TRIM72

Chr 16

tripartite motif containing 72

Also known as: MG53

NCBI Gene: 493829 ENSG00000177238 UniProt: Q6ZMU5 OMIM: 613288

The protein functions as a muscle-specific E3 ubiquitin ligase that plays a central role in cell membrane repair by nucleating assembly of repair machinery at injury sites and regulating membrane budding and exocytosis. Mutations in this gene cause limb-girdle muscular dystrophy, which is inherited in an autosomal recessive pattern. The gene shows very low constraint to loss-of-function variants (pLI near 0), suggesting haploinsufficiency is well-tolerated.

OMIM ResearchSummary from RefSeq, UniProt

Enables identical protein binding activity. Predicted to be involved in several processes, including plasma membrane repair; proteasome-mediated ubiquitin-dependent protein catabolic process; and protein homooligomerization. Predicted to act upstream of or within negative regulation of insulin receptor signaling pathway; negative regulation of insulin-like growth factor receptor signaling pathway; and negative regulation of myotube differentiation. Predicted to be located in cytoplasmic vesicle membrane. Predicted to be active in cytoplasm and sarcolemma. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.05

Clinical Summary— TRIM72

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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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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.05LOEUF

pLI 0.000

Z-score 1.42

OE 0.60 (0.36–1.05)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.45Z-score

OE missense 0.75 (0.67–0.84)

198 obs / 264.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.60 (0.36–1.05)

0≤0.351.4

Missense OE?0.75 (0.67–0.84)

0≤0.61.4

Synonymous OE?0.78

0≤1.21.6

LoF obs/exp: 9 / 14.9Missense obs/exp: 198 / 264.5Syn Z: 1.88

This gene — mechanism propensity

0.80top 25%

GOF

0.84top 5%

LOF

0.1399th %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.