ACTL6B

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

Basic information

Region (hg38): 7:100643097-100656448

Previous symbols: [ "ACTL6" ]

Links

ENSG00000077080 ∙ NCBI:51412 ∙ OMIM:612458 ∙ HGNC:160 ∙ Uniprot:O94805 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• developmental and epileptic encephalopathy, 76 (Definitive), mode of inheritance: AR
• intellectual developmental disorder with severe speech and ambulation defects (Limited), mode of inheritance: AD
• developmental and epileptic encephalopathy, 76 (Strong), mode of inheritance: AR
• undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
• syndromic intellectual disability (Supportive), mode of inheritance: AD
• intellectual developmental disorder with severe speech and ambulation defects (Moderate), mode of inheritance: AD
• developmental and epileptic encephalopathy, 76 (Strong), mode of inheritance: AR
• intellectual developmental disorder with severe speech and ambulation defects (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with severe speech and ambulation defects; Developmental and epileptic encephalopathy 76	AD/AR	General	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	Craniofacial; Musculoskeletal; Neurologic	26539891; 30237576; 30656450; 31031012; 31134736

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACTL6B gene.

• not_provided (60 variants)
• Developmental_and_epileptic_encephalopathy,_76 (42 variants)
• Inborn_genetic_diseases (18 variants)
• ACTL6B-related_recessive_epilepsy (14 variants)
• ACTL6B-related_disorder (12 variants)
• Intellectual_developmental_disorder_with_severe_speech_and_ambulation_defects (12 variants)
• Autism_spectrum_disorder (6 variants)
• ACTL6B-related_BAFopathy (4 variants)
• not_specified (3 variants)
• Intellectual_disability (2 variants)
• Autism (2 variants)
• ACTL6B-related_dominant_intellectual_disability (2 variants)
• ACTL6B-related_neurodevelopmental_disorder (1 variants)
• Congenital_generalized_lipodystrophy_type_2 (1 variants)
• Global_developmental_delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACTL6B gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016188.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				15		15
missense	5	16	62	1		84
nonsense	6	11				17
start loss						0
frameshift	3	7	1			11
splice donor/acceptor (+/-2bp)	1	4	3			8
Total	15	38	66	16	0

Highest pathogenic variant AF is 0.000019915

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACTL6B	protein_coding	protein_coding	ENST00000160382	14	13365

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000283	0.999	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.27	120	272	0.441	0.0000166	2781
Missense in Polyphen		43	99.25	0.43325		998
Synonymous	0.0821	112	113	0.990	0.00000758	828
Loss of Function	3.00	11	28.2	0.390	0.00000160	283

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000272	0.000271
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000933	0.0000924
European (Non-Finnish)	0.0000618	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

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}.
• Pathway: Thermogenesis - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Androgen Receptor Network in Prostate Cancer;Tumor suppressor activity of SMARCB1;Gene expression (Transcription);RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known;Generic Transcription Pathway;RNA Polymerase II Transcription;RMTs methylate histone arginines;Chromatin modifying enzymes;Chromatin organization;Transcriptional regulation by RUNX1 (Consensus)

Recessive Scores

• pRec: 0.448

Intolerance Scores

• loftool: 0.288
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.07

Haploinsufficiency Scores

• pHI: 0.622
• hipred: Y
• hipred_score: 0.837
• ghis: 0.652

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.944

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Actl6b
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: chromatin organization;chromatin remodeling;regulation of transcription by RNA polymerase II;cytoskeleton organization;spinal cord development;positive regulation of nucleic acid-templated transcription
• Cellular component: nucleus;nucleolus;SWI/SNF complex;nBAF complex
• Molecular function: transcription coactivator activity;structural constituent of cytoskeleton