OTULINOTU deubiquitinase with linear linkage specificity
Autism Reports / Total Reports
4 / 6Rare Variants / Common Variants
5 / 0Aliases
-Associated Syndromes
-Chromosome Band
5p15.2Associated Disorders
-Relevance to Autism
TADA analysis of >15,000 Latin American individuals from the GALA Consortium (including 4,717 participants with an ASD diagnosis) in Avila et al., 2026 identified OTULIN as one of 35 genes reaching genome-wide significance (FDR < 0.05); the two Admixed American (AMR) individuals with ASD included in this analysis were SPARK probands with de novo missense variants with MPC scores > 2. Additional de novo variants in OTULIN have been reported in ASD probands from the Simons Simplex Collection and the mAGRE cohort (Krupp et al., 2017; Zhou et al., 2022; Cirnigliaro et al., 2023).
Molecular Function
This gene encodes a member of the peptidase C65 family of ubiquitin isopeptidases. Members of this family remove ubiquitin from proteins. The encoded enzyme specifically recognizes and removes M1(Met1)-linked, or linear, ubiquitin chains from protein substrates. Linear ubiquitin chains are known to regulate the NF-kappa B signaling pathway in the context of immunity and inflammation. OTULIN has been shown to regulate tau expression and RNA metabolism in neurons (Tangavelou et al., 2025), and experimentally reducing linear ubiquitination axis activity by OTULIN overexpression in neonatal mice resulted in persistent synaptic immaturity and adult cognitive deficits due to increased GluN2A degradation (Chu et al., 2026).
External Links
SFARI Genomic Platforms
Reports related to OTULIN (6 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Support | Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder | Krupp DR , et al. (2017) | Yes | - |
| 2 | Support | - | Zhou X et al. (2022) | Yes | - |
| 3 | Support | - | Cirnigliaro M et al. (2023) | Yes | - |
| 4 | Support | - | Chu, Yuanyuan et al. (2026) | No | - |
| 5 | Support | - | Tangavelou, Karthikeyan et al. (2025) | No | - |
| 6 | Primary | - | Natividad Avila, Marina et al. (2026) | Yes | - |
Rare Variants (5)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.67C>G | p.Arg23Gly | missense_variant | De novo | - | Simplex | 35982159 | Zhou X et al. (2022) | |
| c.1038G>T | p.Val346= | synonymous_variant | De novo | - | Simplex | 28867142 | Krupp DR , et al. (2017) | |
| c.916C>T | p.Arg306Trp | missense_variant | De novo | - | Multiplex | 37506195 | Cirnigliaro M et al. (2023) | |
| c.857T>G | p.Leu286Arg | missense_variant | De novo | - | Simplex | 41912808 | Natividad Avila, Marina et al. (2026) | |
| c.857T>G | p.Leu286Arg | missense_variant | De novo | - | Multiplex | 41912808 | Natividad Avila, Marina et al. (2026) |
Common Variants
No common variants reported.
SFARI Gene score
Suggestive Evidence
criteria met
See SFARI Gene'scoring criteriaThe literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.
4/1/2026
Initial score established: 3
Sanders TADA Score
Score 0.91699203795141
Ranking 8574/18665 scored genes
[Show Scoring Methodology]