OSGEP

Chr 14AR

O-sialoglycoprotein endopeptidase

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

NCBI Gene: 55644 ENSG00000092094 UniProt: Q9NPF4 OMIM: 610107

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.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.081 OMIM phenotype

Clinical Summary— OSGEP

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Population Constraint (gnomAD)

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

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ClinVar Variants

29 unique Pathogenic / Likely Pathogenic· 78 VUS of 196 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?

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?

0.76Z-score

OE missense 0.85 (0.75–0.96)

177 obs / 207.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.69 (0.46–1.08)

0≤0.351.4

Missense OE?0.85 (0.75–0.96)

0≤0.61.4

Synonymous OE?0.76

0≤1.21.6

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

This gene — mechanism propensity

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

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

196 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9

Likely Pathogenic20

VUS78

Likely Benign53

Benign26

Conflicting5

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	7	2	0	0	9
Likely Pathogenic	5	15	0	0	20
VUS	1	76	1	0	78
Likely Benign	0	2	32	19	53
Benign	0	0	23	3	26
Conflicting	—				5
Total	13	95	56	22	191

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

View in ClinVar →

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