PYCR1
Chr 17ARpyrroline-5-carboxylate reductase 1
Also known as: ARCL2B, ARCL3B, P5C, P5CR, PIG45, PP222, PRO3, PYCR
This mitochondrial enzyme catalyzes the final step in proline biosynthesis by reducing pyrroline-5-carboxylate to L-proline using NAD(P)H and is involved in cellular oxidative stress responses. Mutations cause autosomal recessive cutis laxa types IIB and IIIB, connective tissue disorders characterized by loose, sagging skin and other systemic features. The gene shows tolerance to loss-of-function variants (low pLI score), consistent with the recessive inheritance pattern.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
300 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 11 | 2 | 17 | 0 | 30 |
Likely Pathogenic | 14 | 9 | 2 | 0 | 25 |
VUS | 2 | 65 | 25 | 0 | 92 |
Likely Benign | 0 | 4 | 50 | 60 | 114 |
Benign | 0 | 3 | 9 | 3 | 15 |
Conflicting | — | 21 | |||
| Total | 27 | 83 | 103 | 63 | 297 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PYCR1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools