TRIM50

Chr 7

tripartite motif containing 50

Also known as: TRIM50A

NCBI Gene: 135892 ENSG00000146755 UniProt: Q86XT4 OMIM: 612548

TRIM50 encodes an E3 ubiquitin-protein ligase that regulates autophagy by ubiquitinating Beclin-1 and promotes NLRP3 inflammasome activation as part of innate immune responses. The gene is not highly constrained against loss-of-function variants (pLI near 0, LOEUF >1), and no definitive human disease associations have been established based on the available data. Further clinical and genetic studies are needed to determine if TRIM50 variants cause human disease.

OMIM ResearchSummary from RefSeq, UniProt

Enables identical protein binding activity. Predicted to be involved in innate immune response. Predicted to act upstream of or within regulation of establishment of protein localization. Located in cytosol. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.25

Clinical Summary— TRIM50

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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

99 VUS of 111 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?

1.25LOEUF

pLI 0.000

Z-score 0.68

OE 0.84 (0.57–1.25)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.13Z-score

OE missense 0.98 (0.89–1.08)

299 obs / 305.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.84 (0.57–1.25)

0≤0.351.4

Missense OE?0.98 (0.89–1.08)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 17 / 20.3Missense obs/exp: 299 / 305.2Syn Z: -1.51

This gene — mechanism propensity

0.76top 25%

GOF

0.83top 10%

LOF

0.2092th %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

111 submitted variants in ClinVar

ClinVar

Classification Summary

VUS99

Likely Benign8

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	99	0	99
Likely Benign	6	2	8
Benign	0	1	1
Total	105	3	108

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

View in ClinVar →

138 pathogenic / likely-pathogenic (of 149) ClinVar copy-number / structural variants overlap TRIM50 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →