OSGEP

Summary

OSGEP (O-sialoglycoprotein endopeptidase, HGNC:18028) is a protein-coding gene on chromosome 14q11.2, encoding tRNA N6-adenosine threonylcarbamoyltransferase (Q9NPF4). 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. It is a common-essential gene (DepMap: required in 97.9% of cancer cell lines).

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.

Source: NCBI Gene 55644 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Galloway-Mowat syndrome 3 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 128 total — 5 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 66
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 97.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_017807

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18028
Approved symbol	OSGEP
Name	O-sialoglycoprotein endopeptidase
Location	14q11.2
Locus type	gene with protein product
Status	Approved
Aliases	PRSMG1, GCPL1, OSGEP1, KAE1, TCS3
Ensembl gene	ENSG00000092094
Ensembl biotype	protein_coding
OMIM	610107
Entrez	55644

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 7 retained_intron, 6 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000206542, ENST00000553292, ENST00000553640, ENST00000554249, ENST00000554699, ENST00000554915, ENST00000555223, ENST00000555656, ENST00000555785, ENST00000556124, ENST00000556252, ENST00000556439, ENST00000883549, ENST00000883550, ENST00000923861, ENST00000956270

RefSeq mRNA: 1 — MANE Select: NM_017807 NM_017807

CCDS: CCDS9549

Canonical transcript exons

ENST00000206542 — 11 exons

Exon	Start	End
ENSE00000652706	20447615	20447690
ENSE00000652708	20447904	20447994
ENSE00001096482	20448106	20448171
ENSE00001245415	20449171	20449266
ENSE00002469128	20454569	20454812
ENSE00002473375	20446401	20447279
ENSE00003469195	20447422	20447520
ENSE00003578105	20448964	20449013
ENSE00003624664	20451974	20452149
ENSE00003627034	20452329	20452448
ENSE00003685348	20448733	20448811

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 97.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.7650 / max 181.0884, expressed in 1819 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142029	19.2278	1815
142028	4.2010	1645
142031	2.4534	956
142030	0.7730	491
142027	0.1098	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	97.35	gold quality
cerebellar hemisphere	UBERON:0002245	97.23	gold quality
cerebellar cortex	UBERON:0002129	97.06	gold quality
adenohypophysis	UBERON:0002196	96.20	gold quality
right lobe of thyroid gland	UBERON:0001119	95.62	gold quality
granulocyte	CL:0000094	95.49	gold quality
left lobe of thyroid gland	UBERON:0001120	95.27	gold quality
right uterine tube	UBERON:0001302	95.22	gold quality
right ovary	UBERON:0002118	95.14	gold quality
left ovary	UBERON:0002119	94.77	gold quality
cerebellum	UBERON:0002037	94.57	gold quality
right frontal lobe	UBERON:0002810	94.42	gold quality
endocervix	UBERON:0000458	94.37	gold quality
body of uterus	UBERON:0009853	94.32	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.30	gold quality
spleen	UBERON:0002106	94.13	gold quality
pituitary gland	UBERON:0000007	94.04	gold quality
tibial nerve	UBERON:0001323	94.02	gold quality
thyroid gland	UBERON:0002046	93.99	gold quality
ectocervix	UBERON:0012249	93.77	gold quality
left uterine tube	UBERON:0001303	93.55	gold quality
transverse colon	UBERON:0001157	93.51	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.46	gold quality
metanephros cortex	UBERON:0010533	93.37	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.20	gold quality
right coronary artery	UBERON:0001625	93.09	gold quality
mucosa of transverse colon	UBERON:0004991	93.06	gold quality
right adrenal gland cortex	UBERON:0035827	92.96	gold quality
body of pancreas	UBERON:0001150	92.91	gold quality
ganglionic eminence	UBERON:0004023	92.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.66

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): APEX1

miRNA regulators (miRDB)

22 targeting OSGEP, 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-23B-5P	99.98	66.07	587
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-3913-3P	99.74	66.53	938
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-12120	98.05	68.44	1768
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-3198	97.84	65.64	579
HSA-MIR-4309	97.84	65.45	588
HSA-MIR-4714-5P	97.04	67.76	955
HSA-MIR-3976	96.67	67.79	1187

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 4)

• Mutation in KAE1 interfering with global protein production was identified in two patients with developmental delay, renal defect and hypomagnesemia. (PMID:28272532)
• This gene was recently identified as causative of Galloway-Mowat syndrome in a large cohort of 907 individuals with nephrotic syndrome. (PMID:30975089)
• The structural and functional workings of KEOPS. (PMID:34614169)
• Novel variants in OSGEP leading to Galloway-Mowat syndrome by altering its subcellular localization. (PMID:34666032)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	osgep	ENSDARG00000045846
mus_musculus	Osgep	ENSMUSG00000006289
rattus_norvegicus	Osgep	ENSRNOG00000009333
drosophila_melanogaster	Tcs3	FBGN0283681
caenorhabditis_elegans		WBGENE00022166

Paralogs (1): OSGEPL1 (ENSG00000128694)

Protein

Protein identifiers

tRNA N6-adenosine threonylcarbamoyltransferase — Q9NPF4 (reviewed: Q9NPF4)

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

All UniProt accessions (3): Q9NPF4, G3V249, G3V445

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Component of the EKC/KEOPS complex composed of at least GON7, TP53RK, TPRKB, OSGEP and LAGE3; the whole complex dimerizes. Interacts with PRAME.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Widely expressed at low level. Expressed in heart, placenta, liver, kidney, lung, brain, skeletal muscle and pancreas.

Disease relevance. Galloway-Mowat syndrome 3 (GAMOS3) [MIM:617729] A form of Galloway-Mowat syndrome, a severe renal-neurological disease characterized by early-onset nephrotic syndrome associated with microcephaly, central nervous system abnormalities, developmental delays, and a propensity for seizures. Brain anomalies include gyration defects ranging from lissencephaly to pachygyria and polymicrogyria, and cerebellar hypoplasia. Most patients show facial dysmorphism characterized by a small, narrow forehead, large/floppy ears, deep-set eyes, hypertelorism and micrognathia. Additional variable features are visual impairment and arachnodactyly. Most patients die in early childhood. The disease is caused by variants affecting the gene represented in this entry.

Cofactor. Binds 1 divalent metal cation per subunit.

Similarity. Belongs to the KAE1 / TsaD family.

RefSeq proteins (1): NP_060277* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000905	Gcp-like_dom	Domain
IPR017860	Peptidase_M22_CS	Conserved_site
IPR017861	KAE1/TsaD	Family
IPR034680	Kae1_archaea_euk	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 (49 total): sequence variant 14, helix 13, strand 11, binding site 9, chain 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6GWJ	X-RAY DIFFRACTION	1.95
9FL9	ELECTRON MICROSCOPY	3.74

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPF4-F1	96.60	0.97

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): 109; 113; 130–134; 130; 162; 177; 181; 266; 294

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6782315	tRNA modification in the nucleus and cytosol

MSigDB gene sets: 0 (showing top):

GO Biological Process (4): tRNA threonylcarbamoyladenosine modification (GO:0002949), tRNA modification (GO:0006400), tRNA processing (GO:0008033), tRNA threonylcarbamoyladenosine metabolic process (GO:0070525)

GO Molecular Function (6): metal ion binding (GO:0046872), tRNA N(6)-L-threonylcarbamoyladenine synthase activity (GO:0061711), protein binding (GO:0005515), transferase activity (GO:0016740), acyltransferase activity (GO:0016746), acyltransferase activity, transferring groups other than amino-acyl groups (GO:0016747)

GO Cellular Component (5): EKC/KEOPS complex (GO:0000408), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

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
cellular anatomical structure	3
tRNA metabolic process	2
tRNA modification	1
tRNA processing	1
RNA modification	1
RNA processing	1
cation binding	1
acyltransferase activity, transferring groups other than amino-acyl groups	1
catalytic activity, acting on a tRNA	1
binding	1
catalytic activity	1
transferase activity	1
acyltransferase activity	1
transferase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

2452 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OSGEP	LAGE3	Q14657	998
OSGEP	TPRKB	Q9Y3C4	998
OSGEP	TP53RK	Q96S44	997
OSGEP	GON7	Q9BXV9	966
OSGEP	SLC4A1AP	Q9BWU0	943
OSGEP	EMCN	Q9ULC0	901
OSGEP	YRDC	Q86U90	872
OSGEP	SLC4A1	P02730	719
OSGEP	ILK	P57043	672
OSGEP	CA2	P00918	615
OSGEP	WDR73	Q6P4I2	614
OSGEP	MUC1	P13931	561
OSGEP	NPHS1	O60500	553
OSGEP	ARPC1B	O15143	536
OSGEP	POLR1B	Q9H9Y6	501

IntAct

84 interactions, top by confidence:

A	B	Type	Score
UBA5	GABARAPL2	psi-mi:“MI:0914”(association)	0.950
GON7	LAGE3	psi-mi:“MI:0915”(physical association)	0.880
GON7	LAGE3	psi-mi:“MI:0914”(association)	0.880
LAGE3	OSGEP	psi-mi:“MI:0915”(physical association)	0.850
TP53RK	GON7	psi-mi:“MI:0914”(association)	0.820
TP53RK	NUP43	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
IFT81	NDC80	psi-mi:“MI:0914”(association)	0.640
NUP43	NUP98	psi-mi:“MI:0914”(association)	0.640
BAG3	OSGEP	psi-mi:“MI:0915”(physical association)	0.560
POP7	RPP40	psi-mi:“MI:0914”(association)	0.530
ANO4	ANO6	psi-mi:“MI:0914”(association)	0.530
LAGE3	CTSA	psi-mi:“MI:0914”(association)	0.530
MBIP	TADA2A	psi-mi:“MI:0914”(association)	0.530
CCDC28B	HSPA1L	psi-mi:“MI:0914”(association)	0.510
rep	NKRF	psi-mi:“MI:0914”(association)	0.500
OSGEP	REX1BD	psi-mi:“MI:0915”(physical association)	0.370
OSGEP	RBM48	psi-mi:“MI:0915”(physical association)	0.370
CIAPIN1	OSGEP	psi-mi:“MI:0915”(physical association)	0.370
OSGEP	CRIP2	psi-mi:“MI:0915”(physical association)	0.370
HPS6	OSGEP	psi-mi:“MI:0915”(physical association)	0.370
LENG1	OSGEP	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (197): OSGEP (Affinity Capture-MS), C14orf142 (Affinity Capture-MS), LAGE3 (Affinity Capture-MS), TPRKB (Affinity Capture-MS), NUP43 (Affinity Capture-MS), HYKK (Affinity Capture-MS), POP7 (Affinity Capture-MS), GLRX3 (Co-fractionation), ILF2 (Co-fractionation), LAGE3 (Co-fractionation), NAA10 (Co-fractionation), NFYB (Co-fractionation), OSGEP (Co-fractionation), OSGEP (Co-fractionation), OSGEP (Co-fractionation)

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: A0B5S0, A1CM94, A1JQW9, A1RVQ8, A1RXD1, A1VM52, A2BJY9, A2SR70, A3CXS0, A3DMS9, A3MSX6, A4FZ86, A4WKT1, A4YIW0, A5IEF9, A5UMH5, A6US28, A6VJ51, A7SXZ6, A8A948, A8MCC8, A9A6L6, B1Y8P8, B4RY33, B4SHI9, B6YUD9, B8F7W7, C3MQY4, C3MWX2, C3N6N9, C3N752, C3NGI3, C4KIB0, C5A3G1, C6A5J5, O05518, O27476, O29153, O57716, O66986

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	7
Uncertain significance	53
Likely benign	37
Benign	14

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
1379064	NM_017807.4(OSGEP):c.912G>A (p.Trp304Ter)	Pathogenic
1483962	NM_017807.4(OSGEP):c.739C>T (p.Arg247Ter)	Pathogenic
3629270	NM_017807.4(OSGEP):c.496C>T (p.Arg166Ter)	Pathogenic
444886	NM_017807.4(OSGEP):c.974G>A (p.Arg325Gln)	Pathogenic
4808706	NM_017807.4(OSGEP):c.901C>T (p.Gln301Ter)	Pathogenic
1236169	NM_017807.4(OSGEP):c.695C>A (p.Ser232Tyr)	Likely pathogenic
1236170	NM_017807.4(OSGEP):c.839G>T (p.Arg280Leu)	Likely pathogenic
1684038	NM_017807.4(OSGEP):c.560G>T (p.Gly187Val)	Likely pathogenic
2002672	NM_017807.4(OSGEP):c.703-2A>C	Likely pathogenic
4803443	NM_017807.4(OSGEP):c.870-2A>G	Likely pathogenic
599157	NM_017807.4(OSGEP):c.892A>T (p.Met298Leu)	Likely pathogenic
992324	NM_017807.4(OSGEP):c.556C>T (p.Arg186Ter)	Likely pathogenic

SpliceAI

1381 predictions. Top by Δscore:

Variant	Effect	Δscore
14:20447417:CTCA:C	donor_loss	1.0000
14:20447418:TCACC:T	donor_loss	1.0000
14:20447419:CACCT:C	donor_loss	1.0000
14:20447420:ACC:A	donor_loss	1.0000
14:20447421:C:CA	donor_loss	1.0000
14:20447421:CCT:C	donor_gain	1.0000
14:20447517:GAAT:G	acceptor_gain	1.0000
14:20447518:AATC:A	acceptor_loss	1.0000
14:20447519:AT:A	acceptor_gain	1.0000
14:20447521:C:CC	acceptor_gain	1.0000
14:20447521:C:CG	acceptor_loss	1.0000
14:20447526:A:AC	acceptor_gain	1.0000
14:20447526:A:C	acceptor_gain	1.0000
14:20447609:CTTTA:C	donor_loss	1.0000
14:20447610:TTTA:T	donor_loss	1.0000
14:20447611:TTA:T	donor_loss	1.0000
14:20447612:TACC:T	donor_loss	1.0000
14:20447613:A:AC	donor_gain	1.0000
14:20447614:C:CC	donor_gain	1.0000
14:20447614:CCT:C	donor_gain	1.0000
14:20447614:CCTCT:C	donor_gain	1.0000
14:20447621:T:C	donor_gain	1.0000
14:20447686:ATTAC:A	acceptor_gain	1.0000
14:20447687:TTAC:T	acceptor_gain	1.0000
14:20447688:TAC:T	acceptor_gain	1.0000
14:20447689:AC:A	acceptor_gain	1.0000
14:20447690:CC:C	acceptor_gain	1.0000
14:20447690:CCTA:C	acceptor_loss	1.0000
14:20447691:C:CC	acceptor_gain	1.0000
14:20447694:C:CT	acceptor_gain	1.0000

AlphaMissense

2167 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:20447509:T:A	D294V	1.000
14:20447505:A:C	N295K	0.999
14:20447505:A:T	N295K	0.999
14:20447508:G:C	D294E	0.999
14:20447508:G:T	D294E	0.999
14:20447509:T:G	D294A	0.999
14:20447510:C:G	D294H	0.999
14:20447915:C:T	G261E	0.999
14:20449193:T:A	D162V	0.999
14:20449193:T:G	D162A	0.999
14:20449205:C:A	G158V	0.999
14:20449205:C:T	G158D	0.999
14:20451980:A:C	N135K	0.999
14:20451980:A:T	N135K	0.999
14:20451987:C:T	G133E	0.999
14:20451989:A:C	S132R	0.999
14:20451989:A:T	S132R	0.999
14:20451990:C:A	S132I	0.999
14:20451991:T:G	S132R	0.999
14:20452055:A:C	C110W	0.999
14:20452056:C:T	C110Y	0.999
14:20452058:G:C	H109Q	0.999
14:20452058:G:T	H109Q	0.999
14:20452060:G:C	H109D	0.999
14:20452061:G:C	N108K	0.999
14:20452061:G:T	N108K	0.999
14:20447251:A:G	W333R	0.998
14:20447251:A:T	W333R	0.998
14:20447509:T:C	D294G	0.998
14:20447510:C:A	D294Y	0.998

dbSNP variants (sampled 300 via entrez): RS1000814795 (14:20454049 C>A), RS1001209361 (14:20454012 C>CT), RS1001259122 (14:20449760 C>G), RS1001360753 (14:20455058 G>A), RS1001429585 (14:20455207 T>C,G), RS1001607147 (14:20449501 A>G), RS1002187642 (14:20446893 T>C), RS1002209869 (14:20450879 G>A), RS1002386972 (14:20447182 G>GC), RS1002463226 (14:20456180 G>C,T), RS1002982802 (14:20446207 A>G), RS1003236982 (14:20451826 C>T), RS1003390179 (14:20445965 C>CAGG), RS1003986206 (14:20447688 T>C), RS1004505521 (14:20453753 G>A)

Disease associations

OMIM: gene MIM:610107 | disease phenotypes: MIM:617729, MIM:251300, MIM:616738

GenCC curated gene-disease

Disease	Classification	Inheritance
Galloway-Mowat syndrome 3	Strong	Autosomal recessive
Galloway-Mowat syndrome	Supportive	Autosomal recessive

Mondo (5): Galloway-Mowat syndrome 3 (MONDO:0033007), Galloway-Mowat syndrome (MONDO:0009627), neurodevelopmental disorder (MONDO:0700092), nephrotic syndrome (MONDO:0005377), radioulnar synostosis with amegakaryocytic thrombocytopenia 2 (MONDO:0014758)

Orphanet (2): Galloway-Mowat syndrome (Orphanet:2065), Radio-ulnar synostosis-amegakaryocytic thrombocytopenia syndrome (Orphanet:71289)

HPO phenotypes

66 total (30 of 66 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000093	Proteinuria
HP:0000096	Glomerular sclerosis
HP:0000100	Nephrotic syndrome
HP:0000112	Nephropathy
HP:0000160	Narrow mouth
HP:0000164	Abnormality of the dentition
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000340	Sloping forehead
HP:0000341	Narrow forehead
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000505	Visual impairment
HP:0000568	Microphthalmia
HP:0000601	Hypotelorism
HP:0000639	Nystagmus
HP:0000750	Delayed speech and language development
HP:0000767	Pectus excavatum
HP:0000822	Hypertension
HP:0000969	Edema
HP:0001166	Arachnodactyly
HP:0001181	Adducted thumb
HP:0001249	Intellectual disability

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003489_7	Food addiction	7.000000e-07

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007829	eating behaviour
EFO:0007830	food addiction measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D009404	Nephrotic Syndrome	C12.050.351.968.419.630.643; C12.200.777.419.630.643; C12.950.419.630.643
D065886	Neurodevelopmental Disorders	F03.625
C537548	Galloway Mowat syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067088 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1760944	Efficacy	3	cisplatin;fluorouracil;radiotherapy	Carcinoma;Squamous Cell;Overall survival

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1130409	APEX1, OSGEP		0.00	0
rs2307486	APEX1, OSGEP		0.00	0
rs1760944	APEX1, OSGEP	3	2.25	1	cisplatin;fluorouracil;radiotherapy

