OSGEPL1

Chr 2

O-sialoglycoprotein endopeptidase like 1

Also known as: OSGEPL, Qri7

NCBI Gene: 64172 ENSG00000128694 UniProt: Q9H4B0 OMIM: 619634

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables N(6)-L-threonylcarbamoyladenine synthase activity. Involved in tRNA threonylcarbamoyladenosine modification. Is active in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.99

Clinical Summary— OSGEPL1

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

47 VUS of 68 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?

0.99LOEUF

pLI 0.000

Z-score 1.58

OE 0.57 (0.34–0.99)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.79Z-score

OE missense 0.85 (0.75–0.96)

176 obs / 208.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.57 (0.34–0.99)

0≤0.351.4

Missense OE?0.85 (0.75–0.96)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 9 / 15.8Missense obs/exp: 176 / 208.2Syn Z: 1.21

This gene — mechanism propensity

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

68 submitted variants in ClinVar

ClinVar

Classification Summary

VUS47

Likely Benign1

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	0	47	0	47
Likely Benign	1	0	0	1
Benign	0	1	1	2
Total	1	48	1	50

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

View in ClinVar →

27 pathogenic / likely-pathogenic (of 28) ClinVar copy-number / structural variants overlap OSGEPL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →