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ZACN

gene
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Also known as LGICZL2ZACZAC1

Summary

ZACN (zinc activated ion channel, HGNC:29504) is a protein-coding gene on chromosome 17q25.1, encoding Ligand-gated cation channel ZACN (Q401N2). Ligand-gated cation channel that allows the movement of sodium and potassium monoatomic cations across cell membranes when activated by zinc (Zn2+), copper (Cu2+), and changes in pH.

LGICZ1 is a zinc-activated ligand-gated ion channel that defines a new subgroup of the cysteine-loop superfamily of ligand-gated ion channels (Davies et al., 2003 [PubMed 12381728]).

Source: NCBI Gene 353174 — RefSeq curated summary.

At a glance

  • Clinical variants (ClinVar): 45 total
  • MANE Select transcript: NM_180990

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:29504
Approved symbolZACN
Namezinc activated ion channel
Location17q25.1
Locus typegene with protein product
StatusApproved
AliasesLGICZ, L2, ZAC, ZAC1
Ensembl geneENSG00000186919
Ensembl biotypeprotein_coding
OMIM610935
Entrez353174

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding

ENST00000334586, ENST00000421794, ENST00000425015, ENST00000524242, ENST00000590045, ENST00000591500

RefSeq mRNA: 1 — MANE Select: NM_180990 NM_180990

CCDS: CCDS11740

Canonical transcript exons

ENST00000334586 — 9 exons

ExonStartEnd
ENSE000013389617608025576080424
ENSE000013389627607988876079994
ENSE000034802527608246376082806
ENSE000035417997608154576081755
ENSE000035450517607918276079361
ENSE000035488867608188276082049
ENSE000035828847608127876081402
ENSE000036506897607943976079563
ENSE000036612137607970276079746

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 93.43.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 6.3635 / max 648.7927, expressed in 107 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
1628155.386177
1628160.977458

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
right hemisphere of cerebellumUBERON:001489093.43gold quality
right frontal lobeUBERON:000281092.80gold quality
lower esophagus mucosaUBERON:003583492.63gold quality
cerebellar hemisphereUBERON:000224592.49gold quality
cerebellar cortexUBERON:000212992.28gold quality
Brodmann (1909) area 9UBERON:001354092.10gold quality
anterior cingulate cortexUBERON:000983591.18gold quality
cortical plateUBERON:000534390.07gold quality
cerebellumUBERON:000203788.80gold quality
adenohypophysisUBERON:000219688.55gold quality
mucosa of transverse colonUBERON:000499188.53gold quality
prefrontal cortexUBERON:000045188.04gold quality
hypothalamusUBERON:000189887.77gold quality
apex of heartUBERON:000209886.61gold quality
amygdalaUBERON:000187686.29gold quality
C1 segment of cervical spinal cordUBERON:000646985.91gold quality
nucleus accumbensUBERON:000188285.62gold quality
putamenUBERON:000187485.19gold quality
pituitary glandUBERON:000000785.11gold quality
caudate nucleusUBERON:000187384.59gold quality
metanephros cortexUBERON:001053384.51gold quality
dorsolateral prefrontal cortexUBERON:000983484.00gold quality
right lobe of thyroid glandUBERON:000111983.95gold quality
ganglionic eminenceUBERON:000402383.92gold quality
left lobe of thyroid glandUBERON:000112083.50gold quality
right uterine tubeUBERON:000130283.30gold quality
neocortexUBERON:000195082.34gold quality
right lobe of liverUBERON:000111482.13gold quality
spinal cordUBERON:000224081.81gold quality
esophagus mucosaUBERON:000246981.36gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3no1.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

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

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-6739-5P99.8067.872806
HSA-MIR-6733-5P99.7467.942759
HSA-MIR-6737-3P98.9568.561577
HSA-MIR-7157-3P98.9568.701582
HSA-MIR-629-5P98.7868.721032
HSA-MIR-5008-3P98.7367.501433
HSA-MIR-5196-3P97.5765.98979
HSA-MIR-4793-5P96.8865.90872

Literature-anchored findings (GeneRIF, showing 2)

  • analysis of ligand-gated ion-channel receptor L2 in central nervous system (PMID:16083862)
  • Probing the molecular basis for signal transduction through the Zinc-Activated Channel (ZAC). (PMID:34560053)

Cross-species orthologs

3 orthologs

OrganismSymbolGene ID
ENSDARG00000111812
danio_rerioENSDARG00000115573
ENSDARG00000115752

