PRODH

Chr 22ADAR

proline dehydrogenase 1

Also known as: HSPOX2, PIG6, POX, PRODH1, TP53I6

NCBI Gene: 5625ENSG00000100033UniProt: O43272

This gene encodes a mitochondrial protein that catalyzes the first step in proline degradation. Mutations in this gene are associated with hyperprolinemia type 1 and susceptibility to schizophrenia 4 (SCZD4). This gene is located on chromosome 22q11.21, a region which has also been associated with the contiguous gene deletion syndromes, DiGeorge and CATCH22. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2010]

Primary Disease Associations & Inheritance

{Schizophrenia, susceptibility to, 4}MIM #600850
AD
Hyperprolinemia, type IMIM #239500
AR
UniProtHyperprolinemia 1
UniProtSchizophrenia 4
917
ClinVar variants
217
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PRODH
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
217 Pathogenic / Likely Pathogenic· 228 VUS of 917 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.
1.10LOEUF
pLI 0.000
Z-score 1.15
OE 0.76 (0.54–1.10)
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.
0.06Z-score
OE missense 0.99 (0.90–1.09)
307 obs / 310.2 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.0.76 (0.54–1.10)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.90–1.09)
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.1.09
0≤1.21.6
LoF obs/exp: 21 / 27.5Missense obs/exp: 307 / 310.2Syn Z: -0.79

ClinVar Variant Classifications

917 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic204
Likely Pathogenic13
VUS228
Likely Benign127
Benign7
Conflicting9
204
Pathogenic
13
Likely Pathogenic
228
VUS
127
Likely Benign
7
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
198
0
204
Likely Pathogenic
5
2
6
0
13
VUS
4
150
69
5
228
Likely Benign
0
3
54
70
127
Benign
0
4
1
2
7
Conflicting
—9
Total1515932877588

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

View in ClinVar →

Protein Context — Lollipop Plot

PRODH · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Schizophrenia, susceptibility to, 4}

MIM #600850

Molecular basis of disorder known

Autosomal dominant

Hyperprolinemia, type I

MIM #239500

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Velo-cardio-facial syndrome.
Shprintzen RJ et al.·Curr Opin Pediatr
2005Review
Proline metabolism supports metastasis formation and could be inhibited to selectively target metastasizing cancer cells.
Elia I et al.·Nat Commun
2017
Structural Biology of Proline Catabolic Enzymes.
Tanner JJ·Antioxid Redox Signal
2019Review
The circUbqln1, regulated by XBP1s, interplays with 14-3-3ζ to inhibit collagen synthesis and promote osteoarthritis by controlling PRODH activity and proline metabolism.
Feng N et al.·J Adv Res
2024
Proline Dehydrogenase (PRODH) Is Expressed in Lung Adenocarcinoma and Modulates Cell Survival and 3D Growth by Inducing Cellular Senescence.
Grossi S et al.·Int J Mol Sci
2024
Impact of COMT, PRODH and DISC1 Genetic Variants on Cognitive Performance of Patients with Schizophrenia.
Fricke-Galindo I et al.·Arch Med Res
2022Cohort
Psychiatric phenotypes associated with hyperprolinemia: A systematic review.
Namavar Y et al.·Am J Med Genet B Neuropsychiatr Genet
2021Review
Prognostic and immunomodulatory roles of schizophrenia-associated genes HTR2A, COMT, and PRODH in pan-cancer analysis and glioma survival prediction model.
Shen J et al.·Front Immunol
2023Functional
Psychiatric manifestations of 22q11.2 deletion syndrome: a literature review.
Bertrán M et al.·Neurologia (Engl Ed)
2018Review
PRODH polymorphisms, cortical volumes and thickness in schizophrenia.
Ota VK et al.·PLoS One
2014
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