OTULIN Gene
OTU Deubiquitinase with Linear Linkage Specificity
Gene Information Card
| Symbol | OTULIN |
|---|---|
| Full Name | OTU deubiquitinase with linear linkage specificity |
| Gene Type | Protein coding |
| Chromosomal Location | 5p15.2 |
| NCBI Gene ID | 90268 ncbi.nlm.nih.gov/gene/90268 |
| Ensembl ID | ENSG00000164124 |
| UniProt ID | Q96BN8 |
| OMIM ID | 615712 |
| HGNC ID | 25118 |
| Aliases | FAM105B, OTU1, GUMB, HOIL-1 interacting protein |
Description
OTULIN encodes a deubiquitinating enzyme that specifically cleaves linear (M1-linked) polyubiquitin chains. It negatively regulates NF-κB signaling by removing linear ubiquitin chains from target proteins such as NEMO and RIPK1. OTULIN is essential for preventing aberrant inflammation and maintaining immune homeostasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| OTULIN-related autoinflammatory syndrome (ORAS) | Loss-of-function mutations in OTULIN lead to accumulation of linear ubiquitin chains, hyperactivation of NF-κB, and excessive pro-inflammatory cytokine production. | OMIM #617099; PMID: 27259083 |
| Susceptibility to infections | Impaired OTULIN function disrupts innate immune signaling, increasing vulnerability to bacterial and viral infections. | PMID: 27259083; PMID: 31006510 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Lymph node | 10.2 | Medium |
| Spleen | 9.8 | Medium |
| Whole blood | 6.3 | Low |
| Liver | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.0 | High expression |
| HeLa | 12.3 | Medium expression |
| Jurkat | 11.5 | Medium expression |
| THP-1 | 14.2 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.493C>T (p.Arg165*) | Nonsense | Rare | Loss of function; truncation of OTULIN protein |
| c.812A>G (p.Tyr271Cys) | Missense | Rare | Loss of function; impaired deubiquitinase activity |
| c.1000C>T (p.Arg334Trp) | Missense | Rare | Loss of function; reduced protein stability |
Mutation functional classification
Loss of Function (LOF)
Most reported OTULIN mutations are loss-of-function, leading to reduced or absent deubiquitinase activity and accumulation of linear ubiquitin chains.
Gain of Function (GOF)
No gain-of-function mutations have been reported for OTULIN.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type OTULIN function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • thiol-dependent deubiquitinase (GO:0004843) | • hydrolase activity (GO:0016787) |
| • cytoplasm (GO:0005737) | • cytosol (GO:0005829) |
| • positive regulation of I-kappaB kinase/NF-kappaB signaling (GO:0043123) | • activation of NF-kappaB-inducing kinase activity (GO:0007250) |
Pathways
• NF-kappaB signaling pathway (KEGG: hsa04064)
• Linear ubiquitination pathway (Reactome: R-HSA-983168)
Protein Summary
OTULIN is a 352-amino acid deubiquitinating enzyme that specifically cleaves M1-linked linear polyubiquitin chains. It contains an OTU (ovarian tumor) domain responsible for its catalytic activity. OTULIN interacts with HOIL-1 and HOIP components of the LUBAC complex, regulating NF-κB activation and preventing autoinflammation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| OTULIN Knockout HEK293 Cell Line | EDJ-KQ2028 | Human | 90268 | Details Get a Quote |
| OTULINL Knockout HEK293 Cell Line | EDJ-KQ11436 | Human | 54491 | Details Get a Quote |
| OTULIN Knockout A-549 Cell Line | EDJ-KQ22066 | Human | 90268 | Details Get a Quote |
| OTULIN Knockout HCT 116 Cell Line | EDJ-KQ22067 | Human | 90268 | Details Get a Quote |
| OTULIN Knockout HeLa Cell Line | EDJ-KQ22068 | Human | 90268 | Details Get a Quote |
| OTULINL Knockout A-549 Cell Line | EDJ-KQ39697 | Human | 54491 | Details Get a Quote |
| OTULINL Knockout HCT 116 Cell Line | EDJ-KQ39698 | Human | 54491 | Details Get a Quote |
| OTULINL Knockout HeLa Cell Line | EDJ-KQ39699 | Human | 54491 | Details Get a Quote |
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