ANO4

anoctamin 4, the group of Anoctamins

Basic information

Region (hg38): 12:100717526-101128641

Previous symbols: [ "TMEM16D" ]

Links

ENSG00000151572 ∙ NCBI:121601 ∙ OMIM:610111 ∙ HGNC:23837 ∙ Uniprot:Q32M45 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Moderate), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ANO4 gene.

• Early infantile epileptic encephalopathy with suppression bursts (5 variants)
• Generalized epilepsy with febrile seizures plus (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ANO4 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					1	1
missense	6		45	1		52
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	6	0	45	1	1

Variants in ANO4

This is a list of pathogenic ClinVar variants found in the ANO4 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-100901819-A-G		not specified	Uncertain significance (Jan 08, 2025)
12-100922312-C-T			Uncertain significance (Sep 01, 2024)
12-100939323-G-A		not specified	Uncertain significance (Dec 25, 2024)
12-100939380-G-A		not specified	Uncertain significance (Jan 03, 2024)
12-100939407-A-C		not specified	Uncertain significance (Dec 13, 2022)
12-100942399-C-T		not specified	Uncertain significance (Dec 27, 2022)
12-100942401-A-G		not specified	Uncertain significance (Mar 03, 2025)
12-100942417-G-A		not specified	Uncertain significance (Sep 30, 2024)
12-100942432-G-A		not specified	Uncertain significance (Jan 16, 2025)
12-100942432-G-T		not specified	Uncertain significance (Dec 31, 2024)
12-100942462-C-A		not specified	Uncertain significance (Jan 04, 2022)
12-100942466-C-G		Early infantile epileptic encephalopathy with suppression bursts	Pathogenic (Mar 26, 2024)
12-100942486-A-G		not specified	Uncertain significance (Aug 04, 2024)
12-100971327-A-G		not specified	Uncertain significance (Oct 05, 2021)
12-100971336-G-A		not specified	Uncertain significance (Jul 27, 2024)
12-100974867-C-T		not specified	Uncertain significance (Nov 13, 2024)
12-100987663-A-T		not specified	Uncertain significance (Apr 08, 2024)
12-101020039-T-G		not specified	Uncertain significance (Aug 11, 2024)
12-101020074-A-G		not specified	Uncertain significance (Jul 08, 2024)
12-101020074-A-T		not specified	Uncertain significance (Jan 30, 2024)
12-101020075-C-G		not specified	Uncertain significance (Nov 29, 2024)
12-101037115-A-G		not specified	Uncertain significance (Feb 27, 2023)
12-101040007-G-A		not specified	Uncertain significance (Nov 25, 2024)
12-101040025-G-T		not specified	Uncertain significance (Sep 30, 2024)
12-101040034-C-G		not specified	Uncertain significance (Feb 27, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ANO4	protein_coding	protein_coding	ENST00000392979	25	411116

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000322	1.00	125702	0	46	125748	0.000183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.53	344	504	0.682	0.0000266	6070
Missense in Polyphen		157	230.72	0.68049		2741
Synonymous	2.04	141	175	0.804	0.00000930	1648
Loss of Function	5.20	19	63.8	0.298	0.00000369	695

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000764	0.000763
Ashkenazi Jewish	0.000106	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000196	0.000193
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000692	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylserine, phosphatidylcholine and galactosylceramide. Does not exhibit calcium-activated chloride channel (CaCC) activity. {ECO:0000250|UniProtKB:Q8C5H1}.
• Pathway: Stimuli-sensing channels;Ion channel transport;Transport of small molecules (Consensus)

Recessive Scores

• pRec: 0.133

Intolerance Scores

• loftool: 0.811
• rvis_EVS: -0.78
• rvis_percentile_EVS: 12.97

Haploinsufficiency Scores

• pHI: 0.339
• hipred: Y
• hipred_score: 0.685
• ghis: 0.584

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0483

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ano4

Gene ontology

• Biological process: chloride transport;ion transmembrane transport;calcium activated phosphatidylserine scrambling;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