TRAP1

Chr 16

TNF receptor associated protein 1

Also known as: HSP 75, HSP75, HSP90L, TRAP-1

NCBI Gene: 10131ENSG00000126602UniProt: Q58FF3OMIM: 606219

The protein is a mitochondrial chaperone of the HSP90 family with ATPase activity that regulates cellular stress responses. Mutations cause autosomal recessive spastic paraplegia and Charcot-Marie-Tooth disease, primarily affecting the nervous system. The gene shows very low constraint against loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 1.41
Clinical Summary— TRAP1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
31 unique Pathogenic / Likely Pathogenic· 231 VUS of 400 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
1.41LOEUF
pLI 0.000
Z-score -0.53
OE 1.09 (0.85–1.41)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-2.72Z-score
OE missense 1.37 (1.28–1.47)
587 obs / 428.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.09 (0.85–1.41)
0≤0.351.4
Missense OE1.37 (1.28–1.47)
0≤0.61.4
Synonymous OE1.41
0≤1.21.6
LoF obs/exp: 42 / 38.5Missense obs/exp: 587 / 428.3Syn Z: -4.33

ClinVar Variant Classifications

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic1
VUS231
Likely Benign74
Benign31
Conflicting7
30
Pathogenic
1
Likely Pathogenic
231
VUS
74
Likely Benign
31
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
29
0
30
Likely Pathogenic
0
0
1
0
1
VUS
15
182
34
0
231
Likely Benign
0
11
29
34
74
Benign
1
9
17
4
31
Conflicting
—7
Total1720211038374

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

View in ClinVar →

Protein Context — Lollipop Plot

TRAP1 · 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
TRAP1 drives smooth muscle cell senescence and promotes atherosclerosis via HDAC3-primed histone H4 lysine 12 lactylation.
Li X et al.·Eur Heart J
2024
Multi-omics profiling reveal cells with novel oncogenic cluster, TRAP1(low)/CAMSAP3(low), emerge more aggressive behavior and poor-prognosis in early-stage endometrial cancer.
Mao X et al.·Mol Cancer
2024
Mutation in the mitochondrial chaperone TRAP1 leads to autism with more severe symptoms in males.
Rydzanicz M et al.·EMBO Mol Med
2024
Targeting TRAP1-dependent metabolic reprogramming to overcome doxorubicin resistance in quiescent breast cancer.
Saleem MZ et al.·Drug Resist Updat
2025
Diagnostic Yield and Novel Candidate Genes by Exome Sequencing in 152 Consanguineous Families With Neurodevelopmental Disorders.
Reuter MS et al.·JAMA Psychiatry
2017
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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