TPRKB

Summary

TPRKB (TP53RK binding protein, HGNC:24259) is a protein-coding gene on chromosome 2p13.1, encoding EKC/KEOPS complex subunit TPRKB (Q9Y3C4). 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.

Enables protein kinase binding activity. Involved in tRNA threonylcarbamoyladenosine modification. Located in cytosol and nucleus. Part of EKC/KEOPS complex. Implicated in Galloway-Mowat syndrome 5.

Source: NCBI Gene 51002 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): Galloway-Mowat syndrome 5 (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 74 total — 1 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 31 tissues, sQTL in 37 (q < 0.05)
• Constraint (gnomAD): pLI 0.31 (intermediate), LOEUF 0.94 (unconstrained)
• MANE Select transcript: NM_016058

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24259
Approved symbol	TPRKB
Name	TP53RK binding protein
Location	2p13.1
Locus type	gene with protein product
Status	Approved
Aliases	CGI-121, CGI121
Ensembl gene	ENSG00000144034
Ensembl biotype	protein_coding
OMIM	608680
Entrez	51002

Gene structure

Transcript identifiers

Ensembl transcripts: 76 — 63 protein_coding, 6 nonsense_mediated_decay, 5 protein_coding_CDS_not_defined, 2 retained_intron

MANE Select: ENST00000272424

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 3, TSL 3: 1, TSL 4: 2, TSL 5: 3

ENST00000272424, ENST00000318190, ENST00000409716, ENST00000462166, ENST00000463231, ENST00000470012, ENST00000484969, ENST00000485758, ENST00000489476, ENST00000497464, ENST00000904803, ENST00000904804, ENST00000904805, ENST00000904806, ENST00000904807, ENST00000904808, ENST00000904809, ENST00000904810, ENST00000904811, ENST00000939335, ENST00000939336, ENST00000939337, ENST00000939338, ENST00000939339, ENST00000939340, ENST00000939341, ENST00000939342, ENST00000939343, ENST00000939344, ENST00000939345, ENST00000939346, ENST00000939347, ENST00000939348, ENST00000939349, ENST00000939350, ENST00000939351, ENST00000939352, ENST00000939353, ENST00000939354, ENST00000939355, ENST00000939356, ENST00000939357, ENST00000939358, ENST00000939359, ENST00000939360, ENST00000939361, ENST00000939362, ENST00000939363, ENST00000965314, ENST00000992914, ENST00000992915, ENST00000992916, ENST00000992917, ENST00000992918, ENST00001050825, ENST00001075209, ENST00001075215, ENST00001075216, ENST00001098762, ENST00001098763, ENST00001098764, ENST00001098765, ENST00001098766, ENST00001098767, ENST00001098768, ENST00001098769, ENST00001098770, ENST00001113805, ENST00001129720, ENST00001129721, ENST00001129722, ENST00001129723, ENST00001129724, ENST00001129725, ENST00001129726, ENST00001138999

RefSeq mRNA: 8 — MANE Select: NM_016058 NM_001330386, NM_001330387, NM_001330388, NM_001330389, NM_001330390, NM_001330391, NM_001330392, NM_016058

CCDS: CCDS1927, CCDS82471

Canonical transcript exons

ENST00000272424 — 5 exons

Exon	Start	End
ENSE00000963339	73729873	73730029
ENSE00003463429	73732163	73732285
ENSE00003638996	73734429	73734591
ENSE00003653356	73730560	73730736
ENSE00003894433	73737302	73737345

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 97.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.0825 / max 448.9475, expressed in 1802 samples.

