OSGEPL1

Summary

OSGEPL1 (O-sialoglycoprotein endopeptidase like 1, HGNC:23075) is a protein-coding gene on chromosome 2q32.2, encoding tRNA N6-adenosine threonylcarbamoyltransferase, mitochondrial (Q9H4B0). Required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in mitochondrial tRNAs that read codons beginning with adenine.

Enables N(6)-L-threonylcarbamoyladenine synthase activity. Involved in tRNA threonylcarbamoyladenosine modification. Is active in mitochondrion.

Source: NCBI Gene 64172 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 5 total
• MANE Select transcript: NM_022353

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23075
Approved symbol	OSGEPL1
Name	O-sialoglycoprotein endopeptidase like 1
Location	2q32.2
Locus type	gene with protein product
Status	Approved
Aliases	Qri7, OSGEPL
Ensembl gene	ENSG00000128694
Ensembl biotype	protein_coding
OMIM	619634
Entrez	64172

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 12 protein_coding, 2 retained_intron

ENST00000264151, ENST00000517895, ENST00000518114, ENST00000519810, ENST00000520350, ENST00000521630, ENST00000522700, ENST00000524043, ENST00000868797, ENST00000868798, ENST00000937445, ENST00000937446, ENST00000937447, ENST00000958410

RefSeq mRNA: 20 — MANE Select: NM_022353 NM_001354347, NM_001376077, NM_001376078, NM_001376079, NM_001376080, NM_001376081, NM_001376082, NM_001376083, NM_001376084, NM_001376085, NM_001376088, NM_001376092, NM_001376094, NM_001376095, NM_001376097, NM_001376098, NM_001376099, NM_001376100, NM_001376101, NM_022353

CCDS: CCDS46472

Canonical transcript exons

ENST00000264151 — 9 exons

Exon	Start	End
ENSE00000964750	189750550	189750656
ENSE00001429667	189746660	189747168
ENSE00001785467	189754141	189754345
ENSE00003583748	189752849	189752979
ENSE00003589291	189761420	189761660
ENSE00003591726	189752653	189752724
ENSE00003789742	189755173	189755560
ENSE00003790676	189753916	189754064
ENSE00003848689	189762685	189762792

Expression profiles

Bgee: expression breadth ubiquitous, 266 present calls, max score 88.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.8950 / max 191.9413, expressed in 1552 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
32877	5.8950	1552

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
biceps brachii	UBERON:0001507	88.20	gold quality
germinal epithelium of ovary	UBERON:0001304	87.95	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.54	gold quality
secondary oocyte	CL:0000655	86.47	gold quality
vastus lateralis	UBERON:0001379	86.16	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	86.12	gold quality
calcaneal tendon	UBERON:0003701	85.52	gold quality
adrenal tissue	UBERON:0018303	85.29	gold quality
quadriceps femoris	UBERON:0001377	84.88	gold quality
pigmented layer of retina	UBERON:0001782	84.43	gold quality
retina	UBERON:0000966	84.41	gold quality
right adrenal gland	UBERON:0001233	84.40	gold quality
tendon	UBERON:0000043	84.26	gold quality
right adrenal gland cortex	UBERON:0035827	83.88	gold quality
buccal mucosa cell	CL:0002336	83.78	gold quality
tendon of biceps brachii	UBERON:0008188	83.48	gold quality
parietal pleura	UBERON:0002400	83.10	gold quality
left adrenal gland	UBERON:0001234	83.02	gold quality
adrenal gland	UBERON:0002369	82.90	gold quality
adrenal cortex	UBERON:0001235	82.84	gold quality
right ovary	UBERON:0002118	82.83	gold quality
ovary	UBERON:0000992	82.72	gold quality
left adrenal gland cortex	UBERON:0035825	82.61	gold quality
triceps brachii	UBERON:0001509	82.56	gold quality
left ovary	UBERON:0002119	82.42	gold quality
hindlimb stylopod muscle	UBERON:0004252	82.30	gold quality
skeletal muscle tissue	UBERON:0001134	82.28	gold quality
tibia	UBERON:0000979	82.18	gold quality
cerebellar hemisphere	UBERON:0002245	81.99	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.10

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

38 targeting OSGEPL1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-1264	99.25	66.81	1317
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-5583-3P	99.06	65.68	1018
HSA-MIR-3145-3P	98.85	69.07	2031
HSA-MIR-11399	98.71	65.69	869
HSA-MIR-3136-5P	98.53	67.68	793

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	osgepl1	ENSDARG00000000651
mus_musculus	Osgepl1	ENSMUSG00000026096
rattus_norvegicus	Osgepl1	ENSRNOG00000004001
drosophila_melanogaster	Tcs4	FBGN0031060
caenorhabditis_elegans		WBGENE00007237

Paralogs (1): OSGEP (ENSG00000092094)

Protein

Protein identifiers

tRNA N6-adenosine threonylcarbamoyltransferase, mitochondrial — Q9H4B0 (reviewed: Q9H4B0)

Alternative names: N6-L-threonylcarbamoyladenine synthase, O-sialoglycoprotein endopeptidase-like protein 1, t(6)A37 threonylcarbamoyladenosine biosynthesis protein OSGEPL1, tRNA threonylcarbamoyladenosine biosynthesis protein OSGEPL1

All UniProt accessions (4): Q9H4B0, E5RGZ1, E5RIL9, E7EVL7

UniProt curated annotations — full annotation on UniProt →

Function. Required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in mitochondrial tRNAs that read codons beginning with adenine. Probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37. Involved in mitochondrial genome maintenance.

Subunit / interactions. Monomer.

Subcellular location. Mitochondrion.

Tissue specificity. Widely expressed, with maximum expression in pituitary gland, prostate, rectum and uterus.

Cofactor. Binds 1 divalent metal cation per subunit.

Similarity. Belongs to the KAE1 / TsaD family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H4B0-1	1	yes
Q9H4B0-2	2
Q9H4B0-3	3

RefSeq proteins (20): NP_001341276, NP_001363006, NP_001363007, NP_001363008, NP_001363009, NP_001363010, NP_001363011, NP_001363012, NP_001363013, NP_001363014, NP_001363017, NP_001363021, NP_001363023, NP_001363024, NP_001363026, NP_001363027, NP_001363028, NP_001363029, NP_001363030, NP_071748* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000905	Gcp-like_dom	Domain
IPR017861	KAE1/TsaD	Family
IPR022450	TsaD	Family
IPR043129	ATPase_NBD	Homologous_superfamily

Pfam: PF00814

Catalyzed reactions (Rhea), 1 shown:

• L-threonylcarbamoyladenylate + adenosine(37) in tRNA = N(6)-L-threonylcarbamoyladenosine(37) in tRNA + AMP + H(+) (RHEA:37059)

UniProt features (27 total): binding site 9, modified residue 6, sequence conflict 4, splice variant 3, mutagenesis site 2, transit peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H4B0-F1	90.80	0.85

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (9): 358; 147; 151; 169–173; 202; 222; 226; 329–330; 357

Post-translational modifications (6): 74, 140, 203, 230, 240, 299

Mutagenesis-validated functional residues (2):

Position	Phenotype
203	mimics acetylation; decreased formation of trna threonylcarbamoyladenosine modification.
299	mimics acetylation; increased formation of trna threonylcarbamoyladenosine modification.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6787450	tRNA modification in the mitochondrion

MSigDB gene sets: 107 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, GOBP_TRNA_METABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_RNA_MODIFICATION, GOBP_MITOCHONDRIAL_RNA_PROCESSING, GOBP_MITOCHONDRIAL_RNA_METABOLIC_PROCESS, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, MAYBURD_RESPONSE_TO_L663536_DN, GOBP_TRNA_THREONYLCARBAMOYLADENOSINE_METABOLIC_PROCESS, GOBP_TRNA_PROCESSING, REACTOME_METABOLISM_OF_RNA, GOBP_TRNA_MODIFICATION, PARENT_MTOR_SIGNALING_UP, NUYTTEN_EZH2_TARGETS_DN

GO Biological Process (3): tRNA threonylcarbamoyladenosine modification (GO:0002949), mitochondrial tRNA modification (GO:0070900), tRNA processing (GO:0008033)

GO Molecular Function (5): metal ion binding (GO:0046872), tRNA N(6)-L-threonylcarbamoyladenine synthase activity (GO:0061711), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), acyltransferase activity, transferring groups other than amino-acyl groups (GO:0016747)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
tRNA processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
tRNA modification	2
mitochondrion	2
mitochondrial tRNA processing	1
mitochondrial RNA modification	1
RNA processing	1
tRNA metabolic process	1
cation binding	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
catalytic activity, acting on a tRNA	1
catalytic activity	1
transferase activity	1
acyltransferase activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1770 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OSGEPL1	YRDC	Q86U90	943
OSGEPL1	ANKAR	Q7Z5J8	932
OSGEPL1	GON7	Q9BXV9	885
OSGEPL1	TPRKB	Q9Y3C4	872
OSGEPL1	LAGE3	Q14657	852
OSGEPL1	TP53RK	Q96S44	842
OSGEPL1	TMF1	P82094	669
OSGEPL1	TRIT1	Q9H3H1	665
OSGEPL1	TRMT5	Q32P41	614
OSGEPL1	GTPBP3	Q969Y2	585
OSGEPL1	POLR1B	Q9H9Y6	583
OSGEPL1	CDK5RAP1	Q96SZ6	555
OSGEPL1	NEMP2	A6NFY4	541
OSGEPL1	TRMU	O75648	525
OSGEPL1	TARS2	Q9BW92	475

IntAct

5 interactions, top by confidence:

A	B	Type	Score
OSGEPL1	API5	psi-mi:“MI:0915”(physical association)	0.400
UQCRFS1	VWA8	psi-mi:“MI:0914”(association)	0.350
MCOLN2	POTEF	psi-mi:“MI:0914”(association)	0.350
CD3D	CLGN	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): OSGEPL1 (Proximity Label-MS), OSGEPL1 (Affinity Capture-MS), OSGEPL1 (Negative Genetic), OSGEPL1 (Affinity Capture-MS), OSGEPL1 (Affinity Capture-MS), OSGEPL1 (Affinity Capture-MS), OSGEPL1 (Co-fractionation), OSGEPL1 (Positive Genetic), OSGEPL1 (Affinity Capture-MS), OSGEPL1 (Affinity Capture-MS)

ESM2 similar proteins: A1CM94, A2SR70, A3CXS0, A4YIW0, A6VJ51, A7SXZ6, A9A6L6, B4RQ33, C6BTU8, O27476, O94637, P0CQ14, P0CQ15, P36132, P37228, P74535, Q0CH39, Q0P4K0, Q0TVK3, Q0VCI1, Q0W2P3, Q12WQ7, Q1E406, Q2FS43, Q2GXN6, Q2U9B5, Q42736, Q4I5V2, Q4V7F3, Q4WDE9, Q55GU1, Q5A6A4, Q5AYR1, Q5FAC2, Q5RHZ6, Q6BNC5, Q6CCZ5, Q6CJ48, Q6FLI1, Q758R9

Diamond homologs: A1AFY6, A1S3S8, A1UQZ7, A1WZH8, A3PG14, A4THT1, A4WWN6, A5E8T8, A5VSL6, A6UDR4, A6WXJ1, A7FE71, A7ZRU6, A8A4M1, A8APV4, A9IZF6, A9M8M3, A9N5Y7, A9R7E3, B0CIE0, B0TIN7, B1IRQ2, B1JM18, B1KHE2, B1LF56, B1XG69, B2K2I3, B2S843, B2U1G7, B3PQA4, B4EW57, B4T678, B4TVU2, B5BG20, B5YRA4, B5ZTC5, B6I436, B7LGZ9, B7LQD8, B7LZL4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

5 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1444 predictions. Top by Δscore:

