ASIC5

Summary

ASIC5 (acid sensing ion channel subunit family member 5, HGNC:17537) is a protein-coding gene on chromosome 4q32.1, encoding Bile acid-sensitive ion channel (Q9NY37). Forms bile acid-gated sodium channels and may play a role in bile acid-dependent absorption and secretion by epithelial cells of the bile ducts.

This gene belongs to the amiloride-sensitive Na+ channel and degenerin (NaC/DEG) family, members of which have been identified in many animal species ranging from the nematode to human. The amiloride-sensitive Na(+) channel encoded by this gene is primarily expressed in the small intestine, however, its exact function is not known.

Source: NCBI Gene 51802 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 95 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_017419

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17537
Approved symbol	ASIC5
Name	acid sensing ion channel subunit family member 5
Location	4q32.1
Locus type	gene with protein product
Status	Approved
Aliases	INAC, HINAC
Ensembl gene	ENSG00000256394
Ensembl biotype	protein_coding
OMIM	616693
Entrez	51802

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000537611

RefSeq mRNA: 1 — MANE Select: NM_017419 NM_017419

CCDS: CCDS3793

Canonical transcript exons

ENST00000537611 — 10 exons

Exon	Start	End
ENSE00000740201	155831824	155831915
ENSE00000856060	155829729	155830046
ENSE00001001790	155866187	155866277
ENSE00001081611	155836689	155836857
ENSE00002210343	155838813	155838869
ENSE00002228275	155854077	155854314
ENSE00002232540	155842207	155842354
ENSE00002259610	155843681	155843830
ENSE00002266776	155852191	155852316
ENSE00002306963	155863448	155863754

Expression profiles

Bgee: expression breadth broad, 17 present calls, max score 64.90.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0035 / max 1.9656, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54541	0.0035	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	64.90	silver quality
duodenum	UBERON:0002114	60.81	gold quality
jejunal mucosa	UBERON:0000399	58.78	silver quality
jejunum	UBERON:0002115	50.36	gold quality
upper leg skin	UBERON:0004262	46.41	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
middle temporal gyrus	UBERON:0002771	42.00	gold quality
colonic epithelium	UBERON:0000397	41.57	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
oviduct epithelium	UBERON:0004804	41.32	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
cartilage tissue	UBERON:0002418	40.06	gold quality
mammary duct	UBERON:0001765	39.98	gold quality
mucosa of sigmoid colon	UBERON:0004993	39.95	gold quality
deltoid	UBERON:0001476	39.83	gold quality
saphenous vein	UBERON:0007318	39.83	gold quality
parotid gland	UBERON:0001831	39.81	gold quality
oocyte	CL:0000023	39.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.64

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting ASIC5, 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-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-2681-3P	98.18	65.28	577
HSA-MIR-96-3P	97.47	68.03	839
HSA-MIR-625-3P	97.32	66.55	554

Literature-anchored findings (GeneRIF, showing 1)

• hBASIC shares further key features with its rat ortholog: it is blocked by extracellular divalent cations, is inhibited by micromolar concentrations of the diarylamidine diminazene, and activated by millimolar concentrations of flufenamic acid. (PMID:23842738)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Asic5	ENSMUSG00000028008
rattus_norvegicus	Asic5	ENSRNOG00000011842
drosophila_melanogaster	ppk	FBGN0020258
drosophila_melanogaster	rpk	FBGN0022981
drosophila_melanogaster	ppk26	FBGN0035785
caenorhabditis_elegans		WBGENE00020897

Paralogs (8): ASIC4 (ENSG00000072182), ASIC2 (ENSG00000108684), ASIC1 (ENSG00000110881), SCNN1A (ENSG00000111319), SCNN1D (ENSG00000162572), SCNN1G (ENSG00000166828), SCNN1B (ENSG00000168447), ASIC3 (ENSG00000213199)

Protein

Protein identifiers

Bile acid-sensitive ion channel — Q9NY37 (reviewed: Q9NY37)

Alternative names: Acid-sensing ion channel subunit family member 5, Amiloride-sensitive cation channel 5, intestinal, Human intestine Na(+) channel

All UniProt accessions (1): Q9NY37

UniProt curated annotations — full annotation on UniProt →

Function. Forms bile acid-gated sodium channels and may play a role in bile acid-dependent absorption and secretion by epithelial cells of the bile ducts. Displays high selectivity for sodium ions but can also permit the permeation of other cations. The gating could be indirect and the consequence of alterations of the membrane environment of the channel by bile acids. As a sodium channel of type II unipolar brush cells of the vestibulocerebellum, controlling the electrical activity of these cells, could play a role in motor coordination and balance.

Subunit / interactions. Forms homotrimeric channels.

Subcellular location. Apical cell membrane. Cell membrane.

Tissue specificity. Detected in small intestine, duodenum and jejunum. Detected at very low levels in testis and rectum.

Activity regulation. Inhibited by the diuretic drug amiloride.

