TRIM28
tripartite motif containing 28, the group of PHD finger proteins|Tripartite motif family|MicroRNA protein coding host genes|Ring finger proteins|Protein phosphatase 1 regulatory subunits|Bromodomain containing
Basic information
Region (hg38): 19:58544064-58550722
Links
Phenotypes
GenCC
Source:
- kidney Wilms tumor (Supportive), mode of inheritance: AD
ClinVar
This is a list of variants' phenotypes submitted to
- Predisposition to Wilms tumor (1 variants)
- Nephroblastoma (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRIM28 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 22 | 27 | ||||
| missense | 43 | 48 | ||||
| nonsense | 2 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 5 | 2 | 7 | |||
| non coding | 11 | |||||
| Total | 2 | 0 | 45 | 31 | 10 |
Variants in TRIM28
This is a list of pathogenic ClinVar variants found in the TRIM28 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 19-58544769-C-T | Likely benign (Oct 01, 2022) | |||
| 19-58544798-C-T | not specified | Uncertain significance (Dec 03, 2024) | ||
| 19-58544808-T-G | Likely benign (Oct 01, 2023) | |||
| 19-58544840-G-T | Wilms tumor 1 | Uncertain significance (Jan 30, 2024) | ||
| 19-58544841-C-T | Likely benign (May 01, 2024) | |||
| 19-58544852-G-T | not specified | Uncertain significance (Sep 27, 2021) | ||
| 19-58544871-C-T | TRIM28-related disorder | Benign/Likely benign (Oct 01, 2024) | ||
| 19-58544876-C-G | not specified | Uncertain significance (Jun 09, 2022) | ||
| 19-58544880-G-GGCCTCT | Predisposition to Wilms tumor | Uncertain significance (Feb 06, 2024) | ||
| 19-58544887-G-C | not specified | Uncertain significance (Nov 15, 2024) | ||
| 19-58544894-C-T | not specified | Uncertain significance (Nov 21, 2022) | ||
| 19-58544897-C-T | not specified | Uncertain significance (Apr 25, 2023) | ||
| 19-58544912-C-G | not specified | Uncertain significance (Mar 01, 2024) | ||
| 19-58544918-G-T | Wilms tumor 1 | Uncertain significance (Nov 03, 2022) | ||
| 19-58544931-G-T | Likely benign (Oct 01, 2024) | |||
| 19-58544946-G-A | TRIM28-related disorder | Likely benign (Jun 01, 2024) | ||
| 19-58544949-C-T | TRIM28-related disorder | Benign (Dec 11, 2023) | ||
| 19-58545044-C-T | not specified | Uncertain significance (Apr 07, 2023) | ||
| 19-58545080-C-T | not specified | Uncertain significance (Nov 27, 2023) | ||
| 19-58545412-C-T | Likely benign (Feb 01, 2024) | |||
| 19-58545438-C-T | Benign (Jun 21, 2018) | |||
| 19-58545464-A-G | Wilms tumor 1 • not specified | Uncertain significance (Mar 16, 2022) | ||
| 19-58545786-A-AT | Predisposition to Wilms tumor | Pathogenic (Mar 07, 2024) | ||
| 19-58547408-G-A | Uncertain significance (Jan 19, 2024) | |||
| 19-58547430-A-T | not specified | Uncertain significance (Mar 25, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TRIM28 | protein_coding | protein_coding | ENST00000253024 | 17 | 6632 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.00000223 | 125411 | 0 | 1 | 125412 | 0.00000399 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.33 | 329 | 471 | 0.698 | 0.0000285 | 5372 |
| Missense in Polyphen | 45 | 135.37 | 0.33243 | 1513 | ||
| Synonymous | -4.55 | 260 | 182 | 1.43 | 0.0000105 | 1737 |
| Loss of Function | 5.59 | 0 | 36.3 | 0.00 | 0.00000184 | 442 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000163 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.000163 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Nuclear corepressor for KRAB domain-containing zinc finger proteins (KRAB-ZFPs). Mediates gene silencing by recruiting CHD3, a subunit of the nucleosome remodeling and deacetylation (NuRD) complex, and SETDB1 (which specifically methylates histone H3 at 'Lys-9' (H3K9me)) to the promoter regions of KRAB target genes. Enhances transcriptional repression by coordinating the increase in H3K9me, the decrease in histone H3 'Lys-9 and 'Lys-14' acetylation (H3K9ac and H3K14ac, respectively) and the disposition of HP1 proteins to silence gene expression. Recruitment of SETDB1 induces heterochromatinization. May play a role as a coactivator for CEBPB and NR3C1 in the transcriptional activation of ORM1. Also corepressor for ERBB4. Inhibits E2F1 activity by stimulating E2F1-HDAC1 complex formation and inhibiting E2F1 acetylation. May serve as a partial backup to prevent E2F1-mediated apoptosis in the absence of RB1. Important regulator of CDKN1A/p21(CIP1). Has E3 SUMO-protein ligase activity toward itself via its PHD-type zinc finger. Also specifically sumoylates IRF7, thereby inhibiting its transactivation activity. Ubiquitinates p53/TP53 leading to its proteosomal degradation; the function is enhanced by MAGEC2 and MAGEA2, and possibly MAGEA3 and MAGEA6. Mediates the nuclear localization of KOX1, ZNF268 and ZNF300 transcription factors. In association with isoform 2 of ZFP90, is required for the transcriptional repressor activity of FOXP3 and the suppressive function of regulatory T-cells (Treg) (PubMed:23543754). Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610). Acts as a corepressor for ZFP568 (By similarity). {ECO:0000250|UniProtKB:Q62318, ECO:0000269|PubMed:10347202, ECO:0000269|PubMed:11959841, ECO:0000269|PubMed:15882967, ECO:0000269|PubMed:16107876, ECO:0000269|PubMed:16862143, ECO:0000269|PubMed:17079232, ECO:0000269|PubMed:17178852, ECO:0000269|PubMed:17704056, ECO:0000269|PubMed:17942393, ECO:0000269|PubMed:18060868, ECO:0000269|PubMed:18082607, ECO:0000269|PubMed:20424263, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:20864041, ECO:0000269|PubMed:21940674, ECO:0000269|PubMed:23543754, ECO:0000269|PubMed:23665872, ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:27029610, ECO:0000269|PubMed:8769649, ECO:0000269|PubMed:9016654}.;
- Pathway
- Corticotropin-releasing hormone signaling pathway;Mesodermal Commitment Pathway;ATM Signaling Network in Development and Disease;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;C-MYB transcription factor network;ATM pathway;E2F transcription factor network;p53 pathway
(Consensus)
Recessive Scores
- pRec
- 0.451
Intolerance Scores
- loftool
- rvis_EVS
- -1.11
- rvis_percentile_EVS
- 6.83
Haploinsufficiency Scores
- pHI
- 0.406
- hipred
- Y
- hipred_score
- 0.840
- ghis
- 0.650
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Trim28
- Phenotype
- endocrine/exocrine gland phenotype; growth/size/body region phenotype; cellular phenotype; embryo phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype;
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;epithelial to mesenchymal transition;DNA repair;chromatin organization;transcription initiation from RNA polymerase II promoter;Ras protein signal transduction;embryo implantation;viral process;protein ubiquitination;protein sumoylation;positive regulation of protein import into nucleus;DNA methylation involved in embryo development;positive regulation of DNA binding;innate immune response;positive regulation of DNA repair;negative regulation of single stranded viral RNA replication via double stranded DNA intermediate;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;protein autophosphorylation;protein complex oligomerization;convergent extension involved in axis elongation;embryonic placenta morphogenesis;positive regulation of methylation-dependent chromatin silencing;negative regulation of DNA demethylation;negative regulation of viral release from host cell;regulation of genetic imprinting
- Cellular component
- chromatin;nucleus;nucleoplasm;nuclear euchromatin;nuclear heterochromatin;RNA polymerase II transcription factor complex
- Molecular function
- DNA binding;chromatin binding;transcription coactivator activity;transcription corepressor activity;RNA binding;protein kinase activity;ubiquitin-protein transferase activity;protein binding;zinc ion binding;SUMO transferase activity;ubiquitin protein ligase binding;Krueppel-associated box domain binding;sequence-specific DNA binding;chromo shadow domain binding;promoter-specific chromatin binding