CHRNA1 (cholinergic receptor nicotinic alpha 1 subunit)

Gene

• Entrez ID: 1134
• Gene name: Cholinergic receptor nicotinic alpha 1 subunit
• Gene symbol: CHRNA1
• Synonyms (NCBI Gene): ACHRA, ACHRD, CHRNA, CMS1A, CMS1B, CMS2A, FCCMS, SCCMS
• Disease Acronyms (UniProt): CMS1A, CMS1B, CMS2A
• Chromosome: 2
• Chromosome location: 2q31.1
• Summary: The muscle acetylcholine receptor consiststs of 5 subunits of 4 different types: 2 alpha subunits and 1 each of the beta, gamma, and delta subunits. This gene encodes an alpha subunit that plays a role in acetlycholine binding/channel gating. Alternativel

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs137852798	G>A,C,T	Uncertain-significance, pathogenic	Synonymous variant, coding sequence variant, missense variant
rs137852799	C>A,G,T	Pathogenic	Coding sequence variant, missense variant
rs137852800	G>A	Pathogenic	Coding sequence variant, missense variant
rs137852801	C>T	Pathogenic	Coding sequence variant, missense variant
rs137852802	C>A	Pathogenic	Coding sequence variant, missense variant
rs137852803	C>A,G,T	Likely-pathogenic, pathogenic	Coding sequence variant, missense variant
rs137852804	C>T	Pathogenic	Coding sequence variant, missense variant
rs137852805	A>C	Pathogenic	Coding sequence variant, missense variant
rs137852806	A>G	Pathogenic	Coding sequence variant, missense variant
rs137852807	C>G,T	Pathogenic	Coding sequence variant, missense variant
rs137852808	G>A,C	Pathogenic	Synonymous variant, coding sequence variant, missense variant
rs137852809	C>A,T	Uncertain-significance, pathogenic	Coding sequence variant, missense variant
rs141733086	G>T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs149292107	A>G,T	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs150638770	G>A,T	Uncertain-significance, likely-benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, missense variant, coding sequence variant
rs199470445	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs374391312	G>A,C	Pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs483353046	G>A,T	Pathogenic	Coding sequence variant, missense variant
rs545520806	G>A	Likely-pathogenic	Synonymous variant, coding sequence variant
rs750329103	G>A	Pathogenic	Coding sequence variant, stop gained
rs768407867	C>T	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant
rs886043372	C>T	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs1064793397	->C	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1064795046	C>T	Likely-pathogenic	Splice acceptor variant
rs1131691893	C>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1291364532	T>G	Likely-pathogenic	Coding sequence variant, missense variant
rs1553469070	C>G	Likely-pathogenic	Coding sequence variant, missense variant
rs1574007436	TT>-	Likely-pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT891681	hsa-miR-3646	CLIP-seq
MIRT891682	hsa-miR-875-3p	CLIP-seq
MIRT2200384	hsa-miR-3922-5p	CLIP-seq
MIRT2200385	hsa-miR-4753-5p	CLIP-seq
MIRT2447005	hsa-miR-3194-3p	CLIP-seq
MIRT2447006	hsa-miR-4490	CLIP-seq
MIRT2447007	hsa-miR-4774-5p	CLIP-seq
MIRT2447008	hsa-miR-767-3p	CLIP-seq
MIRT2447009	hsa-miR-938	CLIP-seq
MIRT2447010	hsa-miR-942	CLIP-seq
MIRT2447005	hsa-miR-3194-3p	CLIP-seq
MIRT2447006	hsa-miR-4490	CLIP-seq
MIRT2447007	hsa-miR-4774-5p	CLIP-seq
MIRT2447008	hsa-miR-767-3p	CLIP-seq
MIRT2447009	hsa-miR-938	CLIP-seq
MIRT2447010	hsa-miR-942	CLIP-seq
MIRT2447005	hsa-miR-3194-3p	CLIP-seq
MIRT2447006	hsa-miR-4490	CLIP-seq
MIRT2447007	hsa-miR-4774-5p	CLIP-seq
MIRT2447008	hsa-miR-767-3p	CLIP-seq
MIRT2447009	hsa-miR-938	CLIP-seq
MIRT2447010	hsa-miR-942	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
AIRE	Unknown	17687331

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003009	Process	Skeletal muscle contraction	IMP	8872460
GO:0005216	Function	Ion channel activity	TAS	6688857
GO:0005886	Component	Plasma membrane	IDA
GO:0005886	Component	Plasma membrane	ISS	8872460
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	IBA	21873635
GO:0005892	Component	Acetylcholine-gated channel complex	ISS	8872460
GO:0006812	Process	Cation transport	IEA
GO:0007165	Process	Signal transduction	IBA	21873635
GO:0007268	Process	Chemical synaptic transmission	IBA	21873635
GO:0007271	Process	Synaptic transmission, cholinergic	IEA
GO:0007274	Process	Neuromuscular synaptic transmission	IMP	9221765
GO:0007528	Process	Neuromuscular junction development	IMP	9221765
GO:0009986	Component	Cell surface	IDA	12928480
GO:0015464	Function	Acetylcholine receptor activity	ISS	8872460
GO:0019228	Process	Neuronal action potential	IMP	8872460
GO:0022848	Function	Acetylcholine-gated cation-selective channel activity	IMP	9221765
GO:0022848	Function	Acetylcholine-gated cation-selective channel activity	ISS	8872460
GO:0030594	Function	Neurotransmitter receptor activity	IBA	21873635
GO:0031594	Component	Neuromuscular junction	IDA	9221765
GO:0031594	Component	Neuromuscular junction	IMP	9221765
GO:0031594	Component	Neuromuscular junction	ISS	8872460
GO:0034220	Process	Ion transmembrane transport	IBA	21873635
GO:0042166	Function	Acetylcholine binding	ISS	8872460
GO:0042391	Process	Regulation of membrane potential	IBA	21873635
GO:0042391	Process	Regulation of membrane potential	IMP	8872460, 9221765
GO:0043005	Component	Neuron projection	IBA	21873635
GO:0045202	Component	Synapse	IBA	21873635
GO:0045211	Component	Postsynaptic membrane	NAS	18252226
GO:0046716	Process	Muscle cell cellular homeostasis	IMP	8872460
GO:0048630	Process	Skeletal muscle tissue growth	IMP	18252226
GO:0050877	Process	Nervous system process	IBA	21873635
GO:0050881	Process	Musculoskeletal movement	IMP	18252226
GO:0050905	Process	Neuromuscular process	IMP	9546329
GO:0060079	Process	Excitatory postsynaptic potential	IEA
GO:0070050	Process	Neuron cellular homeostasis	IMP	8872460
GO:0099060	Component	Integral component of postsynaptic specialization membrane	IEA
GO:1904315	Function	Transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential	IDA	9221765
GO:1904315	Function	Transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential	IMP	9221765

Other IDs

• MIM: 100690
• HGNC: 1955
• e!Ensembl: ENSG00000138435

Protein

• UniProt ID: P02708
• Protein name: Acetylcholine receptor subunit alpha
• Protein function: [Isoform 1]: Upon acetylcholine binding, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. ; [
• PDB: 4ZJS, 5HBT
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02931	Neur_chan_LBD	24 → 79	Neurotransmitter-gated ion-channel ligand binding domain	Family
  PF02931	Neur_chan_LBD	97 → 256	Neurotransmitter-gated ion-channel ligand binding domain	Family
  PF02932	Neur_chan_memb	263 → 403	Neurotransmitter-gated ion-channel transmembrane region	Family
  PF02932	Neur_chan_memb	394 → 471	Neurotransmitter-gated ion-channel transmembrane region	Family

• Tissue specificity: TISSUE SPECIFICITY: Isoform 1 is only expressed in skeletal muscle. Isoform 2 is constitutively expressed in skeletal muscle, brain, heart, kidney, liver, lung and thymus.
• Sequence:

  MEPWPLLLLFSLCSAGLVLGSEHETRLVAKLFKDYSSVVRPVEDHRQVVEVTVGLQLIQL
  INVDEVNQIVTTNVRLKQGDMVDLPRPSCVTLGVPLFSHLQNEQWVDYNLKWNPDDYGGV
  KKIHIPSEKIWRPDLVLYNNADGDFAIVKFTKVLLQYTGHITWTPPAIFKSYCEIIVTHF
  PFDEQNCSMKLGTWTYDGSVVAINPESDQPDLSNFMESGEWVIKESRGWKHSVTYSCCPD
  TPYLDITYHFVMQRLPLYFIVNVIIPCLLFSFLTGLVFYLPTDSGEKMTLSISVLLSLTV
  FLLVIVELIPSTSSAVPLIGKYMLFTMVFVIASIIITVIVINTHHRSPSTHVMPNWVRKV
  FIDTIPNIMFFSTMKRPSREKQDKKIFTEDIDISDISGKPGPPPMGFHSPLIKHPEVKSA
  IEGIKYIAETMKSDQESNNAAAEWKYVAMVMDHILLGVFMLVCIIGTLAVFAGRLIELNQ
  QG

• Sequence length: 482

Pathways

KEGG:

Virion - Ebolavirus, Lyssavirus and Morbillivirus
Neuroactive ligand-receptor interaction

Reactome:

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

Associated diseases

Causal
Disease term	Disease name	dbSNP ID	References
Akinesia	Akinesia	rs606231129, rs606231131, rs606231132, rs118203995, rs606231133, rs104894299, rs104894300, rs786200904, rs786200905, rs104894294, rs121909254, rs121909255, rs121909256, rs150376433, rs863223335, rs751889864, rs559933584, rs761899995, rs797045528, rs551423795, rs886037842, rs560525099, rs775583136, rs1349476281, rs794727884, rs1479498379, rs1555142142, rs1558010146, rs1558003446, rs1554757237, rs770987150, rs768892432, rs1558008455, rs1560224831, rs1558005340, rs747595523, rs1567568217, rs774070092, rs776532930, rs765096923, rs1560200925, rs201947904, rs1595903667, rs376573993, rs778172294, rs759488854, rs761584017, rs769850502
Arthrogryposis multiplex congenita	Arthrogryposis	rs1586285494, rs80358233, rs137853305, rs1559154278, rs398124167, rs398124172, rs587780399, rs786204576, rs786204430, rs769345284, rs749355583, rs793888524, rs793888525, rs878854368, rs555445835, rs758105619, rs886041851, rs794727136, rs755239192, rs760715690, rs773952935, rs112610938, rs1057516676, rs1057516996, rs780022652, rs1057517399, rs1057517360, rs1057518353, rs1057517977, rs1064796311, rs779232987, rs775997446, rs1064797093, rs1064797094, rs1064797095, rs755500591, rs754272530, rs758247804, rs200731870, rs747179265, rs1553740233, rs776569219, rs375628303, rs775631800, rs781667543, rs1553548666, rs928945364, rs763364977, rs1458048713, rs1553883480, rs1472403020, rs1336053002, rs202048855, rs1197561990, rs755531536, rs1554112524, rs762133567, rs1553555882, rs934111355, rs1255744452, rs1366269616, rs1555734932, rs1553548207, rs752582527, rs1257495033, rs113525641, rs755863625, rs374929094, rs539819851, rs1366853918, rs1218073575, rs1553537512, rs1553552384, rs747564597, rs776059611, rs756726488, rs1357811155, rs1553939600, rs772009599, rs1255445731, rs1011425121, rs1553561697, rs1553551748, rs1553552413, rs760935667, rs1553603400, rs1302373559, rs1389892619, rs1553710982, rs757157808, rs1180339426, rs761964375, rs1235589246, rs1443738549, rs1553934586, rs1553934597, rs1553603437, rs749452641, rs1553904694, rs754369875, rs112517981, rs774495973, rs1428597732, rs746999970, rs113091511, rs1553603958, rs1553469502, rs770797137, rs1553608621, rs1159756073, rs776167256, rs778593702, rs1553601066, rs1553689774, rs760768475, rs1559296376, rs201636991, rs1559039815, rs748922882, rs772366030, rs1207534366, rs1259297878, rs762780413, rs1559360386, rs1559940778, rs760200697, rs1344099907, rs750900690, rs1559168230, rs746177326, rs761067911, rs1323364980, rs537560378, rs1319778592, rs1340063197, rs1577833924, rs750585238, rs1600470099, rs1575714905, rs1576203853, rs779909544, rs760124743, rs2096362304, rs1212374733, rs1490309743, rs767709270, rs1374971806, rs2096491549, rs2097886912, rs2099021112, rs2097758221, rs1474341248, rs925947627
Autism	Autistic Disorder	rs121964908, rs62643608, rs181327458, rs797046134, rs869312704, rs1555013332, rs876657679, rs1057518999, rs1057518658, rs771827120, rs1555187899, rs773080572, rs753871454, rs1684130791, rs1684180699, rs1553510219, rs1684182454, rs1559060428, rs1553510677, rs1576352885, rs1574152522, rs1574152672, rs1696658542
Myasthenic syndrome	Myasthenic Syndrome, Congenital, Fast-Channel, Postsynaptic congenital myasthenic syndromes, Myasthenic syndrome, congenital, postsynaptic slow-channel, MYASTHENIC SYNDROME, CONGENITAL, 1A, SLOW-CHANNEL, MYASTHENIC SYNDROME, CONGENITAL, 1B, FAST-CHANNEL	rs606231128, rs606231129, rs606231130, rs606231131, rs606231132, rs118203994, rs118203995, rs863223277, rs606231133, rs121908547, rs121908553, rs121908557, rs104893733, rs104893734, rs121908922, rs769982050, rs759911990, rs121908923, rs121908924, rs1384843815, rs104893735, rs104894299, rs104894300, rs786200904, rs104894301, rs786200905, rs104894294, rs121909254, rs121909255, rs879255561, rs121912821, rs75466054, rs121912822, rs199476396, rs121909510, rs121909511, rs121909514, rs121909512, rs121909513, rs879255562, rs879253722, rs879253723, rs28999110, rs886037628, rs753828284, rs121909515, rs121909516, rs121909517, rs879255563, rs121909502, rs121909503, rs121909504, rs879255564, rs121909505, rs121909508, rs137852810, rs137852811, rs137852798, rs137852800, rs137852801, rs137852802, rs137852804, rs137852805, rs137852806, rs137852807, rs137852808, rs2105350984, rs374391312, rs201322234, rs1671535986, rs1574066341, rs1574058076, rs1574066599, rs387906803, rs387907243, rs376039938, rs397515321, rs387907244, rs387907245, rs377767