CHRNA2 (cholinergic receptor nicotinic alpha 2 subunit)

Gene

• Entrez ID: 1135
• Gene name: Cholinergic receptor nicotinic alpha 2 subunit
• Gene symbol: CHRNA2
• Synonyms (NCBI Gene): -
• Chromosome: 8
• Chromosome location: 8p21.2
• Summary: Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels formed by a pentameric arrangement of alpha and beta subunits to create distinct muscle and neuronal receptors. Neuronal receptors are found throughout the peripheral and central ner

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs74772771	G>A,C	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant, 5 prime UTR variant
rs76140563	G>A	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, synonymous variant
rs77710085	C>T	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, missense variant
rs104894063	A>T	Pathogenic	Coding sequence variant, missense variant
rs138682847	C>T	Uncertain-significance, likely-benign, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant, 5 prime UTR variant
rs140350483	G>A,T	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs141721605	C>T	Likely-benign, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs144185168	T>A	Conflicting-interpretations-of-pathogenicity, likely-benign	5 prime UTR variant, coding sequence variant, missense variant
rs147530139	G>A	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs149142237	G>A	Benign-likely-benign, conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, synonymous variant
rs371858399	G>A	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs1018084204	G>A	Pathogenic	Coding sequence variant, missense variant
rs1554514507	T>A	Pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT025736	hsa-miR-7-5p	Microarray	17612493
MIRT891683	hsa-miR-105	CLIP-seq
MIRT891684	hsa-miR-1224-3p	CLIP-seq
MIRT891685	hsa-miR-1233	CLIP-seq
MIRT891686	hsa-miR-1260	CLIP-seq
MIRT891687	hsa-miR-1260b	CLIP-seq
MIRT891688	hsa-miR-1280	CLIP-seq
MIRT891689	hsa-miR-129-3p	CLIP-seq
MIRT891690	hsa-miR-1321	CLIP-seq
MIRT891691	hsa-miR-1827	CLIP-seq
MIRT891692	hsa-miR-2115	CLIP-seq
MIRT891693	hsa-miR-218	CLIP-seq
MIRT891694	hsa-miR-2467-5p	CLIP-seq
MIRT891695	hsa-miR-3127-3p	CLIP-seq
MIRT891696	hsa-miR-3161	CLIP-seq
MIRT891697	hsa-miR-3179	CLIP-seq
MIRT891698	hsa-miR-3180-5p	CLIP-seq
MIRT891699	hsa-miR-3194-3p	CLIP-seq
MIRT891700	hsa-miR-338-5p	CLIP-seq
MIRT891701	hsa-miR-3622a-3p	CLIP-seq
MIRT891702	hsa-miR-3622b-3p	CLIP-seq
MIRT891703	hsa-miR-3929	CLIP-seq
MIRT891704	hsa-miR-4419a	CLIP-seq
MIRT891705	hsa-miR-4419b	CLIP-seq
MIRT891706	hsa-miR-4475	CLIP-seq
MIRT891707	hsa-miR-4478	CLIP-seq
MIRT891708	hsa-miR-4510	CLIP-seq
MIRT891709	hsa-miR-4690-3p	CLIP-seq
MIRT891710	hsa-miR-4690-5p	CLIP-seq
MIRT891711	hsa-miR-4691-5p	CLIP-seq
MIRT891712	hsa-miR-4727-5p	CLIP-seq
MIRT891713	hsa-miR-4728-5p	CLIP-seq
MIRT891714	hsa-miR-4739	CLIP-seq
MIRT891715	hsa-miR-4756-5p	CLIP-seq
MIRT891716	hsa-miR-4769-3p	CLIP-seq
MIRT891717	hsa-miR-4779	CLIP-seq
MIRT891718	hsa-miR-515-5p	CLIP-seq
MIRT891719	hsa-miR-516a-3p	CLIP-seq
MIRT891720	hsa-miR-520a-5p	CLIP-seq
MIRT891721	hsa-miR-525-5p	CLIP-seq
MIRT891722	hsa-miR-532-3p	CLIP-seq
MIRT891723	hsa-miR-636	CLIP-seq
MIRT891724	hsa-miR-940	CLIP-seq
MIRT1546433	hsa-miR-1343	CLIP-seq
MIRT891684	hsa-miR-1224-3p	CLIP-seq
MIRT891686	hsa-miR-1260	CLIP-seq
MIRT891687	hsa-miR-1260b	CLIP-seq
MIRT891688	hsa-miR-1280	CLIP-seq
MIRT891690	hsa-miR-1321	CLIP-seq
MIRT1964281	hsa-miR-331-3p	CLIP-seq
MIRT891701	hsa-miR-3622a-3p	CLIP-seq
MIRT891702	hsa-miR-3622b-3p	CLIP-seq
MIRT1964282	hsa-miR-4286	CLIP-seq
MIRT891704	hsa-miR-4419a	CLIP-seq
MIRT891708	hsa-miR-4510	CLIP-seq
MIRT1964283	hsa-miR-4651	CLIP-seq
MIRT891713	hsa-miR-4728-5p	CLIP-seq
MIRT1964284	hsa-miR-4731-5p	CLIP-seq
MIRT891714	hsa-miR-4739	CLIP-seq
MIRT891715	hsa-miR-4756-5p	CLIP-seq
MIRT891718	hsa-miR-515-5p	CLIP-seq
MIRT891722	hsa-miR-532-3p	CLIP-seq
MIRT1964285	hsa-miR-608	CLIP-seq
