TBRG4
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Also known as Cpr2KIAA0948H_TD2522F11.8FASTKD4
Summary
TBRG4 (transforming growth factor beta regulator 4, HGNC:17443) is a protein-coding gene on chromosome 7p13, encoding FAST kinase domain-containing protein 4 (Q969Z0). Plays a role in processing of mitochondrial RNA precursors and in stabilization of a subset of mature mitochondrial RNA species, such as MT-CO1, MT-CO2, MT-CYB, MT-CO3, MT-ND3, MT-ND5 and MT-ATP8/6.
Enables RNA binding activity. Involved in mitochondrial mRNA processing and regulation of mitochondrial mRNA stability. Located in mitochondrial matrix.
Source: NCBI Gene 9238 — RefSeq curated summary.
At a glance
- GWAS associations: 2
- Clinical variants (ClinVar): 125 total
- Druggable target: yes
- MANE Select transcript:
NM_004749
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:17443 |
| Approved symbol | TBRG4 |
| Name | transforming growth factor beta regulator 4 |
| Location | 7p13 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | Cpr2, KIAA0948, H_TD2522F11.8, FASTKD4 |
| Ensembl gene | ENSG00000136270 |
| Ensembl biotype | protein_coding |
| OMIM | 611325 |
| Entrez | 9238 |
Gene structure
Transcript identifiers
Ensembl transcripts: 65 — 58 protein_coding, 6 retained_intron, 1 protein_coding_CDS_not_defined
ENST00000258770, ENST00000361278, ENST00000395655, ENST00000461363, ENST00000471142, ENST00000475893, ENST00000477328, ENST00000478116, ENST00000478532, ENST00000482285, ENST00000482482, ENST00000483615, ENST00000484326, ENST00000488222, ENST00000494076, ENST00000495078, ENST00000495973, ENST00000895097, ENST00000895098, ENST00000895099, ENST00000895100, ENST00000895101, ENST00000895102, ENST00000895103, ENST00000895104, ENST00000895105, ENST00000895106, ENST00000895107, ENST00000895108, ENST00000895109, ENST00000895110, ENST00000895111, ENST00000895112, ENST00000895113, ENST00000895114, ENST00000895115, ENST00000934796, ENST00000934797, ENST00000934798, ENST00000934799, ENST00000934800, ENST00000934801, ENST00000934802, ENST00000934803, ENST00000934804, ENST00000934805, ENST00000934806, ENST00000934807, ENST00000934808, ENST00000934809, ENST00000934810, ENST00000934811, ENST00000934812, ENST00000967962, ENST00000967963, ENST00000967964, ENST00000967965, ENST00000967966, ENST00000967967, ENST00000967968, ENST00000967969, ENST00000967970, ENST00000967971, ENST00000967972, ENST00000967973
RefSeq mRNA: 4 — MANE Select: NM_004749
NM_001261834, NM_004749, NM_030900, NM_199122
CCDS: CCDS5501, CCDS5502
Canonical transcript exons
ENST00000258770 — 11 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001391193 | 45105441 | 45105764 |
| ENSE00001873350 | 45111643 | 45111697 |
| ENSE00001893480 | 45100100 | 45100426 |
| ENSE00003516026 | 45108827 | 45109287 |
| ENSE00003522323 | 45102347 | 45102491 |
| ENSE00003528137 | 45104099 | 45104256 |
| ENSE00003540784 | 45101258 | 45101372 |
| ENSE00003653705 | 45103333 | 45103443 |
| ENSE00003659889 | 45101825 | 45102070 |
| ENSE00003785748 | 45104538 | 45104709 |
| ENSE00003791097 | 45101503 | 45101614 |
Expression profiles
Bgee: expression breadth ubiquitous, 214 present calls, max score 96.83.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.5868 / max 394.3942, expressed in 1817 samples.
FANTOM5 promoters (1 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 83934 | 32.5868 | 1817 |
Top tissues by expression
284 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| mucosa of transverse colon | UBERON:0004991 | 96.83 | gold quality |
| apex of heart | UBERON:0002098 | 96.80 | gold quality |
| transverse colon | UBERON:0001157 | 96.04 | gold quality |
| granulocyte | CL:0000094 | 95.56 | gold quality |
| small intestine Peyer’s patch | UBERON:0003454 | 95.41 | gold quality |
| gastrocnemius | UBERON:0001388 | 95.29 | gold quality |
| metanephros cortex | UBERON:0010533 | 95.22 | gold quality |
| rectum | UBERON:0001052 | 95.03 | gold quality |
| muscle of leg | UBERON:0001383 | 94.67 | gold quality |
| hindlimb stylopod muscle | UBERON:0004252 | 94.52 | gold quality |
| lower esophagus mucosa | UBERON:0035834 | 94.51 | gold quality |
| skin of leg | UBERON:0001511 | 94.40 | gold quality |
| right ovary | UBERON:0002118 | 94.36 | gold quality |
| body of stomach | UBERON:0001161 | 94.35 | gold quality |
| minor salivary gland | UBERON:0001830 | 94.25 | gold quality |
| right adrenal gland | UBERON:0001233 | 94.24 | gold quality |
| right lobe of liver | UBERON:0001114 | 94.20 | gold quality |
| right adrenal gland cortex | UBERON:0035827 | 94.18 | gold quality |
| muscle layer of sigmoid colon | UBERON:0035805 | 94.17 | gold quality |
| skin of abdomen | UBERON:0001416 | 94.15 | gold quality |
| lower esophagus muscularis layer | UBERON:0035833 | 94.12 | gold quality |
| lower esophagus | UBERON:0013473 | 94.11 | gold quality |
| right lobe of thyroid gland | UBERON:0001119 | 94.05 | gold quality |
| left ovary | UBERON:0002119 | 93.98 | gold quality |
| esophagus mucosa | UBERON:0002469 | 93.96 | gold quality |
| heart left ventricle | UBERON:0002084 | 93.89 | gold quality |
| esophagogastric junction muscularis propria | UBERON:0035841 | 93.83 | gold quality |
| right uterine tube | UBERON:0001302 | 93.82 | gold quality |
| esophagus | UBERON:0001043 | 93.81 | gold quality |
| right atrium auricular region | UBERON:0006631 | 93.73 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 4.42 |
Regulation
Is transcription factor: no
miRNA regulators (miRDB)
8 targeting TBRG4, 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-4789-5P | 99.98 | 70.76 | 2721 |
| HSA-MIR-122B-3P | 99.21 | 68.90 | 1333 |
| HSA-MIR-21-3P | 99.21 | 68.95 | 1312 |
| HSA-MIR-12135 | 98.99 | 70.26 | 1814 |
| HSA-MIR-4801 | 98.96 | 69.42 | 2096 |
| HSA-MIR-3190-5P | 98.87 | 64.89 | 1345 |
| HSA-MIR-4731-3P | 98.56 | 68.60 | 1860 |
| HSA-MIR-2355-3P | 96.84 | 68.54 | 909 |
Literature-anchored findings (GeneRIF, showing 9)
- Disruption of FASTKD4 reduces the level of ND3 and of other mature mRNAs including ND5 and CYB, and causes accumulation of ND5-CYB precursor RNA. Disrupting FASTKD1 and FASTKD4 decreases ND3 mRNA like depleting FASTKD4 alone, indicating that FASTKD4 loss is epistatic. RAP domain of FASTKD4 has a nuclease fold with a conserved aspartate at the putative active site, mutation of which abolishes its function. (PMID:28335001)
- SLERT is 694 nucleotides & contains SNORA5A & SNORA5C at its ends; it is produced from the human TBRG4 locus via skipping of exons 4 and 5 that leads to both SNORA5A & SNORA5C embedded within one intron, thereby producing SLERT from this alternatively spliced intron; results reveal an important control of ribosome biogenesis by SLERT lncRNA & its regulatory role in DDX21 ring-shaped arrangements acting on Pol I complexes. (PMID:28475895)
- Despite the fact that proteins of the FASTK family FASTKD1-5 share the same domains, they exhibit various-sometimes opposing-functions in almost all steps of mitochondrial RNA metabolism. (PMID:29036396)
- TBRG4 silencing promotes progression of squamous cell carcinoma via regulation of CAV-1 expression and ROS formation. (PMID:32415943)
- Expression quantitative trait loci of genes predicting outcome are associated with survival of multiple myeloma patients. (PMID:33675538)
- The FASTK family proteins fine-tune mitochondrial RNA processing. (PMID:34748562)
- Mitochondrial protein, TBRG4, modulates KSHV and EBV reactivation from latency. (PMID:36417478)
- High expression of TBRG4 in relation to unfavorable outcome and cell ferroptosis in hepatocellular carcinoma. (PMID:38347489)
- 13 human CPR (cell cycle progression restoration) genes and 11 yeast OPY (overproduction-induced pheromone-resistant yeast) genes that specifically block the G1 arrest by mating pheromone. (PMID:9383053)
Cross-species orthologs
4 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| danio_rerio | tbrg4 | ENSDARG00000074807 |
| mus_musculus | Tbrg4 | ENSMUSG00000000384 |
| rattus_norvegicus | Tbrg4 | ENSRNOG00000052477 |
| caenorhabditis_elegans | WBGENE00007207 |
Paralogs (5): FASTKD2 (ENSG00000118246), FASTKD3 (ENSG00000124279), FASTKD1 (ENSG00000138399), FASTK (ENSG00000164896), FASTKD5 (ENSG00000215251)
Protein
Protein identifiers
FAST kinase domain-containing protein 4 — Q969Z0 (reviewed: Q969Z0)
Alternative names: Cell cycle progression restoration protein 2, Protein TBRG4, Transforming growth factor beta regulator 4
All UniProt accessions (7): C9IZN7, C9J347, C9J5A2, C9J618, C9J7P5, Q969Z0, H7C4R5
UniProt curated annotations — full annotation on UniProt →
Function. Plays a role in processing of mitochondrial RNA precursors and in stabilization of a subset of mature mitochondrial RNA species, such as MT-CO1, MT-CO2, MT-CYB, MT-CO3, MT-ND3, MT-ND5 and MT-ATP8/6. May play a role in cell cycle progression.
Subcellular location. Mitochondrion matrix.
Tissue specificity. Ubiquitously expressed. Expression detected in spleen, thymus, testis, ovary, colon, heart, smooth muscle, kidney, brain, lung, liver and white adipose tissue with highest expression in smooth muscle.
Domain organisation. RAP domain is required for TBRG4 function in mRNA stability and translation.
Similarity. Belongs to the FAST kinase family.
Isoforms (2)
| UniProt ID | Names | Canonical? |
|---|---|---|
| Q969Z0-1 | 1 | yes |
| Q969Z0-2 | 2 |
RefSeq proteins (4): NP_001248763, NP_004740, NP_112162, NP_954573 (=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR010622 | FAST_Leu-rich | Domain |
| IPR013579 | FAST_2 | Domain |
| IPR013584 | RAP | Domain |
| IPR050870 | FAST_kinase | Family |
Pfam: PF06743, PF08368, PF08373
UniProt features (11 total): sequence conflict 3, sequence variant 2, transit peptide 1, chain 1, domain 1, modified residue 1, splice variant 1, mutagenesis site 1
Structure
Experimental structures (PDB)
1 structures.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 9GEK | X-RAY DIFFRACTION | 2.15 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-Q969Z0-F1 | 83.29 | 0.51 |
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Post-translational modifications (1): 553
Mutagenesis-validated functional residues (1):
| Position | Phenotype |
|---|---|
| 531 | does not affect location in mitochondria; fails to rescue the increased accumulation of the level of mature mt-nd3, mt-c |
Function
Pathways and Gene Ontology
Reactome pathways
1 pathways
| ID | Pathway |
|---|---|
| R-HSA-9837092 | FASTK family proteins regulate processing and stability of mitochondrial RNAs |
MSigDB gene sets: 179 (showing top):
GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, MATTIOLI_MGUS_VS_PCL, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_308, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, MARTINEZ_RB1_TARGETS_UP, GOBP_REGULATION_OF_CATABOLIC_PROCESS, DOANE_RESPONSE_TO_ANDROGEN_DN, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_MITOCHONDRIAL_RNA_PROCESSING, E4F1_Q6
GO Biological Process (6): mitochondrial RNA processing (GO:0000963), positive regulation of cell population proliferation (GO:0008284), mRNA metabolic process (GO:0016071), regulation of mitochondrial mRNA stability (GO:0044528), regulation of cell cycle (GO:0051726), mitochondrial mRNA processing (GO:0090615)
GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)
GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), ribonucleoprotein granule (GO:0035770)
Reactome top-level categories
Rollup of top-1 pathways:
| Category | Pathways |
|---|---|
| Mitochondrial RNA degradation | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| mitochondrion | 3 |
| mitochondrial RNA metabolic process | 2 |
| RNA processing | 1 |
| mitochondrial gene expression | 1 |
| cell population proliferation | 1 |
| regulation of cell population proliferation | 1 |
| positive regulation of cellular process | 1 |
| RNA metabolic process | 1 |
| regulation of mRNA stability | 1 |
| cell cycle | 1 |
| regulation of cellular process | 1 |
| mitochondrial RNA processing | 1 |
| mRNA processing | 1 |
| nucleic acid binding | 1 |
| binding | 1 |
| cytoplasm | 1 |
| intracellular membrane-bounded organelle | 1 |
| intracellular organelle lumen | 1 |
| intracellular membraneless organelle | 1 |
| supramolecular complex | 1 |
Protein interactions and networks
STRING
1511 interactions, top by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| TBRG4 | FASTKD5 | Q7L8L6 | 650 |
| TBRG4 | SLC49A3 | Q6UXD7 | 589 |
| TBRG4 | SUPV3L1 | Q8IYB8 | 576 |
| TBRG4 | CCDC201 | A0A1B0GTI1 | 562 |
| TBRG4 | KLHL18 | O94889 | 557 |
| TBRG4 | RAMP3 | O60896 | 530 |
| TBRG4 | DNAJA2 | O60884 | 507 |
| TBRG4 | DHX30 | Q7L2E3 | 500 |
| TBRG4 | GRSF1 | Q12849 | 483 |
| TBRG4 | CCNK | O75909 | 447 |
| TBRG4 | ELAC2 | Q9BQ52 | 443 |
| TBRG4 | FASTKD2 | Q9NYY8 | 434 |
| TBRG4 | SRFBP1 | Q8NEF9 | 432 |
| TBRG4 | S100A1 | P23297 | 427 |
| TBRG4 | DDX21 | Q9NR30 | 427 |
IntAct
227 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| CFTR | ESYT2 | psi-mi:“MI:2364”(proximity) | 0.710 |
| CFTR | ESYT2 | psi-mi:“MI:0914”(association) | 0.710 |
| TBRG4 | PNPT1 | psi-mi:“MI:0914”(association) | 0.640 |
| CD27 | TCAF2 | psi-mi:“MI:0914”(association) | 0.640 |
| FAM234B | ABCD4 | psi-mi:“MI:0914”(association) | 0.620 |
| TBRG4 | FAM114A2 | psi-mi:“MI:0915”(physical association) | 0.600 |
| FAM114A2 | TBRG4 | psi-mi:“MI:0915”(physical association) | 0.600 |
| TBRG4 | CALCOCO2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| TBRG4 | AGTRAP | psi-mi:“MI:0915”(physical association) | 0.560 |
| FAM9B | TBRG4 | psi-mi:“MI:0915”(physical association) | 0.560 |
| MAL2 | TBRG4 | psi-mi:“MI:0915”(physical association) | 0.560 |
| CALCOCO2 | TBRG4 | psi-mi:“MI:0915”(physical association) | 0.560 |
| AGTRAP | TBRG4 | psi-mi:“MI:0915”(physical association) | 0.560 |
| TBRG4 | FAM9B | psi-mi:“MI:0915”(physical association) | 0.560 |
| TBRG4 | MAL2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| KRT27 | TBRG4 | psi-mi:“MI:0915”(physical association) | 0.560 |
| TMEM239 | TBRG4 | psi-mi:“MI:0915”(physical association) | 0.560 |
| TBRG4 | GPRASP2 | psi-mi:“MI:0915”(physical association) | 0.560 |
| TBRG4 | TFIP11 | psi-mi:“MI:0915”(physical association) | 0.560 |
| CDR2L | TBRG4 | psi-mi:“MI:0915”(physical association) | 0.560 |
| BICD2 | TBRG4 | psi-mi:“MI:0915”(physical association) | 0.560 |
BioGRID (446): CALCOCO2 (Two-hybrid), AGTRAP (Two-hybrid), MAL2 (Two-hybrid), FAM9B (Two-hybrid), TBRG4 (Affinity Capture-RNA), TBRG4 (Affinity Capture-MS), TBRG4 (Affinity Capture-MS), TBRG4 (Affinity Capture-MS), TBRG4 (Affinity Capture-MS), TBRG4 (Affinity Capture-MS), TBRG4 (Affinity Capture-MS), TBRG4 (Affinity Capture-MS), TBRG4 (Affinity Capture-MS), TBRG4 (Affinity Capture-MS), TBRG4 (Affinity Capture-MS)
ESM2 similar proteins: A2VD13, A6QP29, A7E3N7, B5DFG1, O75127, P54098, P54099, Q05AA6, Q13474, Q3SX05, Q3SZK4, Q3TYG6, Q3U0L2, Q3U5Q7, Q3URY6, Q3ZBK7, Q4R5Q4, Q53GS7, Q58CQ5, Q5R655, Q5RAS2, Q66H85, Q6NUQ4, Q6ZUX3, Q7YS91, Q80UU1, Q8BKF1, Q8BL74, Q8C0R7, Q8C1F5, Q8C2E4, Q8CJ00, Q8N4P6, Q8R322, Q8TE82, Q969Z0, Q96KN7, Q96MK2, Q99MQ3, Q9BQ95
Diamond homologs: Q3SZK4, Q5M9G9, Q6DJ55, Q6PA48, Q7YS91, Q91YM4, Q969Z0
SIGNOR signaling
0 interactions.
Disease & clinical
Clinical variants and AI predictions
ClinVar
125 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 82 |
| Likely benign | 7 |
| Benign | 2 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
2217 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 7:45100422:GGGAC:G | acceptor_gain | 1.0000 |
| 7:45100423:GGAC:G | acceptor_gain | 1.0000 |
| 7:45100424:GAC:G | acceptor_gain | 1.0000 |
| 7:45100425:AC:A | acceptor_gain | 1.0000 |
| 7:45100426:CC:C | acceptor_gain | 1.0000 |
| 7:45100427:C:CA | acceptor_loss | 1.0000 |
| 7:45100427:C:CC | acceptor_gain | 1.0000 |
| 7:45101252:AC:A | donor_loss | 1.0000 |
| 7:45101253:CTC:C | donor_loss | 1.0000 |
| 7:45101254:TCA:T | donor_loss | 1.0000 |
| 7:45101255:CA:C | donor_loss | 1.0000 |
| 7:45101256:A:AC | donor_gain | 1.0000 |
| 7:45101256:ACGT:A | donor_gain | 1.0000 |
| 7:45101256:ACGTC:A | donor_gain | 1.0000 |
| 7:45101257:C:CA | donor_gain | 1.0000 |
| 7:45101257:CG:C | donor_gain | 1.0000 |
| 7:45101257:CGT:C | donor_gain | 1.0000 |
| 7:45101257:CGTC:C | donor_gain | 1.0000 |
| 7:45101257:CGTCC:C | donor_gain | 1.0000 |
| 7:45101259:T:TA | donor_gain | 1.0000 |
| 7:45101368:CTAGC:C | acceptor_gain | 1.0000 |
| 7:45101369:TAGC:T | acceptor_gain | 1.0000 |
| 7:45101370:AGC:A | acceptor_gain | 1.0000 |
| 7:45101371:GC:G | acceptor_gain | 1.0000 |
| 7:45101372:CC:C | acceptor_gain | 1.0000 |
| 7:45101373:C:CC | acceptor_gain | 1.0000 |
| 7:45101498:CCTA:C | donor_loss | 1.0000 |
| 7:45101499:CTA:C | donor_loss | 1.0000 |
| 7:45101500:TACCT:T | donor_loss | 1.0000 |
| 7:45101502:C:A | donor_loss | 1.0000 |
AlphaMissense
4056 scored. Top likely-pathogenic:
| Variant | Protein change | am_pathogenicity |
|---|---|---|
| 7:45100425:A:T | V599D | 0.991 |
| 7:45101292:C:G | R587P | 0.991 |
| 7:45104243:A:C | F307L | 0.990 |
| 7:45104243:A:T | F307L | 0.990 |
| 7:45104245:A:G | F307L | 0.990 |
| 7:45100411:A:G | W604R | 0.989 |
| 7:45100411:A:T | W604R | 0.989 |
| 7:45105535:C:G | R214P | 0.989 |
| 7:45101367:G:T | A562E | 0.988 |
| 7:45105533:A:G | W215R | 0.988 |
| 7:45105533:A:T | W215R | 0.988 |
| 7:45100371:A:G | L617P | 0.987 |
| 7:45100371:A:T | L617H | 0.987 |
| 7:45105652:C:G | R175P | 0.987 |
| 7:45101834:A:G | W520R | 0.985 |
| 7:45101834:A:T | W520R | 0.985 |
| 7:45104615:C:G | R277P | 0.984 |
| 7:45100375:A:C | Y616D | 0.983 |
| 7:45101271:A:G | F594S | 0.982 |
| 7:45101313:C:T | G580D | 0.981 |
| 7:45104618:A:G | L276P | 0.981 |
| 7:45105451:A:G | L242P | 0.981 |
| 7:45100361:C:A | K620N | 0.980 |
| 7:45100361:C:G | K620N | 0.980 |
| 7:45101612:C:G | A524P | 0.980 |
| 7:45104597:A:G | L283P | 0.980 |
| 7:45101314:C:G | G580R | 0.978 |
| 7:45104709:A:G | C246R | 0.978 |
| 7:45103366:G:C | F381L | 0.977 |
| 7:45103366:G:T | F381L | 0.977 |
dbSNP variants (sampled 300 via entrez): RS1000178664 (7:45100719 C>G,T), RS1000194664 (7:45099606 G>A), RS1000204655 (7:45100494 C>T), RS1000253966 (7:45105067 A>G), RS1000539115 (7:45111860 T>A,C), RS1000584871 (7:45103751 G>A), RS1000692262 (7:45106011 A>G), RS1000950876 (7:45103530 C>A,G), RS1001520861 (7:45105646 C>T), RS1001720744 (7:45100049 A>C), RS1002039846 (7:45111459 A>G,T), RS1002066766 (7:45099916 G>A,C), RS1002083237 (7:45100364 G>C,T), RS1002929684 (7:45111867 G>T), RS1003141735 (7:45108922 G>A,C)
Disease associations
OMIM: gene MIM:611325 | disease phenotypes:
GenCC curated gene-disease
Mondo (0):
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
2 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST007856_14 | Colorectal cancer or advanced adenoma | 6.000000e-06 |
| GCST90002400_612 | Plateletcrit | 4.000000e-09 |
EFO canonical traits (1, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0007985 | platelet crit |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL6067265 (SINGLE PROTEIN)
PharmGKB: 1 entry (VIP=true, CPIC=false)
ChEMBL bioactivities
2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 7.01 | Kd | 97.07 | nM | CHEMBL5653589 |
| 7.01 | ED50 | 97.07 | nM | CHEMBL5653589 |
PubChem BioAssay actives
1 with measured affinity, of 2 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 | 2149559: Binding affinity to human TBRG4 incubated for 45 mins by Kinobead based pull down assay | kd | 0.0971 | uM |
CTD chemical–gene interactions
28 total (human), top 28 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| bisphenol A | affects cotreatment, decreases methylation, decreases expression | 4 |
| Valproic Acid | decreases expression, increases expression, increases methylation | 3 |
| sodium arsenite | decreases expression, increases expression | 2 |
| aristolochic acid I | increases expression | 1 |
| FR900359 | increases phosphorylation | 1 |
| beta-lapachone | increases expression | 1 |
| 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone | decreases expression | 1 |
| di-n-butylphosphoric acid | affects expression | 1 |
| pentabromodiphenyl ether | decreases expression | 1 |
| corosolic acid | decreases expression | 1 |
| 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide | affects cotreatment, decreases expression | 1 |
| ICG 001 | decreases expression | 1 |
| 2,2’,4,4’-tetrabromodiphenyl ether | decreases expression | 1 |
| bisphenol S | affects expression | 1 |
| LDN 193189 | affects cotreatment, decreases expression | 1 |
| Fulvestrant | decreases methylation, affects cotreatment | 1 |
| Acetaminophen | decreases expression | 1 |
| Ivermectin | decreases expression | 1 |
| Methyl Methanesulfonate | decreases expression | 1 |
| Methylnitronitrosoguanidine | increases expression | 1 |
| Potassium Dichromate | decreases expression | 1 |
| Ribonucleotides | affects binding | 1 |
| Smoke | decreases expression | 1 |
| Tetrachlorodibenzodioxin | increases expression | 1 |
| Thiram | decreases expression | 1 |
| Tobacco Smoke Pollution | increases expression | 1 |
| Tretinoin | decreases expression | 1 |
| Chlorodiphenyl (54% Chlorine) | 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 |
|---|---|---|---|
| CHEMBL5652601 | Binding | Binding affinity to human TBRG4 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 |
Cellosaurus cell lines
4 cell lines: 3 cancer cell line, 1 transformed cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_B3J3 | Abcam HEK293T TBRG4 KO | Transformed cell line | Female |
| CVCL_C6Y5 | HAP1 FASTKD4-sKO | Cancer cell line | Male |
| CVCL_C6Y7 | HAP1 FASTKD3&4-dKO | Cancer cell line | Male |
| CVCL_C6Y8 | HAP1 FASTKD4&5-dKO | Cancer cell line | Male |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): colorectal adenoma