# TPRKB

> Gene · canonical: https://sugi.bio/atlas/gene/TPRKB/
> Atlas v1.12.2 · generated 2026-10-13T13:32:47+00:00

## 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](https://www.ncbi.nlm.nih.gov/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](https://www.ebi.ac.uk/gxa/sc/experiments/E-HCAD-13) | yes | 20.52 |
| [E-ANND-3](https://www.ebi.ac.uk/gxa/sc/experiments/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](https://gnomad.broadinstitute.org/)

**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](https://www.informatics.jax.org/marker/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](https://www.uniprot.org/uniprotkb/A1CEY5/entry) | 83.7% | Diamond |
| Aspergillus fumigatus Af293 | [Q4WI37](https://www.uniprot.org/uniprotkb/Q4WI37/entry) | 83.7% | Diamond |
| Aspergillus terreus NIH2624 | [Q0C9R3](https://www.uniprot.org/uniprotkb/Q0C9R3/entry) | 75.1% | Diamond |
| Kluyveromyces lactis NRRL Y-1140 | [Q6CT72](https://www.uniprot.org/uniprotkb/Q6CT72/entry) | 48.2% | Diamond |
| Debaryomyces hansenii CBS767 | [Q6BP94](https://www.uniprot.org/uniprotkb/Q6BP94/entry) | 45.9% | Diamond |
| Saccharomyces cerevisiae S288C | [Q03705](https://www.uniprot.org/uniprotkb/Q03705/entry) | 43.5% | Diamond |
| Yarrowia lipolytica CLIB122 | [Q6C7C9](https://www.uniprot.org/uniprotkb/Q6C7C9/entry) | 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](/atlas/gene/DUSP11/) | protein-coding | 8446 |
| [C2orf78](/atlas/gene/C2orf78/) | protein-coding | 388960 |
| [STAMBP](/atlas/gene/STAMBP/) | protein-coding | 10617 |

<a id="protein-Q9Y3C4"></a>

## 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 →](https://www.uniprot.org/uniprotkb/Q9Y3C4/entry)

**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](https://amigo.geneontology.org/amigo/term/GO:0002949) | BP | direct assay |
| [EKC/KEOPS complex](https://amigo.geneontology.org/amigo/term/GO:0000408) | CC | direct assay |
| [cytoplasm](https://amigo.geneontology.org/amigo/term/GO:0005737) | CC | direct assay |
| [cytosol](https://amigo.geneontology.org/amigo/term/GO:0005829) | CC | direct assay |
| [nucleus](https://amigo.geneontology.org/amigo/term/GO:0005634) | CC | direct assay |
| [protein kinase binding](https://amigo.geneontology.org/amigo/term/GO:0019901) | 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](#clinvar) (2 pathogenic / likely pathogenic). Per-variant detail is on [Sugi Variant](https://sugi.bio/variant/gene/TPRKB).

#### 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)](https://sugi.bio/variant/tprkb-p-tyr149asn) | Likely pathogenic | criteria provided, single submitter | 1 |
| 444885 | [NM_016058.5(TPRKB):c.446A>G (p.Tyr149Cys)](https://sugi.bio/variant/tprkb-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](https://sugi.bio/variant/gene/TPRKB).

#### 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](/atlas/disease/galloway-mowat-syndrome-5/) | Strong | Autosomal recessive | 5 |
| [Galloway-Mowat syndrome](/atlas/disease/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](/atlas/disease/galloway-mowat-syndrome-5/) (MONDO:0033009), [Galloway-Mowat syndrome](/atlas/disease/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](https://www.ebi.ac.uk/chembl/compound_report_card/CHEMBL5653589/) |
| 6.26 | ED50 | 550.3 | nM | [CHEMBL5653589](https://www.ebi.ac.uk/chembl/compound_report_card/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](https://pubchem.ncbi.nlm.nih.gov/bioassay/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](https://sugi.bio/predict/target/TPRKB/).

## Related Atlas pages

- **Associated diseases:** [Galloway-Mowat syndrome 5](/atlas/disease/galloway-mowat-syndrome-5/), [Galloway-Mowat syndrome](/atlas/disease/galloway-mowat-syndrome/)
- **Disease cohort memberships** *(association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases)*: [Galloway-Mowat syndrome](/atlas/disease/galloway-mowat-syndrome/), [Galloway-Mowat syndrome 5](/atlas/disease/galloway-mowat-syndrome-5/), [nephrotic syndrome](/atlas/disease/nephrotic-syndrome/)