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 (13 variants)
• Megacystis-microcolon-intestinal hypoperistalsis syndrome 5 (6 variants)
• not provided (5 variants)
• Inborn genetic diseases (4 variants)
• Megacystis;Chronic intestinal pseudoobstruction (2 variants)
• Visceral myopathy 1;Megacystis-microcolon-intestinal hypoperistalsis syndrome 5 (2 variants)
• Visceral neuropathy, familial, 3, autosomal dominant (1 variants)
• Chronic intestinal pseudoobstruction (1 variants)
• ACTG2-related disorder (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.

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	6
missense	14	16	22			52
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)		1				1
splice region			2	1	2	5
non coding					3	3
Total	14	17	22	3	6

Highest pathogenic variant AF is 0.000112

Variants in ACTG2

This is a list of pathogenic ClinVar variants found in the ACTG2 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-73901264-G-C		Megacystis-microcolon-intestinal hypoperistalsis syndrome 5 • Visceral myopathy 1	Benign (Jul 14, 2021)
2-73901306-C-T		Visceral myopathy 1 • Megacystis-microcolon-intestinal hypoperistalsis syndrome 5	Benign (Jul 14, 2021)
2-73901339-G-A		Visceral myopathy 1	Likely pathogenic (Sep 17, 2020)
2-73901378-G-A		Visceral myopathy 1	Uncertain significance (Jun 29, 2016)
2-73901415-T-C		Megacystis-microcolon-intestinal hypoperistalsis syndrome 5	Uncertain significance (Sep 22, 2024)
2-73901424-G-A		Chronic intestinal pseudoobstruction	Pathogenic (May 02, 2015)
2-73901427-C-G		Megacystis-microcolon-intestinal hypoperistalsis syndrome 5	Likely pathogenic (Aug 29, 2022)
2-73901427-C-T		Visceral myopathy 1	Pathogenic (Oct 04, 2019)
2-73901429-C-T		Visceral myopathy 1 • Megacystis-microcolon-intestinal hypoperistalsis syndrome 5 • ACTG2-related disorder	Pathogenic/Likely pathogenic (Apr 22, 2021)
2-73901430-G-A		Visceral myopathy 1 • Chronic intestinal pseudoobstruction • Visceral neuropathy, familial, 3, autosomal dominant • Megacystis-microcolon-intestinal hypoperistalsis syndrome 5 • Megacystis-microcolon-intestinal hypoperistalsis syndrome 5;Visceral myopathy 1	Pathogenic/Likely pathogenic (Jun 02, 2023)
2-73901434-C-A		Visceral myopathy 1	Uncertain significance (Apr 28, 2020)
2-73901442-G-A		not specified	Uncertain significance (Dec 07, 2016)
2-73902364-T-A		Megacystis-microcolon-intestinal hypoperistalsis syndrome 5	Uncertain significance (-)
2-73902367-T-C		Visceral myopathy 1	Pathogenic (Mar 27, 2014)
2-73902370-T-C			Uncertain significance (Nov 01, 2022)
2-73902411-C-G		Visceral myopathy 1	Uncertain significance (Oct 20, 2020)
2-73902416-C-G			Uncertain significance (Sep 16, 2018)
2-73902420-C-G		Visceral myopathy 1	Pathogenic (Dec 20, 2016)
2-73902421-G-A		Visceral myopathy 1 • Megacystis-microcolon-intestinal hypoperistalsis syndrome 5	Pathogenic (Sep 30, 2019)
2-73902421-G-T		Megacystis-microcolon-intestinal hypoperistalsis syndrome 5	Likely pathogenic (Mar 04, 2022)
2-73902450-G-C			Uncertain significance (Jun 14, 2019)
2-73902455-C-T		ACTG2-related disorder	Likely benign (Aug 22, 2022)
2-73902479-C-T		ACTG2-related disorder	Benign (Jan 30, 2018)
2-73902698-C-A		Visceral myopathy 1	Pathogenic (Mar 27, 2014)
2-73902698-C-G		Visceral myopathy 1	Uncertain significance (Sep 30, 2019)

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

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