HERC2 encodes HECT and RLD domain containing E3 ubiquitin protein ligase 2 (4,834 aa). E3 ubiquitin-protein ligase that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes.

Developmental delay with autism spectrum disorder and gait instability is associated with mutations in the HERC2 gene on chromosome 15.

The HERC2 protein participates in PIAS4 SUMOylates HERC2 with SUMO1, HERC2 and PIAS4 are recruited to DNA DSBs, and HERC2 facilitates UBE2N:UBE2V2 binding to RNF8 pathways.

HERC2 is classified as a druggable target (Dna Repair and Enzyme categories) with score 7.0.

Genetic testing for HERC2 is available. Testing is considered confirmatory for diagnosis.

Phenotype severity distribution: 4 always present features, 2 very common features, 2 common features.

Estimated prevalence: <1 in 1,000,000 (VERY_RARE).

No clinical trials have been registered for developmental delay with autism spectrum disorder and gait instability.

9 publications have been identified in PubMed for developmental delay with autism spectrum disorder and gait instability. Research spans Case Report / Case Series (56%), Epidemiology / Natural History (22%), and Review / Meta-Analysis (11%).

Recent Publications

• Baker M (2025). [PMID: 40700090](https://pubmed.ncbi.nlm.nih.gov/40700090/). *Vision (Basel, Switzerland)*. [Review / Meta-Analysis]

• Şenol HB (2025). [PMID: 41059448](https://pubmed.ncbi.nlm.nih.gov/41059448/). *Molecular syndromology*. [Case Report / Case Series]

• Yasar D (2025). [PMID: 39953892](https://pubmed.ncbi.nlm.nih.gov/39953892/). *Journal of pediatric endocrinology &amp; metabolism : JPEM*. [Case Report / Case Series]

• Hernández A (2025). [PMID: 41130596](https://pubmed.ncbi.nlm.nih.gov/41130596/). *Pediatrics*. [Case Report / Case Series]

• Vaughan AM (2025). [PMID: 40742893](https://pubmed.ncbi.nlm.nih.gov/40742893/). *MMWR. Morbidity and mortality weekly report*. [Case Report / Case Series]

• Mattioli F (2025). [PMID: 40229899](https://pubmed.ncbi.nlm.nih.gov/40229899/). *Genome medicine*. [Basic Science / Preclinical]

• Kido J (2025). [PMID: 40840052](https://pubmed.ncbi.nlm.nih.gov/40840052/). *Molecular genetics and metabolism*. [Epidemiology / Natural History]

• Akar HT (2025). [PMID: 39953904](https://pubmed.ncbi.nlm.nih.gov/39953904/). *Journal of pediatric endocrinology &amp; metabolism : JPEM*. [Epidemiology / Natural History]

• Haneda A (2024). [PMID: 37974060](https://pubmed.ncbi.nlm.nih.gov/37974060/). *The Clinical neuropsychologist*. [Case Report / Case Series]