OSGEP

O-sialoglycoprotein endopeptidase, the group of KEOPS complex

Basic information

Region (hg38): 14:20446400-20455089

Links

ENSG00000092094 ∙ NCBI:55644 ∙ OMIM:610107 ∙ HGNC:18028 ∙ Uniprot:Q9NPF4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Galloway-Mowat syndrome 3 (Strong), mode of inheritance: AR
• Galloway-Mowat syndrome 3 (Strong), mode of inheritance: AR
• Galloway-Mowat syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Galloway-Mowat syndrome 3	AR	General	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	Craniofacial; Musculoskeletal; Neurologic; Renal	28272532; 28805828

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the OSGEP gene.

• not provided (93 variants)
• Galloway-Mowat syndrome 3 (26 variants)
• Inborn genetic diseases (23 variants)
• Nephrotic syndrome (2 variants)
• Galloway-Mowat syndrome (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OSGEP gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				9	3	12
missense	4	10	48	1	1	64
nonsense		1	3			4
start loss						0
frameshift			2			2
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region				3	2	5
non coding			1	10	18	29
Total	4	11	56	20	22

Highest pathogenic variant AF is 0.0000723

Variants in OSGEP

This is a list of pathogenic ClinVar variants found in the OSGEP region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-20447274-C-T		Galloway-Mowat syndrome 3 • Galloway-Mowat syndrome	Pathogenic (-)
14-20447275-G-A		Inborn genetic diseases • Galloway-Mowat syndrome 3	Conflicting classifications of pathogenicity (Aug 23, 2022)
14-20447275-G-C			Uncertain significance (Jul 17, 2022)
14-20447277-T-C			Uncertain significance (Feb 24, 2022)
14-20447279-C-T			Likely benign (Nov 01, 2022)
14-20447313-G-A			Benign (May 25, 2021)
14-20447406-G-C			Benign (Dec 30, 2023)
14-20447413-A-G		OSGEP-related disorder	Likely benign (Feb 13, 2024)
14-20447415-C-G		OSGEP-related disorder	Likely benign (Feb 13, 2024)
14-20447434-C-T		Inborn genetic diseases	Uncertain significance (Jul 06, 2022)
14-20447465-C-T		Inborn genetic diseases	Uncertain significance (Aug 15, 2023)
14-20447478-C-T			Uncertain significance (Oct 28, 2021)
14-20447498-T-A		Galloway-Mowat syndrome 3	Uncertain significance (Aug 15, 2018)
14-20447515-C-T		Galloway-Mowat syndrome 3	Uncertain significance (-)
14-20447530-AAG-A			Benign (Jan 26, 2024)
14-20447595-C-G			Likely benign (Nov 08, 2022)
14-20447598-AG-A			Likely benign (Dec 11, 2023)
14-20447601-GAA-G			Benign (Oct 19, 2023)
14-20447624-G-A			Likely benign (Sep 27, 2022)
14-20447634-G-A		Inborn genetic diseases	Uncertain significance (Aug 21, 2017)
14-20447637-G-A			Uncertain significance (Mar 16, 2022)
14-20447643-C-T		Galloway-Mowat syndrome 3 • Inborn genetic diseases	Uncertain significance (Jun 15, 2021)
14-20447645-C-A		Galloway-Mowat syndrome 3	Likely pathogenic (-)
14-20447645-C-T		Galloway-Mowat syndrome 3	Pathogenic (Jun 08, 2020)
14-20447646-G-A		Galloway-Mowat syndrome 3 • Inborn genetic diseases	Likely pathogenic (Feb 23, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
OSGEP	protein_coding	protein_coding	ENST00000206542	11	8695

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.08e-8	0.708	125713	0	35	125748	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.759	177	208	0.852	0.0000116	2165
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000242	0.000242
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000272	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000159	0.000158
Middle Eastern	0.000272	0.000272
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: tRNA modification in the nucleus and cytosol;tRNA processing;Metabolism of RNA (Consensus)

Recessive Scores

• pRec: 0.236

Intolerance Scores

• loftool: 0.748
• rvis_EVS: -0.29
• rvis_percentile_EVS: 32.94

Haploinsufficiency Scores

• pHI: 0.128
• hipred: Y
• hipred_score: 0.564
• ghis: 0.610

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.909

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Osgep

Zebrafish Information Network

• Gene name: osgep
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: decreased diameter

Gene ontology

• Biological process: tRNA threonylcarbamoyladenosine modification
• Cellular component: EKC/KEOPS complex;nucleus;nucleoplasm;cytoplasm;plasma membrane;nuclear speck
• Molecular function: protein binding;metal ion binding;N(6)-L-threonylcarbamoyladenine synthase activity