Similarity. Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC5 subfamily.

RefSeq proteins (1): NP_059115* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001873	ENaC	Family

Pfam: PF00858

Catalyzed reactions (Rhea), 4 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)
• Na(+)(in) = Na(+)(out) (RHEA:34963)
• H(+)(in) = H(+)(out) (RHEA:34979)
• Li(+)(in) = Li(+)(out) (RHEA:78551)

UniProt features (24 total): glycosylation site 8, disulfide bond 6, topological domain 3, transmembrane region 2, mutagenesis site 2, chain 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9MKY	ELECTRON MICROSCOPY	3
9MLV	ELECTRON MICROSCOPY	3.4
9MKZ	ELECTRON MICROSCOPY	3.47

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NY37-F1	84.59	0.53

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 (6): 112–207, 185–192, 298–377, 315–373, 328–350, 330–342

Glycosylation sites (8): 178, 179, 306, 370, 405, 421, 147, 163

Mutagenesis-validated functional residues (2):

Position	Phenotype
443	slightly activates the channel.
443	activates the channel.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

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

MSigDB gene sets: 74 (showing top): chr4q32, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, CATRRAGC_UNKNOWN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, GOMF_PROTON_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_IMPORT_INTO_CELL, GOBP_NEURONAL_ACTION_POTENTIAL, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_SODIUM_ION_TRANSPORT, AP4_01, GOCC_APICAL_PART_OF_CELL, GOBP_REGULATION_OF_MEMBRANE_POTENTIAL, GOCC_PLASMA_MEMBRANE_REGION

GO Biological Process (7): neuronal action potential (GO:0019228), sodium ion transmembrane transport (GO:0035725), sodium ion import across plasma membrane (GO:0098719), monoatomic ion transport (GO:0006811), sodium ion transport (GO:0006814), monoatomic ion transmembrane transport (GO:0034220), proton transmembrane transport (GO:1902600)

GO Molecular Function (4): proton channel activity (GO:0015252), ligand-gated sodium channel activity (GO:0015280), bile acid-gated sodium channel activity (GO:0160228), sodium channel activity (GO:0005272)

GO Cellular Component (3): plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Ion channel transport	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monoatomic cation transmembrane transport	2
monoatomic cation channel activity	2
sodium channel activity	2
action potential	1
transmission of nerve impulse	1
sodium ion transport	1
sodium ion transmembrane transport	1
inorganic cation import across plasma membrane	1
transport	1
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
proton transmembrane transporter activity	1
ligand-gated monoatomic cation channel activity	1
sodium ion transmembrane transporter activity	1
membrane	1
cell periphery	1
apical part of cell	1
plasma membrane region	1
cellular anatomical structure	1

Protein interactions and networks

STRING

350 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASIC5	TAS2R60	P59551	368
ASIC5	GAK	O14976	350
ASIC5	TAS2R42	Q7RTR8	349
ASIC5	GPR22	Q99680	348
ASIC5	SPMIP5	Q8WW14	341
ASIC5	GPR142	Q7Z601	332
ASIC5	GPR171	O14626	318
ASIC5	ATOSA	Q32MH5	313
ASIC5	GLT1D1	Q96MS3	307
ASIC5	KCNK5	O95279	307
ASIC5	GPR174	Q9BXC1	307
ASIC5	TAS2R41	P59536	301
ASIC5	TAS2R1	Q9NYW7	296
ASIC5	LCN9	Q8WX39	291
ASIC5	SDR42E1	Q8WUS8	288

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ASIC5	BLVRA	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): BLVRA (Affinity Capture-MS), FBXO2 (Affinity Capture-MS), VPS13B (Affinity Capture-MS), USP33 (Affinity Capture-MS), CSGALNACT2 (Affinity Capture-MS), SHCBP1 (Affinity Capture-MS), TUBB7P (Affinity Capture-MS), ASIC5 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0ZSE6, A0ZT23, A4KX75, A5PLH4, A7MB71, F4IAL1, G0SDN0, O43173, P09534, P25656, P34389, P38566, P42838, P51578, P53740, P61644, P86091, Q09884, Q10351, Q17678, Q1MTQ5, Q25197, Q25410, Q2T9P5, Q3TT99, Q64663, Q64689, Q66KL4, Q6DE06, Q6ZXC8, Q7RTY8, Q86XS5, Q8BIK6, Q8IA41, Q8IA44, Q91VE2, Q94316, Q95JK4, Q96WW4, Q99572

Diamond homologs: O35240, P55926, P78348, Q10025, Q16515, Q1XA76, Q62962, Q6NXK8, Q6X1Y6, Q708S3, Q708S4, Q708S5, Q708S6, Q708S7, Q708S8, Q7T1N4, Q7TNS7, Q925H0, Q96FT7, Q9JHS6, Q9NY37, Q9R0W5, Q9R0Y1, Q9UHC3, Q25011, P24585, P24612, P34886, Q09274, Q17298, Q19038, O13262, P51169, Q9WU38, O13263, P37090, Q9W754, O01635

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	78
Likely benign	11
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
684614	NM_017419.3(ASIC5):c.680G>T (p.Arg227Ile)	Pathogenic
562985	GRCh37/hg19 4q31.3-32.1(chr4:154763131-158404825)x1	Likely pathogenic

SpliceAI

1789 predictions. Top by Δscore:

Variant	Effect	Δscore
4:155852320:CAATA:C	acceptor_gain	1.0000
4:155852324:A:C	acceptor_gain	1.0000
4:155830044:CTG:C	acceptor_gain	0.9900
4:155831916:C:CC	acceptor_gain	0.9900
4:155852324:A:AC	acceptor_gain	0.9900
4:155854267:C:CT	acceptor_gain	0.9900
4:155863648:CCCA:C	acceptor_gain	0.9900
4:155863649:CCA:C	acceptor_gain	0.9900
4:155863650:C:T	acceptor_gain	0.9900
4:155863650:CA:C	acceptor_gain	0.9900
4:155863767:CCCA:C	acceptor_gain	0.9900
4:155863769:C:CT	acceptor_gain	0.9900
4:155863770:A:AC	acceptor_gain	0.9900
4:155863770:A:C	acceptor_gain	0.9900
4:155831912:CTCC:C	acceptor_gain	0.9800
4:155843748:TGTGG:T	donor_gain	0.9800
4:155854148:T:TA	donor_gain	0.9800
4:155857947:T:C	acceptor_gain	0.9800
4:155863651:A:C	acceptor_gain	0.9800
4:155863764:T:TC	acceptor_gain	0.9800
4:155866181:ACTC:A	donor_loss	0.9800
4:155866182:CTC:C	donor_loss	0.9800
4:155866183:TCA:T	donor_loss	0.9800
4:155866184:CACCG:C	donor_loss	0.9800
4:155866185:A:T	donor_loss	0.9800
4:155866186:C:CG	donor_loss	0.9800
4:155866186:CCGTT:C	donor_gain	0.9800
4:155830047:C:CC	acceptor_gain	0.9700
4:155831914:CC:C	acceptor_gain	0.9700
4:155831915:CC:C	acceptor_gain	0.9700

AlphaMissense

3367 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:155830006:A:C	S456R	0.992
4:155830006:A:T	S456R	0.992
4:155830008:T:G	S456R	0.992
4:155842323:C:G	C298S	0.989
4:155842324:A:T	C298S	0.989
4:155836806:C:G	C373S	0.988
4:155836807:A:T	C373S	0.988
4:155842272:C:G	C315S	0.988
4:155842273:A:T	C315S	0.988
4:155838854:C:G	C342S	0.986
4:155838855:A:T	C342S	0.986
4:155852281:A:C	C207W	0.985
4:155836807:A:G	C373R	0.983
4:155863460:C:G	C112S	0.981
4:155863461:A:T	C112S	0.981
4:155863466:G:T	T110K	0.981
4:155842233:C:G	C328S	0.980
4:155842234:A:T	C328S	0.980
4:155852282:C:G	C207S	0.979
4:155852283:A:T	C207S	0.979
4:155863459:A:C	C112W	0.979
4:155863460:C:T	C112Y	0.979
4:155830022:A:G	L451P	0.975
4:155842324:A:G	C298R	0.975
4:155836807:A:C	C373G	0.974
4:155842227:C:G	C330S	0.974
4:155842228:A:T	C330S	0.974
4:155842273:A:G	C315R	0.974
4:155852283:A:G	C207R	0.974
4:155838855:A:G	C342R	0.973

dbSNP variants (sampled 300 via entrez): RS10001395 (4:155845683 G>A), RS1000154524 (4:155850446 G>A), RS1000157950 (4:155858615 A>G,T), RS1000220469 (4:155857261 C>T), RS1000261173 (4:155835188 A>G), RS1000286451 (4:155835182 A>G), RS1000411735 (4:155868103 T>G), RS1000415258 (4:155852273 A>C), RS1000510487 (4:155857197 C>A,T), RS1000527078 (4:155830899 TAA>T), RS1000596740 (4:155829793 T>A), RS1000619009 (4:155836360 T>C), RS1000626648 (4:155834078 T>A,G), RS1000773742 (4:155842070 C>A,G), RS1000856021 (4:155858384 A>G)

Disease associations

OMIM: gene MIM:616693 | disease phenotypes: MIM:614391

GenCC curated gene-disease

Mondo (1): pregnancy loss, recurrent, susceptibility to, 3 (MONDO:0013729)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002932_9	Manganese levels	6.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects expression, decreases reaction	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
CGP 52608	affects binding, increases reaction	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	decreases methylation	1
Lipopolysaccharides	increases expression, affects response to substance	1
Malathion	increases expression	1
Nickel	affects expression, decreases reaction	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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