ACTG1

actin gamma 1, the group of Actins

Basic information

Region (hg38): 17:81509412-81523847

Previous symbols: [ "ACTG", "DFNA20", "DFNA26" ]

Links

ENSG00000184009 ∙ NCBI:71 ∙ OMIM:102560 ∙ HGNC:144 ∙ Uniprot:P63261 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nonsyndromic hearing loss 20 (Strong), mode of inheritance: AD
• Baraitser-winter syndrome 2 (Strong), mode of inheritance: AD
• Baraitser-Winter cerebrofrontofacial syndrome (Supportive), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• Baraitser-winter syndrome 2 (Definitive), mode of inheritance: AD
• Baraitser-winter syndrome 2 (Strong), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 20 (Strong), mode of inheritance: AD
• Baraitser-winter syndrome 2 (Definitive), mode of inheritance: AD
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Baraitser-Winter syndrome 2	AD	Audiologic/Otolaryngologic; Cardiovascular	Though the condition may be recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Individuals have been described with congenital heart anomalies, and awareness may enable early diagnosis and management	Audiologic/Otolaryngologic;Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic; Renal	5654493; 3351890; 12519370; 14684684; 13680526; 16773128; 19477959; 22366783; 25052316

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACTG1 gene.

• not provided (257 variants)
• Autosomal dominant nonsyndromic hearing loss 20;Baraitser-winter syndrome 2 (137 variants)
• not specified (106 variants)
• Baraitser-winter syndrome 2;Autosomal dominant nonsyndromic hearing loss 20 (93 variants)
• Autosomal dominant nonsyndromic hearing loss 20 (78 variants)
• Baraitser-winter syndrome 2 (77 variants)
• Inborn genetic diseases (15 variants)
• ACTG1-related condition (6 variants)
• Rare genetic deafness (3 variants)
• Hearing impairment (2 variants)
• Intellectual disability (2 variants)
• Lissencephaly (2 variants)
• ACTG1-Related Disorders (1 variants)
• Microcephaly (1 variants)
• Neurodevelopmental delay (1 variants)
• See cases (1 variants)
• Congenital anomaly of kidney and urinary tract (1 variants)
• Nonsyndromic genetic hearing loss (1 variants)
• Baraitser-Winter syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACTG1 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			4	153	18	175
missense	9	34	82	2		127
nonsense			2			2
start loss						0
frameshift			3			3
inframe indel		1	2			3
splice donor/acceptor (+/-2bp)						0
splice region			3	16	1	20
non coding			4	63	43	110
Total	9	35	97	218	61

Variants in ACTG1

This is a list of pathogenic ClinVar variants found in the ACTG1 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-81510406-T-C			Benign (Jun 26, 2018)
17-81510431-G-A			Likely benign (Dec 07, 2019)
17-81510463-G-A			Likely benign (Jul 15, 2018)
17-81510491-T-A			Benign (Jan 29, 2020)
17-81510496-T-G			Likely benign (Jun 04, 2020)
17-81510498-C-G			Benign (Jun 14, 2018)
17-81510544-T-C			Benign (Jan 06, 2020)
17-81510547-C-G			Benign (Jan 06, 2020)
17-81510556-G-A			Likely benign (Aug 03, 2018)
17-81510560-C-T			Likely benign (Feb 17, 2021)
17-81510562-A-C			Benign (Feb 13, 2020)
17-81510564-G-C			Benign (Jan 29, 2020)
17-81510578-G-A			Likely benign (Jun 28, 2018)
17-81510658-T-C			Benign (Jan 22, 2020)
17-81510672-C-T		not specified	Likely benign (Sep 06, 2016)
17-81510679-G-A		not specified	Uncertain significance (Nov 05, 2015)
17-81510684-G-C			Likely benign (Aug 05, 2020)
17-81510688-G-A			Benign (Feb 25, 2020)
17-81510690-T-C		not specified • Autosomal dominant nonsyndromic hearing loss 20;Baraitser-winter syndrome 2 • Autosomal dominant nonsyndromic hearing loss 20 • Baraitser-winter syndrome 2	Benign (Feb 01, 2024)
17-81510696-G-A		Baraitser-winter syndrome 2;Autosomal dominant nonsyndromic hearing loss 20	Likely benign (Aug 22, 2022)
17-81510697-C-T		Baraitser-winter syndrome 2;Autosomal dominant nonsyndromic hearing loss 20	Uncertain significance (Nov 28, 2022)
17-81510699-T-C		ACTG1-related disorder	Likely benign (Apr 27, 2022)
17-81510705-G-A		not specified • Autosomal dominant nonsyndromic hearing loss 20;Baraitser-winter syndrome 2 • Baraitser-winter syndrome 2 • Autosomal dominant nonsyndromic hearing loss 20	Benign (Jan 22, 2024)
17-81510708-G-A		Autosomal dominant nonsyndromic hearing loss 20;Baraitser-winter syndrome 2	Likely benign (Oct 24, 2022)
17-81510708-G-T		not specified • Autosomal dominant nonsyndromic hearing loss 20;Baraitser-winter syndrome 2	Likely benign (May 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACTG1	protein_coding	protein_coding	ENST00000575842	5	13877

