GeneBe

ACTL6B

protein-coding

actin like 6B, the group of BAF complex|GBAF complex|PBAF complex|Actin related proteins

Gene summary

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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

Previous symbols:
  • ACTL6

MANE transcript

NM_016188.5

Inheritance

AR, AD

ClinVar variants

P:59U:98B:31

Top phenotype

Intellectual developmental disorder with severe speech and ambulation defects; Developmental and epileptic encephalopathy 76

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr7:100,643,097-100,656,448

External References & Databases

Ensembl (ENSG00000077080)NCBI Gene (51412)OMIM (612458)HGNC:160GenCCUniProt (O94805)AlphaFoldClinVar (ACTL6B)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~13.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

developmental and epileptic encephalopathy, 76STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032768

Submitter: Ambry Genetics

intellectual developmental disorder with severe speech and ambulation defectsSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032770

Submitter: Labcorp Genetics (formerly Invitae)

undetermined early-onset epileptic encephalopathySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0018614

Submitter: Orphanet

intellectual developmental disorder with severe speech and ambulation defectsMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0032770

Submitter: Ambry Genetics

syndromic intellectual disabilitySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0000508

Submitter: Orphanet

intellectual developmental disorder with severe speech and ambulation defectsSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0032770

Submitter: PanelApp Australia

intellectual developmental disorder with severe speech and ambulation defectsLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0032770

Submitter: G2P

developmental and epileptic encephalopathy, 76DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0032768

Submitter: G2P

developmental and epileptic encephalopathy, 76STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032768

Submitter: PanelApp Australia

developmental and epileptic encephalopathy, 76STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032768

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Intellectual developmental disorder with severe speech and ambulation defects; Developmental and epileptic encephalopathy 76AD/AR

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 26539891; 30237576; 30656450; 31031012; 31134736Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ACTL6B variants in ClinVar

16 Conditions Cataloged
not providedTotal: 88
Developmental and epileptic encephalopathy, 76Total: 48
Inborn genetic diseasesTotal: 31
not specifiedTotal: 30
ACTL6B-related disorderTotal: 19
Intellectual developmental disorder with severe speech and ambulation defectsTotal: 19
ACTL6B-related recessive epilepsyTotal: 14
Autism spectrum disorderTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016188.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
30
clinvar
 30
missense
5
clinvar
18
clinvar
93
clinvar
1
clinvar
 117
nonsense
6
clinvar
11
clinvar
1
clinvar
 18
start loss
1
clinvar
 1
frameshift
3
clinvar
7
clinvar
1
clinvar
 11
splice donor/acceptor (+/-2bp)
1
clinvar
7
clinvar
3
clinvar
 11
Total164398310188

Highest pathogenic variant AF is 0.00001991501

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_016188.5RefSeqNP_057272.114MANE Select
ENST00000160382.10EnsemblENSP00000160382.514MANE Select
ENST00000461605.1EnsemblENSP00000420151.13Standard
ENST00000863236.1EnsemblENSP00000533295.112Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Thermogenesis - Homo sapiens (human)
  • Hepatocellular carcinoma - Homo sapiens (human)
  • Androgen Receptor Network in Prostate Cancer
  • Tumor suppressor activity of SMARCB1
  • Gene expression (Transcription)

Biological Process

  • chromatin organization
  • chromatin remodeling
  • regulation of transcription by RNA polymerase II
  • cytoskeleton organization
  • spinal cord development

Molecular Function

  • transcription coactivator activity
  • structural constituent of cytoskeleton

Cellular Component

  • nucleus
  • nucleolus
  • SWI/SNF complex
  • nBAF complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000160382
Coding exons
14
Length
13365
Individuals with no LoFs
125729
Homozygous LoFs
0
Heterozygous LoFs
19
Defined
125748
p
0.0000756
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense3.271202720.4410.00001662781
Missense (PolyPhen)4399.250.43325998
Synonymous0.08211121130.9900.00000758828
Loss of Function3.001128.20.3900.00000160283

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000180.00018rare
Latino/Admixed American0.0000870.000087rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish0.0000930.000092rare
European (Non-Finnish)0.0000620.000062rare
South Asian0.000130.00013rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
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). {ECO:0000250|UniProtKB:Q99MR0, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}.;

Recessive Scores

pRec
0.448

Intolerance Scores

LoFtool
0.288
RVIS EVS
-0.34
RVIS percentile EVS
30.07

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.944

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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