ANO8

Summary

ANO8 (anoctamin 8, HGNC:29329) is a protein-coding gene on chromosome 19p13.11, encoding Anoctamin-8 (Q9HCE9). Does not exhibit calcium-activated chloride channel (CaCC) activity.

Enables intracellularly calcium-gated chloride channel activity. Involved in chloride transmembrane transport. Located in plasma membrane.

Source: NCBI Gene 57719 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 229 total — 1 likely-pathogenic
• MANE Select transcript: NM_020959

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29329
Approved symbol	ANO8
Name	anoctamin 8
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000074855
Ensembl biotype	protein_coding
OMIM	610216
Entrez	57719

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000159087, ENST00000597643, ENST00000600711, ENST00000630631

RefSeq mRNA: 1 — MANE Select: NM_020959 NM_020959

CCDS: CCDS32949

Canonical transcript exons

ENST00000159087 — 18 exons

Exon	Start	End
ENSE00000349542	17329757	17329831
ENSE00000665455	17328162	17328983
ENSE00000665579	17329959	17330014
ENSE00000665580	17330125	17330251
ENSE00000665581	17330352	17330504
ENSE00000665582	17330828	17330989
ENSE00000870983	17331088	17331215
ENSE00001049943	17332930	17333026
ENSE00001049945	17331295	17331411
ENSE00001049946	17333690	17333800
ENSE00001505816	17333101	17333239
ENSE00001505817	17333422	17333554
ENSE00003466721	17323223	17323884
ENSE00003487999	17327235	17327345
ENSE00003567054	17324717	17325386
ENSE00003589023	17327689	17327880
ENSE00003691708	17327438	17327569
ENSE00003847818	17334565	17334855

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 93.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.9737 / max 176.3602, expressed in 1722 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179854	4.1904	1408
179855	2.5788	1155
179856	2.2045	1150

Top tissues by expression

243 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	93.32	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.91	gold quality
ganglionic eminence	UBERON:0004023	89.79	gold quality
right adrenal gland	UBERON:0001233	89.61	gold quality
cerebellar hemisphere	UBERON:0002245	89.55	gold quality
cerebellar cortex	UBERON:0002129	89.37	gold quality
left adrenal gland cortex	UBERON:0035825	89.27	gold quality
right adrenal gland cortex	UBERON:0035827	89.22	gold quality
left adrenal gland	UBERON:0001234	88.89	gold quality
lower esophagus mucosa	UBERON:0035834	88.57	gold quality
ventricular zone	UBERON:0003053	88.14	gold quality
cerebellum	UBERON:0002037	87.70	gold quality
adrenal cortex	UBERON:0001235	87.14	gold quality
right frontal lobe	UBERON:0002810	85.98	gold quality
adrenal gland	UBERON:0002369	85.72	gold quality
skin of leg	UBERON:0001511	85.27	gold quality
skin of abdomen	UBERON:0001416	84.50	gold quality
anterior cingulate cortex	UBERON:0009835	83.86	gold quality
caudate nucleus	UBERON:0001873	83.52	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.00	gold quality
amygdala	UBERON:0001876	82.91	gold quality
apex of heart	UBERON:0002098	82.64	gold quality
zone of skin	UBERON:0000014	82.60	gold quality
esophagus mucosa	UBERON:0002469	82.57	gold quality
granulocyte	CL:0000094	82.43	gold quality
nucleus accumbens	UBERON:0001882	82.31	gold quality
hypothalamus	UBERON:0001898	81.59	gold quality
putamen	UBERON:0001874	81.39	gold quality
neocortex	UBERON:0001950	81.26	gold quality
gastrocnemius	UBERON:0001388	81.14	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	103.61
E-ANND-3	no	1.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting ANO8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-1253	99.12	67.08	1688
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-6738-3P	99.03	67.14	1326
HSA-MIR-1257	98.97	68.02	1133
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-153-3P	98.96	72.51	1644
HSA-MIR-367-5P	98.84	67.18	902
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-1267	98.24	69.05	837
HSA-MIR-7706	95.96	63.68	172

Literature-anchored findings (GeneRIF, showing 3)

• Human TMEM16H gene, consisting of 18 exons, is located at human chromosome 19p13.11. (PMID:15647853)
• Anoctamin 8 (ANO8) as a key tether in the formation of the Endoplasmic reticulum/Plasma membrane (ER/PM) junctions that is essential for STIM1-STIM1 interaction and STIM1-Orai1 interaction and channel activation at a ER/PM PI(4,5)P2-rich compartment. Ano8 assembles all core Calcium signaling proteins. (PMID:31061173)
• Whole-exome sequencing reveals ANO8 as a genetic risk factor for intrahepatic cholestasis of pregnancy. (PMID:32942997)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ano8a	ENSDARG00000076265
danio_rerio	ano8b	ENSDARG00000077229
mus_musculus	Ano8	ENSMUSG00000034863
rattus_norvegicus	Ano8	ENSRNOG00000058662
drosophila_melanogaster	wwk	FBGN0028879
caenorhabditis_elegans		WBGENE00013326

Paralogs (10): ANO2 (ENSG00000047617), PPP1R7 (ENSG00000115685), ANO1 (ENSG00000131620), ANO3 (ENSG00000134343), ANO7 (ENSG00000146205), ANO4 (ENSG00000151572), ANO10 (ENSG00000160746), ANO5 (ENSG00000171714), ANO6 (ENSG00000177119), ANO9 (ENSG00000185101)

Protein

Protein identifiers

Anoctamin-8 — Q9HCE9 (reviewed: Q9HCE9)

Alternative names: Transmembrane protein 16H

All UniProt accessions (2): Q9HCE9, M0QYD2

UniProt curated annotations — full annotation on UniProt →

Function. Does not exhibit calcium-activated chloride channel (CaCC) activity.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in embryonic stem cells, fetal brain and neural tissues.

Miscellaneous. The term ‘anoctamin’ was coined because these channels are anion selective and have eight (OCT) transmembrane segments. There is some dissatisfaction in the field with the Ano nomenclature because it is not certain that all the members of this family are anion channels or have the 8-transmembrane topology.

Similarity. Belongs to the anoctamin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9HCE9-1	1	yes
Q9HCE9-2	2

RefSeq proteins (1): NP_066010* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007632	Anoctamin	Family
IPR049452	Anoctamin_TM	Domain

Pfam: PF04547

UniProt features (43 total): compositionally biased region 10, topological domain 9, transmembrane region 8, region of interest 6, modified residue 6, splice variant 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCE9-F1	63.82	0.29

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6): 2, 318, 669, 801, 1020, 1020

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-2672351	Stimuli-sensing channels
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275	Post-translational protein phosphorylation
R-HSA-9733458	Induction of Cell-Cell Fusion
R-HSA-1643685	Disease
R-HSA-382551	Transport of small molecules
R-HSA-392499	Metabolism of proteins
R-HSA-5663205	Infectious disease
R-HSA-597592	Post-translational protein modification
R-HSA-9679506	SARS-CoV Infections
R-HSA-9694516	SARS-CoV-2 Infection
R-HSA-9772573	Late SARS-CoV-2 Infection Events
R-HSA-9824446	Viral Infection Pathways
R-HSA-983712	Ion channel transport

MSigDB gene sets: 134 (showing top): GOBP_INORGANIC_ANION_TRANSPORT, GOBP_CHLORIDE_TRANSPORT, BENPORATH_NOS_TARGETS, GOBP_TRANSMEMBRANE_TRANSPORT, BENPORATH_OCT4_TARGETS, GOCC_ENDOPLASMIC_RETICULUM_LUMEN, chr19p13, GOMF_GATED_CHANNEL_ACTIVITY, GOMF_PASSIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_MONOATOMIC_ANION_CHANNEL_ACTIVITY, GOMF_MONOATOMIC_ANION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_TRANSPORTER_ACTIVITY, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP, GOMF_MONOATOMIC_ION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY

GO Biological Process (2): monoatomic ion transmembrane transport (GO:0034220), chloride transmembrane transport (GO:1902476)

GO Molecular Function (2): intracellularly calcium-gated chloride channel activity (GO:0005229), chloride channel activity (GO:0005254)

GO Cellular Component (3): endoplasmic reticulum lumen (GO:0005788), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Metabolism of proteins	2
Ion channel transport	1
Post-translational protein modification	1
Late SARS-CoV-2 Infection Events	1
Disease	1
Viral Infection Pathways	1
SARS-CoV Infections	1
SARS-CoV-2 Infection	1
Infectious disease	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monoatomic ion transport	1
transmembrane transport	1
chloride transport	1
monoatomic anion transmembrane transport	1
chloride channel activity	1
ligand-gated monoatomic anion channel activity	1
intracellularly calcium-gated channel activity	1
monoatomic anion channel activity	1
chloride transmembrane transporter activity	1
endoplasmic reticulum	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

622 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ANO8	C10orf71	Q711Q0	521
ANO8	BTBD17	A6NE02	520
ANO8	STIM1	Q13586	502
ANO8	GFOD2	Q3B7J2	499
ANO8	TBCCD1	Q9NVR7	499
ANO8	ARL14EPL	P0DKL9	497
ANO8	ANO1	Q5XXA6	462
ANO8	ANO5	Q75V66	459
ANO8	TM9SF4	Q92544	440
ANO8	POPDC1	Q8NE79	424
ANO8	BCKDHB	P21953	422
ANO8	TLK2	Q86UE8	420
ANO8	ESYT1	Q9BSJ8	416
ANO8	GINS1	Q14691	411
ANO8	ICMT	O60725	408

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ANO8	ADRA1A	psi-mi:“MI:0915”(physical association)	0.370
TMEM241	FAAH	psi-mi:“MI:0914”(association)	0.350
COQ9	ANO8	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (21): ANO8 (Affinity Capture-RNA), ANO8 (Proximity Label-MS), ANO8 (Proximity Label-MS), ANO8 (Two-hybrid), ANO8 (Affinity Capture-RNA), ANO8 (Proximity Label-MS), ANO8 (Proximity Label-MS), ANO8 (Proximity Label-MS), ANO8 (Proximity Label-MS), ANO8 (Proximity Label-MS), ANO8 (Affinity Capture-RNA), ANO8 (Proximity Label-MS), ANO8 (Proximity Label-MS), ANO8 (Proximity Label-MS), ANO8 (Proximity Label-MS)

ESM2 similar proteins: A2A6C4, A5D7M7, A7MBM2, A9JSM3, B2RXF0, B9EJI9, E9PY61, F1SAM7, O75949, Q08E36, Q17QQ5, Q29RK8, Q2MJR0, Q2T9K0, Q3U5Q7, Q49LS1, Q49LS4, Q49LS8, Q5EBM0, Q5GH56, Q5GH59, Q5GH64, Q5GH67, Q5GH72, Q5GH73, Q5GH76, Q5SNT2, Q5T442, Q66K66, Q68FE7, Q6P6N5, Q6PB70, Q6PRD1, Q80XF7, Q80ZU9, Q8BG75, Q8BQU6, Q8CIV2, Q8IUH8, Q8N144

Diamond homologs: A0MFS9, Q0JJZ6, Q6PB70, Q9HCE9, Q9NW15, A1A5B4, A2AHL1, A6QLE6, P86044, Q14AT5, Q32M45, Q4KMQ2, Q5XXA6, Q6IFT6, Q6IWH7, Q6P9J9, Q75UR0, Q75V66, Q8BHY3, Q8C5H1, Q8CFW1, Q9BYT9, Q9NQ90, O13621

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

229 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	203
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
442665	GRCh37/hg19 19p13.12-13.11(chr19:15921132-17479860)x1	Likely pathogenic

SpliceAI

3150 predictions. Top by Δscore:

Variant	Effect	Δscore
19:17325410:CAGGA:C	acceptor_gain	1.0000
19:17325415:C:CC	acceptor_gain	1.0000
19:17327229:CCCTA:C	donor_loss	1.0000
19:17327230:CCTA:C	donor_loss	1.0000
19:17327231:CTAC:C	donor_loss	1.0000
19:17327233:A:T	donor_loss	1.0000
19:17327238:AAAGG:A	donor_gain	1.0000
19:17327707:TTCC:T	donor_gain	1.0000
19:17327708:T:A	donor_gain	1.0000
19:17328159:CACC:C	donor_loss	1.0000
19:17328161:C:CG	donor_loss	1.0000
19:17328167:A:AC	donor_gain	1.0000
19:17328168:C:CC	donor_gain	1.0000
19:17328168:CTT:C	donor_gain	1.0000
19:17328170:T:TA	donor_gain	1.0000
19:17329408:A:AC	donor_gain	1.0000
19:17329409:C:CC	donor_gain	1.0000
19:17329751:TCTCA:T	donor_loss	1.0000
19:17329752:CTCAC:C	donor_loss	1.0000
19:17329753:TCA:T	donor_loss	1.0000
19:17329754:CA:C	donor_loss	1.0000
19:17329755:A:AC	donor_gain	1.0000
19:17329756:C:CC	donor_gain	1.0000
19:17329756:C:CG	donor_loss	1.0000
19:17329756:CCT:C	donor_gain	1.0000
19:17329827:TGGAA:T	acceptor_gain	1.0000
19:17329828:GGAA:G	acceptor_gain	1.0000
19:17329829:GAA:G	acceptor_gain	1.0000
19:17329830:AA:A	acceptor_gain	1.0000
19:17329832:C:CC	acceptor_gain	1.0000

AlphaMissense

7944 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:17331328:A:G	W224R	1.000
19:17331328:A:T	W224R	1.000
19:17332950:A:G	F189S	1.000
19:17333524:A:G	L83P	1.000
19:17333528:A:G	W82R	1.000
19:17333528:A:T	W82R	1.000
19:17327528:G:C	N820K	0.999
19:17327528:G:T	N820K	0.999
19:17327779:G:C	N776K	0.999
19:17327779:G:T	N776K	0.999
19:17330884:A:G	W313R	0.999
19:17330884:A:T	W313R	0.999
19:17330941:A:G	W294R	0.999
19:17330941:A:T	W294R	0.999
19:17331168:A:G	W251R	0.999
19:17331168:A:T	W251R	0.999
19:17331339:A:G	L220P	0.999
19:17331402:A:G	L199P	0.999
19:17333022:C:G	R165P	0.999
19:17333111:A:G	F160S	0.999
19:17333237:A:G	L118P	0.999
19:17333434:G:T	A113D	0.999
19:17333491:A:G	L94P	0.999
19:17333521:A:G	L84P	0.999
19:17333526:C:A	W82C	0.999
19:17333526:C:G	W82C	0.999
19:17325115:A:G	L978S	0.998
19:17327520:A:G	L823S	0.998
19:17327527:A:G	C821R	0.998
19:17327694:A:G	W805R	0.998

dbSNP variants (sampled 300 via entrez): RS1000200183 (19:17334532 C>A,T), RS1000485306 (19:17328549 C>T), RS1000530852 (19:17333122 C>A), RS1000705150 (19:17327787 C>A,T), RS1001070672 (19:17324615 G>A), RS1001222376 (19:17327371 G>A), RS1001226080 (19:17336734 T>A), RS1001517785 (19:17329557 C>T), RS1001737667 (19:17323540 A>G), RS1001771880 (19:17323275 CAA>C), RS1001884575 (19:17328082 C>A,G,T), RS1001950815 (19:17329265 C>A,T), RS1002183787 (19:17330631 C>T), RS1002284886 (19:17324267 C>A,T), RS1002294767 (19:17323514 G>A)

Disease associations

OMIM: gene MIM:610216 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST005547_7	Major depressive disorder	5.000000e-07
GCST007394_2	Mitochondrial DNA copy number	1.000000e-14
GCST010002_51	Refractive error	4.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006312	mitochondrial DNA measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	increases abundance, increases expression, decreases expression	2
GSK-J4	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
monomethylarsonous acid	increases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, increases expression	1
Cytarabine	increases expression	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1
Antirheumatic Agents	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_DX15	HAP1 ANO8 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.