Features include always present findings: Flared metaphysis, Decreased body weight, Short stature, and Decreased serum insulin-like growth factor 1 and others; and very common findings: Small for gestational age, Hypothyroidism, and Nail dystrophy. 39 total HPO annotations.

DNA2 encodes DNA replication helicase/nuclease 2 (1,060 aa). Key enzyme involved in DNA replication and DNA repair in nucleus and mitochondrion. Highest expression in Cells EBV-transformed lymphocytes (19.3 TPM) and Brain Cerebellum (6.4 TPM).

Rothmund-Thomson syndrome type 4 is associated with mutations in the DNA2 gene on chromosome 10.

The DNA2 protein participates in Recruitment of Dna2 endonuclease, Recruitment of DNA2 endonuclease to the C strand, and Removal of RNA primer and dissociation of RPA and Dna2 pathways.

DNA2 is classified as a druggable target (Enzyme category) with score 13.1.

Genetic testing for DNA2 is available. Testing is considered confirmatory for diagnosis.

Phenotype severity distribution: 18 always present features, 3 very common features, 9 common features.

No clinical trials have been registered for Rothmund-Thomson syndrome type 4.

2 publications have been identified in PubMed for Rothmund-Thomson syndrome type 4. Research spans Review / Meta-Analysis (50%) and Case Report / Case Series (50%).

Recent Publications

• Ay B (2025). [PMID: 40693833](https://pubmed.ncbi.nlm.nih.gov/40693833/). *American journal of medical genetics. Part A*. [Case Report / Case Series]

• Nakano Y (2024). [PMID: 39264246](https://pubmed.ncbi.nlm.nih.gov/39264246/). *Clinical cancer research : an official journal of the American Association for Cancer Research*. [Review / Meta-Analysis]