ACTL6A

Chr 3

actin like 6A

Also known as: ACTL6, ARPN-BETA, Arp4, BAF53A, INO80K, SMARCN1

NCBI Gene: 86 ENSG00000136518 UniProt: O96019 OMIM: 604958

This gene encodes ACTL6A, a 53 kDa subunit of the BAF chromatin remodeling complex that is essential for transcriptional regulation during neural development, specifically required for neural progenitor proliferation and the transition to postmitotic neurons. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability, developmental delay, and epilepsy, typically presenting in early childhood. The gene is highly constrained against loss-of-function variants (pLI 0.997), indicating intolerance to protein-disrupting mutations.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a family member of actin-related proteins (ARPs), which share significant amino acid sequence identity to conventional actins. Both actins and ARPs have an actin fold, which is an ATP-binding cleft, as a common feature. The ARPs are involved in diverse cellular processes, including vesicular transport, spindle orientation, nuclear migration and chromatin remodeling. This gene encodes a 53 kDa subunit protein of the BAF (BRG1/brm-associated factor) complex in mammals, which is functionally related to SWI/SNF complex in S. cerevisiae and Drosophila; the latter is thought to facilitate transcriptional activation of specific genes by antagonizing chromatin-mediated transcriptional repression. Together with beta-actin, it is required for maximal ATPase activity of BRG1, and for the association of the BAF complex with chromatin/matrix. Three transcript variants that encode two different protein isoforms have been described. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Gene-disease validity (ClinGen)

ACTL6A-related BAFopathy · ADModerateconsider for supplementary testing

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.25

LOEUF· LoF intol.

LOF

Mechanism· G2P