OSGEP

Chr 14AR

O-sialoglycoprotein endopeptidase

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

NCBI Gene: 55644ENSG00000092094UniProt: Q9NPF4

Enables N(6)-L-threonylcarbamoyladenine synthase activity. Involved in tRNA threonylcarbamoyladenosine modification. Located in cytosol and nucleoplasm. Part of EKC/KEOPS complex. Implicated in Galloway-Mowat syndrome 3. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Galloway-Mowat syndrome 3MIM #617729
AR
218
ClinVar variants
51
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— OSGEP
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
51 Pathogenic / Likely Pathogenic· 83 VUS of 218 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.08LOEUF
pLI 0.000
Z-score 1.28
OE 0.69 (0.46–1.08)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.76Z-score
OE missense 0.85 (0.75–0.96)
177 obs / 207.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.69 (0.46–1.08)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.75–0.96)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.76
0≤1.21.6
LoF obs/exp: 14 / 20.2Missense obs/exp: 177 / 207.8Syn Z: 1.65

ClinVar Variant Classifications

218 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic21
VUS83
Likely Benign53
Benign26
Conflicting5
30
Pathogenic
21
Likely Pathogenic
83
VUS
53
Likely Benign
26
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
2
26
0
30
Likely Pathogenic
3
15
3
0
21
VUS
1
75
7
0
83
Likely Benign
0
2
32
19
53
Benign
0
0
23
3
26
Conflicting
—5
Total6949122218

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.

Gene2Phenotype Curations

OSGEP-related nephrotic syndrome with primary microcephaly

strong
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Galloway-Mowat syndrome 3

MIM #617729

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly.
Braun DA et al.·Nat Genet
2017
Novel homozygous OSGEP gene pathogenic variants in two unrelated patients with Galloway-Mowat syndrome: case report and review of the literature.
Domingo-Gallego A et al.·BMC Nephrol
2019Review
Galloway-Mowat syndrome in Taiwan: OSGEP mutation and unique clinical phenotype.
Lin PY et al.·Orphanet J Rare Dis
2018
Genetics and phenotypic heterogeneity of Galloway-Mowat syndrome.
Huang L et al.·Cell Commun Signal
2025Review
Phenotype, genotype, and clinical outcome of Taiwanese with congenital nephrotic syndrome.
Tseng MH et al.·J Formos Med Assoc
2024
Novel variants in OSGEP leading to Galloway-Mowat syndrome by altering its subcellular localization.
Teng H et al.·Clin Chim Acta
2021
The transcription factor ATF4 mediates endoplasmic reticulum stress-related podocyte injury and slit diaphragm defects.
Krausel V et al.·Kidney Int
2023
Galloway-mowat syndrome 3 (GAMOS3): a novel disease-causing variant in OSGEP gene and expansion of the clinical spectrum.
Yari A et al.·Neurol Sci
2025Case report
Whole-exome sequencing revealed a novel homozygous missense variant in OSGEP gene: a case report of Galloway-Mowat syndrome in Iran.
Esmaeilzadeh E et al.·CEN Case Rep
2023Case report
Next-Generation Sequencing for Congenital Nephrotic Syndrome: A Multi-Center Cross-Sectional Study from India.
Joshi A et al.·Indian Pediatr
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools