ANO3
protein-codinganoctamin 3, the group of Anoctamins
Gene summary
The protein encoded by this gene belongs to the TMEM16 family of predicted membrane proteins, that are also known as anoctamins. While little is known about the function of this gene, mutations in this gene have been associated with some cases of autosomal dominant craniocervical dystonia. Cells from individuals with a mutation in this gene exhibited abnormalities in endoplasmic reticulum-dependent calcium signaling. Studies in rat show that the rat ortholog of this protein interacts with, and modulates the activity of a sodium-activated potassium channel. Deletion of this gene caused increased pain sensitivity in the rat model system. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]
- C11orf25
- TMEM16C
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~474.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0014019
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0014019
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0014019
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0014019
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0014019
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Neurologic
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ANO3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_031418.4. 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 | 8 | 86 | 7 | 101 | ||
| missense | 5 | 8 | 239 | 18 | 3 | 273 |
| nonsense | 16 | 16 | ||||
| start loss | 0 | |||||
| frameshift | 4 | 4 | ||||
| splice donor/acceptor (+/-2bp) | 7 | 1 | 8 | |||
| Total | 5 | 8 | 274 | 105 | 10 | 402 |
Highest pathogenic variant AF is 0.000013023547
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_113606.2 | 27 | MANE Select | |
| Ensembl | ENSP00000256737.3 | 27 | MANE Select | |
| RefSeq | NP_001300655.1 | 28 | Standard | |
| RefSeq | NP_001300656.1 | 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
- detection of temperature stimulus
- ion transmembrane transport
- detection of mechanical stimulus
- calcium activated phosphatidylcholine scrambling
- calcium activated galactosylceramide scrambling
Molecular Function
- intracellular calcium activated chloride channel activity
- phospholipid scramblase activity
- protein dimerization activity
Cellular Component
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000256737
- Coding exons
- 27
- Length
- 474007
- Individuals with no LoFs
- 125660
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 88
- Defined
- 125748
- p
- 0.000350
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.46 | 378 | 538 | 0.702 | 0.0000285 | 6517 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0015 | 0.0015 | notable |
| Latino/Admixed American | 0.00030 | 0.00029 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.00037 | 0.00037 | rare |
| European (Non-Finnish) | 0.00028 | 0.00028 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- 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}.;
Recessive Scores
- pRec
- 0.129
Intolerance Scores
- LoFtool
- 0.876
- RVIS EVS
- -1.35
- RVIS percentile EVS
- 4.58
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.251
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |