TRIM42

Chr 3

tripartite motif containing 42

Also known as: PPP1R40, T4A1

NCBI Gene: 287015 ENSG00000155890 UniProt: Q8IWZ5 OMIM: 620334

This gene encodes a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, namely a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. [provided by RefSeq, Jul 2008]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.32

Clinical Summary— TRIM42

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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

103 VUS of 110 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.32LOEUF

pLI 0.000

Z-score 0.16

OE 0.97 (0.72–1.32)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.39Z-score

OE missense 0.95 (0.87–1.03)

399 obs / 421.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.97 (0.72–1.32)

0≤0.351.4

Missense OE?0.95 (0.87–1.03)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 29 / 30.0Missense obs/exp: 399 / 421.6Syn Z: -0.68

This gene — mechanism propensity

0.6842th %ile

GOF

0.6930th %ile

LOF

0.3843th %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

110 submitted variants in ClinVar

ClinVar

Classification Summary

VUS103

Likely Benign5

103

VUS

Likely 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	103	0	103
Likely Benign	3	2	5
Benign	0	0	0
Total	106	2	108

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 28) ClinVar copy-number / structural variants overlap TRIM42 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →