TRIM59

Chr 3

tripartite motif containing 59

Also known as: IFT80L, MRF1, RNF104, TRIM57, TSBF1

NCBI Gene: 286827 ENSG00000213186 UniProt: Q8IWR1 OMIM: 616148

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 0.87

Clinical Summary— TRIM59

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

51 VUS of 56 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.87LOEUF

pLI 0.001

Z-score 1.92

OE 0.47 (0.26–0.87)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.50Z-score

OE missense 0.90 (0.80–1.02)

182 obs / 202.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.47 (0.26–0.87)

0≤0.351.4

Missense OE?0.90 (0.80–1.02)

0≤0.61.4

Synonymous OE?0.94

0≤1.21.6

LoF obs/exp: 7 / 15.0Missense obs/exp: 182 / 202.2Syn Z: 0.40

This gene — mechanism propensity

0.7132th %ile

GOF

0.73top 25%

LOF

0.2483th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

56 submitted variants in ClinVar

ClinVar

Classification Summary

VUS51

Likely Benign3

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	51	51
Likely Benign	3	3
Benign	0	0
Total	54	54

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

21 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap TRIM59 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →