TRIM49

Chr 11

tripartite motif containing 49

Also known as: RNF18, TRIM49A, TRIM49L2

NCBI Gene: 57093ENSG00000168930UniProt: P0CI25OMIM: 606124

The TRIM49 protein contains a RING zinc finger domain involved in protein-protein interactions and is preferentially expressed in testis. This gene is extremely intolerant to loss-of-function variation (pLI near 1.0), but no definitive disease associations have been established in the current literature. Additional research is needed to determine if TRIM49 mutations cause human disease.

OMIMResearchSummary from RefSeq
MultiplemechanismLOEUF 1.82
Clinical Summary— TRIM49
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 98 VUS of 127 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
1.82LOEUF
pLI 0.000
Z-score -0.38
OE 1.15 (0.68–1.82)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.41Z-score
OE missense 1.09 (0.96–1.23)
186 obs / 170.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.15 (0.68–1.82)
0≤0.351.4
Missense OE1.09 (0.96–1.23)
0≤0.61.4
Synonymous OE1.16
0≤1.21.6
LoF obs/exp: 9 / 7.8Missense obs/exp: 186 / 170.9Syn Z: -1.01
DN
0.78top 25%
GOF
0.79top 25%
LOF
0.1697th %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

127 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic1
VUS98
Likely Benign11
Benign1
16
Pathogenic
1
Likely Pathogenic
98
VUS
11
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
16
0
16
Likely Pathogenic
0
0
1
0
1
VUS
0
91
7
0
98
Likely Benign
0
6
4
1
11
Benign
0
0
1
0
1
Total097291127

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

View in ClinVar →

Protein Context — Lollipop Plot

TRIM49 · 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

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Retinitis Pigmentosa-Associated Gene TRIM49 Regulates ULK1-Mediated Autophagy and Photoreceptor Phagocytosis by the Retinal Pigment Epithelium.
Yi Z et al.·Adv Sci (Weinh)
2025
TRIM49 Deficiency Stabilizes a Galectin-3/EGR1 Transcriptional Complex That Drives Invasiveness of Gastric Adenocarcinoma.
Qin ZY et al.·Cancer Res
2026
Expression, purification, and characterization of the TRIM49 protein.
Guimarães DS et al.·Protein Expr Purif
2018
Novel susceptibility loci for steroid-associated osteonecrosis of the femoral head in systemic lupus erythematosus.
Suetsugu H et al.·Hum Mol Genet
2022Meta-analysis
Overexpression of Tripartite Motif-Containing 48 (TRIM48) Inhibits Growth of Human Glioblastoma Cells by Suppressing Extracellular Signal Regulated Kinase 1/2 (ERK1/2) Pathway.
Xue LP et al.·Med Sci Monit
2019
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients