ACTG2

protein-coding

actin gamma 2, smooth muscle, the group of Actins

Gene summary

Actins are highly conserved proteins that are involved in various types of cell motility and in the maintenance of the cytoskeleton. Three types of actins, alpha, beta and gamma, have been identified in vertebrates. Alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins co-exist in most cell types as components of the cytoskeleton and as mediators of internal cell motility. This gene encodes actin gamma 2; a smooth muscle actin found in enteric tissues. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Based on similarity to peptide cleavage of related actins, the mature protein of this gene is formed by removal of two N-terminal peptides.[provided by RefSeq, Dec 2010]

Previous symbols:

ACTL3
ACTA3

MANE transcript

NM_001615.4

Inheritance

AR, AD

ClinVar variants

P:42U:57B:10

Top phenotype

Visceral myopathy 1; Megacystis-microcolon-intestinal hypoperistalsis syndrome 5

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr2:73,892,314-73,919,865

External References & Databases

Ensembl (ENSG00000163017)

Transcript & Mutation Effects

hg38 • Region Span ~27.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

visceral myopathy 1LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0020754

Submitter: Ambry Genetics

familial visceral myopathySTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0016829

Submitter: PanelApp Australia

megacystis-microcolon-intestinal hypoperistalsis syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007960

Submitter: Orphanet

visceral myopathy 1STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0020754

Submitter: Labcorp Genetics (formerly Invitae)

familial visceral myopathySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0016829

Submitter: Orphanet

Clinical Genomic Database (CGD)

Visceral myopathy 1; Megacystis-microcolon-intestinal hypoperistalsis syndrome 5AD

Manifestation: Gastrointestinal; Genitourinary; Neurologic

Intervention: Gastrointestinal

Rationale: 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

Comments: Conditions related to variants in ACTG2 are reported to overlap phenotypically

Refs: 19098683; 24676022; 24777424; 26647307; 27481187; 28422808; 31769566

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ACTG2 variants in ClinVar

14 Conditions Cataloged

not providedTotal: 50

Visceral myopathy 1Total: 42

Megacystis-microcolon-intestinal hypoperistalsis syndrome 5Total: 23

Inborn genetic diseasesTotal: 17

ACTG2-related disorderTotal: 17

Chronic intestinal pseudoobstructionTotal: 6

MegacystisTotal: 2

not specifiedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001615.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				7 clinvar	2 clinvar	9
missense	17 clinvar	24 clinvar	57 clinvar	1 clinvar		99
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)		1 clinvar				1
Total	17	25	57	8	2	109

Highest pathogenic variant AF is 0.0001669419

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 58 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001615.4	RefSeq	NP_001606.1	8	MANE Select
ENST00000345517.8	Ensembl	ENSP00000295137.3	8	MANE Select
NM_001199893.2	RefSeq	NP_001186822.1	7	Standard
ENST00000409624.1	Ensembl	ENSP00000386857.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vascular smooth muscle contraction - Homo sapiens (human)
Common Pathways Underlying Drug Addiction
Smooth Muscle Contraction
Muscle contraction

Biological Process

muscle contraction
positive regulation of gene expression
mesenchyme migration

Molecular Function

ATP binding

Cellular Component

extracellular space
cytoplasm
cytosol
lamellipodium
filopodium

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000409624
Coding exons: 8
Length: 27552
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125748
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.35	86	228	0.376	0.0000129	2480
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000037	0.000035	rare
South Asian	0.00011	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.673

Intolerance Scores

LoFtool: 0.301
RVIS EVS: -0.36
RVIS percentile EVS: 28.63

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.702

Gene Damage Prediction

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