Highest expression (Bgee): uterine tube, ganglionic eminence, testis, monocyte, mononuclear cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

TPRKB is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 31 tissues and its splicing (sQTL) in 37 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 68 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	4.1e-26	+0.30	2:73809191:T:C
Artery Tibial	sqtl	2.1e-22	-0.59	2:73737715:G:C
Pancreas	eqtl	5.5e-22	+0.46	2:73734184:T:C
Adipose Subcutaneous	sqtl	1.1e-21	-0.55	2:73763514:G:A
Esophagus Mucosa	eqtl	5.1e-21	+0.26	2:73748910:C:G
Skin Sun Exposed Lower leg	sqtl	2.2e-20	-0.49	2:73759294:C:T
Breast Mammary Tissue	sqtl	3.2e-20	-0.61	2:73729617:C:T
Thyroid	sqtl	1.7e-19	-0.56	2:73741096:G:A
Muscle Skeletal	eqtl	2.3e-19	+0.18	2:73711168:C:T
Skin Not Sun Exposed Suprapubic	sqtl	3.2e-19	-0.51	2:73737715:G:C
Esophagus Mucosa	sqtl	3.2e-19	-0.59	2:73737715:G:C
Artery Tibial	eqtl	4.5e-17	+0.24	2:73716957:A:G
Brain Spinal cord cervical c-1	eqtl	4.2e-15	-0.47	2:73710041:G:A
Nerve Tibial	sqtl	1.5e-13	-0.48	2:73728987:T:C
Esophagus Muscularis	eqtl	5.8e-13	-0.26	2:73543035:A:C
Cells Cultured fibroblasts	eqtl	8.2e-13	+0.12	2:73755847:C:T
Artery Aorta	eqtl	7.3e-12	+0.25	2:73695348:T:C
Adipose Visceral Omentum	sqtl	7.5e-12	-0.47	2:73763514:G:A
Esophagus Muscularis	sqtl	3.1e-11	+0.52	2:73715106:G:A
Cells Cultured fibroblasts	sqtl	4.1e-11	-0.39	2:73729617:C:T

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
29146	22.9887	1800
202237	0.5721	363
29145	0.5217	296

