ANO6

Chr 12AR

anoctamin 6

Also known as: BDPLT7, SCTS, TMEM16F

NCBI Gene: 196527ENSG00000177119UniProt: Q4KMQ2

This gene encodes a multi-pass transmembrane protein that belongs to the anoctamin family. This protein is an essential component for the calcium-dependent exposure of phosphatidylserine on the cell surface. The scrambling of phospholipid occurs in various biological systems, such as when blood platelets are activated, they expose phosphatidylserine to trigger the clotting system. Mutations in this gene are associated with Scott syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2011]

Primary Disease Associations & Inheritance

Scott syndromeMIM #262890
AR
412
ClinVar variants
50
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ANO6
🧬
Gene-Disease Validity (ClinGen)
Scott syndrome · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
50 Pathogenic / Likely Pathogenic· 153 VUS of 412 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.14LOEUF
pLI 0.000
Z-score 0.67
OE 0.90 (0.72–1.14)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.90Z-score
OE missense 0.89 (0.82–0.96)
452 obs / 509.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.90 (0.72–1.14)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.82–0.96)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 51 / 56.5Missense obs/exp: 452 / 509.3Syn Z: 0.08

ClinVar Variant Classifications

412 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic14
VUS153
Likely Benign148
Benign41
Conflicting20
36
Pathogenic
14
Likely Pathogenic
153
VUS
148
Likely Benign
41
Benign
20
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
0
28
0
36
Likely Pathogenic
10
0
4
0
14
VUS
0
143
9
1
153
Likely Benign
0
8
56
84
148
Benign
0
2
34
5
41
Conflicting
—20
Total1815313190412

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ANO6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
ANOCTAMIN 6; ANO6
MIM #608663 · *

Scott syndrome

MIM #262890

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Analysis of a new therapeutic target and construction of a prognostic model for breast cancer based on ferroptosis genes.
Li Q et al.·Comput Biol Med
2023Functional
Fusion of Tumor Cells with Lipid-Associated Macrophages Drives Metastatic Progression of Breast Cancer.
Cheng Y et al.·Cancer Res
2026
Pan-Cancer Analysis of ANO6 and Experimental Validation in Metastatic Melanoma.
An Y et al.·Biochem Genet
2026
Pathogenic Relationships in Cystic Fibrosis and Renal Diseases: CFTR, SLC26A9 and Anoctamins.
Kunzelmann K et al.·Int J Mol Sci
2023Review
ANO6 Confers Paclitaxel Resistance by Targeting Ferroptosis in Cervical Cancer.
Cao Y et al.·Biofactors
2026
Haploinsufficiency of ANO6, NELL2 and DBX2 in a boy with intellectual disability and growth delay.
Carlsen EØ et al.·Am J Med Genet A
2015Case report
Selective serotonin reuptake inhibitors facilitate ANO6 (TMEM16F) current activation and phosphatidylserine exposure.
Kim HJ et al.·Pflugers Arch
2015
Temperature-dependent increase in the calcium sensitivity and acceleration of activation of ANO6 chloride channel variants.
Lin H et al.·Sci Rep
2019
Significance of Anoctamin 6 in progression and prognostic prediction of gastric adenocarcinoma.
Li B et al.·Histol Histopathol
2022
Comprehensive functional characterization of a novel ANO6 variant in a new patient with Scott syndrome.
Montague SJ et al.·J Thromb Haemost
2024Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools