TRIM25

protein-coding

tripartite motif containing 25, the group of Tripartite motif family|MicroRNA protein coding host genes|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. The protein is an RNA binding protein, functions as a ubiquitin E3 ligase and is involved in multiple cellular processes, including regulation of antiviral innate immunity. [provided by RefSeq, Sep 2021]

Previous symbols:

ZNF147

MANE transcript

NM_005082.5

Inheritance

—

ClinVar variants

U:79B:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr17:56,836,387-56,914,080

External References & Databases

Ensembl (ENSG00000121060)

Transcript & Mutation Effects

hg38 • Region Span ~77.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TRIM25 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 83

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005082.5. 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			1 clinvar	1 clinvar	2 clinvar	4
missense			75 clinvar	8 clinvar	1 clinvar	84
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	79	9	3	91

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005082.5	RefSeq	NP_005073.2	9	MANE Select
ENST00000316881.9	Ensembl	ENSP00000323889.4	9	MANE Select
ENST00000537230.3	Ensembl	ENSP00000445961.1	9	Standard
ENST00000537230.4	Ensembl	ENSP00000445961.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Influenza A - Homo sapiens (human)
NF-kappa B signaling pathway - Homo sapiens (human)
RIG-I-like receptor signaling pathway - Homo sapiens (human)
RIG-I-like Receptor Signaling
DNA Repair

Biological Process

ubiquitin-dependent protein catabolic process
protein monoubiquitination
viral process
translesion synthesis
ubiquitin-dependent ERAD pathway

Molecular Function

RNA binding
ubiquitin-protein transferase activity
protein binding
zinc ion binding
ligase activity

Cellular Component

nucleoplasm
cytosol
nuclear body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000316881
Coding exons: 9
Length: 26130
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125748
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.859	303	348	0.870	0.0000189	4099
Missense (PolyPhen)		84	111.81	0.75126		1428
Synonymous	0.603	144	154	0.938	0.00000901	1224
Loss of Function	3.16	9	26.6	0.339	0.00000122	329

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.000078	0.000065	rare
Other	0.00018	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Functions as a ubiquitin E3 ligase and as an ISG15 E3 ligase. Involved in innate immune defense against viruses by mediating ubiquitination of DDX58. Mediates 'Lys-63'-linked polyubiquitination of the DDX58 N-terminal CARD-like region which is crucial for triggering the cytosolic signal transduction that leads to the production of interferons in response to viral infection. Promotes ISGylation of 14-3-3 sigma (SFN), an adapter protein implicated in the regulation of a large spectrum signaling pathway. Mediates estrogen action in various target organs. Mediates the ubiquitination and subsequent proteasomal degradation of ZFHX3 (PubMed:22452784). {ECO:0000269|PubMed:16352599, ECO:0000269|PubMed:17069755, ECO:0000269|PubMed:17392790, ECO:0000269|PubMed:22452784}.;

Recessive Scores

pRec: 0.170

Intolerance Scores

LoFtool: 0.520
RVIS EVS: -0.22
RVIS percentile EVS: 37.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.833

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium