USP6

Chr 17

ubiquitin specific peptidase 6

Also known as: HRP1, TRE17, TRE2, TRESMCR, Tre-2, USP6-short

NCBI Gene: 9098ENSG00000129204UniProt: P35125OMIM: 604334

The USP6 protein is a deubiquitinase that removes ubiquitin from target proteins and regulates endocytic trafficking and postsynaptic neurotransmitter receptor internalization at glutamatergic synapses. This gene is not constrained against loss-of-function variants and is not currently associated with established Mendelian neurological disorders in pediatric patients.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.97
Clinical Summary— USP6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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
0.97LOEUF
pLI 0.000
Z-score 1.74
OE 0.79 (0.64–0.97)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.14Z-score
OE missense 1.01 (0.96–1.08)
792 obs / 780.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.79 (0.64–0.97)
0≤0.351.4
Missense OE1.01 (0.96–1.08)
0≤0.61.4
Synonymous OE1.04
0≤1.21.6
LoF obs/exp: 63 / 79.8Missense obs/exp: 792 / 780.8Syn Z: -0.50
DN
0.6743th %ile
GOF
0.5856th %ile
LOF
0.3746th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

ClinVar

Protein Context — Lollipop Plot

USP6 · 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 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Nodular fasciitis of the intradural cervical spine with *MIR22HG::USP6* fusion a rare postoperative occurrence and novel molecular pathogenesis.
Xie D et al.·Eur Spine J
2026
Low-grade Myofibroblastic Sarcoma Represents An Epigenetically Distinct Myofibroblastic Tumor With USP6 Upregulation and Stable Genome.
Yeung MCF et al.·Mod Pathol
2026
Primary malignant aneurysmal bone cyst of the metatarsal with PAFAH1B1::USP6 fusion: expanding the clinicopathologic spectrum of malignant USP6 translocated neoplasms.
Bennett J et al.·Skeletal Radiol
2026
Morphologically Malignant Nodular Fasciitis With COL3A1::USP6 Fusion and aTP53 Mutation.
Suchi M et al.·Ann Plast Surg
2026
Clinical and Pathologic Description of Three Aneurysmal Bone Cyst Cases With Novel USP6 Fusion Partners Including SEC24D, HNRNPC, and ERRFI1.
Blackburn PR et al.·Genes Chromosomes Cancer
2025Cohort
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