PRODH

Chr 22ADAR

proline dehydrogenase 1

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

NCBI Gene: 5625ENSG00000100033UniProt: O43272OMIM: 606810

The protein converts proline to delta-1-pyrroline-5-carboxylate in the mitochondria as the first step of proline degradation. Mutations cause hyperprolinemia type I and confer susceptibility to schizophrenia, with both autosomal dominant and autosomal recessive inheritance patterns reported. The gene is extremely tolerant to loss-of-function variants (pLI near zero) and is located in the 22q11.21 deletion syndrome region.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismAD/ARLOEUF 1.102 OMIM phenotypes
Clinical Summary— PRODH
🧬
Gene-Disease Validity (ClinGen)
hyperprolinemia type 1 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
249 unique Pathogenic / Likely Pathogenic· 149 VUS of 599 total submissions
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — PRODH
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
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
0.06Z-score
OE missense 0.99 (0.90–1.09)
307 obs / 310.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.76 (0.54–1.10)
0≤0.351.4
Missense OE0.99 (0.90–1.09)
0≤0.61.4
Synonymous OE1.09
0≤1.21.6
LoF obs/exp: 21 / 27.5Missense obs/exp: 307 / 310.2Syn Z: -0.79
DN
0.7132th %ile
GOF
0.4973th %ile
LOF
0.2871th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

599 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic238
Likely Pathogenic11
VUS149
Likely Benign97
Benign80
Conflicting12
238
Pathogenic
11
Likely Pathogenic
149
VUS
97
Likely Benign
80
Benign
12
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
234
0
238
Likely Pathogenic
5
2
4
0
11
VUS
6
99
39
5
149
Likely Benign
0
3
40
54
97
Benign
1
9
60
10
80
Conflicting
—12
Total1611337769587

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Proline metabolism supports metastasis formation and could be inhibited to selectively target metastasizing cancer cells.
Elia I et al.·Nat Commun
2017
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
Impact of COMT, PRODH and DISC1 Genetic Variants on Cognitive Performance of Patients with Schizophrenia.
Fricke-Galindo I et al.·Arch Med Res
2022Cohort
Metformin Treatment or PRODH/POX-Knock out Similarly Induces Apoptosis by Reprograming of Amino Acid Metabolism, TCA, Urea Cycle and Pentose Phosphate Pathway in MCF-7 Breast Cancer Cells.
Huynh TYL et al.·Biomolecules
2021
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
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients