ANO6

anoctamin 6, the group of Anoctamins

Basic information

Region (hg38): 12:45215986-45482280

Previous symbols: [ "TMEM16F" ]

Links

ENSG00000177119 ∙ NCBI:196527 ∙ OMIM:608663 ∙ HGNC:25240 ∙ Uniprot:Q4KMQ2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Scott syndrome (Strong), mode of inheritance: AR
• Scott syndrome (Supportive), mode of inheritance: AR
• Scott syndrome (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Scott syndrome	AR	Hematologic	Though manifestations tend to be milder than in other bleeding disorders, precautions related to certain circumstances, such as in surgery or during pregnancy and delivery, may be beneficial	Hematologic	572637; 7989579; 21107324; 37455884

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ANO6 gene.

• not provided (123 variants)
• Inborn genetic diseases (44 variants)
• not specified (18 variants)
• ANO6-related condition (6 variants)
• SCOTT SYNDROME (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ANO6 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				24	7	31
missense			61	7	6	74
nonsense	1	1				2
start loss						0
frameshift	2	3				5
inframe indel						0
splice donor/acceptor (+/-2bp)	2	3				5
splice region			1	3	5	9
non coding				12	24	36
Total	5	7	61	43	37

Highest pathogenic variant AF is 0.000119

Variants in ANO6

This is a list of pathogenic ClinVar variants found in the ANO6 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-45216341-A-G			Uncertain significance (Aug 23, 2022)
12-45216369-G-C		Inborn genetic diseases	Likely benign (Nov 06, 2023)
12-45216643-C-T			Benign (Nov 10, 2018)
12-45270430-G-A			Benign (Jun 18, 2021)
12-45293197-A-C			Benign (Jun 18, 2021)
12-45301952-C-A			Benign (Jun 18, 2021)
12-45301996-AT-A			Likely benign (Jan 12, 2024)
12-45301998-A-G			Likely benign (Nov 23, 2022)
12-45302005-CG-C			Likely benign (Aug 10, 2023)
12-45302010-T-C			Likely benign (Jan 11, 2024)
12-45302014-T-C		Inborn genetic diseases	Uncertain significance (Sep 29, 2023)
12-45302037-A-T		ANO6-related disorder	Benign (Jan 18, 2024)
12-45302044-C-T		Inborn genetic diseases	Uncertain significance (Jul 25, 2023)
12-45302045-C-T		not specified	Benign (Jan 31, 2024)
12-45302049-T-G		Inborn genetic diseases	Uncertain significance (Dec 21, 2023)
12-45302051-G-A			Likely benign (Jun 22, 2022)
12-45302070-C-T		Inborn genetic diseases	Uncertain significance (Jan 30, 2024)
12-45302086-C-T			Uncertain significance (Aug 06, 2022)
12-45302087-G-A			Likely benign (Jul 29, 2023)
12-45302107-C-T		not specified	Benign (Jan 29, 2024)
12-45331006-G-A			Benign (Jun 18, 2021)
12-45331275-T-C			Likely benign (Apr 29, 2023)
12-45331303-T-C			Benign (Dec 17, 2023)
12-45331305-A-G		Inborn genetic diseases	Uncertain significance (May 26, 2023)
12-45331318-C-G			Uncertain significance (Oct 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ANO6	protein_coding	protein_coding	ENST00000423947	21	224418

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.32e-32	0.000296	125592	1	155	125748	0.000620

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.902	452	509	0.888	0.0000281	6165
Missense in Polyphen		169	223.21	0.75714		2712
Synonymous	0.0826	179	180	0.992	0.0000101	1708
Loss of Function	0.674	51	56.5	0.903	0.00000330	622

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00101	0.00101
Ashkenazi Jewish	0.000401	0.000397
East Asian	0.000490	0.000489
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000723	0.000721
Middle Eastern	0.000490	0.000489
South Asian	0.00102	0.000980
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Small-conductance calcium-activated nonselective cation (SCAN) channel which acts as a regulator of phospholipid scrambling in platelets and osteoblasts. Phospholipid scrambling results in surface exposure of phosphatidylserine which in platelets is essential to trigger the clotting system whereas in osteoblasts is essential for the deposition of hydroxyapatite during bone mineralization. Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylserine, phosphatidylcholine and galactosylceramide (By similarity). Can generate outwardly rectifying chloride channel currents in airway epithelial cells and Jurkat T lymphocytes. {ECO:0000250|UniProtKB:Q6P9J9, ECO:0000269|PubMed:20056604, ECO:0000269|PubMed:21107324, ECO:0000269|PubMed:21908539, ECO:0000269|PubMed:22006324, ECO:0000269|PubMed:22946059}.
• Pathway: Neutrophil degranulation;Stimuli-sensing channels;Ion channel transport;Innate Immune System;Immune System;Transport of small molecules (Consensus)

Intolerance Scores

• loftool: 0.996
• rvis_EVS: -0.08
• rvis_percentile_EVS: 47.2

Haploinsufficiency Scores

• pHI: 0.187
• hipred: N
• hipred_score: 0.251
• ghis: 0.504

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.137

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ano6
• Phenotype: hematopoietic system phenotype; 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); skeleton phenotype; limbs/digits/tail phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype

Zebrafish Information Network

• Gene name: ano6
• Affected structure: dorsal longitudinal anastomotic vessel
• Phenotype tag: abnormal
• Phenotype quality: aplastic

Gene ontology

• Biological process: dendritic cell chemotaxis;activation of blood coagulation via clotting cascade;cation transport;chloride transport;blood coagulation;plasma membrane phospholipid scrambling;positive regulation of bone mineralization;bleb assembly;ion transmembrane transport;positive regulation of ion transmembrane transport;purinergic nucleotide receptor signaling pathway;bone mineralization involved in bone maturation;sodium ion transmembrane transport;positive regulation of apoptotic process;neutrophil degranulation;negative regulation of cell volume;pore complex assembly;positive regulation of phagocytosis, engulfment;calcium activated phosphatidylserine scrambling;calcium activated phosphatidylcholine scrambling;calcium activated galactosylceramide scrambling;calcium ion transmembrane transport;positive regulation of monocyte chemotaxis;phosphatidylserine exposure on blood platelet;chloride transmembrane transport;positive regulation of potassium ion export across plasma membrane;positive regulation of endothelial cell apoptotic process
• Cellular component: cytosol;plasma membrane;cell surface;membrane;chloride channel complex;specific granule membrane;extracellular exosome;tertiary granule membrane
• Molecular function: calcium activated cation channel activity;intracellular calcium activated chloride channel activity;voltage-gated ion channel activity;voltage-gated chloride channel activity;protein binding;phospholipid scramblase activity;protein homodimerization activity