ACTN3 actinin alpha 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ACTN3provided by HGNC
Official Full Name: actinin alpha 3provided by HGNC
Primary source: HGNC:HGNC:165
See related: Ensembl:ENSG00000248746 MIM:102574; AllianceGenome:HGNC:165
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ACTN3D
Summary: This gene encodes a member of the alpha-actin binding protein gene family. The encoded protein is primarily expressed in skeletal muscle and functions as a structural component of sarcomeric Z line. This protein is involved in crosslinking actin containing thin filaments. An allelic polymorphism in this gene results in both coding and non-coding variants; the reference genome represents the coding allele. The non-functional allele of this gene is associated with elite athlete status. [provided by RefSeq, Apr 2024]
Annotation information: Note: Genetic polymorphisms result in both protein coding and non-coding alleles of this gene.
Expression: Biased expression in testis (RPKM 1.6), prostate (RPKM 0.6) and 2 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q13.2

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (66546395..66563334)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (66542637..66559581)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (66313866..66330805)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Association between Complex ACTN3 and ACE Gene Polymorphisms and Elite Endurance Sports in Koreans: A Case-Control Study.
Title: Association between Complex ACTN3 and ACE Gene Polymorphisms and Elite Endurance Sports in Koreans: A Case-Control Study.
ACTN3 XX Genotype Negatively Affects Running Performance and Increases Muscle Injury Incidence in LaLiga Football Players.
Title: ACTN3 XX Genotype Negatively Affects Running Performance and Increases Muscle Injury Incidence in LaLiga Football Players.
Principal components analysis to evaluate complex association of polymorphisms in ACE and ACTN3 genes and the extent of cardiovascular adaptive changes in elite athletes.
Title: Principal components analysis to evaluate complex association of polymorphisms in ACE and ACTN3 genes and the extent of cardiovascular adaptive changes in elite athletes.
Genetic polymorphisms in the angiotensin converting enzyme, actinin 3 and paraoxonase 1 genes in women with diabetes and hypertension.
Title: Genetic polymorphisms in the angiotensin converting enzyme, actinin 3 and paraoxonase 1 genes in women with diabetes and hypertension.
Association of the ACTN3 Gene's Single-Nucleotide Variant Rs1815739 (R577X) with Sports Qualification and Competitive Distance in Caucasian Athletes of the Southern Urals.
Title: Association of the ACTN3 Gene's Single-Nucleotide Variant Rs1815739 (R577X) with Sports Qualification and Competitive Distance in Caucasian Athletes of the Southern Urals.
The Association between ACTN3 R577X Polymorphism and Range of Motion: A Systematic Review and Meta-analysis.
Title: The Association between ACTN3 R577X Polymorphism and Range of Motion: A Systematic Review and Meta-analysis.
Association of ACTN3 R577X Polymorphism with Elite Basketball Player Status and Training Responses.
Title: Association of ACTN3 R577X Polymorphism with Elite Basketball Player Status and Training Responses.
Genetic polymorphisms related to muscular strength and flexibility are associated with artistic gymnastic performance in the Japanese population.
Title: Genetic polymorphisms related to muscular strength and flexibility are associated with artistic gymnastic performance in the Japanese population.
Association between ACE and ACTN3 genes polymorphisms and athletic performance in elite and sub-elite Chinese youth male football players.
Title: Association between ACE and ACTN3 genes polymorphisms and athletic performance in elite and sub-elite Chinese youth male football players.
Prevalence of Polymorphism and Post-Training Expression of ACTN3 (R/X) and ACE (I/D) Genes in CrossFit Athletes.
Title: Prevalence of Polymorphism and Post-Training Expression of ACTN3 (R/X) and ACE (I/D) Genes in CrossFit Athletes.

Submit: New GeneRIF Correction See all GeneRIFs (208)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Actn3 deficiency MedGen: C3888204 OMIM: 617749 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH47283 (e-PCR)
- UniSTS:60704

GDB:197568 (e-PCR)
- UniSTS:155948

ACTN3 (e-PCR)
- UniSTS:9576

STS-M86407 (e-PCR)
- UniSTS:61809

Actn3 (e-PCR), detects polymorphism
- UniSTS:228476

G54071 (e-PCR)
- UniSTS:109453

ACTN3 (e-PCR)
- UniSTS:504722

STS-W72567 (e-PCR)
- UniSTS:54739

NoName (e-PCR)
- UniSTS:483815

NoName (e-PCR)
- UniSTS:481531

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables actin filament binding	IBA Inferred from Biological aspect of Ancestor more info
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables integrin binding	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables structural constituent of muscle	TAS Traceable Author Statement more info	PubMed
enables transmembrane transporter binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in actin cytoskeleton organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in bone morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in focal adhesion assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in muscle cell development	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of calcineurin-NFAT signaling cascade	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of cold-induced thermogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in negative regulation of glycolytic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of oxidative phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of relaxation of muscle	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of bone mineralization involved in bone maturation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of fast-twitch skeletal muscle fiber contraction	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of glucose catabolic process to lactate via pyruvate	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of skeletal muscle fiber development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of skeletal muscle tissue growth	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of aerobic respiration	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of apoptotic process	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of the force of skeletal muscle contraction	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to denervation involved in regulation of muscle adaptation	ISS Inferred from Sequence or Structural Similarity more info
involved_in skeletal muscle atrophy	ISS Inferred from Sequence or Structural Similarity more info
involved_in transition between fast and slow fiber	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
is_active_in Z disc	IBA Inferred from Biological aspect of Ancestor more info
located_in actin filament	TAS Traceable Author Statement more info	PubMed
located_in brush border	IEA Inferred from Electronic Annotation more info
is_active_in cell junction	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cell projection	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cortical actin cytoskeleton	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in focal adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in pseudopodium	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: alpha-actinin-3

Names: F-actin cross-linking protein; alpha-actinin skeletal muscle

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_013304.2 RefSeqGene

Range

4984..21415

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001104.4 → NP_001095.2 alpha-actinin-3 isoform 1

See identical proteins and their annotated locations for NP_001095.2

Status: REVIEWED

Description

Transcript Variant: This variant (1, coding) represents the protein-coding allele and encodes isoform 1.

Source sequence(s)

AJ346025, AK125851, AK303044, AP002748, BC099647, DA915904

Consensus CDS

CCDS53663.1

UniProtKB/Swiss-Prot

A6NP77, Q08043, Q4KKV2

UniProtKB/TrEMBL

B2R8Y4

Related

ENSP00000426797.1, ENST00000513398.2

Conserved Domains (6) summary

COG5126
Location:757 → 861

FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]

cd00176
Location:409 → 636

SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

pfam00435
Location:644 → 747

Spectrin; Spectrin repeat

pfam08726
Location:831 → 897

EFhand_Ca_insen; Ca2+ insensitive EF hand

cd21214
Location:42 → 146

CH_ACTN_rpt1; first calponin homology (CH) domain found in the alpha-actinin family

cd21216
Location:150 → 264

CH_ACTN_rpt2; second calponin homology (CH) domain found in the alpha-actinin family
NM_001258371.3 → NP_001245300.2 alpha-actinin-3 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate exon in the 5' UTR and coding region and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) is longer and has a distinct N-terminus, compared to isoform 1.

Source sequence(s)

AJ346025, AK303044, AP002748, BC099647

Consensus CDS

CCDS76439.1

UniProtKB/TrEMBL

A0A087WSZ2, B4DZQ2

Related

ENSP00000422007.1, ENST00000502692.5

Conserved Domains (7) summary

cd00014
Location:202 → 307

CH; Calponin homology domain; actin-binding domain which may be present as a single copy or in tandem repeats (which increases binding affinity). The CH domain is found in cytoskeletal and signal transduction proteins, including actin-binding proteins like ...

cd00051
Location:807 → 869

EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...

cd00176
Location:452 → 679

SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

pfam00307
Location:90 → 187

CH; Calponin homology (CH) domain

pfam00435
Location:331 → 440

Spectrin; Spectrin repeat

pfam08726
Location:874 → 940

EFhand_Ca_insen; Ca2+ insensitive EF hand

pfam13499
Location:809 → 868

EF-hand_7; EF-hand domain pair