449, rs193919341, rs398122830, rs397515450, rs587777298, rs587777299, rs587777781, rs730882050, rs730882123, rs730882051, rs786204773, rs786205885, rs794727884, rs761899995, rs797045040, rs797045528, rs200783529, rs551423795, rs756877019, rs864309662, rs864309663, rs756623659, rs773526895, rs763258280, rs762368691, rs1555794286, rs886037842, rs147656110, rs886039767, rs886039768, rs770045897, rs763281993, rs755236236, rs886043239, rs764497513, rs1057517666, rs370019023, rs769114543, rs922548333, rs139574075, rs767507908, rs759226183, rs1057523690, rs55868108, rs755303686, rs1085307792, rs775583136, rs376808313, rs1131691986, rs776927709, rs1279554995, rs1553850100, rs1156634884, rs1553390600, rs1349476281, rs1555546465, rs199875082, rs200761047, rs1553360075, rs971863968, rs369251527, rs372760913, rs1479498379, rs1555547003, rs1423995073, rs1555546315, rs1555546765, rs201033437, rs1430654625, rs1554943789, rs1316112168, rs781689096, rs1553354962, rs753545038, rs1011196447, rs1553389102, rs185829251, rs28929768, rs1555546096, rs932032926, rs1553846331, rs756015202, rs1555142142, rs1436090495, rs1553352792, rs145356495, rs770987150, rs768892432, rs1557700705, rs1172015222, rs1558749457, rs1361739547, rs775517492, rs1558773839, rs1559510978, rs771879602, rs777102590, rs1567635954, rs1407243713, rs1567638401, rs756675414, rs781908532, rs1306593300, rs1559519107, rs199470447, rs1557721600, rs1558762013, rs746220436, rs1565527239, rs1565527137, rs1565527140, rs1567636493, rs1558761046, rs143766249, rs1447564693, rs757060689, rs1309292778, rs1575460231, rs1570193864, rs1570195582, rs1239736447, rs779488471, rs201947904, rs1597612665, rs1597613302, rs781774131, rs760022829, rs1597619440, rs1597621353, rs1187421976, rs977512223, rs1239393228, rs762875734, rs148092524, rs1269227357, rs1208462125, rs1597622118, rs1597749210, rs1570190059, rs1574007436, rs781974501, rs748639083, rs1597613479, rs1597621396, rs1570242061, rs149020371, rs1595903667, rs1597618787, rs1600807788, rs1579484850, rs1577153029, rs779816027, rs1598406692, rs1577153124, rs778172294, rs1590576560, rs753652169, rs1595902947, rs1369980189, rs762345055, rs1675812434, rs375268742, rs1671813157, rs759488854, rs761584017, rs1969834618, rs1969839736, rs1255916068, rs1597618854, rs1969973509, rs1908994498, rs1320610655, rs373710822	9158151, 15079006, 9221765, 7619526, 8872460, 16685696, 12588888, 10195214
Developmental delay	Gross motor development delay	rs28941770, rs199469464, rs281865469, rs143747297, rs398123009, rs587777428, rs786205133, rs606231459, rs797044854, rs797045027, rs864309504, rs878853160, rs886039902, rs886042046, rs886041291, rs886041382, rs1057518991, rs1057518699, rs753254213, rs748294403, rs762552974, rs1135401795, rs1553121073, rs1553122926, rs1364690005, rs1554086554, rs1554210415, rs1554168326, rs1554776342, rs1553873247, rs1567860112, rs779009256, rs1557447255, rs1564568350, rs780011005, rs1597464953, rs1200336864, rs1569513017, rs1587459606, rs1570332505, rs748888652, rs1575155995, rs2087029320, rs1589669105, rs1601769604, rs1184981709, rs749201074
Hydrops fetalis	Hydrops Fetalis, Non-Immune	rs28935477, rs1131691986	26036949
Lethal multiple pterygium syndrome	Lethal multiple pterygium syndrome	rs121912670, rs267606726, rs121912672, rs767503038, rs121909502, rs879255564, rs121909505, rs121909506, rs121909507, rs137852801, rs137852805, rs374391312, rs797044677, rs765746795, rs777219451, rs1060499782, rs1064793397, rs55868108, rs1064795719, rs747067203, rs750329103, rs780249576, rs768407867, rs774279192, rs137852798, rs1553578312, rs776218605, rs764266722, rs1574630951, rs762875734, rs1574007436, rs1574645121, rs375623674, rs1683929269, rs771260711
Leukemia	Leukemia, Myelocytic, Acute	rs121909646, rs121913488, rs587776834, rs752746786, rs869312821, rs767454740, rs1554564297	27903959
Multiple pterygium syndrome	MULTIPLE PTERYGIUM SYNDROME, LETHAL TYPE	rs267606725, rs121912670, rs121912671, rs267606726, rs121912672, rs767503038, rs797044677, rs765746795, rs777219451, rs747067203, rs780249576, rs774279192, rs764266722, rs1574643342	24121633, 7619526, 30177536, 6287911, 18252226, 27748205, 9158151
Myasthenia gravis	Myasthenias	rs5030818, rs121912815, rs121912817, rs121912818, rs121912821, rs75466054, rs121912822, rs121912823, rs794727516, rs764497513, rs376808313, rs1279554995, rs1554802792, rs369251527, rs372760913, rs1554802808, rs769234940, rs201439531, rs1272947184, rs757303526, rs760936252, rs1590576560, rs1838635262
Hypotonia	Neonatal Hypotonia	rs141138948, rs397517172, rs869312824, rs1583169151
Scoliosis	Scoliosis, unspecified	rs1057518828, rs147296805, rs758163506, rs1555613564, rs1596852902, rs1596853067, rs1596853085

Unknown
Disease term	Disease name	Evidence	References	Source
Cirrhosis	Cirrhosis		19690163	ClinVar
Pulmonary hypoplasia	Congenital hypoplasia of lung			ClinVar
Ptosis	Blepharoptosis, Ptosis			ClinVar
Myasthenic Syndrome	congenital myasthenic syndrome 1A, postsynaptic congenital myasthenic syndrome			GenCC
Myasthenia Gravis	Myasthenia Gravis			GWAS

Associations from Text Mining
Disease Name	Relationship Type	References
Colitis Ulcerative	Associate	37055577
Fatigue	Associate	8827715
Fetal akinesia syndrome X linked	Associate	18179903, 23037934
Fetal Diseases	Associate	23037934
Lung Neoplasms	Associate	20234319, 23094028, 23232035
Multiple pterygium syndrome	Associate	18179903
Multiple Pterygium Syndrome Autosomal Dominant	Associate	23037934
Muscle Weakness	Associate	21316238, 33216040
Myasthenia Gravis	Associate	10227809, 15627975, 16891216, 1979338, 2564730, 35074870, 7910962, 8827715
Myasthenic Syndromes Congenital	Associate	12588888, 15731194, 19147685, 20562457, 21316238, 22728938, 31570625, 33216040, 33652901, 35466948
Ophthalmoplegia	Associate	21316238
Pena Shokeir syndrome type 1	Associate	25537362
Ptosis Hereditary Congenital 2	Associate	21316238
Schizophrenia	Associate	31342675