On this page
OTUD6B
OTU deubiquitinase 6B
OTUD6B is located on the long (q) arm of chromosome 8, at band 8q21.3. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 8 in the library →Available at Jeen Health
Clinical tests that include this
Overview
OTUD6B (OTU deubiquitinase 6B) is a member of the ovarian tumour protease family, a group of enzymes that cleave ubiquitin chains from target proteins. Ubiquitination is a cellular process in which small proteins called ubiquitin molecules are attached to other proteins, often marking them for breakdown or changing their activity. By removing these ubiquitin tags, deubiquitinases like OTUD6B help control protein levels and signalling networks within cells.
The gene is located on chromosome 8 and produces an enzyme whose full biological significance is still being investigated. Unlike some related deubiquitinases that have well-characterised roles in cancer or immune function, OTUD6B has not yet been firmly linked to specific clinical conditions through large-scale genetic studies. Research continues to explore how variations in this gene might influence cellular processes.
What the gene does
The OTUD6B protein functions as a deubiquitinating enzyme, catalysing the removal of ubiquitin molecules from substrate proteins. This activity represents a key regulatory step in the ubiquitin-proteasome system, which governs protein turnover throughout the cell. When ubiquitin chains accumulate on a protein, they typically signal for its destruction by the proteasome, a cellular machine that degrades unwanted proteins. Deubiquitinases counterbalance this process by rescuing proteins from degradation or modifying ubiquitin signals to redirect cellular responses.
The OTU family of deubiquitinases, to which OTUD6B belongs, is characterised by a conserved catalytic domain that recognises and cleaves specific types of ubiquitin linkages. Different deubiquitinases show preferences for particular chain types, influencing whether they affect protein stability, DNA repair, inflammatory signalling, or other pathways. The specific substrates and pathways regulated by OTUD6B remain incompletely defined, though evidence suggests it may participate in general cellular homeostasis. Further research is needed to clarify which proteins OTUD6B targets and under what physiological conditions its activity becomes most important.
Video: Genetics 101
Chromosome location
OTUD6B is located on the long arm of chromosome 8 at position 21.3, designated as 8q21.3. This chromosomal region contains numerous genes involved in diverse cellular functions. The precise number of exons and full genomic structure for OTUD6B have not been extensively characterised in publicly available databases, reflecting the relatively limited research focus on this particular gene compared to other deubiquitinases.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein. While OTUD6B is classified within the OTU deubiquitinase family based on sequence homology, specific domain boundaries and structural features have not been comprehensively mapped in structural databases. OTU family members typically contain a catalytic OTU domain responsible for cleaving ubiquitin chains, but additional regulatory regions or protein-interaction modules for OTUD6B await detailed investigation.
Key variants
Genetic variants in OTUD6B have been identified through population sequencing projects, though the clinical significance of most changes remains uncertain. Because the gene's function is not yet fully understood and it has not been definitively associated with a recognised inherited condition, most variants are classified as having uncertain significance. Researchers continue to evaluate whether particular changes in OTUD6B might contribute to disease susceptibility or other phenotypes in combination with variants in other genes.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.189_190del | p.His63fs | Pathogenic | ★★☆☆ | Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies |
c.192_195del | p.Glu65fs | Pathogenic/Likely pathogenic | ★★☆☆ | Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies |
c.343C>T | p.Arg115Ter | Pathogenic | ★★☆☆ | Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies |
c.527_528del | p.Val176fs | Pathogenic/Likely pathogenic | ★★☆☆ | Inborn genetic diseases |
c.631G>T | p.Glu211Ter | Pathogenic | ★★☆☆ | Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies |
c.287del | p.Pro96fs | Pathogenic | ★☆☆☆ | Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies |
c.381_388del | p.Leu127fs | Pathogenic | ★☆☆☆ | Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies |
c.521dup | p.Thr175fs | Pathogenic | ★☆☆☆ | not provided |
c.776C>G | p.Ser259Ter | Pathogenic | ★☆☆☆ | not provided |
c.83-1del | - | Pathogenic | ★☆☆☆ | Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Currently, OTUD6B has not been firmly associated with any specific inherited condition or syndrome through robust clinical genetic evidence. While some deubiquitinases play established roles in cancer predisposition, neurodevelopmental disorders, or immune dysfunction, OTUD6B does not appear on gene panels for these conditions. As research techniques improve and larger patient cohorts are studied, it remains possible that rare variants in this gene could be linked to clinical phenotypes in the future.
No disease links recorded for this gene in our reference set.
UK clinical status
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What does the OTUD6B gene do?
OTUD6B encodes a deubiquitinating enzyme that removes ubiquitin molecules from proteins, potentially influencing protein stability and cellular signalling. The full range of its biological roles is still under investigation.
Is OTUD6B linked to any medical conditions?
At present, OTUD6B has not been conclusively associated with any specific inherited condition or syndrome through clinical genetic research. Most identified variants in this gene remain of uncertain significance.
Where is the OTUD6B gene located?
The OTUD6B gene is located on chromosome 8 at position 8q21.3, on the long arm of the chromosome.