protein
Actin-like protein 6B
Gene
ACTL6B
Organism
Homo sapiens(9606)
Length
426 aa
Mass
46,877 Da
Actin-like protein 6B (ACTL6B) is a 426-amino-acid protein that functions as a component of the neuron-specific BAF (nBAF) chromatin remodeling complex (UniProt: O94805). It mediates transcriptional activation and repression through ATP-dependent alterations of DNA-nucleosome topology. ACTL6B is essential for neuronal maturation and dendritic outgrowth, playing a critical role in the developmental switch from neural progenitor cells to postmitotic neurons by replacing its paralog ACTL6A within chromatin remodeling complexes.
ACTL6B is expressed in neurons and functions within the nBAF complex alongside CREST to regulate genes essential for dendrite growth and neural development. Mutations in ACTL6B are associated with severe neurodevelopmental disorders, including developmental and epileptic encephalopathy 76 (DEE76) and intellectual developmental disorder with severe speech and ambulation defects (IDDSSAD), both characterized by global developmental delay and neurological impairment (UniProt: O94805).
In Alzheimer's disease, ACTL6B is consistently downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.57 (Chaparral AD proteomics). This reduction may reflect compromised chromatin remodeling capacity and impaired neuronal function in the AD brain.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.573
P2
not detected
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.5735 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Belongs to the neuron-specific chromatin remodeling complex (nBAF complex), as such plays a role in remodeling mononucleosomes in an ATP-dependent fashion, and is required for postmitotic neural development and dendritic outgrowth. During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth. ACTL6B/BAF53B is not essential for assembly of the nBAF complex but is required for targeting the complex and CREST to the promoter of genes essential for dendritic growth (By similarity). Essential for neuronal maturation and dendrite development (PubMed:31031012)
Disease associations
Developmental and epileptic encephalopathy 76DEE76
A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. DEE76 is an autosomal recessive form that may result in death in childhood.
Intellectual developmental disorder with severe speech and ambulation defectsIDDSSAD
An autosomal dominant neurodevelopmental disorder with onset in infancy, and characterized by global developmental delay, intellectual disability, ambulation deficits, severe language impairment, and minor dysmorphic features including a wide mouth, diastema, and bulbous nose. Additional manifestations are spasticity, hypotonia and autistic features including stereotypies. Brain imaging show thin corpus callosum, generalized atrophy, and mild periventricular gliosis.
Sources
Last updated 5/8/2026, 6:37:29 AM