ASIC3

Summary

ASIC3 (acid sensing ion channel subunit 3, HGNC:101) is a protein-coding gene on chromosome 7q36.1, encoding Acid-sensing ion channel 3 (Q9UHC3). Forms pH-gated heterotrimeric sodium channels that act as postsynaptic excitatory receptors in the nervous system.

This gene encodes a member of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. The members of this family are amiloride-sensitive sodium channels that contain intracellular N and C termini, two hydrophobic transmembrane regions, and a large extracellular loop, which has many cysteine residues with conserved spacing. The member encoded by this gene is an acid sensor and may play an important role in the detection of lasting pH changes. In addition, a heteromeric association between this member and acid-sensing (proton-gated) ion channel 2 has been observed as proton-gated channels sensitive to gadolinium. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 9311 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 133 total — 1 pathogenic
• GTEx eGene: eQTL in 29 tissues, sQTL in 9 (q < 0.05)
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.02 (unconstrained)
• MANE Select transcript: NM_004769
• Notable: 133 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:101
Approved symbol	ASIC3
Name	acid sensing ion channel subunit 3
Location	7q36.1
Locus type	gene with protein product
Status	Approved
Aliases	TNaC1, DRASIC
Ensembl gene	ENSG00000213199
Ensembl biotype	protein_coding
OMIM	611741
Entrez	9311

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000349064

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 4, TSL 3: 1

ENST00000349064, ENST00000297512, ENST00000357922, ENST00000377904, ENST00000468325, ENST00000474135, ENST00000485929, ENST00000490540, ENST00000498105, ENST00000962796, ENST00001142058

RefSeq mRNA: 3 — MANE Select: NM_004769 NM_004769, NM_020321, NM_020322

CCDS: CCDS5914, CCDS5915, CCDS5916

Canonical transcript exons

ENST00000349064 — 11 exons

Exon	Start	End
ENSE00001088222	151051172	151051319
ENSE00001088224	151050758	151050953
ENSE00001088239	151050106	151050256
ENSE00001900066	151048531	151049419
ENSE00002503559	151050481	151050608
ENSE00003488528	151051039	151051095
ENSE00003532275	151052416	151052474
ENSE00003563324	151052574	151052754
ENSE00003596447	151051983	151052062
ENSE00003659648	151051810	151051901
ENSE00003689739	151052166	151052237

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 97.27.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2776 / max 21.9539, expressed in 79 samples.

Highest expression (Bgee): hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex, testis, cerebellum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

ASIC3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 29 tissues and its splicing (sQTL) in 9 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 38 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	eqtl	3.9e-17	+0.89	7:151041967:G:A
Testis	sqtl	4.0e-16	-0.89	7:151050659:A:G
Esophagus Mucosa	eqtl	3.1e-15	+0.35	7:151051782:C:G
Thyroid	eqtl	3.2e-14	+0.31	7:151039289:TC:T
Breast Mammary Tissue	eqtl	3.1e-12	+0.95	7:151041967:G:A
Brain Cerebellar Hemisphere	sqtl	3.2e-11	-0.93	7:151050659:A:G
Testis	eqtl	4.5e-08	-0.24	7:151033133:G:A
Heart Atrial Appendage	eqtl	4.9e-08	-0.23	7:151028635:A:C
Brain Cerebellum	sqtl	7.2e-08	+0.89	7:151054979:T:C
Esophagus Muscularis	eqtl	8.6e-08	+0.21	7:151045898:G:A
Nerve Tibial	eqtl	3.6e-07	+0.18	7:151051782:C:G
Adipose Visceral Omentum	eqtl	8.2e-07	+0.56	7:151041967:G:A
Esophagus Gastroesophageal Junction	eqtl	2.5e-06	+0.26	7:151035376:G:A
Colon Transverse	eqtl	1.1e-05	+0.20	7:151030667:C:T
Colon Sigmoid	eqtl	1.4e-05	+0.22	7:151051782:C:G
Nerve Tibial	sqtl	1.7e-05	-0.44	7:151050659:A:G
Adrenal Gland	eqtl	2.1e-05	+0.30	7:151045898:G:A
Skin Not Sun Exposed Suprapubic	sqtl	2.3e-05	-0.48	7:151050659:A:G
Artery Tibial	eqtl	2.3e-05	+0.20	7:151051782:C:G
Brain Cerebellum	eqtl	4.0e-05	+0.24	7:151094165:C:T

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
82038	0.2689	77
82037	0.0087	3

Top tissues by expression

showing 100 of 287 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	97.27	gold quality
cerebellar hemisphere	UBERON:0002245	96.62	gold quality
cerebellar cortex	UBERON:0002129	96.40	gold quality
right testis	UBERON:0004534	93.28	gold quality
cerebellum	UBERON:0002037	93.18	gold quality
left testis	UBERON:0004533	92.90	gold quality
right frontal lobe	UBERON:0002810	92.05	gold quality
apex of heart	UBERON:0002098	91.69	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.56	gold quality
adenohypophysis	UBERON:0002196	91.42	gold quality
nucleus accumbens	UBERON:0001882	89.80	gold quality
pituitary gland	UBERON:0000007	89.29	gold quality
caudate nucleus	UBERON:0001873	88.83	gold quality
putamen	UBERON:0001874	88.17	gold quality
anterior cingulate cortex	UBERON:0009835	87.96	gold quality
cingulate cortex	UBERON:0003027	87.95	gold quality
testis	UBERON:0000473	87.90	gold quality
spinal cord	UBERON:0002240	87.57	gold quality
right uterine tube	UBERON:0001302	86.00	gold quality
amygdala	UBERON:0001876	85.91	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.74	gold quality
hypothalamus	UBERON:0001898	85.31	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.38	gold quality
body of uterus	UBERON:0009853	83.91	gold quality
endocervix	UBERON:0000458	83.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.97	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.82	gold quality
muscle layer of sigmoid colon	UBERON:0035805	82.61	gold quality
heart left ventricle	UBERON:0002084	82.47	gold quality
prefrontal cortex	UBERON:0000451	82.15	gold quality
central nervous system	UBERON:0001017	81.93	gold quality
brain	UBERON:0000955	81.76	gold quality
forebrain	UBERON:0001890	81.30	gold quality
cardiac ventricle	UBERON:0002082	81.22	gold quality
neocortex	UBERON:0001950	81.21	gold quality
gastrocnemius	UBERON:0001388	81.20	gold quality
lower esophagus	UBERON:0013473	81.11	gold quality
lower esophagus muscularis layer	UBERON:0035833	81.11	gold quality
ectocervix	UBERON:0012249	80.88	gold quality
lower esophagus mucosa	UBERON:0035834	80.63	gold quality
telencephalon	UBERON:0001893	80.59	gold quality
left ovary	UBERON:0002119	80.54	gold quality
right atrium auricular region	UBERON:0006631	80.48	gold quality
frontal cortex	UBERON:0001870	80.45	gold quality
left uterine tube	UBERON:0001303	80.44	gold quality
right ovary	UBERON:0002118	80.41	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	79.84	gold quality
cortical plate	UBERON:0005343	79.78	gold quality
tibial nerve	UBERON:0001323	79.43	gold quality
muscle of leg	UBERON:0001383	79.33	gold quality
cerebral cortex	UBERON:0000956	78.74	gold quality
hindlimb stylopod muscle	UBERON:0004252	78.28	gold quality
Ammon’s horn	UBERON:0001954	78.26	gold quality
stromal cell of endometrium	CL:0002255	78.10	gold quality
cardiac atrium	UBERON:0002081	78.10	gold quality
ganglionic eminence	UBERON:0004023	77.50	gold quality
heart	UBERON:0000948	76.99	gold quality
substantia nigra	UBERON:0002038	76.93	gold quality
right lobe of liver	UBERON:0001114	76.77	gold quality
ventricular zone	UBERON:0003053	76.41	gold quality
small intestine Peyer’s patch	UBERON:0003454	76.07	gold quality
left lobe of thyroid gland	UBERON:0001120	76.01	gold quality
body of stomach	UBERON:0001161	75.72	gold quality
mucosa of transverse colon	UBERON:0004991	75.71	gold quality
mucosa of stomach	UBERON:0001199	75.54	gold quality
skin of leg	UBERON:0001511	75.53	gold quality
transverse colon	UBERON:0001157	75.37	gold quality
sural nerve	UBERON:0015488	75.34	gold quality
esophagus	UBERON:0001043	75.13	gold quality
sigmoid colon	UBERON:0001159	74.78	gold quality
right lobe of thyroid gland	UBERON:0001119	74.61	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	74.58	gold quality
midbrain	UBERON:0001891	74.56	gold quality
omental fat pad	UBERON:0010414	74.54	gold quality
peritoneum	UBERON:0002358	74.48	gold quality
granulocyte	CL:0000094	74.25	gold quality
metanephros cortex	UBERON:0010533	74.19	gold quality
Brodmann (1909) area 10	UBERON:0013541	74.16	silver quality
upper lobe of left lung	UBERON:0008952	74.10	gold quality
skin of abdomen	UBERON:0001416	74.06	gold quality
ascending aorta	UBERON:0001496	73.75	gold quality
thyroid gland	UBERON:0002046	73.69	gold quality
temporal lobe	UBERON:0001871	73.53	gold quality
right adrenal gland	UBERON:0001233	73.46	gold quality
thoracic aorta	UBERON:0001515	73.44	gold quality
ovary	UBERON:0000992	73.42	gold quality
left coronary artery	UBERON:0001626	73.33	gold quality
right lung	UBERON:0002167	73.32	gold quality
left adrenal gland	UBERON:0001234	73.15	gold quality
left adrenal gland cortex	UBERON:0035825	73.14	gold quality
middle frontal gyrus	UBERON:0002702	73.10	gold quality
adipose tissue of abdominal region	UBERON:0007808	72.77	gold quality
right adrenal gland cortex	UBERON:0035827	72.50	gold quality
small intestine	UBERON:0002108	72.45	gold quality
coronary artery	UBERON:0001621	72.04	gold quality
upper lobe of lung	UBERON:0008948	71.99	gold quality
right coronary artery	UBERON:0001625	71.91	gold quality
muscle organ	UBERON:0001630	71.78	gold quality
vagina	UBERON:0000996	71.65	gold quality
anatomical system	UBERON:0000467	71.63	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.81

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 74 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Pituitary gland	tissue	17.5
Nucleus accumbens	tissue	11.3
Postcentral gyrus	tissue	10.1
Locus coeruleus	tissue	8.9
Hippocampus	tissue	8.6	medium
Choroid plexus	tissue	8.3
Retina	tissue	8.0
Corpus callosum	tissue	4.1
Testis	tissue	4.0	low
Vagina	tissue	4.0	not detected
Skeletal muscle	tissue	3.7	not detected
Cerebellum	tissue	3.1	medium
Putamen	tissue	3.0
Ventral forebrain	tissue	3.0
Olfactory bulb	tissue	3.0
Basal ganglia	tissue	2.9	medium
Midbrain	tissue	2.9
Periaqueductal gray	tissue	2.9
Cerebral cortex	tissue	2.8	medium
Spinal cord	tissue	2.8
Hippocampal formation	tissue	2.8
Insular cortex	tissue	2.8
Amygdala	tissue	2.7
Medulla oblongata	tissue	2.7
Superior colliculi	tissue	2.7
Substantia nigra	tissue	2.7
Thalamus	tissue	2.6
Retrosplenial and cingulate cortex	tissue	2.6
Septum	tissue	2.6
Somatosensory cortex	tissue	2.6
Retrosplenial cortex	tissue	2.6
Occipital cortex	tissue	2.6
Prefrontal cortex	tissue	2.5
Hypothalamus	tissue	2.5
Entorhinal cortex	tissue	2.5
Temporal cortex	tissue	2.5
Pons	tissue	2.4
Motor cortex	tissue	2.4
Endometrium 1	tissue	1.9	not detected
Epididymis	tissue	1.4	not detected
Skin 1	tissue	1.3	not detected
Lung	tissue	1.0	not detected
Duodenum	tissue	1.0	not detected
Stomach 1	tissue	0.9	not detected
Ovary	tissue	0.9	not detected
Adipose tissue	tissue	0.9	not detected
Lymph node	tissue	0.8	not detected
Smooth muscle	tissue	0.8	not detected
Tongue	tissue	0.8
Spleen	tissue	0.8	not detected
Small intestine	tissue	0.8	not detected
Adrenal gland	tissue	0.8	not detected
Fallopian tube	tissue	0.8	not detected
Heart muscle	tissue	0.7	not detected
Gallbladder	tissue	0.7	not detected
Rectum	tissue	0.6	not detected
Placenta	tissue	0.6	not detected
Prostate	tissue	0.6	not detected
Thymus	tissue	0.6
Bone marrow	tissue	0.6	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Flocculonodular lobe (18.5), Vermis (18.2), Parieto-temporal junction (white matter) (17.5), Temporal white matter (15.7), Lateral lemniscal nuclei (15.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, SMAD3

miRNA regulators (miRDB)

Targeting ASIC3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

8 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-5572	98.55	65.84	970
HSA-MIR-6819-5P	97.96	66.59	1071
HSA-MIR-450A-2-3P	97.91	67.56	1459
HSA-MIR-6737-5P	97.75	66.54	1044
HSA-MIR-6812-5P	97.56	65.39	1059
HSA-MIR-3117-3P	95.96	67.82	473
HSA-MIR-8083	95.93	67.55	694

Functional genomics

gnomAD constraint: pLI 4.65e-13, LOEUF 1.02, missense Z -0.355 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000349064 — one region, missense o/e 1.05.

Literature-anchored findings (GeneRIF, showing 32)

• role in modulating high-intensity pain stimuli (PMID:12060708)
• PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current (PMID:15317815)
• Diclofenac studies show ASIC3 is a significant contributor to cutaneous acid-induced pain. (PMID:15574747)
• the interaction of ASIC3 and CFTR may contribute to defective salt and fluid transepithelial transport in the cystic fibrotic pulmonary system (PMID:17012229)
• These results suggest that the ASIC3 may be involved in blood pressure regulation. (PMID:18854755)
• The biological features of ASIC3 is discussed and recent advances on the role of ASIC3 in the pathogenesis and treatment of arthritis pain, are summarized. (PMID:19885742)
• an independent association between an ASIC3 genetic polymorphism and insulin resistance in Taiwanese (PMID:20416288)
• Neither ASIC3 or ASIC1 knockout influences the development or maintenance of experimental neuropathic pain after nerve injury. (PMID:20693874)
• Used coincidentally by sensory neurons to detect lactic acidosis, ASIC3 (amiloride-sensitive cation channel 3) interacts with adenosine triphosphate (ATP) to detect muscle ischemia. (PMID:21092862)
• Atomic level characterization of the nonproton ligand-sensing domain of ASIC3 channels. (PMID:21586569)
• The results showed that there was a significant increase in the mean relative optical density of ASIC2 and ASIC3 but not ASIC1a in the lining epithelium and glandular tubes of gastric mucosa in patients with Henoch-Schonlein purpura. (PMID:22157923)
• A mechanism of induction of ASIC-3 expression relevant to AR was suggested by the finding that eosinophil peroxidase (EPO), acting via ERK1/2, induced the expression of ASIC-3 in epithelial cells. (PMID:22702502)
• The highly proton sensitive ASIC3 channels are predominantly distributed in peripheral sensory neurons, correlating with their roles in multimodal sensory perception, including nociception, mechanosensation, and chemosensation. (PMID:22778854)
• CAR and ASIC3 co-immunoprecipitate only when co-expressed with PSD-95. (PMID:22809504)
• ASIC3 is able to sense the extracellular pH in both directions and to dynamically adapt its activity between pH 5.0 and 8.0, playing a role in fine tuning neuronal membrane potentials and neuron sensitization in various pH environments. (PMID:22829666)
• Experiments with Asic3 inhibitors show that Asic3 inhibition leads to loss of pressure-induced vasodilation due to pressure detection failure rather than endothelial mechanisms. (PMID:22842475)
• Lignan from thyme possesses inhibitory effect on ASIC3 channel current. (PMID:22854960)
• Sea anemone peptide with uncommon beta-hairpin structure inhibits acid-sensing ion channel 3 (ASIC3) and reveals analgesic activity. (PMID:23801332)
• Blocking ASIC3 in interneurons from temporal lobe epilepsy patients decreased the frequency of action potential firing. (PMID:25476599)
• This study suggests that ASIC23may play a role as mediators of inflammatory pain and be involved in the pathogenesis of frozen shoulder. (PMID:26033064)
• These findings open new perspectives on the roles of ASIC3 in the absence of tissue pH variation, as well as on the contribution of those channels to lipid-mediated signaling. (PMID:26772186)
• Acidic pH resulted in an increase in ASIC-3 expressionin the discs of paitents with intervertebral disc degeneration. (PMID:27853274)
• Respiratory syncytial virus and measles virus infection upregulates ASICS3 expression in bronchial epithelial cells. (PMID:28187208)
• the data demonstrate a functional link between ASICs and [Ca(2+)]i/RhoA pathway, which contributes to the acidity-induced epithelial-mesenchymal transition. (PMID:28518134)
• The results show that acid-sensing ion channel 1, acid-sensing ion channel 2, and acid-sensing ion channel 3 are expressed in A549 cells at the messenger RNA and protein levels, and acid-sensing ion channel-like currents were elicited by extracellular acid stimuli. (PMID:28618956)
• The present review discusses the dual nature of ASIC3 in joint inflammation with possible mechanisms. (PMID:30035658)
• Heartburn sensation in nonerosive reflux disease: pattern of superficial sensory nerves expressing TRPV1 and epithelial cells expressing ASIC3 receptors. (PMID:33655767)
• ASIC1 and ASIC3 mediate cellular senescence of human nucleus pulposus mesenchymal stem cells during intervertebral disc degeneration. (PMID:33824228)
• TRPV1 Responses in the Cerebellum Lobules VI, VII, VIII Using Electroacupuncture Treatment for Chronic Pain and Depression Comorbidity in a Murine Model. (PMID:34068557)
• Upregulation of acid sensing ion channels is associated with esophageal hypersensitivity in GERD. (PMID:34918385)
• Lysophosphatidylcholine 16:0 mediates chronic joint pain associated to rheumatic diseases through acid-sensing ion channel 3. (PMID:35086123)
• Acid-sensing ion channel 3 is a new potential therapeutic target for the control of glioblastoma cancer stem cells growth. (PMID:39227705)