MIRT1964286	hsa-miR-637	CLIP-seq
MIRT2200386	hsa-miR-1207-5p	CLIP-seq
MIRT1546433	hsa-miR-1343	CLIP-seq
MIRT891691	hsa-miR-1827	CLIP-seq
MIRT2200387	hsa-miR-2861	CLIP-seq
MIRT2200388	hsa-miR-3150a-3p	CLIP-seq
MIRT2200389	hsa-miR-3173-3p	CLIP-seq
MIRT2200390	hsa-miR-3175	CLIP-seq
MIRT891701	hsa-miR-3622a-3p	CLIP-seq
MIRT891702	hsa-miR-3622b-3p	CLIP-seq
MIRT2200391	hsa-miR-3622b-5p	CLIP-seq
MIRT2200392	hsa-miR-3918	CLIP-seq
MIRT2200393	hsa-miR-4316	CLIP-seq
MIRT2200394	hsa-miR-4512	CLIP-seq
MIRT2200395	hsa-miR-4533	CLIP-seq
MIRT2200396	hsa-miR-4640-5p	CLIP-seq
MIRT1964283	hsa-miR-4651	CLIP-seq
MIRT2200397	hsa-miR-4667-5p	CLIP-seq
MIRT2200398	hsa-miR-4700-5p	CLIP-seq
MIRT2200399	hsa-miR-4726-5p	CLIP-seq
MIRT891713	hsa-miR-4728-5p	CLIP-seq
MIRT2200400	hsa-miR-4736	CLIP-seq
MIRT2200401	hsa-miR-4747-5p	CLIP-seq
MIRT2200402	hsa-miR-4763-3p	CLIP-seq
MIRT891718	hsa-miR-515-5p	CLIP-seq
MIRT1964285	hsa-miR-608	CLIP-seq
MIRT2200403	hsa-miR-661	CLIP-seq
MIRT2200404	hsa-miR-939	CLIP-seq
MIRT891684	hsa-miR-1224-3p	CLIP-seq
MIRT891686	hsa-miR-1260	CLIP-seq
MIRT891687	hsa-miR-1260b	CLIP-seq
MIRT891688	hsa-miR-1280	CLIP-seq
MIRT891701	hsa-miR-3622a-3p	CLIP-seq
MIRT891702	hsa-miR-3622b-3p	CLIP-seq
MIRT891718	hsa-miR-515-5p	CLIP-seq
MIRT891722	hsa-miR-532-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004888	Function	Transmembrane signaling receptor activity	IEA
GO:0005216	Function	Monoatomic ion channel activity	IEA
GO:0005230	Function	Extracellular ligand-gated monoatomic ion channel activity	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0005892	Component	Acetylcholine-gated channel complex	IBA
GO:0005892	Component	Acetylcholine-gated channel complex	IDA	8906617, 24467848
GO:0005892	Component	Acetylcholine-gated channel complex	IEA
GO:0006811	Process	Monoatomic ion transport	IEA
GO:0006811	Process	Monoatomic ion transport	NAS	8906617
GO:0007165	Process	Signal transduction	IDA	8906617
GO:0007271	Process	Synaptic transmission, cholinergic	IBA
GO:0007274	Process	Neuromuscular synaptic transmission	IBA
GO:0015464	Function	Acetylcholine receptor activity	IDA	8906617
GO:0015464	Function	Acetylcholine receptor activity	IEA
GO:0016020	Component	Membrane	IEA
GO:0016020	Component	Membrane	NAS	8906617
GO:0022848	Function	Acetylcholine-gated monoatomic cation-selective channel activity	IBA
GO:0022848	Function	Acetylcholine-gated monoatomic cation-selective channel activity	IDA	8906617
GO:0022848	Function	Acetylcholine-gated monoatomic cation-selective channel activity	IEA
GO:0032991	Component	Protein-containing complex	IEA
GO:0034220	Process	Monoatomic ion transmembrane transport	IBA
GO:0034220	Process	Monoatomic ion transmembrane transport	IEA
GO:0034703	Component	Cation channel complex	IDA	24467848
GO:0035094	Process	Response to nicotine	IBA
GO:0043005	Component	Neuron projection	IBA
GO:0045171	Component	Intercellular bridge	IDA
GO:0045202	Component	Synapse	IBA
GO:0045202	Component	Synapse	IEA
GO:0045211	Component	Postsynaptic membrane	IEA
GO:0048167	Process	Regulation of synaptic plasticity	IEA
GO:0050997	Function	Quaternary ammonium group binding	IEA
GO:0051899	Process	Membrane depolarization	IBA
GO:0060078	Process	Regulation of postsynaptic membrane potential	IEA
GO:0060079	Process	Excitatory postsynaptic potential	IEA
GO:0071316	Process	Cellular response to nicotine	IEA
GO:0071944	Component	Cell periphery	IEA
GO:0095500	Process	Acetylcholine receptor signaling pathway	IBA
GO:0097060	Component	Synaptic membrane	IEA
GO:0098793	Component	Presynapse	IEA
GO:0098828	Process	Modulation of inhibitory postsynaptic potential	IEA
GO:0098878	Component	Neurotransmitter receptor complex	IDA	24467848
GO:0099171	Process	Presynaptic modulation of chemical synaptic transmission	IBA
GO:0120111	Component	Neuron projection cytoplasm	IEA
GO:1901363	Function	Heterocyclic compound binding	IEA
GO:1905144	Process	Response to acetylcholine	IEA

Other IDs

• MIM: 118502
• HGNC: 1956
• e!Ensembl: ENSG00000120903

Protein

• UniProt ID: Q15822
• Protein name: Neuronal acetylcholine receptor subunit alpha-2 (Nicotinic acetylcholine receptor subunit alpha-2)
• Protein function: Component of neuronal acetylcholine receptors (nAChRs) that function as pentameric, ligand-gated cation channels with high calcium permeability among other activities. nAChRs are excitatory neurotrasnmitter receptors formed by a collection of nA
• PDB: 5FJV
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02931	Neur_chan_LBD	59 → 265	Neurotransmitter-gated ion-channel ligand binding domain	Family
  PF02932	Neur_chan_memb	272 → 520	Neurotransmitter-gated ion-channel transmembrane region	Family

• Sequence:

  MGPSCPVFLSFTKLSLWWLLLTPAGGEEAKRPPPRAPGDPLSSPSPTALPQGGSHTETED
  RLFKHLFRGYNRWARPVPNTSDVVIVRFGLSIAQLIDVDEKNQMMTTNVWLKQEWSDYKL
  RWNPTDFGNITSLRVPSEMIWIPDIVLYNNADGEFAVTHMTKAHLFSTGTVHWVPPAIYK
  SSCSIDVTFFPFDQQNCKMKFGSWTYDKAKIDLEQMEQTVDLKDYWESGEWAIVNATGTY
  NSKKYDCCAEIYPDVTYAFVIRRLPLFYTINLIIPCLLISCLTVLVFYLPSDCGEKITLC
  ISVLLSLTVFLLLITEIIPSTSLVIPLIGEYLLFTMIFVTLSIVITVFVLNVHHRSPSTH
  TMPHWVRGALLGCVPRWLLMNRPPPPVELCHPLRLKLSPSYHWLESNVDAEEREVVVEEE
  DRWACAGHVAPSVGTLCSHGHLHSGASGPKAEALLQEGELLLSPHMQKALEGVHYIADHL
  RSEDADSSVKEDWKYVAMVIDRIFLWLFIIVCFLGTIGLFLPPFLAGMI

• Sequence length: 529

Pathways

KEGG:

Neuroactive ligand-receptor interaction

Reactome:

Highly calcium permeable postsynaptic nicotinic acetylcholine receptors
Highly calcium permeable nicotinic acetylcholine receptors

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Autosomal dominant nocturnal frontal lobe epilepsy 4	Pathogenic	rs104894063, rs1554514507	RCV000019056 RCV000625720	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autosomal dominant nocturnal frontal lobe epilepsy	Uncertain significance; Conflicting classifications of pathogenicity; Likely benign; Benign	ClinVar Disgenet, GWAS catalog Disgenet, GWAS catalog	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Benign familial infantile epilepsy	Uncertain significance	ClinVar ClinGen	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
BENIGN FAMILIAL INFANTILE SEIZURES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRNA2-related disorder	Likely benign; Conflicting classifications of pathogenicity; Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEPRESSIVE DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EPILEPSY, NOCTURNAL FRONTAL LOBE, 4	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EPILEPSY, NOCTURNAL FRONTAL LOBE, TYPE 4	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial sleep-related hypermotor epilepsy	Benign; Conflicting classifications of pathogenicity; Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GASTROESOPHAGEAL REFLUX DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intellectual disability	Conflicting classifications of pathogenicity; Likely benign	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
LUNG ADENOCARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG NEOPLASMS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MENTAL DEPRESSION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Myoclonic epilepsy	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Seizure	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Seizures, benign familial infantile, 6	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
SQUAMOUS CELL CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Alzheimer`s Disease	Alzheimer disease	GWASCAT_DG	29777097, 30617256		★☆☆☆☆ Found in Text Mining only
Anxiety	Anxiety Disorder	BEFREE	15048644		★☆☆☆☆ Found in Text Mining only
Anxiety Disorders	Anxiety Disorder	BEFREE	15048644		★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	GWASDB_DG	19426955, 20698975		★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	Pubtator	39596607	Associate	★☆☆☆☆ Found in Text Mining only
Autosomal Dominant Nocturnal Frontal Lobe Epilepsy	Nocturnal Epilepsy	ORPHANET_DG	16826524		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Autosomal dominant nocturnal frontal lobe epilepsy	Nocturnal Epilepsy	Orphanet			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Autosomal Dominant Nocturnal Frontal Lobe Epilepsy	Nocturnal Epilepsy	BEFREE	17602836, 17662253, 17900292, 18456869, 19058950, 21497487, 25770198, 25847220		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Autosomal Dominant Nocturnal Frontal Lobe Epilepsy	Nocturnal frontal lobe epilepsy	Pubtator	17900292, 25770198, 25847220	Associate	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Autosomal Dominant Nocturnal Frontal Lobe Epilepsy	Nocturnal Epilepsy	CLINVAR_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Bipolar Disorder	Bipolar Disorder	PSYGENET_DG	15996750, 19204725		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bipolar I disorder	Bipolar Disorder	BEFREE	15996750		★☆☆☆☆ Found in Text Mining only
Borderline Personality Disorder	Borderline personality disorder	BEFREE	15996750		★☆☆☆☆ Found in Text Mining only
Bronchopulmonary Dysplasia	Bronchopulmonary Dysplasia	BEFREE	15996750		★☆☆☆☆ Found in Text Mining only
Carcinoma Mucoepidermoid	Mucoepidermoid carcinoma	Pubtator	25823930	Associate	★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular disease	Pubtator	34040693	Associate	★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	PSYGENET_DG	19204725		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Epilepsies Partial	Partial epilepsy	Pubtator	16826524	Associate	★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	16826524, 19383498, 25847220		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	Pubtator	25847220, 37095367	Associate	★☆☆☆☆ Found in Text Mining only
Epilepsy Frontal Lobe	Frontal lobe epilepsy	Pubtator	25770198	Associate	★☆☆☆☆ Found in Text Mining only
Epilepsy Nocturnal Frontal Lobe Type 1	Nocturnal frontal lobe epilepsy	Pubtator	25847220	Associate	★☆☆☆☆ Found in Text Mining only
Epilepsy, Frontal Lobe	Epilepsy	LHGDN	12121305		★☆☆☆☆ Found in Text Mining only
Epilepsy, Frontal Lobe	Epilepsy	BEFREE	17602836, 18226955, 25770198		★☆☆☆☆ Found in Text Mining only
Epilepsy, Nocturnal Frontal Lobe, Type 4	Epilepsy	GENOMICS_ENGLAND_DG	16826524		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Epilepsy, Nocturnal Frontal Lobe, Type 4	Epilepsy	UNIPROT_DG	16826524, 25847220		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Epilepsy, Nocturnal Frontal Lobe, Type 4	Epilepsy	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Epilepsy, Nocturnal Frontal Lobe, Type 4	Epilepsy	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung Neoplasms	Lung Neoplasms	CTD_human_DG	28604730		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung Neoplasms	Lung neoplasms	Pubtator	29924316	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant neoplasm of lung	Lung Cancer	CTD_human_DG	28604730		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	PSYGENET_DG	19204725		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Metabolic Diseases	Metabolic Diseases	BEFREE	29785025		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	18588430, 29785025		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	GWASCAT_DG	26198764		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Seizures	Seizures	Pubtator	25847220	Associate	★☆☆☆☆ Found in Text Mining only
Seizures Febrile	Seizures	Pubtator	39596607	Associate	★☆☆☆☆ Found in Text Mining only
SEIZURES, BENIGN FAMILIAL INFANTILE, 6	Benign seizures	CLINVAR_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)