Paralogs (45): GABRA3 (ENSG00000011677), GABRA1 (ENSG00000022355), CHRNA3 (ENSG00000080644), GABRP (ENSG00000094755), CHRNA4 (ENSG00000101204), GLRA2 (ENSG00000101958), GABRE (ENSG00000102287), CHRNE (ENSG00000108556), GABRA4 (ENSG00000109158), GLRB (ENSG00000109738), GABRR2 (ENSG00000111886), GABRG2 (ENSG00000113327), CHRNB4 (ENSG00000117971), CHRNA2 (ENSG00000120903), CHRNA10 (ENSG00000129749), CHRND (ENSG00000135902), CHRNA1 (ENSG00000138435), GLRA3 (ENSG00000145451), GABRA6 (ENSG00000145863), GABRB2 (ENSG00000145864), GLRA1 (ENSG00000145888), GABRR1 (ENSG00000146276), CHRNB3 (ENSG00000147432), CHRNA6 (ENSG00000147434), HTR3B (ENSG00000149305), GABRA2 (ENSG00000151834), CHRNB2 (ENSG00000160716), GABRG1 (ENSG00000163285), GABRB1 (ENSG00000163288), GABRB3 (ENSG00000166206), CHRFAM7A (ENSG00000166664), HTR3A (ENSG00000166736), CHRNA5 (ENSG00000169684), CHRNB1 (ENSG00000170175), CHRNA9 (ENSG00000174343), CHRNA7 (ENSG00000175344), HTR3C (ENSG00000178084), GABRG3 (ENSG00000182256), GABRR3 (ENSG00000183185), HTR3E (ENSG00000186038)

Protein

Protein identifiers

Ligand-gated cation channel ZACN — Q401N2 (reviewed: Q401N2)

Alternative names: Ligand-gated ion channel zinc-activated 1, Ligand-gated ion-channel receptor L2, Zinc-activated channel

All UniProt accessions (1): Q401N2

UniProt curated annotations — full annotation on UniProt →

Function. Ligand-gated cation channel that allows the movement of sodium and potassium monoatomic cations across cell membranes when activated by zinc (Zn2+), copper (Cu2+), and changes in pH. Could also transport cesium.

Subcellular location. Cell membrane.

Tissue specificity. Detected in pancreas, brain, liver, placenta, trachea, kidney, spinal cord, stomach and fetal brain. In the adult brain region expression is detected in the hippocampus, striatum, amygdala and thalamus.

Post-translational modifications. Glycosylated.

Activity regulation. Inhibited by the divalent cations magnesium and calcium.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the ligand-gated ion channel (TC 1.A.9) family.

Isoforms (3)

UniProt IDNamesCanonical?
Q401N2-11yes
Q401N2-22
Q401N2-33

RefSeq proteins (1): NP_851321* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR006201Neur_channelFamily
IPR006202Neur_chan_lig-bdDomain
IPR018000Neurotransmitter_ion_chnl_CSConserved_site
IPR036719Neuro-gated_channel_TM_sfHomologous_superfamily
IPR036734Neur_chan_lig-bd_sfHomologous_superfamily
IPR038050Neuro_actylchol_recHomologous_superfamily

Pfam: PF02931

Catalyzed reactions (Rhea), 2 shown:

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

UniProt features (23 total): topological domain 5, glycosylation site 4, splice variant 4, transmembrane region 4, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

9 structures.

PDBMethodResolution (Å)
9LEZELECTRON MICROSCOPY2.54
9LETELECTRON MICROSCOPY2.62
9LEUELECTRON MICROSCOPY2.63
8YX7ELECTRON MICROSCOPY2.8
8YX8ELECTRON MICROSCOPY2.8
9LEXELECTRON MICROSCOPY2.85
8YX6ELECTRON MICROSCOPY2.9
9LEYELECTRON MICROSCOPY2.97
9LEVELECTRON MICROSCOPY3.35

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q401N2-F178.090.44

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 (1): 157–171

Glycosylation sites (4): 41, 55, 99, 170

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 30 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_RESPONSE_TO_ZINC_ION, GCANCTGNY_MYOD_Q6, SCHLESINGER_METHYLATED_DE_NOVO_IN_CANCER, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_RESPONSE_TO_METAL_ION, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_TRANSPORTER_COMPLEX, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOMF_GATED_CHANNEL_ACTIVITY, GOMF_PASSIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_MONOATOMIC_CATION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_TRANSMEMBRANE_SIGNALING_RECEPTOR_ACTIVITY, GOMF_EXTRACELLULAR_LIGAND_GATED_MONOATOMIC_ION_CHANNEL_ACTIVITY

GO Biological Process (4): response to zinc ion (GO:0010043), monoatomic ion transmembrane transport (GO:0034220), monoatomic ion transport (GO:0006811), monoatomic cation transmembrane transport (GO:0098655)

GO Molecular Function (7): transmembrane signaling receptor activity (GO:0004888), extracellular ligand-gated monoatomic ion channel activity (GO:0005230), zinc ion binding (GO:0008270), ligand-gated monoatomic ion channel activity (GO:0015276), ligand-gated monoatomic cation channel activity (GO:0099094), pH-gated monoatomic ion channel activity (GO:0160128), monoatomic ion channel activity (GO:0005216)

GO Cellular Component (3): plasma membrane (GO:0005886), transmembrane transporter complex (GO:1902495), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
ligand-gated monoatomic ion channel activity3
response to metal ion1
monoatomic ion transport1
transmembrane transport1
transport1
monoatomic cation transport1
monoatomic ion transmembrane transport1
signaling receptor activity1
transition metal ion binding1
monoatomic ion channel activity1
ligand-gated channel activity1
monoatomic cation channel activity1
monoatomic ion transmembrane transporter activity1
channel activity1
membrane1
cell periphery1
membrane protein complex1
transporter complex1
cellular anatomical structure1

Protein interactions and networks

STRING

524 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
ZACNGALR2O43603819
ZACNEXOC7Q9UPT5791
ZACNCDHR4A6H8M9452
ZACNSPRYD7Q5W111440
ZACNAMZ2Q86W34406
ZACNZNF385CQ66K41400
ZACNABITRAMQ9NX38386
ZACNPNMA8AQ86V59384
ZACNHSDL1Q3SXM5383
ZACNROPN1BQ9BZX4378
ZACNFAM81BQ96LP2370
ZACNTMTC2Q8N394370
ZACNNHERF4Q86UT5358
ZACNPRAMEF2O60811356
ZACNSERAC1Q96JX3347

IntAct

4 interactions, top by confidence:

ABTypeScore
ZACNGPAA1psi-mi:“MI:0914”(association)0.530
ZACNFAM234Bpsi-mi:“MI:0914”(association)0.350
ZACNNEMP1psi-mi:“MI:0914”(association)0.350

BioGRID (170): KIAA1467 (Affinity Capture-MS), EMC1 (Affinity Capture-MS), HLA-A (Affinity Capture-MS), KIAA2013 (Affinity Capture-MS), SLC12A2 (Affinity Capture-MS), ALG9 (Affinity Capture-MS), ITGA2 (Affinity Capture-MS), MFAP3 (Affinity Capture-MS), FLVCR1 (Affinity Capture-MS), TMEM214 (Affinity Capture-MS), GPAA1 (Affinity Capture-MS), TMTC3 (Affinity Capture-MS), CCPG1 (Affinity Capture-MS), GJC1 (Affinity Capture-MS), RANBP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTW7, G7PWZ3, I6M4H4, O08852, O54766, O70174, O95838, P00545, P09483, P43021, P43681, P60852, Q02644, Q07104, Q15822, Q19AE6, Q28680, Q401N2, Q58Y75, Q5DID0, Q5IS52, Q5IS77, Q5IXF8, Q62005, Q6IE08, Q6PDE7, Q6QNU9, Q6R5J1, Q6R5P0, Q7TN88, Q7Z7M1, Q80ZD5, Q866Y9, Q8BGX3, Q8BXQ3, Q8C2S7, Q8CIP5, Q8IU80, Q8IZF5, Q8N967

Diamond homologs: Q401N2, Q866Y9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance37
Likely benign4
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1911 predictions. Top by Δscore:

VariantEffectΔscore
17:76072296:A:ACdonor_gain1.0000
17:76072297:C:CCdonor_gain1.0000
17:76075250:AGG:Adonor_loss1.0000
17:76075251:GGT:Gdonor_loss1.0000
17:76075252:G:GGdonor_gain1.0000
17:76075252:GTG:Gdonor_loss1.0000
17:76075253:T:Adonor_loss1.0000
17:76079559:ATGTG:Adonor_gain1.0000
17:76079561:GTG:Gdonor_gain1.0000
17:76079562:TG:Tdonor_gain1.0000
17:76079563:GG:Gdonor_gain1.0000
17:76079563:GGT:Gdonor_loss1.0000
17:76079564:G:Adonor_loss1.0000
17:76079564:G:GGdonor_gain1.0000
17:76079565:T:Gdonor_loss1.0000
17:76079995:G:GGdonor_gain1.0000
17:76080436:G:Tdonor_gain1.0000
17:76080449:GGT:Gdonor_gain1.0000
17:76081683:C:Gdonor_gain1.0000
17:76081751:GCTCA:Gdonor_gain1.0000
17:76081880:A:AGacceptor_gain1.0000
17:76081881:G:GGacceptor_gain1.0000
17:76072297:CT:Cdonor_gain0.9900
17:76072306:A:ACdonor_gain0.9900
17:76072307:C:CCdonor_gain0.9900
17:76072310:T:Adonor_gain0.9900
17:76072385:T:TAdonor_gain0.9900
17:76072386:C:Adonor_gain0.9900
17:76075247:GACAG:Gdonor_gain0.9900
17:76076622:C:CAacceptor_gain0.9900

AlphaMissense

2661 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
17:76079968:G:CW116C0.961
17:76079968:G:TW116C0.961
17:76080370:T:CF164L0.959
17:76080372:C:AF164L0.959
17:76080372:C:GF164L0.959
17:76081293:T:CF187S0.956
17:76079893:G:CW91C0.950
17:76079893:G:TW91C0.950
17:76081292:T:CF187L0.944
17:76081293:T:GF187C0.944
17:76081294:C:AF187L0.944
17:76081294:C:GF187L0.944
17:76080371:T:GF164C0.941
17:76081686:A:CS271R0.940
17:76081688:T:AS271R0.940
17:76081688:T:GS271R0.940
17:76079891:T:AW91R0.927
17:76079891:T:CW91R0.927
17:76079966:T:AW116R0.926
17:76079966:T:CW116R0.926
17:76081670:G:CK265N0.922
17:76081670:G:TK265N0.922
17:76079991:A:TE124V0.921
17:76080403:T:CF175L0.920
17:76080405:C:AF175L0.920
17:76080405:C:GF175L0.920
17:76080349:T:AC157S0.919
17:76080350:G:CC157S0.919
17:76080404:T:CF175S0.919
17:76081391:T:CF220L0.915

dbSNP variants (sampled 300 via entrez): RS1000579419 (17:76079848 G>A), RS1000607854 (17:76081563 G>A,T), RS1000650918 (17:76080643 A>G), RS1001156691 (17:76077516 C>A,G,T), RS1001201583 (17:76077970 G>GA,GC,GCGGAT,GT), RS1001523212 (17:76080226 G>A,C,T), RS1002050683 (17:76081195 C>T), RS1003378900 (17:76078344 T>A), RS1003541244 (17:76078050 T>G), RS1004011277 (17:76082924 G>A), RS1004369940 (17:76078765 A>G), RS1004718374 (17:76082398 C>T), RS1004920342 (17:76082103 G>A,C,T), RS1005207890 (17:76081191 T>A,C), RS1005950413 (17:76079051 G>C)

Disease associations

OMIM: gene MIM:610935 | disease phenotypes: MIM:619072

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder with seizures and brain atrophy (MONDO:0033658)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: lgic — ZAC

Most potent curated ligand interactions (6 total), top 6:

LigandActionAffinityParameter
H+Agonist5.6pEC50
TTFBAntagonist5.5pIC50
Cu2+Agonist5.4pEC50
tubocurarineAntagonist5.2pIC50
Zn2+Agonist3.7pEC50
Ca2+Antagonist2.03pIC50

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

ChemicalActions (top 5)PubMed papers
sotorasibaffects cotreatment, increases expression1
tris(1,3-dichloro-2-propyl)phosphatedecreases expression1
sodium arsenitedecreases expression1
CGP 52608affects binding, increases reaction1
abrineincreases expression1
licochalcone Bincreases expression1
trametinibaffects cotreatment, increases expression1
NVP-BKM120affects cotreatment, increases expression1
Benzo(a)pyrenedecreases methylation1
Tubocurarinedecreases activity1
Urethaneincreases expression1
Zincdecreases activity1
Okadaic Acidincreases expression1

Clinical trials (associated diseases)

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

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
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BioBTree
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Sources 75

This page pulls from 75 datasets indexed by BioBTree:

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