PYCR2

Chr 1AR

pyrroline-5-carboxylate reductase 2

Also known as: HLD10, P5CR2

NCBI Gene: 29920ENSG00000143811UniProt: Q96C36

This gene belongs to the pyrroline-5-carboxylate reductase family. The encoded mitochondrial protein catalyzes the conversion of pyrroline-5-carboxylate to proline, which is the last step in proline biosynthesis. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Nov 2012]

Primary Disease Associations & Inheritance

Leukodystrophy, hypomyelinating, 10MIM #616420
AR
204
ClinVar variants
63
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PYCR2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
63 Pathogenic / Likely Pathogenic· 72 VUS of 204 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.34LOEUF
pLI 0.000
Z-score 0.69
OE 0.79 (0.49–1.34)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.95Z-score
OE missense 0.81 (0.71–0.92)
156 obs / 193.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.79 (0.49–1.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.71–0.92)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 10 / 12.6Missense obs/exp: 156 / 193.1Syn Z: -0.52

ClinVar Variant Classifications

204 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic41
Likely Pathogenic22
VUS72
Likely Benign53
Benign8
Conflicting8
41
Pathogenic
22
Likely Pathogenic
72
VUS
53
Likely Benign
8
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
2
34
0
41
Likely Pathogenic
10
9
3
0
22
VUS
0
64
7
1
72
Likely Benign
0
2
18
33
53
Benign
0
1
4
3
8
Conflicting
—8
Total15786637204

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PYCR2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

PYCR2-related postnatal microcephaly, hypomyelination, and reduced cerebral white-matter volume

strong
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Leukodystrophy, hypomyelinating, 10

MIM #616420

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Integrated Proteogenomic Characterization of HBV-Related Hepatocellular Carcinoma.
Gao Q et al.·Cell
2019
Exploring metabolic alterations in PYCR2 deficiency: Unveiling pathways and clinical presentations of hypomyelinating leukodystrophy 10.
Gürbüz BB et al.·Am J Med Genet A
2024Case report
Pyrroline-5-Carboxylate Reductase-2 Promotes Colorectal Cancer Progression via Activating PI3K/AKT/mTOR Pathway.
Yin F et al.·Dis Markers
2021
Pyrroline-5-Carboxylate Reductase-2 Promotes Colorectal Carcinogenesis by Modulating Microtubule-Associated Serine/Threonine Kinase-like/Wnt/β-Catenin Signaling.
Lama Tamang R et al.·Cells
2023
PYCR2 promotes growth and aerobic glycolysis in human liver cancer by regulating the AKT signaling pathway.
Wang S et al.·Biochem Biophys Res Commun
2023
Genetic analysis of Pycr1 and Pycr2 in mice.
Stum MG et al.·Genetics
2021
Homozygous variants in pyrroline-5-carboxylate reductase 2 (PYCR2) in patients with progressive microcephaly and hypomyelinating leukodystrophy.
Meng L et al.·Am J Med Genet A
2017Review
PYCR in Kidney Renal Papillary Cell Carcinoma: Expression, Prognosis, Gene Regulation Network, and Regulation Targets.
Shao Z et al.·Front Biosci (Landmark Ed)
2022
Deciphering the Effects of the PYCR Family on Cell Function, Prognostic Value, Immune Infiltration in ccRCC and Pan-Cancer.
Chen H et al.·Int J Mol Sci
2024
Pyrroline-5-carboxylate reductase 2 (PYCR2) deficiency causes hereditary spastic paraplaegia in late childhood.
Sager G et al.·Eur J Paediatr Neurol
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools