PYCR2

Description

The PYCR2 (pyrroline-5-carboxylate reductase 2) is a protein-coding gene located on chromosome 1.

The PYCR2 gene encodes a mitochondrial protein belonging to the pyrroline-5-carboxylate reductase family. It catalyzes the conversion of pyrroline-5-carboxylate to proline, the final step in proline biosynthesis. While loss of PYCR2 does not significantly impact mitochondrial protein synthesis, its loss of function leads to increased apoptosis under oxidative stress. Mutations in the PYCR2 gene are associated with a unique syndrome characterized by postnatal microcephaly, hypomyelination, and reduced cerebral white matter volume. The hypomyelination and absence of wrinkly skin differentiate this condition from that caused by mutations in the gene encoding PYCR2's isozyme, PYCR1, suggesting a specific and essential role for PYCR2 in human CNS development. This is supported by the fact that PYCR2 mRNA is moderately expressed in the developing human brain, at levels higher than either of the other two isoforms. While PYCR2 is involved in proline biosynthesis, systemic proline deprivation does not appear to be the underlying cause of this condition, as plasma amino acid analysis in affected individuals did not reveal low proline levels. Furthermore, mitochondrial protein synthesis was unaffected in PYCR2-deficient cells, suggesting that proline deficiency, as a protein building block, may not be the primary cause of the observed pathology.

PYCR2 is a housekeeping enzyme that catalyzes the final step in proline biosynthesis. In certain cell types, like erythrocytes, its primary function might be the generation of NADP(+). It can utilize both NAD and NADP as cofactors. While exhibiting a higher affinity for NADP, it displays greater catalytic efficiency with NADH. (PubMed:2722838, PubMed:6894153). PYCR2 plays a role in the cellular response to oxidative stress. (PubMed:25865492)

PYCR2 is also known as HLD10, P5CR2.

Associated Diseases

Comprehensive carrier screening

WES Whole Exome Sequencing