OSGEP

Chr 14AR

O-sialoglycoprotein endopeptidase

Also known as: GAMOS3, GCPL1, KAE1, OSGEP1, PRSMG1, TCS3

OSGEP encodes a component of the EKC/KEOPS complex that catalyzes threonylcarbamoyl modification of adenosine at position 37 in specific tRNAs, which is essential for proper protein translation. Mutations cause Galloway-Mowat syndrome 3, an autosomal recessive disorder characterized by early-onset nephrotic syndrome and microcephaly with developmental delay. The gene shows extreme intolerance to loss-of-function variants (pLI near 1.0), indicating that complete loss of protein function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismARLOEUF 1.081 OMIM phenotype
Clinical SummaryOSGEP
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 32 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.08LOEUF
pLI 0.000
Z-score 1.28
OE 0.69 (0.461.08)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.76Z-score
OE missense 0.85 (0.750.96)
177 obs / 207.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.69 (0.461.08)
00.351.4
Missense OE0.85 (0.750.96)
00.61.4
Synonymous OE0.76
01.21.6
LoF obs/exp: 14 / 20.2Missense obs/exp: 177 / 207.8Syn Z: 1.65
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongOSGEP-related nephrotic syndrome with primary microcephalyOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7326th %ile
GOF
0.6930th %ile
LOF
0.3355th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic10
VUS32
Likely Benign20
Benign26
Conflicting4
7
Pathogenic
10
Likely Pathogenic
32
VUS
20
Likely Benign
26
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
5
0
7
Likely Pathogenic
2
8
0
0
10
VUS
0
29
3
0
32
Likely Benign
0
2
11
7
20
Benign
0
0
23
3
26
Conflicting
4
Total439421099

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

View in ClinVar →

Protein Context — Lollipop Plot

OSGEP · 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.

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Clinical Literature
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