TRIM28
protein-codingtripartite 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
Gene summary
The protein encoded by this gene mediates transcriptional control by interaction with the Kruppel-associated box repression domain found in many transcription factors. The protein localizes to the nucleus and is thought to associate with specific chromatin regions. The protein is a member of the tripartite motif family. This tripartite motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0019004
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0024676
Submitter: G2P
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TRIM28 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005762.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 12 | 99 | 6 | 117 | ||
| missense | 146 | 10 | 156 | |||
| nonsense | 3 | 1 | 4 | |||
| start loss | 0 | |||||
| frameshift | 6 | 2 | 8 | |||
| splice donor/acceptor (+/-2bp) | 4 | 10 | 14 | |||
| Total | 9 | 7 | 168 | 109 | 6 | 299 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005753.1 | 17 | MANE Select | |
| Ensembl | ENSP00000253024.4 | 17 | MANE Select | |
| Ensembl | ENSP00000342232.5 | 15 | Standard | |
| Ensembl | ENSP00000342232.5 | 15 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Corticotropin-releasing hormone signaling pathway
- Mesodermal Commitment Pathway
- ATM Signaling Network in Development and Disease
- Gene expression (Transcription)
- Generic Transcription Pathway
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
Molecular Function
- DNA binding
- chromatin binding
- transcription coactivator activity
- transcription corepressor activity
- RNA binding
Cellular Component
- chromatin
- nucleus
- nucleoplasm
- nuclear euchromatin
- nuclear heterochromatin
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000253024
- Coding exons
- 17
- Length
- 6632
- Individuals with no LoFs
- 125411
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 125412
- p
- 0.00000399
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.33 | 329 | 471 | 0.698 | 0.0000285 | 5372 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
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}.;
Recessive Scores
- pRec
- 0.451
Intolerance Scores
- RVIS EVS
- -1.11
- RVIS percentile EVS
- 6.83
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |