PYCR1

Chr 17AR

pyrroline-5-carboxylate reductase 1

Also known as: ARCL2B, ARCL3B, P5C, P5CR, PIG45, PP222, PRO3, PYCR

NCBI Gene: 5831 ENSG00000183010 UniProt: P32322 OMIM: 179035

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an enzyme that catalyzes the NAD(P)H-dependent conversion of pyrroline-5-carboxylate to proline. This enzyme may also play a physiologic role in the generation of NADP(+) in some cell types. The protein forms a homopolymer and localizes to the mitochondrion. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cutis laxa, autosomal recessive, type IIBMIM #612940

Cutis laxa, autosomal recessive, type IIIBMIM #614438

Clinical highlights

Gene-disease validity (ClinGen)

autosomal recessive cutis laxa type 2B · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.26

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — PYCR1