ACTG2

actin gamma 2, smooth muscle, the group of Actins

Basic information

Region (hg38): 2:73892314-73919865

Previous symbols: [ "ACTL3", "ACTA3" ]

Links

ENSG00000163017

∙ NCBI:72 ∙ OMIM:102545 ∙ HGNC:145 ∙ Uniprot:P63267 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

visceral myopathy 1 (Strong), mode of inheritance: AD
familial visceral myopathy (Supportive), mode of inheritance: AD
megacystis-microcolon-intestinal hypoperistalsis syndrome (Supportive), mode of inheritance: AD
visceral myopathy 1 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Visceral myopathy 1; Megacystis-microcolon-intestinal hypoperistalsis syndrome 5	AD	Gastrointestinal	Individuals have been described as presenting with findings including chronic intestinal pseudo-obstruction and related abdominal signs and symptoms, and genetic knowledge may help avoid unnecessary surgery (medical management has been described as at least partially effective in some individuals); TPN and urinary catheterization may be beneficial	Gastrointestinal; Genitourinary; Neurologic	19098683; 24676022; 24777424; 26647307; 27481187; 28422808; 31769566
Conditions related to variants in ACTG2 are reported to overlap phenotypically

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACTG2 gene.

Visceral_myopathy_1 (39 variants)
not_provided (37 variants)
Megacystis-microcolon-intestinal_hypoperistalsis_syndrome_5 (20 variants)
Inborn_genetic_diseases (13 variants)
ACTG2-related_disorder (9 variants)
Chronic_intestinal_pseudoobstruction (6 variants)
Megacystis (2 variants)
Visceral_neuropathy,_familial,_3,_autosomal_dominant (2 variants)
not_specified (1 variants)
Intestinal_pseudo-obstruction (1 variants)
Constipation (1 variants)
Intestinal_obstruction (1 variants)
Megacystis,_microcolon,_hypoperistalsis_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACTG2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001615.4. 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				3 clinvar	3 clinvar	6
missense	19 clinvar	22 clinvar	40 clinvar			81
nonsense						0
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	19	24	40	3	3

Highest pathogenic variant AF is 0.000166942

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACTG2	protein_coding	protein_coding	ENST00000409624	8	27552

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0710	0.927	125734	0	14	125748	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.35	86	228	0.376	0.0000129	2480
Missense in Polyphen		30	86.641	0.34625		971
Synonymous	0.640	77	84.5	0.911	0.00000461	735
Loss of Function	2.66	5	16.7	0.299	8.65e-7	197

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000185	0.000182
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000114	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000367	0.0000352
Middle Eastern	0.000114	0.000109
South Asian	0.000109	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.;
Disease: DISEASE: Visceral myopathy (VSCM) [MIM:155310]: A rare inherited form of myopathic pseudo-obstruction characterized by impaired function of enteric smooth muscle cells, resulting in abnormal intestinal motility, severe abdominal pain, malnutrition, and even death. The disease shows inter- and intrafamilial variability. Most severely affected patients exhibit prenatal bladder enlargement, intestinal malrotation, neonatal functional gastrointestinal obstruction, and dependence on total parenteral nutrition and urinary catheterization. {ECO:0000269|PubMed:22960657, ECO:0000269|PubMed:24337657, ECO:0000269|PubMed:24676022, ECO:0000269|PubMed:24777424}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Vascular smooth muscle contraction - Homo sapiens (human);Common Pathways Underlying Drug Addiction;Smooth Muscle Contraction;Muscle contraction (Consensus)

Recessive Scores

pRec: 0.673

Intolerance Scores

loftool: 0.301
rvis_EVS: -0.36
rvis_percentile_EVS: 28.63

Haploinsufficiency Scores

pHI: 0.894
hipred: Y
hipred_score: 0.782
ghis: 0.545

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.702

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Actg2
Phenotype

Gene ontology

Biological process: muscle contraction;positive regulation of gene expression;mesenchyme migration
Cellular component: extracellular space;cytoplasm;cytosol;lamellipodium;filopodium;myosin filament;cell body;extracellular exosome;cell periphery;blood microparticle
Molecular function: ATP binding