ANO3

anoctamin 3, the group of Anoctamins

Basic information

Region (hg38): 11:26188842-26663289

Previous symbols: [ "C11orf25", "TMEM16C" ]

Links

ENSG00000134343 ∙ NCBI:63982 ∙ OMIM:610110 ∙ HGNC:14004 ∙ Uniprot:Q9BYT9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dystonia 24 (Strong), mode of inheritance: AD
• dystonia 24 (Strong), mode of inheritance: AD
• dystonia 24 (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dystonia 24	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	23200863

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ANO3 gene.

• Dystonic disorder (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ANO3 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	59	12	75
missense	2	5	143	9		159
nonsense			13			13
start loss						0
frameshift			2			2
inframe indel			1	1		2
splice donor/acceptor (+/-2bp)			4	1		5
splice region			12	14	4	30
non coding			26	81	117	224
Total	2	5	193	151	129

Variants in ANO3

This is a list of pathogenic ClinVar variants found in the ANO3 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-26189222-T-C			Uncertain significance (May 26, 2023)
11-26189234-C-T		Dystonia 24	Pathogenic (May 20, 2023)
11-26189280-C-G			Uncertain significance (Jul 01, 2022)
11-26331890-C-G			Benign (Jul 05, 2018)
11-26332014-T-C			Benign (Jul 05, 2018)
11-26332096-T-A			Benign (Jul 30, 2018)
11-26332133-G-A			Likely benign (Oct 14, 2018)
11-26332222-C-T			Likely benign (Aug 03, 2020)
11-26332264-C-T			Benign (Aug 11, 2018)
11-26332285-C-A		Inborn genetic diseases	Uncertain significance (Jun 07, 2023)
11-26332287-T-C		Dystonic disorder	Likely benign (Jun 25, 2020)
11-26332292-G-T		Dystonic disorder	Uncertain significance (Nov 14, 2021)
11-26332321-G-T		Dystonic disorder	Uncertain significance (Oct 13, 2023)
11-26332324-C-T		Dystonic disorder	Uncertain significance (Aug 27, 2023)
11-26332404-G-T		Dystonia 24	Benign (Dec 05, 2021)
11-26332444-TA-T			Benign (May 13, 2021)
11-26332444-T-TA			Benign (Sep 20, 2019)
11-26332444-T-TAA			Likely benign (Sep 08, 2020)
11-26332444-T-TAAA			Likely benign (Oct 22, 2019)
11-26332444-T-TAAAA			Benign (Nov 14, 2019)
11-26441908-G-C		Dystonic disorder	Likely benign (Jan 18, 2024)
11-26441918-G-T		Dystonic disorder	Uncertain significance (Jan 26, 2022)
11-26441920-A-G			Uncertain significance (Feb 01, 2024)
11-26441958-G-C		Dystonic disorder • ANO3-related disorder	Likely benign (Jun 26, 2021)
11-26441971-C-G		Dystonic disorder	Uncertain significance (Apr 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ANO3	protein_coding	protein_coding	ENST00000256737	27	474007

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.25e-17	0.998	125660	0	88	125748	0.000350

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.46	378	538	0.702	0.0000285	6517
Missense in Polyphen		157	272.9	0.5753		3313
Synonymous	-0.148	184	181	1.01	0.00000969	1710
Loss of Function	3.11	38	65.0	0.584	0.00000354	749

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00183	0.00178
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000383	0.000381
Finnish	0.000370	0.000370
European (Non-Finnish)	0.000284	0.000281
Middle Eastern	0.000383	0.000381
South Asian	0.000196	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylcholine and galactosylceramide. Seems to act as potassium channel regulator and may inhibit pain signaling; can facilitate KCNT1/Slack channel activity by promoting its full single-channel conductance at very low sodium concentrations and by increasing its sodium sensitivity (By similarity). Does not exhibit calcium-activated chloride channel (CaCC) activity. {ECO:0000250|UniProtKB:A2AHL1, ECO:0000269|PubMed:21984732}.
• Pathway: Stimuli-sensing channels;Ion channel transport;Transport of small molecules (Consensus)

Recessive Scores

• pRec: 0.129

Intolerance Scores

• loftool: 0.876
• rvis_EVS: -1.35
• rvis_percentile_EVS: 4.58

Haploinsufficiency Scores

• pHI: 0.281
• hipred: Y
• hipred_score: 0.725
• ghis: 0.560

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.251

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ano3

Gene ontology

• Biological process: detection of temperature stimulus;ion transmembrane transport;detection of mechanical stimulus;calcium activated phosphatidylcholine scrambling;calcium activated galactosylceramide scrambling
• Cellular component: plasma membrane;integral component of membrane
• Molecular function: intracellular calcium activated chloride channel activity;phospholipid scramblase activity;protein dimerization activity