OSGEP
protein-codingO-sialoglycoprotein endopeptidase, the group of KEOPS complex
Gene summary
Enables tRNA 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, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~8.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009627
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0033007
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0033007
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0033007
Submitter: G2P
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Musculoskeletal; Neurologic; Renal
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to OSGEP variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017807.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 19 | 1 | 20 | |||
| missense | 2 | 16 | 75 | 5 | 98 | |
| nonsense | 5 | 3 | 8 | |||
| start loss | 0 | |||||
| frameshift | 2 | 1 | 3 | |||
| splice donor/acceptor (+/-2bp) | 3 | 2 | 5 | |||
| Total | 9 | 22 | 78 | 24 | 1 | 134 |
Highest pathogenic variant AF is 0.0004535642
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060277.1 | 11 | MANE Select | |
| Ensembl | ENSP00000206542.4 | 11 | MANE Select | |
| Ensembl | ENSP00000451580.1 | 4 | Standard | |
| Ensembl | ENSP00000450464.2 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| osgep | Danio rerio | Structure: head Quality: decreased diameter abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- tRNA modification in the nucleus and cytosol
- tRNA processing
- Metabolism of RNA
Biological Process
- tRNA threonylcarbamoyladenosine modification
Molecular Function
- protein binding
- metal ion binding
- N(6)-L-threonylcarbamoyladenine synthase activity
Cellular Component
- EKC/KEOPS complex
- nucleus
- nucleoplasm
- cytoplasm
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000206542
- Coding exons
- 11
- Length
- 8695
- Individuals with no LoFs
- 125713
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 35
- Defined
- 125748
- p
- 0.000139
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.759 | 177 | 208 | 0.852 | 0.0000116 | 2165 |
| Missense (PolyPhen) | 49 | 81.94 | 0.598 | 849 | ||
| Synonymous | 1.65 | 58 | 76.3 | 0.760 | 0.00000404 | 701 |
| Loss of Function | 1.28 | 14 | 20.2 | 0.693 | 0.00000118 | 205 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00016 | 0.00016 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Component of the EKC/KEOPS complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine. The complex is probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37. OSGEP likely plays a direct catalytic role in this reaction, but requires other protein(s) of the complex to fulfill this activity. {ECO:0000255|HAMAP-Rule:MF_03180, ECO:0000269|PubMed:28272532, ECO:0000269|PubMed:28805828, ECO:0000305|PubMed:22912744, ECO:0000305|PubMed:27903914}.;
Recessive Scores
- pRec
- 0.236
Intolerance Scores
- LoFtool
- 0.748
- RVIS EVS
- -0.29
- RVIS percentile EVS
- 32.94
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.909
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |