OPLAH

Chr 8ADAR

5-oxoprolinase, ATP-hydrolysing

Also known as: 5-Opase, OPLA, OPLAHD

NCBI Gene: 26873ENSG00000178814UniProt: O14841

The protein catalyzes the ATP-dependent cleavage of 5-oxo-L-proline to form L-glutamate as part of the gamma-glutamyl cycle. Mutations cause 5-oxoprolinase deficiency, which can be inherited in either autosomal dominant or autosomal recessive patterns. The gene is not highly constrained against loss-of-function variants.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

5-oxoprolinase deficiencyMIM #260005
ADAR
0
Active trials
5
Pubs (1 yr)
44
P/LP submissions
2%
P/LP missense
0.87
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— OPLAH
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
43 unique Pathogenic / Likely Pathogenic· 261 VUS of 500 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.87LOEUF
pLI 0.000
Z-score 2.33
OE 0.65 (0.49–0.87)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.27Z-score
OE missense 0.97 (0.92–1.03)
816 obs / 837.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.65 (0.49–0.87)
0≤0.351.4
Missense OE0.97 (0.92–1.03)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 34 / 52.2Missense obs/exp: 816 / 837.6Syn Z: -0.02
DN
0.6745th %ile
GOF
0.7028th %ile
LOF
0.3357th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
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

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic23
Likely Pathogenic20
VUS261
Likely Benign157
Benign13
Conflicting3
23
Pathogenic
20
Likely Pathogenic
261
VUS
157
Likely Benign
13
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
0
16
0
23
Likely Pathogenic
12
1
7
0
20
VUS
2
249
7
3
261
Likely Benign
0
11
66
80
157
Benign
0
2
7
4
13
Conflicting
—3
Total2126310387477

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

View in ClinVar →

Protein Context — Lollipop Plot

OPLAH · protein map & ClinVar variants

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

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
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