Cross-species orthologs

26 orthologs

Organism	Symbol	Gene ID
mus_musculus	Asic3	ENSMUSG00000038276
rattus_norvegicus	Asic3	ENSRNOG00000008380
drosophila_melanogaster	Nach	FBGN0024319
drosophila_melanogaster	ppk28	FBGN0030795
drosophila_melanogaster	ppk17	FBGN0032602
drosophila_melanogaster	ppk6	FBGN0034489
drosophila_melanogaster	ppk12	FBGN0034730
drosophila_melanogaster	ppk29	FBGN0034965
drosophila_melanogaster	ppk24	FBGN0039839
drosophila_melanogaster	ppk22	FBGN0051105
drosophila_melanogaster	ppk8	FBGN0052792
drosophila_melanogaster	ppk5	FBGN0053289
drosophila_melanogaster	ppk16	FBGN0065108
drosophila_melanogaster	ppk11	FBGN0065109
drosophila_melanogaster	ppk9	FBGN0085398
drosophila_melanogaster	ppk18	FBGN0265001
caenorhabditis_elegans		WBGENE00003168
caenorhabditis_elegans		WBGENE00003174
caenorhabditis_elegans		WBGENE00007518
caenorhabditis_elegans		WBGENE00009073
caenorhabditis_elegans		WBGENE00011891
caenorhabditis_elegans	delm-2	WBGENE00016063
caenorhabditis_elegans	acd-1	WBGENE00016064
caenorhabditis_elegans	acd-2	WBGENE00016066
caenorhabditis_elegans		WBGENE00016699
caenorhabditis_elegans		WBGENE00017879

Paralogs (8): ASIC4 (ENSG00000072182), ASIC2 (ENSG00000108684), ASIC1 (ENSG00000110881), SCNN1A (ENSG00000111319), SCNN1D (ENSG00000162572), SCNN1G (ENSG00000166828), SCNN1B (ENSG00000168447), ASIC5 (ENSG00000256394)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2159339) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 32 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal mechanical nociception	2
abnormal liver morphology	1
small liver	1
abnormal spleen morphology	1
enlarged spleen	1
abnormal sensory neuron morphology	1
decreased body length	1
cataract	1
abnormal nervous system electrophysiology	1
hyperresponsive to tactile stimuli	1
decreased thermal nociceptive threshold	1
abnormal rod electrophysiology	1
abnormal auditory brainstem response	1
abnormal gallbladder morphology	1
abnormal brainstem morphology	1
hyperalgesia	1
hyporesponsive to tactile stimuli	1
abnormal eye electrophysiology	1
abnormal retina apoptosis	1
retina ganglion cell degeneration	1
amacrine cell degeneration	1
disorganized retina inner nuclear layer	1
disorganized retina outer nuclear layer	1
retina outer nuclear layer degeneration	1
thin retina outer plexiform layer	1

+7 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Gallus gallus	Q1XA76	89.9%	Diamond
Opsanus tau	Q7T1N4	76.7%	Diamond
Danio rerio	Q708S7	72.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
FASTK	protein-coding	10922
ABCB8	protein-coding	11194
SLC4A2	protein-coding	6522
CDK5	protein-coding	1020
ATG9B	protein-coding	285973
NOS3	protein-coding	4846
KCNH2	protein-coding	3757
TMUB1	protein-coding	83590

Protein

Protein identifiers

Acid-sensing ion channel 3 — Q9UHC3 (reviewed: Q9UHC3)

Alternative names: Amiloride-sensitive cation channel 3, Neuronal amiloride-sensitive cation channel 3, Testis sodium channel 1

All UniProt accessions (6): A0A090N7X8, A0A090N8Q1, A0A090N8Z6, H7C4W0, H7C5N6, Q9UHC3

UniProt curated annotations — full annotation on UniProt →

Function. Forms pH-gated heterotrimeric sodium channels that act as postsynaptic excitatory receptors in the nervous system. Upon extracellular acidification, these channels generate a biphasic current with a fast inactivating and a slow sustained phase. ASIC3 is more sensitive to protons and gates between closed, open, and desensitized states faster than other ASICs. Displays high selectivity for sodium ions but can also permit the permeation of other cations. As a neuronal acid sensor, probably contributes to mechanoreception, acid nociception, and heat nociception. By forming heterotrimeric channels with ASIC2, generates a biphasic current with a fast inactivating and a slow sustained phase, which in sensory neurons is proposed to mediate the pain induced by acidosis that occurs in ischemic, damaged or inflamed tissues.

Subunit / interactions. Can form homotrimeric channels. Heterotrimer; forms functional heterotrimers producing channel with different properties. Forms heterotrimers with ASIC2; gives rise to a biphasic current with a sustained current which discriminates poorly between Na(+) and K(+). Interacts with STOM; inhibits ASIC3 acid-evoked current. Interacts with LIN7B (via PDZ domain); increases ASIC3 expression at the plasma membrane. Interacts with MAGI1 (via PDZ domain); probably regulates ASIC3. Interacts with GOPC (via PDZ domain); probably regulates ASIC3. Interacts with DLG4 (via PDZ domain); reduces ASIC3 expression at the plasma membrane.

Subcellular location. Cell membrane. Cytoplasm.

Tissue specificity. Expressed by sensory neurons. Strongly expressed in brain, spinal cord, lung, lymph nodes, kidney, pituitary, heart and testis.

Activity regulation. Inhibited by the diuretic drug amiloride. Inhibited by the diuretic drug triamterene. Potentiated by the vertebrate neuropeptide FF (NPFF) and the related FMRFamide. Specifically and reversibly inhibited by the a sea anemone toxin APETx2.

Domain organisation. The PDZ-binding motif mediates the interaction with PDZ-domain containing proteins including DLG4, GOPC, MAGI1 and LIN7A.

Similarity. Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC3 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9UHC3-1	1	yes
Q9UHC3-2	2, ASIC3b
Q9UHC3-3	3, ASIC3c
Q9UHC3-4	4, c

RefSeq proteins (3): NP_004760, NP_064717, NP_064718 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001873	ENaC	Family
IPR004724	ENaC_chordates	Family
IPR020903	ENaC_CS	Conserved_site

Pfam: PF00858

Catalyzed reactions (Rhea)

• K(+)(in) = K(+)(out) (RHEA:29463)
• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• Na(+)(in) = Na(+)(out) (RHEA:34963)

UniProt features (35 total): sequence conflict 8, disulfide bond 7, splice variant 4, mutagenesis site 4, topological domain 3, glycosylation site 2, transmembrane region 2, short sequence motif 2, chain 1, sequence variant 1, region of interest 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHC3-F1	83.15	0.60

Human Protein Atlas

Protein class: Predicted membrane proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nucleoplasm

Antibody reliability (HPA): IH enhanced · IF approved

Functional residue map

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

Disulfide bonds (7)

Type	Positions
Disulfide bond	92–186, 164–171, 282–370, 315–366, 319–364, 328–350, 330–342

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	398, 175

Mutagenesis-validated functional residues (4)

Position	Phenotype
528	no effect on interaction with lin7b. no effect on interaction with magi1. no effect on interaction with gopc.
529	loss of interaction with lin7b. loss of interaction with magi1.
530	loss of interaction with gopc. no effect on interaction with lin7b. no effect on interaction with magi1.
531	loss of interaction with lin7b. loss of interaction with magi1. loss of interaction with gopc.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-2672351	Stimuli-sensing channels	curated
R-HSA-983712	Ion channel transport	—
R-HSA-382551	Transport of small molecules	—

MSigDB gene sets: 106 (showing top): GOBP_MEMBRANE_DEPOLARIZATION, GOBP_SENSORY_PERCEPTION_OF_TEMPERATURE_STIMULUS, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_DETECTION_OF_MECHANICAL_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, SP3_Q3, GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, GOBP_MONOATOMIC_CATION_TRANSPORT, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A5, GOBP_DETECTION_OF_MECHANICAL_STIMULUS, GOBP_SENSORY_PERCEPTION_OF_PAIN, GOBP_DETECTION_OF_TEMPERATURE_STIMULUS, MODULE_379, GOBP_SENSORY_PERCEPTION_OF_TASTE, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS

GO Biological Process (7): sodium ion transmembrane transport (GO:0035725), sensory perception of sour taste (GO:0050915), detection of chemical stimulus involved in sensory perception of pain (GO:0050968), membrane depolarization (GO:0051899), monoatomic ion transport (GO:0006811), sodium ion transport (GO:0006814), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (7): sodium channel activity (GO:0005272), monoatomic ion-gated channel activity (GO:0022839), pH-gated sodium channel activity (GO:0160125), pH-gated monoatomic ion channel activity (GO:0160128), monoatomic cation channel activity (GO:0005261), protein binding (GO:0005515), ligand-gated sodium channel activity (GO:0015280)

GO Cellular Component (3): cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Ion channel transport	1
Transport of small molecules	1

GO top-level categories

25 GO namespaces:

Category	Terms
cellular anatomical structure	2
sodium ion transport	1
monoatomic cation transmembrane transport	1
sensory perception of taste	1
sensory perception of pain	1
detection of chemical stimulus involved in sensory perception	1
regulation of membrane potential	1
transport	1
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
monoatomic cation channel activity	1
sodium ion transmembrane transporter activity	1
ligand-gated channel activity	1
ligand-gated sodium channel activity	1
pH-gated monoatomic ion channel activity	1
ligand-gated monoatomic ion channel activity	1
monoatomic ion channel activity	1
monoatomic cation transmembrane transporter activity	1
binding	1
sodium channel activity	1
ligand-gated monoatomic cation channel activity	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
membrane depolarization	BP	direct assay
sensory perception of sour taste	BP	mutant phenotype
plasma membrane	CC	direct assay
pH-gated monoatomic ion channel activity	MF	direct assay
pH-gated sodium channel activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 642 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASIC3	TRPV1	Q8NER1	802
ASIC3	P2RX3	P56373	706
ASIC3	TRPA1	O75762	683
ASIC3	NGF	P01138	678
ASIC3	P2RX4	Q99571	676
ASIC3	SCN10A	Q9Y5Y9	636
ASIC3	PIEZO2	Q9H5I5	604
ASIC3	GPR65	Q8IYL9	591
ASIC3	TRPM8	Q7Z2W7	584
ASIC3	TAC1	P20366	579
ASIC3	SCN9A	Q15858	579
ASIC3	TRPV4	Q9HBA0	568
ASIC3	ASIC4	Q96FT7	566
ASIC3	TRPV2	Q9Y5S1	556
ASIC3	STOML3	Q8TAV4	553

IntAct

Human interaction partners of ASIC3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 126 partners by confidence:

Partner	Interaction type	MIscore	Records
SCRIB	direct interaction	0.610	5
DLG4	direct interaction	0.610	4
MAST2	direct interaction	0.610	3
SNX27	direct interaction	0.610	3
MPDZ	direct interaction	0.440	11
GRIP1	direct interaction	0.440	7
MAGI3	direct interaction	0.440	6
PATJ	direct interaction	0.440	6
GRIP2	direct interaction	0.440	5
MAGI1	direct interaction	0.440	5
PDZD2	direct interaction	0.440	5
MAGI2	direct interaction	0.440	4
PTPN13	direct interaction	0.440	4
DLG1	direct interaction	0.440	3
DLG2	direct interaction	0.440	3
IL16	direct interaction	0.440	3
LNX2	direct interaction	0.440	3
PARD3B	direct interaction	0.440	3
PDZD7	direct interaction	0.440	3
PDZK1	direct interaction	0.440	3
TJP1	direct interaction	0.440	3
USH1C	direct interaction	0.440	3
APBA2	direct interaction	0.440	2
APBA3	direct interaction	0.440	2
DLG5	direct interaction	0.440	2
GRID2IP	direct interaction	0.440	2
NHERF1	direct interaction	0.440	2
NHERF2	direct interaction	0.440	2
NHERF4	direct interaction	0.440	2
PARD3	direct interaction	0.440	2

BioGRID (14 interactions; top human partners by supporting records): GOPC (Affinity Capture-Western; 2 records), LIN7B (Affinity Capture-Western; 2 records), MAGI1 (Two-hybrid; 2 records), ASIC2 (Affinity Capture-Western), DLG4 (Affinity Capture-Western), PRKACA (Biochemical Activity), STOM (Affinity Capture-Western)

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 126 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	38.1×	7e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	36.2×	7e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	36.2×	7e-06
Long-term potentiation	5	31.7×	1e-05
Neurexins and neuroligins	12	31.5×	5e-13
Tight junction interactions	6	29.5×	3e-06
Assembly and cell surface presentation of NMDA receptors	8	27.1×	6e-08
Protein-protein interactions at synapses	7	24.8×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	15	73.9×	9e-23
protein localization to synapse	7	45.4×	1e-08
receptor clustering	7	37.0×	6e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	8	33.6×	1e-08
positive regulation of excitatory postsynaptic potential	6	26.8×	6e-06
establishment or maintenance of cell polarity	6	20.4×	2e-05
protein-containing complex assembly	13	12.5×	1e-08
regulation of small GTPase mediated signal transduction	10	12.2×	8e-07

Disease & clinical

Genetic variants

Variant evidence for ASIC3: 133 ClinVar records (1 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	107
Likely benign	14
Benign	2

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
146075	GRCh38/hg38 7p22.3-q36.3(chr7:54185-159282390)x1	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore ASIC3’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 836):

Position(s)	Effect	Δscore	Sites
7:151051037–151051038	acceptor_loss	1.0000	3
7:151051321	donor_loss	1.0000	2
7:151051325	donor_gain	1.0000
7:151051902–151051903	donor_loss	1.0000	3
7:151051981–151051982	acceptor_loss	1.0000	4
7:151052063–151052064	donor_loss	1.0000	5
7:151049420–151049421	donor_loss	0.9900	5
7:151051028	acceptor_gain	0.9900
7:151051037–151051038	acceptor_loss	0.9900	3
7:151051096–151051097	donor_loss	0.9900	5

AlphaMissense

829 missense substitutions predicted likely pathogenic (of 3,450 scored), across 248 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F189	8	0.946	0.995
D106	8	0.945	0.973
F176	8	0.945	0.993
F86	8	0.936	0.993
S449	8	0.879	0.995
F20	8	0.874	0.973
N407	8	0.865	0.983
D437	8	0.834	0.911
D458	8	0.756	0.839
C342	7	0.990	0.996
C92	7	0.988	0.995
C186	7	0.987	0.996
C330	7	0.980	0.993
C328	7	0.977	0.993
C164	7	0.968	0.987
C171	7	0.962	0.984
C282	7	0.959	0.979
C350	7	0.953	0.974
C315	7	0.949	0.977
N190	7	0.939	0.991

HPA cancer prognostics

RNA cancer specificity: Group enriched (Glioblastoma Multiforme, Testicular Germ Cell Tumor)

Disease associations

OMIM: gene MIM:611741 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST003476_6	Eyebrow thickness	7e-6

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5368 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 64,123 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL945	AMILORIDE	4	64,123

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: lgic — Acid-sensing (proton-gated) ion channels (ASICs)

Most potent curated ligand interactions (17 total), top 17:

Ligand	Action	Affinity	Parameter
APETx2	Channel blocker	7.2	pIC50
diminazene	Channel blocker	6.5	pIC50
A-317567	Channel blocker	5.99	pIC50
NS383	Channel blocker	5.7	pIC50
nafamostat	Channel blocker	5.6	pIC50
lysophosphatidylcholine	Partial agonist	5.4	pEC50
Ugr 9-1	Channel blocker	5.0	pIC50
amiloride	Channel blocker	4.8	pIC50
Gd3+	Channel blocker	4.4	pIC50
H+	Activator	4.3	pEC50
Zn2+	Channel blocker	4.2	pIC50
diclofenac	Channel blocker	4.0	pIC50
aspirin	Channel blocker	4.0	pIC50
salicylic acid	Channel blocker	3.6	pIC50
GMQ	Activator	3.0	pEC50
arcaine	Activator	2.9	pEC50
agmatine	Activator	2.0	pEC50

Binding affinities (BindingDB)

58 measured of 60 human assays (61 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL1800440	IC50	190 nM
CHEMBL1800430	IC50	224 nM
CHEMBL1800432	IC50	230 nM
CHEMBL1800436	IC50	230 nM
CHEMBL1800428	IC50	270 nM
CHEMBL1800433	IC50	310 nM
CHEMBL1800331	IC50	460 nM
3-amino-5-(biphenyl-3-yl)-N-(diaminomethylene)pyrazine-2-carboxamide	IC50	490 nM
3-amino-6-chloro-N-(diaminomethylene)-5-(naphthalen-2-ylamino)pyrazine-2-carboxamide	IC50	510 nM
CHEMBL1800437	IC50	510 nM
3-amino-N-(diaminomethylene)-5-(3-(thiophen-3-yl)phenyl)pyrazine-2-carboxamide	IC50	640 nM
CHEMBL1800431	IC50	680 nM
2-(3-(phenylethynyl)phenyl)pyridin-4-amine	IC50	1200 nM
6-(6-(2-methylpiperidin-1-yl)pyridin-2-yl)-1,2,3,4-tetrahydroisoquinoline	IC50	1700 nM
CHEMBL1800438	IC50	2500 nM
4-(3-(4-aminopyridin-2-yl)phenyl)but-3-yn-1-ol	IC50	2600 nM
CHEMBL1800427	IC50	2800 nM
6-(4-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline	IC50	3100 nM
6-(3,5-dichlorophenyl)-1,2,3,4-tetrahydroisoquinoline	IC50	3300 nM
CHEMBL1800334	IC50	3400 nM
6-methyl-N-(4-(6-(piperazin-1-yl)pyridin-3-yl)phenyl)pyridin-2-amine	IC50	3800 nM
CHEMBL1800439	IC50	4300 nM
CHEMBL1800333	IC50	4800 nM
2-phenyl-6-(pyridin-2-ylmethyl)pyridin-4-amine	IC50	5800 nM
CHEMBL1800332	IC50	6300 nM
2-phenylpyridin-4-amine	IC50	6900 nM
6-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline	IC50	7100 nM
N-(6-methylpyridin-2-yl)furo[2,3-c]pyridin-7-amine	IC50	9000 nM
4-amino-N-(4-chlorophenethyl)-2-propylquinoline-6-carboxamide	IC50	9600 nM
CHEMBL1800434	IC50	10200 nM
6-bromo-2-((5-methoxy-1H-indol-3-yl)methyl)-1,2,3,4-tetrahydroisoquinoline	IC50	10900 nM
6-(4-(4-methylpiperazin-1-yl)phenyl)-1,2,3,4-tetrahydroisoquinoline	IC50	14400 nM
2-methyl-4-(4-(6-methylpyridin-2-ylamino)phenyl)but-3-yn-2-ol	IC50	17000 nM
CHEMBL1800079	IC50	17100 nM
6-(2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-5-yl)-1,2,3,4-tetrahydroisoquinoline	IC50	19400 nM
4-(6-bromo-3,4-dihydroisoquinolin-2(1H)-yl)-2-methylquinoline	IC50	27600 nM
2-(3-chloro-5-methylphenyl)-1H-indole-5-carboximidamide	IC50	51000 nM
2-(3-bromo-5-fluorophenyl)-1H-indole-5-carboximidamide	IC50	59000 nM
2-(3,5-dibromophenyl)-1H-indole-5-carboximidamide	IC50	59000 nM
2-(3-(benzylamino)-5-chlorophenyl)-1H-indole-5-carboximidamide	IC50	77000 nM
2-(3-amino-5-chlorophenyl)-1H-indole-5-carboximidamide	IC50	95000 nM
benzo[b]thiophen-2-ylmethanamine	IC50	97000 nM
2-((5-methoxy-1H-indol-3-yl)methyl)-6-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline	IC50	103000 nM
2-(3-chloro-5-((phenylamino)methyl)phenyl)-1H-indole-5-carboximidamide	IC50	114000 nM
6-phenylpyrimidin-4-amine	IC50	130000 nM
2-(3,5-dichlorophenyl)-1H-indole-5-carboximidamide	IC50	133000 nM
2-(2,3,5-trichlorophenyl)-1H-indole-5-carboximidamide	IC50	135000 nM
(4-(1H-imidazol-4-yl)phenyl)methanamine	IC50	160000 nM
(3-Methoxy-pyridin-2-yl)-(6-methyl-pyridin-2-yl)-amine	IC50	190000 nM
2-(3,5-dichloro-4-cyanophenyl)-1H-indole-5-carboximidamide	IC50	272000 nM

ChEMBL bioactivities

30 potent at pChembl≥5 of 50 total, top 30 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.72	IC50	190	nM	CHEMBL1800440
6.66	IC50	220	nM	CHEMBL1800430
6.64	IC50	230	nM	CHEMBL1800432
6.64	IC50	230	nM	CHEMBL1800436
6.57	IC50	270	nM	CHEMBL1800428
6.51	IC50	310	nM	CHEMBL1800433
6.34	IC50	460	nM	CHEMBL1800331
6.31	IC50	490	nM	CHEMBL513153
6.29	IC50	510	nM	CHEMBL466668
6.29	IC50	510	nM	CHEMBL1800437
6.19	IC50	640	nM	CHEMBL467724
6.17	IC50	680	nM	CHEMBL1800431
5.92	IC50	1200	nM	CHEMBL1770740
5.77	IC50	1700	nM	CHEMBL1770745
5.60	IC50	2500	nM	CHEMBL1800438
5.58	IC50	2600	nM	CHEMBL1770739
5.55	IC50	2800	nM	CHEMBL1800427
5.51	IC50	3100	nM	CHEMBL1770750
5.48	IC50	3300	nM	CHEMBL1770744
5.47	IC50	3400	nM	CHEMBL1800334
5.42	IC50	3800	nM	CHEMBL1770752
5.37	IC50	4300	nM	CHEMBL1800439
5.36	IC50	4400	nM	AMILORIDE
5.32	IC50	4800	nM	CHEMBL1800333
5.24	IC50	5800	nM	CHEMBL1770741
5.20	IC50	6300	nM	CHEMBL1800332
5.16	IC50	6900	nM	CHEMBL1770738
5.15	IC50	7100	nM	CHEMBL1770746
5.05	IC50	9000	nM	CHEMBL1770730
5.02	IC50	9600	nM	CHEMBL1770753

PubChem BioAssay actives

30 with measured affinity, of 220 total; 30 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-[2-[2-(aminomethyl)-3-chloro-1-benzothiophen-6-yl]ethynyl]-N,N-dimethyl-2,3-dihydro-1H-inden-1-amine	607550: Inhibition of ASIC3 assessed as inhibition of peak current by electrophysiology method	ic50	0.1900	uM
[3-chloro-6-[2-(1,2,3,4-tetrahydroisoquinolin-7-yl)ethynyl]-1-benzothiophen-2-yl]methanamine	607550: Inhibition of ASIC3 assessed as inhibition of peak current by electrophysiology method	ic50	0.2200	uM
[3-chloro-6-[2-(2-ethyl-3,4-dihydro-1H-isoquinolin-7-yl)ethynyl]-1-benzothiophen-2-yl]methanamine	607550: Inhibition of ASIC3 assessed as inhibition of peak current by electrophysiology method	ic50	0.2300	uM
5-[2-[2-(aminomethyl)-3-chloro-1-benzothiophen-6-yl]ethynyl]-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-1-amine	607550: Inhibition of ASIC3 assessed as inhibition of peak current by electrophysiology method	ic50	0.2300	uM
[3-chloro-6-[2-(1,2-dimethyl-3,4-dihydro-1H-isoquinolin-7-yl)ethynyl]-1-benzothiophen-2-yl]methanamine	607550: Inhibition of ASIC3 assessed as inhibition of peak current by electrophysiology method	ic50	0.2700	uM
[3-chloro-6-[2-(2-propan-2-yl-3,4-dihydro-1H-isoquinolin-7-yl)ethynyl]-1-benzothiophen-2-yl]methanamine	607550: Inhibition of ASIC3 assessed as inhibition of peak current by electrophysiology method	ic50	0.3100	uM
6-[2-(2-methyl-1-propan-2-yl-3,4-dihydro-1H-isoquinolin-7-yl)ethynyl]naphthalene-2-carboximidamide	607550: Inhibition of ASIC3 assessed as inhibition of peak current by electrophysiology method	ic50	0.4600	uM
3-amino-N-(diaminomethylidene)-5-(3-phenylphenyl)pyrazine-2-carboxamide	352717: Inhibition of ASIC3 assessed as inhibition of peak current by patch clamp electrophysiology	ic50	0.4900	uM
3-amino-6-chloro-N-(diaminomethylidene)-5-(naphthalen-2-ylamino)pyrazine-2-carboxamide	352717: Inhibition of ASIC3 assessed as inhibition of peak current by patch clamp electrophysiology	ic50	0.5100	uM
5-[2-[2-(aminomethyl)-3-chloro-1-benzothiophen-6-yl]ethynyl]-N,N-diethyl-3,4-dihydro-2H-quinolin-1-amine	607550: Inhibition of ASIC3 assessed as inhibition of peak current by electrophysiology method	ic50	0.5100	uM
3-amino-N-(diaminomethylidene)-5-(3-thiophen-3-ylphenyl)pyrazine-2-carboxamide	352717: Inhibition of ASIC3 assessed as inhibition of peak current by patch clamp electrophysiology	ic50	0.6400	uM
[3-chloro-6-[2-(2-methyl-3,4-dihydro-1H-isoquinolin-7-yl)ethynyl]-1-benzothiophen-2-yl]methanamine	607550: Inhibition of ASIC3 assessed as inhibition of peak current by electrophysiology method	ic50	0.6800	uM
2-[3-(2-phenylethynyl)phenyl]pyridin-4-amine	594904: Inhibition of human ASIC3 expressed in HEK293 cells assessed as inhibition of acid-evoked current by manual patch-clamp electrophysiology assay	ic50	1.2000	uM
6-[6-(2-methylpiperidin-1-yl)-2-pyridinyl]-1,2,3,4-tetrahydroisoquinoline	594904: Inhibition of human ASIC3 expressed in HEK293 cells assessed as inhibition of acid-evoked current by manual patch-clamp electrophysiology assay	ic50	1.7000	uM
[3-chloro-6-[2-(5-pyrrolidin-1-yl-5,6,7,8-tetrahydronaphthalen-1-yl)ethynyl]-1-benzothiophen-2-yl]methanamine	607550: Inhibition of ASIC3 assessed as inhibition of peak current by electrophysiology method	ic50	2.5000	uM
4-[3-(4-amino-2-pyridinyl)phenyl]but-3-yn-1-ol	594904: Inhibition of human ASIC3 expressed in HEK293 cells assessed as inhibition of acid-evoked current by manual patch-clamp electrophysiology assay	ic50	2.6000	uM
[3-chloro-6-(2-phenylethynyl)-1-benzothiophen-2-yl]methanamine	607550: Inhibition of ASIC3 assessed as inhibition of peak current by electrophysiology method	ic50	2.8000	uM
6-[4-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydroisoquinoline	594904: Inhibition of human ASIC3 expressed in HEK293 cells assessed as inhibition of acid-evoked current by manual patch-clamp electrophysiology assay	ic50	3.1000	uM
6-(3,5-dichlorophenyl)-1,2,3,4-tetrahydroisoquinoline	594904: Inhibition of human ASIC3 expressed in HEK293 cells assessed as inhibition of acid-evoked current by manual patch-clamp electrophysiology assay	ic50	3.3000	uM
3-chloro-6-(2-phenylethynyl)-1-benzothiophene-2-carboximidamide	607550: Inhibition of ASIC3 assessed as inhibition of peak current by electrophysiology method	ic50	3.4000	uM
6-methyl-N-[4-(6-piperazin-1-yl-3-pyridinyl)phenyl]pyridin-2-amine	594904: Inhibition of human ASIC3 expressed in HEK293 cells assessed as inhibition of acid-evoked current by manual patch-clamp electrophysiology assay	ic50	3.8000	uM
1-[3-[2-[2-(aminomethyl)-3-chloro-1-benzothiophen-6-yl]ethynyl]phenyl]-N,N-dimethylethanamine	607550: Inhibition of ASIC3 assessed as inhibition of peak current by electrophysiology method	ic50	4.3000	uM
Amiloride	352717: Inhibition of ASIC3 assessed as inhibition of peak current by patch clamp electrophysiology	ic50	4.4000	uM
[6-(2-phenylethynyl)naphthalen-2-yl]methanamine	607550: Inhibition of ASIC3 assessed as inhibition of peak current by electrophysiology method	ic50	4.8000	uM
2-phenyl-6-(pyridin-2-ylmethyl)pyridin-4-amine	594904: Inhibition of human ASIC3 expressed in HEK293 cells assessed as inhibition of acid-evoked current by manual patch-clamp electrophysiology assay	ic50	5.8000	uM
6-(2-phenylethynyl)naphthalene-2-carboximidamide	607550: Inhibition of ASIC3 assessed as inhibition of peak current by electrophysiology method	ic50	6.3000	uM
2-phenylpyridin-4-amine	594904: Inhibition of human ASIC3 expressed in HEK293 cells assessed as inhibition of acid-evoked current by manual patch-clamp electrophysiology assay	ic50	6.9000	uM
6-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydroisoquinoline	594904: Inhibition of human ASIC3 expressed in HEK293 cells assessed as inhibition of acid-evoked current by manual patch-clamp electrophysiology assay	ic50	7.1000	uM
N-(6-methyl-2-pyridinyl)furo[2,3-c]pyridin-7-amine	594904: Inhibition of human ASIC3 expressed in HEK293 cells assessed as inhibition of acid-evoked current by manual patch-clamp electrophysiology assay	ic50	9.0000	uM
4-amino-N-[2-(4-chlorophenyl)ethyl]-2-propylquinoline-6-carboxamide	594904: Inhibition of human ASIC3 expressed in HEK293 cells assessed as inhibition of acid-evoked current by manual patch-clamp electrophysiology assay	ic50	9.6000	uM

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
tetramethylpyrazine	increases expression	1
butyraldehyde	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Sunitinib	increases expression	1
Arsenic	increases methylation	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Estradiol	decreases expression	1
Lovastatin	increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Gold Compounds	increases expression	1
Acrylamide	decreases expression	1
S-Nitrosoglutathione	increases expression	1

ChEMBL screening assays

14 unique, capped per target: 14 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1060810	Binding	Inhibition of ASIC3 at 1 uM by patch-clamp electrophysiology assay relative to baseline peak current	Amidine derived inhibitors of acid-sensing ion channel-3 (ASIC3). — *Bioorg Med Chem Lett*

Cellosaurus cell lines

2 cell lines: 1 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0XT	B’SYS CHO ASIC3	Spontaneously immortalized cell line	Female
CVCL_D1JC	PrecisION hASIC3-HEK	Transformed cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for ASIC3 across ~30M SureChEMBL compounds — explore on Sugi Predict.