: curved abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Arginine and proline metabolism - Homo sapiens (human)
- Urea cycle and metabolism of amino groups
- Metabolism of amino acids and derivatives
- Metabolism
- Arginine Proline metabolism
Biological Process
- cellular amino acid biosynthetic process
- oxidation-reduction process
- L-proline biosynthetic process
Molecular Function
- pyrroline-5-carboxylate reductase activity
- protein binding
Cellular Component
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000220966
- Coding exons
- 6
- Length
- 5861
- Individuals with no LoFs
- 125531
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 57
- Defined
- 125589
- p
- 0.000231
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.00535 | 172 | 172 | 0.999 | 0.0000105 | 1779 |
| Missense (PolyPhen) | 67 | 70.038 | 0.95662 | 697 | ||
| Synonymous | -1.47 | 93 | 76.6 | 1.21 | 0.00000499 | 637 |
| Loss of Function | 0.605 | 8 | 10.1 | 0.794 | 5.29e-7 | 115 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000065 | 0.000062 | rare |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00039 | 0.00038 | rare |
| Finnish | 0.000098 | 0.000092 | rare |
| European (Non-Finnish) | 0.00028 | 0.00027 | rare |
| South Asian | 0.00037 | 0.00033 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Enzyme that catalyzes the last step in proline biosynthesis. Proline is synthesized from either glutamate or ornithine; both are converted to pyrroline-5-carboxylate (P5C), and then to proline via pyrroline-5-carboxylate reductases (PYCRs). PYCRL is exclusively linked to the conversion of ornithine to proline. {ECO:0000269|PubMed:23024808}.;
Recessive Scores
- pRec
- 0.126
Intolerance Scores
- RVIS EVS
- -0.02
- RVIS percentile EVS
- 52.09
Essentials
- Essential (gene trap)
- N