Top tissues by expression

showing 100 of 288 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.38	gold quality
ganglionic eminence	UBERON:0004023	97.07	gold quality
right testis	UBERON:0004534	95.86	gold quality
monocyte	CL:0000576	95.82	gold quality
left testis	UBERON:0004533	95.82	gold quality
mononuclear cell	CL:0000842	95.78	gold quality
embryo	UBERON:0000922	95.68	gold quality
leukocyte	CL:0000738	95.43	gold quality
calcaneal tendon	UBERON:0003701	95.33	gold quality
ventricular zone	UBERON:0003053	95.29	gold quality
cortical plate	UBERON:0005343	95.27	gold quality
gastrocnemius	UBERON:0001388	95.26	gold quality
rectum	UBERON:0001052	95.20	gold quality
muscle of leg	UBERON:0001383	95.19	gold quality
left ovary	UBERON:0002119	95.16	gold quality
right ovary	UBERON:0002118	95.10	gold quality
testis	UBERON:0000473	94.83	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.71	gold quality
muscle organ	UBERON:0001630	94.59	gold quality
islet of Langerhans	UBERON:0000006	94.57	gold quality
body of pancreas	UBERON:0001150	94.52	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.39	gold quality
left uterine tube	UBERON:0001303	94.32	gold quality
biceps brachii	UBERON:0001507	94.27	gold quality
lower esophagus mucosa	UBERON:0035834	94.22	gold quality
cerebellar hemisphere	UBERON:0002245	94.07	gold quality
ovary	UBERON:0000992	94.02	gold quality
cerebellar cortex	UBERON:0002129	94.00	gold quality
triceps brachii	UBERON:0001509	93.81	gold quality
body of uterus	UBERON:0009853	93.80	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.77	gold quality
heart left ventricle	UBERON:0002084	93.71	gold quality
endocervix	UBERON:0000458	93.66	gold quality
cardiac ventricle	UBERON:0002082	93.52	gold quality
esophagus mucosa	UBERON:0002469	93.43	gold quality
pancreas	UBERON:0001264	93.41	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.38	gold quality
right atrium auricular region	UBERON:0006631	93.33	gold quality
metanephros cortex	UBERON:0010533	93.33	gold quality
ectocervix	UBERON:0012249	93.24	gold quality
spinal cord	UBERON:0002240	93.03	gold quality
mucosa of transverse colon	UBERON:0004991	92.91	gold quality
minor salivary gland	UBERON:0001830	92.90	gold quality
heart	UBERON:0000948	92.89	gold quality
vastus lateralis	UBERON:0001379	92.89	gold quality
granulocyte	CL:0000094	92.88	gold quality
skeletal muscle tissue	UBERON:0001134	92.86	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.80	gold quality
left coronary artery	UBERON:0001626	92.76	gold quality
quadriceps femoris	UBERON:0001377	92.72	gold quality
gluteal muscle	UBERON:0002000	92.71	gold quality
cerebellum	UBERON:0002037	92.71	gold quality
esophagus	UBERON:0001043	92.65	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.59	gold quality
heart right ventricle	UBERON:0002080	92.49	gold quality
oral cavity	UBERON:0000167	92.45	gold quality
transverse colon	UBERON:0001157	92.45	gold quality
descending thoracic aorta	UBERON:0002345	92.44	gold quality
deltoid	UBERON:0001476	92.42	gold quality
jejunum	UBERON:0002115	92.42	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.34	gold quality
mouth mucosa	UBERON:0003729	92.32	gold quality
body of stomach	UBERON:0001161	92.31	gold quality
endometrium	UBERON:0001295	92.22	gold quality
duodenum	UBERON:0002114	92.21	gold quality
spleen	UBERON:0002106	92.15	gold quality
cardiac atrium	UBERON:0002081	92.13	gold quality
jejunal mucosa	UBERON:0000399	92.12	gold quality
right coronary artery	UBERON:0001625	92.08	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.06	gold quality
vagina	UBERON:0000996	92.04	gold quality
saliva-secreting gland	UBERON:0001044	91.95	gold quality
large intestine	UBERON:0000059	91.93	gold quality
lower esophagus	UBERON:0013473	91.92	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.91	gold quality
colon	UBERON:0001155	91.90	gold quality
peritoneum	UBERON:0002358	91.90	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.90	gold quality
tibial artery	UBERON:0007610	91.89	gold quality
omental fat pad	UBERON:0010414	91.89	gold quality
popliteal artery	UBERON:0002250	91.88	gold quality
intestine	UBERON:0000160	91.81	gold quality
penis	UBERON:0000989	91.77	gold quality
bone marrow	UBERON:0002371	91.75	gold quality
aorta	UBERON:0000947	91.73	gold quality
coronary artery	UBERON:0001621	91.71	gold quality
female reproductive system	UBERON:0000474	91.68	gold quality
thoracic aorta	UBERON:0001515	91.68	gold quality
apex of heart	UBERON:0002098	91.67	gold quality
ascending aorta	UBERON:0001496	91.58	gold quality
adrenal tissue	UBERON:0018303	91.55	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.54	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.53	gold quality
tibial nerve	UBERON:0001323	91.50	gold quality
uterus	UBERON:0000995	91.48	gold quality
right adrenal gland	UBERON:0001233	91.48	gold quality
left adrenal gland	UBERON:0001234	91.45	gold quality
lymph node	UBERON:0000029	91.44	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.43	gold quality
vermiform appendix	UBERON:0001154	91.38	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	20.52
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 160 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Caudate putamen	tissue	76.9
Bone marrow	tissue	66.0	medium
Skeletal muscle	tissue	63.8	not detected
Frontal cortex	tissue	56.8
Fallopian tube	tissue	51.5	medium
Testis	tissue	48.3	high
Tongue	tissue	47.5
Ovary	tissue	44.7	medium
Breast	tissue	39.9	low
Liver	tissue	36.6	low
Duodenum	tissue	36.3	high
Lymph node	tissue	34.5	medium
Thymus	tissue	34.4
Colon	tissue	34.1	medium
Epididymis	tissue	33.8	high
Small intestine	tissue	33.4	high
Kidney	tissue	33.0	medium
Rectum	tissue	31.8	medium
Tonsil	tissue	31.5	medium
Cervix	tissue	30.7	medium
Salivary gland	tissue	29.2	medium
Vagina	tissue	28.3	medium
Endometrium 1	tissue	28.2	medium
Esophagus	tissue	27.5	medium
Heart muscle	tissue	27.1	low
Smooth muscle	tissue	27.0	medium
Pancreas	tissue	25.2	medium
Urinary bladder	tissue	24.5	medium
Skin 1	tissue	24.2	medium
Cerebellum	tissue	23.7	medium
Stomach 1	tissue	23.4	high
Prostate	tissue	23.4	medium
Adrenal gland	tissue	21.7	high
Corpus callosum	tissue	21.6
Placenta	tissue	21.2	high
Appendix	tissue	21.1	medium
Spleen	tissue	21.0	medium
Adipose tissue	tissue	20.6	not detected
Spinal cord	tissue	20.2
Thyroid gland	tissue	19.9	medium
Gallbladder	tissue	18.9	high
Medulla oblongata	tissue	18.8
Substantia nigra	tissue	18.8
Pons	tissue	18.4
Thalamus	tissue	18.1
Septum	tissue	18.0
Seminal vesicle	tissue	17.9	medium
Midbrain	tissue	17.9
Periaqueductal gray	tissue	17.7
Pons	tissue	17.7
Putamen	tissue	17.5
Parathyroid gland	tissue	17.3	low
Cerebellum	tissue	17.1	medium
Midbrain	tissue	17.1
Olfactory bulb	tissue	17.0
Frontal cortex	tissue	16.9
Superior colliculi	tissue	16.8
Thalamus	tissue	16.3
Lung	tissue	16.3	low
Cerebral cortex	tissue	16.3	medium

