ACTL6A
actin like 6A, the group of Actin related proteins|BAF complex|GBAF complex|PBAF complex|Tip60/Nua4 histone acetyltransferase complex subunits|SRCAP complex|INO80 complex
Basic information
Region (hg38): 3:179562886-179588407
Links
Phenotypes
GenCC
Source:
- intellectual disability (Limited), mode of inheritance: AD
- syndromic intellectual disability (Supportive), mode of inheritance: AD
- syndromic intellectual disability (Moderate), mode of inheritance: AD
- ACTL6A-related BAFopathy (Moderate), mode of inheritance: AD
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACTL6A gene is commonly pathogenic or not.
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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | |||||
| missense | 19 | 23 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| splice region | 1 | 1 | ||||
| non coding | 1 | |||||
| Total | 0 | 0 | 21 | 5 | 3 |
Variants in ACTL6A
This is a list of pathogenic ClinVar variants found in the ACTL6A region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 3-179569865-G-A | Uncertain significance (May 01, 2022) | |||
| 3-179569880-G-A | Uncertain significance (Jul 02, 2024) | |||
| 3-179569899-A-G | Uncertain significance (Apr 01, 2024) | |||
| 3-179570103-A-G | Uncertain significance (Jan 21, 2022) | |||
| 3-179570134-A-T | Inborn genetic diseases | Uncertain significance (Aug 27, 2024) | ||
| 3-179570157-G-A | Inborn genetic diseases | Uncertain significance (Jul 25, 2023) | ||
| 3-179570231-A-C | Uncertain significance (Jun 02, 2024) | |||
| 3-179570239-T-C | Inborn genetic diseases | Uncertain significance (Mar 06, 2023) | ||
| 3-179573405-A-G | Inborn genetic diseases | Uncertain significance (Sep 27, 2021) | ||
| 3-179573467-C-T | Inborn genetic diseases | Uncertain significance (Oct 04, 2024) | ||
| 3-179573468-C-T | ACTL6A-related BAFopathy | Uncertain significance (Jun 10, 2021) | ||
| 3-179574376-A-G | Inborn genetic diseases | Uncertain significance (May 14, 2024) | ||
| 3-179574414-T-G | Inborn genetic diseases | Uncertain significance (Feb 14, 2023) | ||
| 3-179574447-C-T | Likely benign (Feb 01, 2024) | |||
| 3-179576215-A-G | Uncertain significance (Dec 31, 2023) | |||
| 3-179576301-C-T | Likely benign (Jun 01, 2022) | |||
| 3-179576616-A-G | Inborn genetic diseases | Uncertain significance (Oct 29, 2021) | ||
| 3-179576652-A-G | Inborn genetic diseases | Uncertain significance (Mar 01, 2024) | ||
| 3-179576692-T-C | Uncertain significance (Aug 25, 2022) | |||
| 3-179576700-G-A | ACTL6A-related disorder • Inborn genetic diseases | Likely benign (Oct 13, 2021) | ||
| 3-179576703-C-T | Uncertain significance (Jul 01, 2022) | |||
| 3-179576714-G-A | Uncertain significance (Feb 23, 2022) | |||
| 3-179576721-T-A | Benign (Sep 01, 2024) | |||
| 3-179576824-G-C | Global developmental delay;Delayed speech and language development | Uncertain significance (Jun 11, 2017) | ||
| 3-179576896-C-T | Inborn genetic diseases | Uncertain significance (Nov 21, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ACTL6A | protein_coding | protein_coding | ENST00000429709 | 14 | 25529 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.997 | 0.00335 | 125721 | 0 | 3 | 125724 | 0.0000119 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.94 | 110 | 237 | 0.463 | 0.0000119 | 2825 |
| Missense in Polyphen | 30 | 96.123 | 0.3121 | 1185 | ||
| Synonymous | 0.284 | 75 | 78.2 | 0.959 | 0.00000403 | 784 |
| Loss of Function | 4.32 | 2 | 25.6 | 0.0781 | 0.00000118 | 322 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000616 | 0.0000615 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000176 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- 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. Required for maximal ATPase activity of SMARCA4/BRG1/BAF190A and for association of the SMARCA4/BRG1/BAF190A containing remodeling complex BAF with chromatin/nuclear matrix. Belongs to the neural progenitors- specific chromatin remodeling complex (npBAF complex) and is required for the proliferation of neural progenitors. 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 (By similarity). Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Putative core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. {ECO:0000250|UniProtKB:Q9Z2N8, ECO:0000269|PubMed:14966270, ECO:0000269|PubMed:29374058, ECO:0000303|PubMed:15196461, ECO:0000303|PubMed:22952240, ECO:0000303|PubMed:26601204}.;
- Disease
- DISEASE: Note=ACTL6A mutations have been found in patients with intellectual disability of variable severity, developmental delay, dysmorphic features and digit abnormalities. Additional features may include genitourinary and cardiac defects. The disease phenotype resembles Coffin-Siris syndrome and brachymorphism- onychodysplasia-dysphalangism syndrome. {ECO:0000269|PubMed:28649782}.;
- Pathway
- Thermogenesis - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Androgen Receptor Network in Prostate Cancer;Gastric Cancer Network 1;Tumor suppressor activity of SMARCB1;DNA Repair;Gene expression (Transcription);RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known;Generic Transcription Pathway;Post-translational protein modification;Metabolism of proteins;RNA Polymerase II Transcription;RMTs methylate histone arginines;Chromatin modifying enzymes;HATs acetylate histones;UCH proteinases;Deubiquitination;Chromatin organization;C-MYC pathway;TNFalpha;DNA Damage Recognition in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);Transcriptional regulation by RUNX1;Validated targets of C-MYC transcriptional activation;Nucleotide Excision Repair
(Consensus)
Recessive Scores
- pRec
- 0.718
Intolerance Scores
- loftool
- 0.0202
- rvis_EVS
- 0.28
- rvis_percentile_EVS
- 71.27
Haploinsufficiency Scores
- pHI
- 0.785
- hipred
- Y
- hipred_score
- 0.819
- ghis
- 0.587
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.857
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Actl6a
- Phenotype
- immune system phenotype; 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); hematopoietic system phenotype; cellular phenotype;
Zebrafish Information Network
- Gene name
- actl6a
- Affected structure
- head
- Phenotype tag
- abnormal
- Phenotype quality
- edematous
Gene ontology
- Biological process
- blastocyst formation;neural retina development;DNA repair;DNA recombination;chromatin remodeling;regulation of transcription by RNA polymerase II;signal transduction;protein deubiquitination;spinal cord development;regulation of growth;ATP-dependent chromatin remodeling;histone H4 acetylation;histone H2A acetylation;positive regulation of nucleic acid-templated transcription
- Cellular component
- nuclear chromatin;nucleus;nucleoplasm;plasma membrane;SWI/SNF complex;Ino80 complex;protein-containing complex;NuA4 histone acetyltransferase complex;npBAF complex
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;chromatin binding;transcription coactivator activity;protein binding;nucleosomal DNA binding