TRIML2

Chr 4

tripartite motif family like 2

Also known as: SPRYD6

NCBI Gene: 205860 ENSG00000179046 UniProt: Q8N7C3 OMIM: 620480

This protein is a member of the TRIM family that may regulate the tumor suppressor p53 through enhancement of p53 SUMOylation. The gene shows no constraint against loss-of-function variants (pLI near 0, LOEUF >1), and no established Mendelian diseases have been associated with TRIML2 mutations in current medical literature.

OMIM ResearchSummary from RefSeq

This gene encodes a member of the tri-partite motif (TRIM) family of proteins. This protein may be regulated by the tumor suppressor p53 and may regulate p53 through the enhancement of p53 SUMOylation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.29

Clinical Summary— TRIML2

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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

55 VUS of 67 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?

1.29LOEUF

pLI 0.000

Z-score 0.84

OE 0.74 (0.45–1.29)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.12Z-score

OE missense 0.98 (0.87–1.10)

208 obs / 213.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.74 (0.45–1.29)

0≤0.351.4

Missense OE?0.98 (0.87–1.10)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 9 / 12.2Missense obs/exp: 208 / 213.0Syn Z: -0.04

This gene — mechanism propensity

0.82top 10%

GOF

0.74top 25%

LOF

0.12100th %ile

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

DNprediction above median

GOFprediction 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

67 submitted variants in ClinVar

ClinVar

Classification Summary

VUS55

Likely Benign9

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	54	1	0	55
Likely Benign	9	0	0	9
Benign	1	0	2	3
Total	64	1	2	67

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

View in ClinVar →

112 pathogenic / likely-pathogenic (of 160) ClinVar copy-number / structural variants overlap TRIML2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →