TRIM59

protein-coding

tripartite motif containing 59, the group of Tripartite motif family|Ring finger proteins

Gene summary

Predicted to enable ubiquitin protein ligase activity. Acts upstream of or within negative regulation of canonical NF-kappaB signal transduction. Predicted to be located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

TRIM57

MANE transcript

NM_173084.3

Inheritance

—

ClinVar variants

U:51B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.47

Max pathogenic AF

—

Genomic locus

chr3:160,432,445-160,485,773

External References & Databases

Ensembl (ENSG00000213186)

Transcript & Mutation Effects

hg38 • Region Span ~53.3 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 TRIM59 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 54

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173084.3. 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						0
missense			51 clinvar	3 clinvar		54
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	51	3	0	54

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173084.3	RefSeq	NP_775107.1	1	MANE Select
ENST00000309784.9	Ensembl	ENSP00000311219.4	1	MANE Select
ENST00000468542.1	Ensembl	ENSP00000420451.1	2	Standard
ENST00000471155.5	Ensembl	ENSP00000418699.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Validated nuclear estrogen receptor alpha network

Biological Process

protein ubiquitination
negative regulation of I-kappaB kinase/NF-kappaB signaling
innate immune response
negative regulation of viral entry into host cell

Molecular Function

protein binding
zinc ion binding
ubiquitin protein ligase activity

Cellular Component

endoplasmic reticulum
endoplasmic reticulum membrane
centrosome
cilium
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000309784
Coding exons: 1
Length: 53329
Individuals with no LoFs: 125049
Homozygous LoFs: 6
Heterozygous LoFs: 664
Defined: 125719
p: 0.00267

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.504	182	202	0.900	0.00000945	2675
Missense (PolyPhen)		53	55.619	0.95292		729
Synonymous	0.403	66	70.3	0.939	0.00000344	732
Loss of Function	1.92	7	15.0	0.466	8.99e-7	179

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0028	0.0028	notable
Latino/Admixed American	0.0036	0.0035	notable
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.0033	0.0033	notable
Finnish	0.0011	0.0011	notable
European (Non-Finnish)	0.0025	0.0024	notable
South Asian	0.0045	0.0042	notable
Other	0.0020	0.0020	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May serve as a multifunctional regulator for innate immune signaling pathways. {ECO:0000250|UniProtKB:Q922Y2}.;

Recessive Scores

pRec: 0.0870

Intolerance Scores

RVIS EVS: 0.13
RVIS percentile EVS: 63.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.369

Gene Damage Prediction

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