TRIM23
protein-codingtripartite motif containing 23, the group of ARF GTPase family|Tripartite motif family|Ring finger proteins
Gene summary
The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This protein is also a member of the ADP ribosylation factor family of guanine nucleotide-binding family of proteins. Its carboxy terminus contains an ADP-ribosylation factor domain and a guanine nucleotide binding site, while the amino terminus contains a GTPase activating protein domain which acts on the guanine nucleotide binding site. The protein localizes to lysosomes and the Golgi apparatus. It plays a role in the formation of intracellular transport vesicles, their movement from one compartment to another, and phopholipase D activation. Three alternatively spliced transcript variants for this gene have been described. [provided by RefSeq, Jul 2008]
- ARFD1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~36.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0100038
Submitter: Ambry Genetics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TRIM23 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001656.4. 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 | 4 | 1 | 5 | |||
| missense | 47 | 1 | 48 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 53 | 1 | 1 | 55 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001647.1 | 11 | MANE Select | |
| Ensembl | ENSP00000231524.9 | 11 | MANE Select | |
| RefSeq | NP_150230.1 | 13 | Standard | |
| RefSeq | NP_150231.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- intracellular protein transport
- Golgi to plasma membrane transport
- viral process
- vesicle-mediated transport
- protein ubiquitination
Molecular Function
- nucleic acid binding
- GTPase activity
- ubiquitin-protein transferase activity
- protein binding
- GTP binding
Cellular Component
- Golgi membrane
- nucleus
- cytoplasm
- lysosomal membrane
- Golgi apparatus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000231524
- Coding exons
- 11
- Length
- 36296
- Individuals with no LoFs
- 125709
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 38
- Defined
- 125747
- p
- 0.000151
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.50 | 191 | 316 | 0.605 | 0.0000166 | 3736 |
| Missense (PolyPhen) | 45 | 113.29 | 0.39721 | 1375 | ||
| Synonymous | 0.724 | 99 | 109 | 0.912 | 0.00000528 | 1109 |
| Loss of Function | 3.44 | 12 | 33.5 | 0.358 | 0.00000203 | 373 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00023 | 0.00023 | rare |
| Ashkenazi Jewish | 0.00079 | 0.00079 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00013 | 0.00013 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as an E3 ubiquitin-protein ligase. Plays an essential role in autophagy activation during viral infection. Mechanistically, activates TANK-binding kinase 1/TBK1 by facilitating its dimerization and ability to phosphorylate the selective autophagy receptor SQSTM1. In order to achieve this function, TRIM23 mediates 'Lys-27'-linked auto-ubiquitination of its ADP-ribosylation factor (ARF) domain to induce its GTPase activity and its recruitment to autophagosomes (PubMed:28871090). {ECO:0000269|PubMed:15684077, ECO:0000269|PubMed:28871090}.;
Recessive Scores
- pRec
- 0.124
Intolerance Scores
- LoFtool
- 0.518
- RVIS EVS
- -0.62
- RVIS percentile EVS
- 17.16
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.984
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |