ANO9

protein-coding

anoctamin 9, the group of Anoctamins

Gene summary

The protein encoded by this gene is a member of the TMEM16 (anoctamin) family of proteins, some of which form integral membrane calcium-activated chloride channels. The function of the encoded protein has yet to be elucidated, although it may have channel-forming abilities and also may have phospholipid scramblase activity. This gene has been observed to be upregulated in stage II and III colorectal cancers. [provided by RefSeq, Dec 2016]

Previous symbols:

TP53I5
TMEM16J

MANE transcript

NM_001012302.3

Inheritance

—

ClinVar variants

U:144B:14

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr11:417,933-442,011

External References & Databases

Ensembl (ENSG00000185101)

Transcript & Mutation Effects

hg38 • Region Span ~24.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ANO9 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 139

not providedTotal: 7

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001012302.3. 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			2 clinvar	4 clinvar	1 clinvar	7
missense			135 clinvar	9 clinvar		144
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	144	13	1	158

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001012302.3	RefSeq	NP_001012302.2	23	MANE Select
ENST00000332826.7	Ensembl	ENSP00000332788.6	23	MANE Select
NM_001347882.2	RefSeq	NP_001334811.1	17	Standard
ENST00000884101.1	Ensembl	ENSP00000554160.1	23	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Stimuli-sensing channels
Ion channel transport
Transport of small molecules

Biological Process

chloride transport
ion transmembrane transport
calcium activated phosphatidylserine scrambling
calcium activated phosphatidylcholine scrambling
calcium activated galactosylceramide scrambling

Molecular Function

intracellular calcium activated chloride channel activity
protein binding
phospholipid scramblase activity

Cellular Component

plasma membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000332826
Coding exons: 23
Length: 24079
Individuals with no LoFs: 125642
Homozygous LoFs: 0
Heterozygous LoFs: 71
Defined: 125713
p: 0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.21	443	520	0.851	0.0000352	5107
Missense (PolyPhen)		165	215.66	0.7651		2209
Synonymous	0.563	216	227	0.952	0.0000167	1520
Loss of Function	2.04	31	45.9	0.675	0.00000232	472

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00055	0.00055	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00028	0.00027	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00026	0.00026	rare
South Asian	0.00039	0.00039	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Has calcium-dependent phospholipid scramblase activity; scrambles phosphatidylserine, phosphatidylcholine and galactosylceramide (By similarity). Does not exhibit calcium- activated chloride channel (CaCC) activity. Can inhibit the activity of ANO1. {ECO:0000250|UniProtKB:P86044, ECO:0000269|PubMed:20056604, ECO:0000269|PubMed:22946059}.;

Recessive Scores

pRec: 0.0969

Intolerance Scores

LoFtool: 0.851
RVIS EVS: -0.26
RVIS percentile EVS: 34.98

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0987

Gene Damage Prediction

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