Features include always present findings: Global developmental delay and Intellectual disability; and very common findings: Everted lower lip vermilion. 18 total HPO annotations.

KMT2C encodes lysine methyltransferase 2C (4,911 aa). Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4). Highest expression in Brain Cerebellum (26.7 TPM) and Brain Cerebellar Hemisphere (23.4 TPM).

Kleefstra syndrome 2 is associated with mutations in the KMT2C gene on chromosome 7.

The KMT2C protein participates in Activation of HOX genes during differentiation pathway.

KMT2C is classified as a druggable target (Clinically Actionable, Drug Resistance, Enzyme, and Nuclear Hormone Receptor categories) with score 26.1.

Genetic testing for KMT2C is available. Testing is considered confirmatory for diagnosis.

Phenotype severity distribution: 2 always present features, 1 very common feature, 4 common features.

No clinical trials have been registered for Kleefstra syndrome 2.

7 publications have been identified in PubMed for Kleefstra syndrome 2. Research spans Case Report / Case Series (43%), Basic Science / Preclinical (43%), and Epidemiology / Natural History (14%).

Recent Publications

• O'Sullivan R (2026). [PMID: 42249343](https://pubmed.ncbi.nlm.nih.gov/42249343/). *BMC Pediatr*. [Epidemiology / Natural History]

• Sedláčková L (2026). [PMID: 41914216](https://pubmed.ncbi.nlm.nih.gov/41914216/). *Molecular genetics & genomic medicine*. [Case Report / Case Series]

• Chen Z (2025). [PMID: 40329253](https://pubmed.ncbi.nlm.nih.gov/40329253/). *BMC neurology*. [Case Report / Case Series]

• Ma K (2025). [PMID: 41301465](https://pubmed.ncbi.nlm.nih.gov/41301465/). *Biomolecules*. [Basic Science / Preclinical]

• Kumar S (2025). [PMID: 39812948](https://pubmed.ncbi.nlm.nih.gov/39812948/). *Indian journal of pediatrics*. [Basic Science / Preclinical]