ACTN3

actinin alpha 3, the group of Actinins

Basic information

Region (hg38): 11:66546394-66563334

Links

ENSG00000248746 ∙ NCBI:89 ∙ OMIM:102574 ∙ HGNC:165 ∙ Uniprot:Q08043 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
ACTN3 deficiency	AR	General	The clinical relevance is unclear	Musculoskeletal	10192379; 11845199; 12879365; 15886711; 17033684; 17627799; 17828264

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACTN3 gene.

• Inborn genetic diseases (55 variants)
• not provided (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACTN3 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				3		3
missense			54	1	1	56
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	54	4	1

Variants in ACTN3

This is a list of pathogenic ClinVar variants found in the ACTN3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-66546544-T-C		ACTN3-related disorder	Likely benign (Sep 13, 2022)
11-66546753-C-G		ACTN3-related disorder	Benign (Mar 26, 2019)
11-66546762-C-T		ACTN3-related disorder	Benign (Apr 05, 2019)
11-66546977-G-A		not specified	Uncertain significance (Nov 03, 2023)
11-66546978-A-C		not specified	Uncertain significance (Jul 11, 2023)
11-66547017-T-G		not specified	Uncertain significance (Aug 12, 2021)
11-66547043-G-C		ACTN3-related disorder	Likely benign (Jul 10, 2019)
11-66547080-G-A		not specified	Uncertain significance (Feb 14, 2023)
11-66551296-A-G		not specified	Uncertain significance (Feb 27, 2024)
11-66551312-G-A		not specified	Uncertain significance (Aug 16, 2021)
11-66551326-C-T		not specified	Uncertain significance (Oct 03, 2022)
11-66551332-C-T			Likely benign (Feb 01, 2023)
11-66551340-G-A			Likely benign (Mar 01, 2022)
11-66551534-G-A		not specified	Uncertain significance (Dec 12, 2023)
11-66551553-A-T		not specified	Uncertain significance (Dec 16, 2023)
11-66551609-C-A		not specified	Uncertain significance (Feb 01, 2023)
11-66551639-G-A		not specified	Uncertain significance (May 23, 2023)
11-66551645-A-C		not specified	Uncertain significance (Feb 14, 2023)
11-66554050-G-A		not specified	Uncertain significance (Jun 22, 2023)
11-66554056-G-A		not specified	Uncertain significance (Nov 06, 2023)
11-66554072-C-T		not specified	Uncertain significance (Oct 13, 2023)
11-66554084-T-C		not specified	Uncertain significance (Apr 07, 2022)
11-66554096-T-C		not specified	Uncertain significance (Nov 17, 2023)
11-66554107-G-A		not specified	Uncertain significance (Oct 26, 2022)
11-66554126-T-C		not specified	Uncertain significance (Sep 06, 2022)

GnomAD

Source: gnomAD

dbNSFP

Source: dbNSFP

• Function: FUNCTION: F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein.
• Pathway: Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Arrhythmogenic Right Ventricular Cardiomyopathy;Striated Muscle Contraction;erk and pi-3 kinase are necessary for collagen binding in corneal epithelia;ucalpain and friends in cell spread;integrin signaling pathway;Striated Muscle Contraction;Muscle contraction;Nephrin family interactions;Cell-Cell communication;Signaling events mediated by focal adhesion kinase (Consensus)

Haploinsufficiency Scores

• pHI: 0.901

Essentials

• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Mouse Genome Informatics

• Gene name: Actn3
• Phenotype: homeostasis/metabolism phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: actn3a
• Affected structure: atrium
• Phenotype tag: abnormal
• Phenotype quality: dilated

Gene ontology

• Biological process: regulation of the force of skeletal muscle contraction;skeletal muscle atrophy;transition between fast and slow fiber;response to denervation involved in regulation of muscle adaptation;muscle filament sliding;regulation of apoptotic process;negative regulation of glycolytic process;focal adhesion assembly;positive regulation of skeletal muscle tissue growth;negative regulation of calcineurin-NFAT signaling cascade;negative regulation of oxidative phosphorylation;negative regulation of cold-induced thermogenesis;regulation of aerobic respiration;positive regulation of glucose catabolic process to lactate via pyruvate
• Cellular component: cytosol;actin filament;focal adhesion;pseudopodium;extracellular exosome
• Molecular function: actin binding;integrin binding;calcium ion binding;protein binding;structural constituent of muscle;protein homodimerization activity;ion channel binding