OSGEPL1

Chr 2

O-sialoglycoprotein endopeptidase like 1

Also known as: OSGEPL, Qri7

The protein functions as an N(6)-L-threonylcarbamoyladenine synthase that modifies mitochondrial tRNAs by adding threonylcarbamoyl groups to adenosine at position 37, which is essential for proper mitochondrial protein synthesis and genome maintenance. Mutations cause autosomal recessive mitochondrial complex I deficiency with neurodegeneration and distinctive brain MRI abnormalities. This gene shows minimal constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.99
Clinical SummaryOSGEPL1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
27 unique Pathogenic / Likely Pathogenic· 48 VUS of 96 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.99LOEUF
pLI 0.000
Z-score 1.58
OE 0.57 (0.340.99)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.79Z-score
OE missense 0.85 (0.750.96)
176 obs / 208.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.57 (0.340.99)
00.351.4
Missense OE0.85 (0.750.96)
00.61.4
Synonymous OE0.81
01.21.6
LoF obs/exp: 9 / 15.8Missense obs/exp: 176 / 208.2Syn Z: 1.21
DN
0.76top 25%
GOF
0.5759th %ile
LOF
0.3161th %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

96 submitted variants in ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic1
VUS48
Likely Benign1
Benign2
26
Pathogenic
1
Likely Pathogenic
48
VUS
1
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
26
0
26
Likely Pathogenic
0
0
1
0
1
VUS
0
47
1
0
48
Likely Benign
1
0
0
0
1
Benign
0
1
0
1
2
Total14828178

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

View in ClinVar →

Protein Context — Lollipop Plot

OSGEPL1 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC