TRIM14

Chr 9

tripartite motif containing 14

TRIM14 encodes a protein that promotes antiviral and antibacterial innate immune responses by facilitating type I interferon signaling pathways and promoting degradation of viral proteins. Mutations cause autosomal recessive severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to viral infections. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIMResearchSummary from UniProt
MultiplemechanismLOEUF 0.87
Clinical SummaryTRIM14
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.87LOEUF
pLI 0.005
Z-score 1.92
OE 0.44 (0.240.87)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.82Z-score
OE missense 0.81 (0.700.94)
121 obs / 149.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.44 (0.240.87)
00.351.4
Missense OE0.81 (0.700.94)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 6 / 13.7Missense obs/exp: 121 / 149.1Syn Z: 0.21
DN
0.75top 25%
GOF
0.77top 25%
LOF
0.2387th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TRIM14 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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