Brain sub-regions (HPA Brain Atlas): detected in 384; highest nTPM — Blood vessel (25.8), White matter (21.6), Ventral spinal cord (20.2), Ventromedial nucleus (19.7), Dorsal spinal cord (18.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting TPRKB by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

7 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-155-5P	99.35	70.16	1509

Functional genomics

gnomAD constraint: pLI 0.31, LOEUF 0.94, missense Z -0.663 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000272424 — one region, missense o/e 1.15.

Literature-anchored findings (GeneRIF, showing 2)

• Crystal structure of the human PRPK-TPRKB complex. (PMID:33547416)
• METTL5 enhances the mRNA stability of TPRKB through m[6]A modification to facilitate the aggressive phenotypes of hepatocellular carcinoma cell. (PMID:39182664)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tprkb	ENSDARG00000014941
mus_musculus	Tprkb	ENSMUSG00000054226
rattus_norvegicus	Tprkb	ENSRNOG00000050645
caenorhabditis_elegans		WBGENE00020994

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1917036) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
preweaning lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Aspergillus clavatus NRRL 1	A1CEY5	83.7%	Diamond
Aspergillus fumigatus Af293	Q4WI37	83.7%	Diamond
Aspergillus terreus NIH2624	Q0C9R3	75.1%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q6CT72	48.2%	Diamond
Debaryomyces hansenii CBS767	Q6BP94	45.9%	Diamond
Saccharomyces cerevisiae S288C	Q03705	43.5%	Diamond
Yarrowia lipolytica CLIB122	Q6C7C9	40.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
DUSP11	protein-coding	8446
C2orf78	protein-coding	388960
STAMBP	protein-coding	10617

Protein

Protein identifiers

EKC/KEOPS complex subunit TPRKB — Q9Y3C4 (reviewed: Q9Y3C4)

Alternative names: PRPK-binding protein, TP53RK-binding protein

All UniProt accessions (1): Q9Y3C4

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. TPRKB acts as an allosteric effector that regulates the t(6)A activity of the complex. TPRKB is not required for tRNA modification.

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

Subcellular location. Cytoplasm. Cytosol. Nucleus.

Tissue specificity. Widely expressed.

Disease relevance. Galloway-Mowat syndrome 5 (GAMOS5) [MIM:617731] 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.

Similarity. Belongs to the CGI121/TPRKB family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y3C4-1	1	yes
Q9Y3C4-2	2, S1
Q9Y3C4-3	3, L1

RefSeq proteins (8): NP_001317315, NP_001317316, NP_001317317, NP_001317318, NP_001317319, NP_001317320, NP_001317321, NP_057142* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013926	CGI121/TPRKB	Family
IPR036504	CGI121/TPRKB_sf	Homologous_superfamily

Pfam: PF08617

UniProt features (26 total): helix 12, strand 8, splice variant 2, sequence variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

7 structures by resolution:

PDB	Title	Method	Resolution (Å)
7SZC	Crystal Structure Analysis of human PRPK complex with a compound	X-RAY DIFFRACTION	1.71
7SZA	Crystal Structure Analysis of human PRPK complex with a compound	X-RAY DIFFRACTION	1.9
7SZB	Crystal Structure Analysis of human PRPK complex with a compound	X-RAY DIFFRACTION	2.02
7SZD	Crystal Structure Analysis of human PRPK complex with a compound	X-RAY DIFFRACTION	2.05
3ENP	Crystal structure of human cgi121	X-RAY DIFFRACTION	2.48
6WQX	Human PRPK-TPRKB complex	X-RAY DIFFRACTION	2.53
9FL9	Cryo-EM structure of the human KEOPS complex	ELECTRON MICROSCOPY	3.74

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y3C4-F1	95.47	0.91

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes, Human disease related genes, Congenital malformations, Congenital malformations of the nervous system, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH approved · IF supported

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-8953854	Metabolism of RNA	—
R-HSA-6782315	tRNA modification in the nucleus and cytosol	electronic
R-HSA-72306	tRNA processing	—

MSigDB gene sets: 219 (showing top): MODULE_151, GOBP_TRNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_TRANSLATION, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_RNA_MODIFICATION, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, GARCIA_TARGETS_OF_FLI1_AND_DAX1_DN, BASAKI_YBX1_TARGETS_UP, GOBP_TRNA_THREONYLCARBAMOYLADENOSINE_METABOLIC_PROCESS, GOBP_TRNA_PROCESSING, MODULE_114, REACTOME_METABOLISM_OF_RNA, GOBP_TRNA_MODIFICATION

GO Biological Process (3): tRNA threonylcarbamoyladenosine modification (GO:0002949), maintenance of translational fidelity (GO:1990145), tRNA processing (GO:0008033)

GO Molecular Function (2): protein kinase binding (GO:0019901), protein binding (GO:0005515)

GO Cellular Component (4): EKC/KEOPS complex (GO:0000408), nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

2 top-level categories:

Category	Pathways
tRNA processing	1
Metabolism of RNA	1

GO top-level categories

12 GO namespaces:

Category	Terms
cellular anatomical structure	2
tRNA modification	1
translation	1
macromolecule biosynthetic process	1
RNA processing	1
tRNA metabolic process	1
kinase binding	1
binding	1
transferase complex	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 9 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
tRNA threonylcarbamoyladenosine modification	BP	direct assay
EKC/KEOPS complex	CC	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
nucleus	CC	direct assay
protein kinase binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,158 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TPRKB	TP53RK	Q96S44	995
TPRKB	OSGEP	Q9NPF4	906
TPRKB	LAGE3	Q14657	905
TPRKB	GON7	Q9BXV9	880
TPRKB	YRDC	Q86U90	846
TPRKB	OSGEPL1	Q9H4B0	840
TPRKB	THUMPD2	Q9BTF0	505
TPRKB	TP53	P04637	489
TPRKB	RIOK2	Q9BVS4	445
TPRKB	SH2D2A	Q9NP31	443
TPRKB	MITD1	Q8WV92	423
TPRKB	MRPL30	Q8TCC3	422
TPRKB	CTU1	Q7Z7A3	394
TPRKB	ITGB3BP	Q13352	387
TPRKB	PARS2	Q7L3T8	378

IntAct

Human interaction partners of TPRKB in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

4 partners by confidence:

Partner	Interaction type	MIscore	Records
TP53RK	physical association	0.850	3
TRIM27	physical association	0.560	3
H1-5	physical association	0.400	1
E6	physical association	0.370	3

BioGRID (98 interactions; top human partners by supporting records): TP53RK (Affinity Capture-MS; 19 records), OSGEP (Affinity Capture-MS; 7 records), LAGE3 (Affinity Capture-MS; 4 records), MBIP (Affinity Capture-MS; 3 records), NUP43 (Affinity Capture-MS; 3 records), BAG3 (Affinity Capture-MS; 2 records), GORASP1 (Affinity Capture-MS; 2 records), ACTR2 (Co-fractionation), ACTR3 (Co-fractionation), AGFG1 (Co-fractionation), ANO4 (Affinity Capture-MS), ARPC1A (Co-fractionation), ARPC1B (Co-fractionation), ARPC2 (Co-fractionation), ARPC4 (Co-fractionation)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
KEOPS complex	4	LAGE3, OSGEP, TP53RK, TPRKB

Disease & clinical

Genetic variants

Variant evidence for TPRKB: 74 ClinVar records (2 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	44
Likely benign	11
Benign	8

Top pathogenic / likely-pathogenic (2)

Showing all 2 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
3065453	NM_016058.5(TPRKB):c.445T>A (p.Tyr149Asn)	Likely pathogenic	criteria provided, single submitter	1
444885	NM_016058.5(TPRKB):c.446A>G (p.Tyr149Cys)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore TPRKB’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

AlphaMissense

208 missense substitutions predicted likely pathogenic (of 1,141 scored), across 80 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
E78	7	0.874	0.956
F20	7	0.784	0.910
K172	6	0.890	0.969
F81	6	0.775	0.904
G128	6	0.743	0.912
E155	6	0.645	0.679
R168	5	0.834	0.909
K60	5	0.823	0.910
F96	5	0.822	0.962
N25	5	0.698	0.836
T72	4	0.855	0.921
I89	4	0.838	0.923
G97	4	0.809	0.924
A57	4	0.800	0.962
M70	4	0.759	0.808
Q53	4	0.691	0.738
R73	4	0.670	0.741
K150	4	0.656	0.774
L83	3	0.917	0.963
F10	3	0.860	0.860

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

8 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (validation)	unfavorable	2.18e-06
Skin Cutaneous Melanoma (TCGA)	unfavorable	9.98e-06
Pancreatic Adenocarcinoma (TCGA)	unfavorable	1.6e-05
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	1.66e-05
Lung Adenocarcinoma (TCGA)	unfavorable	3.07e-05
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	3.38e-05
Ovary Serous Cystadenocarcinoma (validation)	unfavorable	0.000118
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000716

Disease associations

OMIM: gene MIM:608680 | disease phenotypes: MIM:617731

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
Galloway-Mowat syndrome 5	Strong	Autosomal recessive	5
Galloway-Mowat syndrome	Supportive	Autosomal recessive

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (3 panels, 3 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

3 panels:

Panel	Rating
Fetal anomalies	green
Proteinuric renal disease	green
Unexplained young onset end-stage renal disease	green

Mondo (2): Galloway-Mowat syndrome 5 (MONDO:0033009), Galloway-Mowat syndrome (MONDO:0009627)

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
C537548	Galloway Mowat syndrome *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066493 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.28	Kd	521	nM	CHEMBL5653589
6.26	ED50	550.3	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149648: Binding affinity to human TPRKB incubated for 45 mins by Kinobead based pull down assay	kd	0.5210	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	3
bisphenol A	decreases methylation, decreases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Arsenic	affects cotreatment, increases abundance, increases expression, decreases expression	2
Valproic Acid	affects expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
dicrotophos	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
arsenite	affects binding, increases reaction	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	decreases expression, affects cotreatment	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Copper	affects binding, decreases expression	1
Disulfiram	affects binding, decreases expression	1
Estradiol	decreases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Rotenone	decreases expression	1
Thimerosal	increases 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
CHEMBL5652690	Binding	Binding affinity to human TPRKB 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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 107 trials:

NCT	Phase	Status	Title
NCT00308321	Phase 4	UNKNOWN	Long Term Tapering or Standard Steroids for Nephrotic Syndrome
NCT01021540	Phase 4	COMPLETED	Prospective Study Evaluating the Effect of Repository Corticotropin in the Treatment of Various Nephrotic Syndromes
NCT01028287	Phase 4	COMPLETED	Adrenocorticotropic Hormone (ACTH) Treatment of Nephrotic Range Proteinuria in Diabetic Nephropathy (NRDN)
NCT01162005	Phase 4	COMPLETED	Therapeutic Effect of Tacrolimus on Primary Nephrotic Syndrome in Children
NCT01895894	Phase 4	COMPLETED	Mycophenolate Mofetil in Pediatric Steroid Dependent Nephrotic Syndrome
NCT02238418	Phase 4	COMPLETED	Efficacy of Usual Vitamin D Supplementation and Its Impact on Children and Adolescents Calciuria.
NCT02382575	Phase 4	UNKNOWN	Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Resistant Nephrotic Syndrome
NCT02427880	Phase 4	COMPLETED	Role of Acetazolamide and Hydrochlorothiazide Followed by Furosemide in Treating Nephrotic Edema
NCT03210688	Phase 4	COMPLETED	Active Vitamin D And Reduced Dose Prednisolone for Treatment in Minimal Change Nephropathy
NCT03347357	Phase 4	COMPLETED	Pharmacokinetics of Tacrolimus in Children
NCT05696977	Phase 4	UNKNOWN	Effect of Obesity on Cyclosporine Blood Trough Level in Nephrotic Syndrome Patients
NCT05966818	Phase 4	UNKNOWN	Effect of Dapagliflozin in Non-Diabetic Patients With Nephrotic Syndrome.
NCT06026787	Phase 4	COMPLETED	Clinical Value of Adding Dapagliflozin in Patients With Nephrotic Syndrome
NCT00354731	Phase 3	COMPLETED	Efficacy of Pentoxifylline on Primary Nephrotic Syndrome
NCT00615667	Phase 3	COMPLETED	Prospective, Multicenter Study of the Efficacy and Tolerance of Tacrolimus on Refractory Nephrotic Syndrome (RNS)
NCT00981838	Phase 3	COMPLETED	Rituximab in Multirelapsing Minimal Change Disease (MCD) or Focal Segmental Glomerulosclerosis (FSGS)
NCT01197040	Phase 3	COMPLETED	Evaluation of Low Dose Corticosteroids Efficiency, Associated With Myfortic ® in the Treatment of Nephrotic Syndrome
NCT01309477	Phase 3	COMPLETED	The Efficacy and Tolerance of Tacrolimus Sustained-release Capsules on Refractory Nephrotic Syndrome (RNS)
NCT02132195	Phase 3	COMPLETED	Adrenocorticotropic Hormone (ACTH) for Frequently Relapsing and Steroid Dependent Nephrotic Syndrome
NCT02257697	Phase 3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mizoribine in the Treatment of Refractory Nephrotic Syndrome
NCT02438982	Phase 3	COMPLETED	Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Dependent Nephrotic Syndrome
NCT03141970	Phase 3	COMPLETED	Prednisolone Trial in Children Younger Than 4 Years
NCT03501459	Phase 3	UNKNOWN	Lymphocyte Markers As Predictors Of Responsiveness To Rituximab Among Patients With Idiopathic Nephrotic Syndrome
NCT05079789	Phase 3	TERMINATED	Amiloride in Nephrotic Syndrome
NCT05716880	Phase 3	RECRUITING	Ketoanalogues for Muscle Mass Loss in Nephrotic Syndrome
NCT06635720	Phase 3	ACTIVE_NOT_RECRUITING	REduced-dose Steroid PrOtocol for Childhood Nephrotic SyndromE (RESPONSE)
NCT07765914	Phase 3	NOT_YET_RECRUITING	Zuberitamab in the First Episode of Paediatric Nephrotic Syndrome
NCT00001212	Phase 2	COMPLETED	Drug Therapy in Lupus Nephropathy
NCT00001959	Phase 2	COMPLETED	Pirfenidone to Treat Kidney Disease (Focal Segmental Glomerulosclerosis)
NCT00004466	Phase 2	TERMINATED	Pilot Study of Atorvastatin in Children With Chronic Hyperlipidemia Secondary to Nephrotic Syndrome
NCT00004990	Phase 2	COMPLETED	Once-A-Month Steroid Treatment for Patients With Focal Segmental Glomerulosclerosis
NCT00977977	Phase 2	RECRUITING	Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy
NCT02394106	Phase 2	TERMINATED	Ofatumumab in Children With Drug Resistant Idiopathic Nephrotic Syndrome
NCT02394119	Phase 2	COMPLETED	Ofatumumab Versus Rituximab in Children With Steroid and Calcineurin Inhibitor Dependent Idiopathic Nephrotic Syndrome
NCT02592798	Phase 2	COMPLETED	Pilot Study to Evaluate the Safety and Efficacy of Abatacept in Adults and Children 6 Years and Older With Excessive Loss of Protein in the Urine Due to Either Focal Segmental Glomerulosclerosis (FSGS) or Minimal Change Disease (MCD)
NCT02966717	Phase 2	UNKNOWN	Rituximab Combined With MSCs in the Treatment of PNS (3-4 Stage of CKD)
NCT03004001	Phase 2	TERMINATED	Effect of PCSK9-Antibody (Alirocumab) on Dyslipidemia Secondary to Nephrotic Syndrome
NCT03949855	Phase 2	RECRUITING	Belimumab With Rituximab for Primary Membranous Nephropathy
NCT05599815	Phase 2	WITHDRAWN	Part 1 - A Clinical Trial in Patients With Frequently Relapsing and Steroid-Dependent Nephrotic Syndrome
NCT05704400	Phase 2	UNKNOWN	Efficacy of Anti-CD20 Ab Associated With Anti-CD38 in the Childhood Multidrug Dependent and Resistant Nephrotic Syndrome
NCT06983028	Phase 2	RECRUITING	Atacicept in Multiple Glomerular Diseases
NCT07313787	Phase 2	NOT_YET_RECRUITING	Effects of Meal Macronutrients on Postprandial Lipids
NCT01447485	Phase 1	COMPLETED	Pharmacokinetics Following Single-dose of Valsartan in Japanese Pediatric Patients
NCT01845428	Phase 1	COMPLETED	Lipid Lowering Agents to Limit Lipid Oxidation and Activation of Clotting System in Nephrotic Syndrome
NCT02599532	Phase 1	COMPLETED	Pharmacokinetics of Apixaban in Nephrotic Syndrome
NCT04278729	Phase 1	COMPLETED	A Prospective Multi-dose Study of Apixaban in Subjects With Nephrotic Syndrome
NCT07320612	Phase 1	COMPLETED	Efficacy And Safety Of Azithromycin To Achieve Remissionin In Children With Steroid Sensitive Nephrotic Syndrome
NCT00035334	Phase 2/3	COMPLETED	Study of the Safety and Efficacy of NC-503 in Secondary (AA) Amyloidosis
NCT00362531	Phase 2/3	COMPLETED	Tacrolimus Combined With Prednisone Treatment of Idiopathic Membranous Nephropathy and Nephrotic Syndrome
NCT04558892	Phase 2/3	TERMINATED	Anti-Xa Activity of Enoxaparin for Prevention of Venous Thromboembolism in Severe Nephrotic Syndrome.
NCT07214818	Phase 2/3	RECRUITING	SGLT2 Inhibitors in Adult Primary Nephrotic Syndrome
NCT02455908	Phase 1/2	COMPLETED	IL-2 for Multi Drug Resistant Nephrotic Syndrome
NCT04850378	Phase 1/2	COMPLETED	Causes and Prevention of Thromboembolic Disease in Nephrotic Syndrome
NCT00001979	Not specified	RECRUITING	Immune System Related Kidney Disease
NCT00172276	Not specified	COMPLETED	Angiotensin Converting Enzyme Gene Polymorphism in Children With Idiopathic Nephrotic Syndrome
NCT00286910	Not specified	COMPLETED	Urinary Aquaporin 2 and Expression of the NPHS2 Gene in Adults Suffering From Nephrotic Syndrome
NCT00289328	Not specified	COMPLETED	Glucocorticoid-induced Osteopenia in Children
NCT00690586	Not specified	COMPLETED	Fluid Balance, Hormones and Urine Proteomics in Nephrotic Syndrome in Childhood
NCT00883636	Not specified	TERMINATED	Cardiomyopathy in Steroid-resistant Nephrotic Syndrome: Impact of Focal Segmental Glomerulosclerosis
NCT00983034	Not specified	COMPLETED	The Effects of Helicobacter Pylori Eradication on Proteinuria in Patients With Membranous Nephropathy

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for TPRKB across ~30M SureChEMBL compounds — explore on Sugi Predict.