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…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.87

LOEUF

Multiple*

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in TRIM59?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 79

532 rare PASS variants

Rare truncating (LoF)

1 in 250

132 rare PASS variants

Rare synonymous (reference)

1 in 350

174 rare PASS variants

Rare missense and truncating variants are carried at similar rates in TRIM59; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 210	1 in 300
South Asian	~43k	1 in 89	1 in 160
Remaining (unassigned)	~30k	1 in 86	1 in 250
European (Finnish)	~27k	1 in 390	1 in 230
Admixed American	~22k	1 in 92	1 in 280
African / African American	~21k	1 in 80	1 in 330
East Asian	~20k	1 in 110	1 in 200
Ashkenazi Jewish	~13k	≈ 1 in 3,300	1 in 440
Middle Eastern	~2,884	1 in 72	1 in 240

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