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00478	0.969	125738	0	7	125745	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.16	72	197	0.366	0.0000101	2431
Missense in Polyphen		49	124.26	0.39435		1569
Synonymous	-19.0	291	78.0	3.73	0.00000434	746
Loss of Function	1.95	6	13.8	0.435	6.16e-7	151

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000529	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000163	0.000163

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. {ECO:0000305|PubMed:29581253}.
• Disease: DISEASE: Deafness, autosomal dominant, 20 (DFNA20) [MIM:604717]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:13680526, ECO:0000269|PubMed:14684684, ECO:0000269|PubMed:16773128, ECO:0000269|PubMed:18804074, ECO:0000269|PubMed:19477959, ECO:0000269|PubMed:22938506, ECO:0000269|PubMed:25388789}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Baraitser-Winter syndrome 2 (BRWS2) [MIM:614583]: A rare developmental disorder characterized by the combination of congenital ptosis, high-arched eyebrows, hypertelorism, ocular colobomata, and a brain malformation consisting of anterior- predominant lissencephaly. Other typical features include postnatal short stature and microcephaly, intellectual disability, seizures, and hearing loss. {ECO:0000269|PubMed:22366783}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Defects in ACTG1 has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea. {ECO:0000269|PubMed:28493397}.
• Pathway: Platelet activation - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Oxytocin signaling pathway - Homo sapiens (human);Salmonella infection - Homo sapiens (human);Adherens junction - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Viral myocarditis - Homo sapiens (human);Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Tight junction - Homo sapiens (human);Influenza A - Homo sapiens (human);Phagosome - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Fluid shear stress and atherosclerosis - Homo sapiens (human);Vibrio cholerae infection - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Shigellosis - Homo sapiens (human);Pathogenic Escherichia coli infection - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Apoptosis - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);Arrhythmogenic Right Ventricular Cardiomyopathy;Pathogenic Escherichia coli infection;Common Pathways Underlying Drug Addiction;Myometrial Relaxation and Contraction Pathways;Focal Adhesion;Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;Striated Muscle Contraction;Regulation of Actin Cytoskeleton;Developmental Biology;Signal Transduction;Fcgamma receptor (FCGR) dependent phagocytosis;EPH-Ephrin signaling;Innate Immune System;Immune System;EPHB-mediated forward signaling;RHO GTPases Activate WASPs and WAVEs;RHO GTPases Activate Formins;RHO GTPase Effectors;Signaling by Rho GTPases;Regulation of actin dynamics for phagocytic cup formation;Axon guidance (Consensus)

Intolerance Scores

• loftool: 0.0321
• rvis_EVS: -1.93
• rvis_percentile_EVS: 1.91

Haploinsufficiency Scores

• pHI: 0.930
• hipred: Y
• hipred_score: 0.711
• ghis: 0.631

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.970

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Actg1
• Phenotype: hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); muscle phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: retina homeostasis;cell junction assembly;Fc-gamma receptor signaling pathway involved in phagocytosis;sarcomere organization;ephrin receptor signaling pathway;synaptic vesicle endocytosis;membrane organization;platelet aggregation;cellular response to interferon-gamma
• Cellular component: extracellular space;nucleus;cytosol;cytoskeleton;actin filament;plasma membrane;focal adhesion;membrane;myofibril;filamentous actin;myelin sheath;calyx of Held;phagocytic vesicle;extracellular exosome;blood microparticle;dense body;Schaffer collateral - CA1 synapse
• Molecular function: structural constituent of cytoskeleton;protein binding;profilin binding;ATP binding;ubiquitin protein ligase binding;identical protein binding