ACTB
actin beta, the group of BAF complex|GBAF complex|PBAF complex|Actins
Basic information
Region (hg38): 7:5526409-5563902
Links
Phenotypes
GenCC
Source:
- developmental malformations-deafness-dystonia syndrome (Limited), mode of inheritance: AD
- Baraitser-Winter syndrome 1 (Strong), mode of inheritance: AD
- developmental malformations-deafness-dystonia syndrome (Strong), mode of inheritance: AD
- developmental malformations-deafness-dystonia syndrome (Strong), mode of inheritance: AD
- Baraitser-Winter syndrome 1 (Strong), mode of inheritance: AD
- Baraitser-Winter cerebrofrontofacial syndrome (Supportive), mode of inheritance: AD
- developmental malformations-deafness-dystonia syndrome (Supportive), mode of inheritance: AD
- Baraitser-Winter syndrome 1 (Definitive), mode of inheritance: AD
- Baraitser-Winter syndrome 1 (Strong), mode of inheritance: AD
- developmental malformations-deafness-dystonia syndrome (Strong), mode of inheritance: AD
- ACTB-associated syndromic thrombocytopenia (Moderate), mode of inheritance: AD
- Baraitser-Winter cerebrofrontofacial syndrome (Definitive), mode of inheritance: AD
- ACTB-associated syndromic thrombocytopenia (Moderate), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Baraitser-Winter syndrome 1; Dystonia-deafness syndrome 1; Thrombocytopenia 8, with dysmorphic features and developmental delay | AD | Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular | For individuals with Baraitser-Winter syndrome 1 or Dystonia-deafness syndrome, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Individuals with Baraitser-Winter syndrome and Thrombocytopenia 8, with dysmorphic features and developmental delay have been described with congenital heart anomalies, and awareness may enable early diagnosis and management; Thrombocytopenia 8, with dysmorphic features and developmental delay has been described as involving susceptibilty to infections in some individuals, and awareness may allow early and aggressive treatment of infections | Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dermatologic; Hematologic; Musculoskeletal; Neurologic; Ophthalmologic; Renal | 3351890; 10411937; 12325076; 16685646; 22366783; 23649928; 25052316; 28487785; 30315159; 30921093; 36564926 |
ClinVar
This is a list of variants' phenotypes submitted to
- Baraitser-Winter_syndrome_1 (429 variants)
- not_provided (194 variants)
- Developmental_malformations-deafness-dystonia_syndrome (48 variants)
- ACTB-related_disorder (39 variants)
- Inborn_genetic_diseases (24 variants)
- not_specified (23 variants)
- ACTB-related_BAFopathy (9 variants)
- ACTB-associated_syndromic_thrombocytopenia (7 variants)
- Congenital_smooth_muscle_hamartoma (5 variants)
- Intellectual_disability (5 variants)
- Neurodevelopmental_disorder (5 variants)
- CONGENITAL_SMOOTH_MUSCLE_HAMARTOMA,_SOMATIC,_MOSAIC (5 variants)
- Baraitser-Winter_syndrome (4 variants)
- Becker_nevus_syndrome (3 variants)
- Thrombocytopenia (3 variants)
- See_cases (2 variants)
- Aminoacylase_1_deficiency (1 variants)
- Microcephaly (1 variants)
- Congenital_smooth_muscle_hamartoma,_with_or_without_hemihypertrophy (1 variants)
- BECKER_NEVUS,_ISOLATED,_SOMATIC,_MOSAIC (1 variants)
- Dystonic_disorder (1 variants)
- Neurodevelopmental_delay (1 variants)
- CONGENITAL_SMOOTH_MUSCLE_HAMARTOMA_WITH_HEMIHYPERTROPHY,_SOMATIC,_MOSAIC (1 variants)
- Abnormal_brain_morphology (1 variants)
- Short_stature (1 variants)
- BECKER_NEVUS_SYNDROME,_SOMATIC,_MOSAIC (1 variants)
- Cleft_palate (1 variants)
- ACTB_Haploinsufficiency_syndrome (1 variants)
- BECKER_NEVUS,_SOMATIC,_MOSAIC (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACTB gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001101.5. 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 | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 185 | 199 | ||||
| missense | 36 | 85 | 118 | 239 | ||
| nonsense | 5 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 25 | |||||
| splice donor/acceptor (+/-2bp) | 2 | |||||
| Total | 47 | 96 | 135 | 185 | 8 |
Highest pathogenic variant AF is 0.0000065716
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ACTB | protein_coding | protein_coding | ENST00000331789 | 5 | 36634 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.986 | 0.0144 | 125685 | 0 | 1 | 125686 | 0.00000398 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 5.02 | 14 | 227 | 0.0617 | 0.0000141 | 2462 |
| Missense in Polyphen | 4 | 121.92 | 0.03281 | 1370 | ||
| Synonymous | -7.44 | 190 | 96.9 | 1.96 | 0.00000664 | 751 |
| Loss of Function | 3.32 | 0 | 12.9 | 0.00 | 5.73e-7 | 146 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells (PubMed:29581253). Actin exists in both monomeric (G- actin) and polymeric (F-actin) forms, both forms playing key functions, such as cell motility and contraction (PubMed:29581253). In addition to their role in the cytoplasmic cytoskeleton, G- and F-actin also localize in the nucleus, and regulate gene transcription and motility and repair of damaged DNA (PubMed:29925947). {ECO:0000269|PubMed:29581253, ECO:0000269|PubMed:29925947}.;
- Disease
- DISEASE: Dystonia, juvenile-onset (DJO) [MIM:607371]: A form of dystonia with juvenile onset. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. Patients with juvenile-onset dystonia manifest progressive, generalized, dopa-unresponsive dystonia, developmental malformations and sensory hearing loss. {ECO:0000269|PubMed:16685646}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Baraitser-Winter syndrome 1 (BRWS1) [MIM:243310]: A rare developmental disorder characterized by the combination of congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata, and a brain malformation consisting of anterior- predominant lissencephaly. Other typical features include postnatal short stature and microcephaly, intellectual disability, seizures, and hearing loss. {ECO:0000269|PubMed:22366783}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Platelet activation - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Salmonella infection - Homo sapiens (human);Adherens junction - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Viral myocarditis - Homo sapiens (human);Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Tight junction - Homo sapiens (human);Influenza A - Homo sapiens (human);Phagosome - Homo sapiens (human);Gastric acid secretion - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Vibrio cholerae infection - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Shigellosis - Homo sapiens (human);Pathogenic Escherichia coli infection - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Apoptosis - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Arrhythmogenic Right Ventricular Cardiomyopathy;Pathogenic Escherichia coli infection;Common Pathways Underlying Drug Addiction;Myometrial Relaxation and Contraction Pathways;Focal Adhesion;Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;Regulation of Actin Cytoskeleton;Developmental Biology;B-WICH complex positively regulates rRNA expression;Positive epigenetic regulation of rRNA expression;DNA Repair;Signal Transduction;Epigenetic regulation of gene expression;Gene expression (Transcription);the information processing pathway at the ifn beta enhancer;Post-translational protein modification;Metabolism of proteins;Fcgamma receptor (FCGR) dependent phagocytosis;Chromatin modifying enzymes;EPH-Ephrin signaling;Chaperonin-mediated protein folding;Innate Immune System;Immune System;EPHB-mediated forward signaling;RHO GTPases Activate WASPs and WAVEs;RHO GTPases Activate Formins;HATs acetylate histones;RHO GTPase Effectors;Signaling by Rho GTPases;UCH proteinases;Integrin;EGFR1;Regulation of actin dynamics for phagocytic cup formation;Protein folding;Deubiquitination;Chromatin organization;chromatin remodeling by hswi/snf atp-dependent complexes;Axon guidance;Prefoldin mediated transfer of substrate to CCT/TriC;Folding of actin by CCT/TriC;Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding;DNA Damage Recognition in GG-NER;Global Genome Nucleotide Excision Repair (GG-NER);Nucleotide Excision Repair
(Consensus)
Intolerance Scores
- loftool
- 0.00310
- rvis_EVS
- -0.67
- rvis_percentile_EVS
- 15.62
Haploinsufficiency Scores
- pHI
- 0.994
- hipred
- Y
- hipred_score
- 0.771
- ghis
- 0.604
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Low | Low | Low |
| Cancer | Low | Low | Low |
Mouse Genome Informatics
- Gene name
- Actb
- Phenotype
- muscle phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); growth/size/body region phenotype; reproductive 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); normal phenotype; 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); hearing/vestibular/ear phenotype; immune system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; neoplasm;
Gene ontology
- Biological process
- regulation of cyclin-dependent protein serine/threonine kinase activity;retina homeostasis;protein deubiquitination;substantia nigra development;regulation of transmembrane transporter activity;negative regulation of protein binding;cell junction assembly;Fc-gamma receptor signaling pathway involved in phagocytosis;ATP-dependent chromatin remodeling;positive regulation of gene expression, epigenetic;ephrin receptor signaling pathway;cell motility;regulation of norepinephrine uptake;positive regulation of norepinephrine uptake;membrane organization;platelet aggregation;cellular response to cytochalasin B;postsynaptic actin cytoskeleton organization;regulation of protein localization to plasma membrane
- Cellular component
- nuclear chromatin;extracellular space;nucleus;nucleoplasm;cytoplasm;cytosol;cytoskeleton;plasma membrane;focal adhesion;actin cytoskeleton;membrane;vesicle;protein-containing complex;NuA4 histone acetyltransferase complex;cytoplasmic ribonucleoprotein granule;extracellular exosome;blood microparticle;dense body;presynapse;postsynaptic actin cytoskeleton;glutamatergic synapse;ribonucleoprotein complex
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;structural constituent of cytoskeleton;protein binding;ATP binding;kinesin binding;protein kinase binding;Tat protein binding;nucleosomal DNA binding;identical protein binding;tau protein binding;nitric-oxide synthase binding;structural constituent of postsynaptic actin cytoskeleton