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.14	Kd	7260	nM	CHEMBL3752910
5.12	ED50	7564	nM	CHEMBL3752910
5.09	Kd	8134	nM	CHEMBL5653589
5.07	ED50	8475	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148919: Binding affinity to human OSGEP incubated for 45 mins by Kinobead based pull down assay	kd	7.2602	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148919: Binding affinity to human OSGEP incubated for 45 mins by Kinobead based pull down assay	kd	8.1343	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases expression	4
sodium arsenite	decreases expression, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Temozolomide	increases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Cadmium	increases abundance, increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Selenium	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Asbestos, Crocidolite	decreases expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651961	Binding	Binding affinity to human OSGEP incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00308321	PHASE4	UNKNOWN	Long Term Tapering or Standard Steroids for Nephrotic Syndrome
NCT01021540	PHASE4	COMPLETED	Prospective Study Evaluating the Effect of Repository Corticotropin in the Treatment of Various Nephrotic Syndromes
NCT01028287	PHASE4	COMPLETED	Adrenocorticotropic Hormone (ACTH) Treatment of Nephrotic Range Proteinuria in Diabetic Nephropathy (NRDN)
NCT01162005	PHASE4	COMPLETED	Therapeutic Effect of Tacrolimus on Primary Nephrotic Syndrome in Children
NCT01895894	PHASE4	COMPLETED	Mycophenolate Mofetil in Pediatric Steroid Dependent Nephrotic Syndrome
NCT02238418	PHASE4	COMPLETED	Efficacy of Usual Vitamin D Supplementation and Its Impact on Children and Adolescents Calciuria.
NCT02382575	PHASE4	UNKNOWN	Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Resistant Nephrotic Syndrome
NCT02427880	PHASE4	COMPLETED	Role of Acetazolamide and Hydrochlorothiazide Followed by Furosemide in Treating Nephrotic Edema
NCT03210688	PHASE4	COMPLETED	Active Vitamin D And Reduced Dose Prednisolone for Treatment in Minimal Change Nephropathy
NCT03347357	PHASE4	COMPLETED	Pharmacokinetics of Tacrolimus in Children
NCT05696977	PHASE4	UNKNOWN	Effect of Obesity on Cyclosporine Blood Trough Level in Nephrotic Syndrome Patients
NCT05966818	PHASE4	UNKNOWN	Effect of Dapagliflozin in Non-Diabetic Patients With Nephrotic Syndrome.
NCT06026787	PHASE4	COMPLETED	Clinical Value of Adding Dapagliflozin in Patients With Nephrotic Syndrome
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00354731	PHASE3	COMPLETED	Efficacy of Pentoxifylline on Primary Nephrotic Syndrome
NCT00615667	PHASE3	COMPLETED	Prospective, Multicenter Study of the Efficacy and Tolerance of Tacrolimus on Refractory Nephrotic Syndrome (RNS)
NCT00981838	PHASE3	COMPLETED	Rituximab in Multirelapsing Minimal Change Disease (MCD) or Focal Segmental Glomerulosclerosis (FSGS)
NCT01197040	PHASE3	COMPLETED	Evaluation of Low Dose Corticosteroids Efficiency, Associated With Myfortic ® in the Treatment of Nephrotic Syndrome
NCT01309477	PHASE3	COMPLETED	The Efficacy and Tolerance of Tacrolimus Sustained-release Capsules on Refractory Nephrotic Syndrome (RNS)
NCT02132195	PHASE3	COMPLETED	Adrenocorticotropic Hormone (ACTH) for Frequently Relapsing and Steroid Dependent Nephrotic Syndrome
NCT02257697	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mizoribine in the Treatment of Refractory Nephrotic Syndrome
NCT02438982	PHASE3	COMPLETED	Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Dependent Nephrotic Syndrome
NCT03141970	PHASE3	COMPLETED	Prednisolone Trial in Children Younger Than 4 Years
NCT03501459	PHASE3	UNKNOWN	Lymphocyte Markers As Predictors Of Responsiveness To Rituximab Among Patients With Idiopathic Nephrotic Syndrome
NCT05079789	PHASE3	TERMINATED	Amiloride in Nephrotic Syndrome
NCT05716880	PHASE3	RECRUITING	Ketoanalogues for Muscle Mass Loss in Nephrotic Syndrome
NCT06635720	PHASE3	ACTIVE_NOT_RECRUITING	REduced-dose Steroid PrOtocol for Childhood Nephrotic SyndromE (RESPONSE)
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00001212	PHASE2	COMPLETED	Drug Therapy in Lupus Nephropathy
NCT00001959	PHASE2	COMPLETED	Pirfenidone to Treat Kidney Disease (Focal Segmental Glomerulosclerosis)
NCT00004466	PHASE2	TERMINATED	Pilot Study of Atorvastatin in Children With Chronic Hyperlipidemia Secondary to Nephrotic Syndrome
NCT00004990	PHASE2	COMPLETED	Once-A-Month Steroid Treatment for Patients With Focal Segmental Glomerulosclerosis
NCT00977977	PHASE2	RECRUITING	Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy