Features include always present findings: Severe global developmental delay, Severe intellectual disability, and Bulbous nose; and very common findings: Absent speech and Low muscle tone (hypotonia). 20 total HPO annotations.

ACTL6B encodes actin like 6B (426 aa). Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Highest expression in Brain Cerebellar Hemisphere (129.5 TPM) and Brain Cerebellum (122.0 TPM).

Intellectual developmental disorder with severe speech and ambulation defects is associated with mutations in the ACTL6B gene on chromosome 7.

The ACTL6B protein participates in Formation of neuronal progenitor and neuronal BAF (npBAF and nBAF) and Formation of neural BAF (nBAF) pathways.

ACTL6B is classified as a druggable target with score 0.0.

47 pathogenic variants reported in ACTL6B in ClinVar, including hotspot variants 635103 and NP_057272.1:p.Gly343Arg (2-star review).

Genetic testing for ACTL6B is available. Testing is considered confirmatory for diagnosis.

Phenotype severity distribution: 3 always present features, 2 very common features, 7 common features.

No clinical trials have been registered for intellectual developmental disorder with severe speech and ambulation defects.

3 publications have been identified in PubMed for intellectual developmental disorder with severe speech and ambulation defects. Research spans Review / Meta-Analysis (33%), Case Report / Case Series (33%), and Basic Science / Preclinical (33%).

Recent Publications

• Al Ojaimi M (2025). [PMID: 40301961](https://pubmed.ncbi.nlm.nih.gov/40301961/). *Hum Genomics*. [Review / Meta-Analysis]

• Okamoto N (2025). [PMID: 40546132](https://pubmed.ncbi.nlm.nih.gov/40546132/). *Am J Med Genet A*. [Case Report / Case Series]

• Ng JK (2025). [PMID: 40073865](https://pubmed.ncbi.nlm.nih.gov/40073865/). *Cell Genom*. [Basic Science / Preclinical]