Variant	Effect	Δscore
2:189752651:A:AC	donor_gain	1.0000
2:189752652:C:CC	donor_gain	1.0000
2:189753910:ACTT:A	donor_loss	1.0000
2:189753911:CTTA:C	donor_loss	1.0000
2:189753912:TTA:T	donor_loss	1.0000
2:189753913:TACCA:T	donor_loss	1.0000
2:189753914:A:AC	donor_gain	1.0000
2:189753914:ACCA:A	donor_loss	1.0000
2:189753915:C:CA	donor_loss	1.0000
2:189753915:C:CC	donor_gain	1.0000
2:189753915:CCAGT:C	donor_gain	1.0000
2:189754061:ATACC:A	acceptor_loss	1.0000
2:189754063:ACCT:A	acceptor_loss	1.0000
2:189754066:T:C	acceptor_loss	1.0000
2:189754259:T:TA	donor_gain	1.0000
2:189755408:C:CA	donor_gain	1.0000
2:189755422:AAGT:A	donor_gain	1.0000
2:189755425:T:TA	donor_gain	1.0000
2:189761418:A:AC	donor_gain	1.0000
2:189761419:C:CC	donor_gain	1.0000
2:189761419:CT:C	donor_gain	1.0000
2:189762566:CGTGA:C	donor_gain	1.0000
2:189750654:CAT:C	acceptor_gain	0.9900
2:189752645:C:CT	donor_gain	0.9900
2:189752833:ATAT:A	donor_gain	0.9900
2:189752843:GCTTA:G	donor_loss	0.9900
2:189752844:CTTAC:C	donor_loss	0.9900
2:189752845:TTAC:T	donor_loss	0.9900
2:189752846:TAC:T	donor_loss	0.9900
2:189752847:A:AC	donor_gain	0.9900

AlphaMissense

2700 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:189752870:T:A	D358V	0.998
2:189761506:A:C	S45R	0.997
2:189761506:A:T	S45R	0.997
2:189761508:T:G	S45R	0.997
2:189752869:A:C	D358E	0.996
2:189752869:A:T	D358E	0.996
2:189752870:T:G	D358A	0.996
2:189752871:C:G	D358H	0.996
2:189755389:G:C	S131R	0.996
2:189755389:G:T	S131R	0.996
2:189755391:T:G	S131R	0.996
2:189761487:C:G	A52P	0.996
2:189755343:G:C	H147D	0.993
2:189755413:G:C	S123R	0.993
2:189755413:G:T	S123R	0.993
2:189755415:T:G	S123R	0.993
2:189755444:G:T	A113E	0.993
2:189752953:G:C	N330K	0.992
2:189752953:G:T	N330K	0.992
2:189755523:G:C	H87D	0.992
2:189752870:T:C	D358G	0.991
2:189761493:C:G	A50P	0.991
2:189761501:T:A	D47V	0.991
2:189761513:T:A	E43V	0.991
2:189752871:C:A	D358Y	0.990
2:189753969:C:G	A304P	0.990
2:189755257:A:C	C175W	0.990
2:189755534:G:T	A83D	0.990
2:189752719:C:T	G367D	0.989
2:189755341:A:C	H147Q	0.989

dbSNP variants (sampled 300 via entrez): RS1000017156 (2:189762886 G>A,T), RS1000081282 (2:189757267 A>G), RS1000194293 (2:189760565 G>T), RS1000538019 (2:189757769 C>A,T), RS1000591391 (2:189756153 T>G), RS1000883596 (2:189748710 T>A), RS1001483476 (2:189750453 A>T), RS1001565889 (2:189747871 A>G), RS1001586996 (2:189758120 C>A,T), RS1001645808 (2:189757951 C>A,G), RS1001692537 (2:189761927 T>C), RS1001810857 (2:189755933 C>T), RS1001856421 (2:189763166 T>C,G), RS1001934378 (2:189750141 T>C), RS1002095311 (2:189754026 T>C)

Disease associations

OMIM: gene MIM:619634 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002578_1	Ferritin levels	2.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004459	ferritin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, decreases expression	3
Cisplatin	affects cotreatment, increases expression, decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Valproic Acid	affects expression, decreases methylation, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
dimethylselenide	decreases expression, increases expression, increases oxidation	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	decreases expression	1
Arsenic Trioxide	increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	decreases methylation	1
Lipopolysaccharides	increases expression, decreases expression, affects response to substance	1
Ozone	affects expression, increases abundance	1
Quercetin	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.