Human Gene Module / Chromosome 7 / ACTL6B

ACTL6Bactin like 6B

Score
-
No Rating
Autism Reports / Total Reports
1 / 5
Rare Variants / Common Variants
17 / 0
Aliases
ACTL6B, ACTL6,  BAF53B,  arpNalpha
Associated Syndromes
Rett syndrome
Genetic Category
Rare Single Gene Mutation, Syndromic
Chromosome Band
7q22.1
Associated Disorders
EPS, ASD, EP
Relevance to Autism

Bell et al., 2019 demonstrated that individuals harboring biallelic mutations in the ACTL6B gene presented with a neurodevelopmental disorder characterized by global developmental delay, epileptic encephalopathy, axial hypotonia, and spasticity, whereas individuals with de novo heterozygous missense variants in the same gene presented with intellectual disability, developmental delay, delayed or absent speech, ambulation deficits, hypotonia, autism or autistic features, Rett-like stereotypies such as handwringing, and minor facial dysmorphisms (wide mouth, diastema, bulbous nose). Homozygous variants in the ACTL6B gene had previously been identified in three individuals from two families presenting with severe developmental and epileptic encephalopathy in Fichera et al., 2019, as well as in two siblings presenting with intellectual disability, seizures, and autistic behaviors (Karaca et al., 2015) and a female patient diagnosed with atypical Rett syndrome (Sajan et al., 2017). A postzygotic mosaic coding-synonymous variant that was predicted to create a new exonic splicing site in the ACTL6B gene was observed in an ASD proband from the Simons Simplex Collection in Krupp et al., 2017.

Molecular Function

The protein encoded by this gene is a member of a family 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 subunit 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. This subunit may be involved in the regulation of genes by structural modulation of their chromatin, specifically in the brain.

Reports related to ACTL6B (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease. Karaca E , et al. (2015) No Autistic behavior, microcephaly
2 Support Enrichment of mutations in chromatin regulators in people with Rett syndrome lacking mutations in MECP2. Sajan SA , et al. (2016) No -
3 Support Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder. Krupp DR , et al. (2017) Yes -
4 Support Mutations in ACTL6B, coding for a subunit of the neuron-specific chromatin remodeling complex nBAF, cause early onset severe developmental and epil... Fichera M , et al. (2019) No -
5 Primary Mutations in ACTL6B Cause Neurodevelopmental Deficits and Epilepsy and Lead to Loss of Dendrites in Human Neurons. Bell S , et al. (2019) No Epilepsy/seizures, ASD or autistic features
Rare Variants   (17)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.230A>G p.Asp77Gly missense_variant De novo - - 31031012 Bell S , et al. (2019)
c.1027G>A p.Gly343Arg missense_variant De novo - - 31031012 Bell S , et al. (2019)
c.360C>T p.(=) synonymous_variant De novo - Simplex 28867142 Krupp DR , et al. (2017)
c.[852C>G];[740G>A] p.[Tyr284Ter];[Trp247Ter] stop_gained;stop_gained Familial - Simplex 31031012 Bell S , et al. (2019)
c.[1231C>T];[669+1G>A] p.[Gln411Ter];[?] stop_gained;splice_site_variant Familial - Simplex 31031012 Bell S , et al. (2019)
c.[389G>A];[556C>T] p.[Arg130Gln];[Gln186Ter] missense_variant;stop_gained Familial - Simplex 31031012 Bell S , et al. (2019)
c.[724C>T];[617T>C] p.[Gln242Ter];[Leu206Pro] stop_gained;missense_variant Familial - Simplex 31031012 Bell S , et al. (2019)
c.[289C>T];[289C>T] p.[Arg97Ter];[Arg97Ter] stop_gained;stop_gained Familial Both parents Simplex 31031012 Bell S , et al. (2019)
c.[820C>T];[820C>T] p.[Gln274Ter];[Gln274Ter] stop_gained;stop_gained Familial Both parents Multiplex 30656450 Fichera M , et al. (2019)
c.[695delC];[1275C>A] p.[Pro232GlnfsTer24];[Cys425Ter] frameshift_variant;stop_gained Familial - Multiplex 31031012 Bell S , et al. (2019)
c.[1045G>A];[1045G>A] p.[Gly349Ser];[Gly349Ser] missense_variant;missense_variant Familial Both parents Multiplex 31031012 Bell S , et al. (2019)
c.[893G>A];[893G>A] p.[Arg298Gln];[Arg298Gln] missense_variant;missense_variant Familial Both parents Multiplex 26539891 Karaca E , et al. (2015)
c.[1045G>A];[1045G>A] p.[Gly349Ser];[Gly349Ser] missense_variant;missense_variant Familial Both parents Multiplex 30656450 Fichera M , et al. (2019)
c.[441_443delCTT];[441_443delCTT] p.[Phe147del];[Phe147del] inframe_deletion;inframe_deletion Familial Both parents Unknown 31031012 Bell S , et al. (2019)
c.[1279del];[1279del] p.[Ter427AspextTer33];[Ter427AspextTer33] frameshift_variant;frameshift_variant Familial Both parents Simplex 31031012 Bell S , et al. (2019)
c.[1279del];[1279del] p.[Ter427AspextTer33];[Ter427AspextTer33] frameshift_variant;frameshift_variant Familial Both parents Multiplex 31031012 Bell S , et al. (2019)
c.[1279delT];[1279delT] p.[Ter427AspextTer32];[Ter427AspextTer32] frameshift_variant;frameshift_variant Familial Both parents Simplex 27171548 Sajan SA , et al. (2016)
Common Variants  

No common variants reported.

CNVs associated with ACTL6B(1 CNVs)
7q22.1 21 Deletion-Duplication 37  /  143
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