NRG1 (neuregulin 1)

Gene

• Entrez ID: 3084
• Gene name: Neuregulin 1
• Gene symbol: NRG1
• Synonyms (NCBI Gene): ARIA, GGF, GGF2, HGL, HRG, HRG1, HRGA, MST131, MSTP131, NDF, NRG1-IT2, SMDF
• Chromosome: 8
• Chromosome location: 8p12
• Summary: The protein encoded by this gene is a membrane glycoprotein that mediates cell-cell signaling and plays a critical role in the growth and development of multiple organ systems. An extraordinary variety of different isoforms are produced from this gene thr

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT022506	hsa-miR-124-3p	Microarray	18668037
MIRT736520	hsa-miR-1207-5p	qRT-PCR	34288395
MIRT1193909	hsa-miR-409-3p	CLIP-seq
MIRT1193910	hsa-miR-1322	CLIP-seq
MIRT1193911	hsa-miR-421	CLIP-seq
MIRT1193912	hsa-miR-4272	CLIP-seq
MIRT1193913	hsa-miR-4310	CLIP-seq
MIRT1193914	hsa-miR-505	CLIP-seq
MIRT2056233	hsa-miR-4753-3p	CLIP-seq
MIRT2056234	hsa-miR-942	CLIP-seq
MIRT2686551	hsa-miR-1228	CLIP-seq
MIRT2686552	hsa-miR-1273c	CLIP-seq
MIRT2686553	hsa-miR-1827	CLIP-seq
MIRT2686554	hsa-miR-2053	CLIP-seq
MIRT2686555	hsa-miR-2117	CLIP-seq
MIRT2686556	hsa-miR-2467-3p	CLIP-seq
MIRT2686557	hsa-miR-2682	CLIP-seq
MIRT2686558	hsa-miR-302f	CLIP-seq
MIRT2686559	hsa-miR-3125	CLIP-seq
MIRT2686560	hsa-miR-3140-3p	CLIP-seq
MIRT2686561	hsa-miR-329	CLIP-seq
MIRT2686562	hsa-miR-362-3p	CLIP-seq
MIRT2686563	hsa-miR-3683	CLIP-seq
MIRT2686564	hsa-miR-374c	CLIP-seq
MIRT2686565	hsa-miR-377	CLIP-seq
MIRT2686566	hsa-miR-3916	CLIP-seq
MIRT1193909	hsa-miR-409-3p	CLIP-seq
MIRT2686567	hsa-miR-4273	CLIP-seq
MIRT2686568	hsa-miR-4330	CLIP-seq
MIRT2686569	hsa-miR-449c	CLIP-seq
MIRT2686570	hsa-miR-4514	CLIP-seq
MIRT2686571	hsa-miR-4666-3p	CLIP-seq
MIRT2686572	hsa-miR-4692	CLIP-seq
MIRT2686573	hsa-miR-569	CLIP-seq
MIRT2686574	hsa-miR-655	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000165	Process	MAPK cascade	TAS
GO:0000187	Process	Activation of MAPK activity	IMP	20682778
GO:0003222	Process	Ventricular trabecula myocardium morphogenesis	IDA	17336907
GO:0003712	Function	Transcription coregulator activity	IDA	15073182
GO:0005102	Function	Signaling receptor binding	IBA	21873635
GO:0005125	Function	Cytokine activity	TAS	10372964
GO:0005178	Function	Integrin binding	IDA	20682778
GO:0005576	Component	Extracellular region	NAS	1348215, 1350381, 8096067
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA	21873635
GO:0005654	Component	Nucleoplasm	IDA
GO:0005886	Component	Plasma membrane	IEA
GO:0007154	Process	Cell communication	TAS	17432114
GO:0007171	Process	Activation of transmembrane receptor protein tyrosine kinase activity	IBA	21873635
GO:0007399	Process	Nervous system development	IBA	21873635
GO:0007399	Process	Nervous system development	TAS	17432114
GO:0008083	Function	Growth factor activity	NAS	8096067
GO:0008284	Process	Positive regulation of cell population proliferation	IMP	20682778
GO:0014032	Process	Neural crest cell development	TAS	17432114
GO:0016020	Component	Membrane	NAS	8096067
GO:0016021	Component	Integral component of membrane	IEA
GO:0030154	Process	Cell differentiation	IBA	21873635
GO:0030296	Function	Protein tyrosine kinase activator activity	IBA	21873635
GO:0030297	Function	Transmembrane receptor protein tyrosine kinase activator activity	NAS	1348215, 1350381
GO:0030879	Process	Mammary gland development	TAS	17432114
GO:0030971	Function	Receptor tyrosine kinase binding	NAS	1348215, 1350381
GO:0031334	Process	Positive regulation of protein-containing complex assembly	IDA	10559227
GO:0031334	Process	Positive regulation of protein-containing complex assembly	TAS	16412517
GO:0032148	Process	Activation of protein kinase B activity	IMP	20682778
GO:0035556	Process	Intracellular signal transduction	IBA	21873635
GO:0038127	Process	ERBB signaling pathway	IDA	11389077
GO:0038127	Process	ERBB signaling pathway	IMP	20682778
GO:0038128	Process	ERBB2 signaling pathway	TAS
GO:0038129	Process	ERBB3 signaling pathway	IDA	27353365
GO:0042060	Process	Wound healing	TAS	16412517
GO:0043125	Function	ErbB-3 class receptor binding	IDA	20682778
GO:0045499	Function	Chemorepellent activity	IBA	21873635
GO:0045892	Process	Negative regulation of transcription, DNA-templated	IDA	15073182
GO:0048513	Process	Animal organ development	IBA	21873635
GO:0050919	Process	Negative chemotaxis	IEA
GO:0051048	Process	Negative regulation of secretion	IDA	10559227
GO:0051155	Process	Positive regulation of striated muscle cell differentiation	ISS
GO:0051897	Process	Positive regulation of protein kinase B signaling	TAS
GO:0055007	Process	Cardiac muscle cell differentiation	ISS
GO:0060379	Process	Cardiac muscle cell myoblast differentiation	IDA	17336907
GO:0060956	Process	Endocardial cell differentiation	IDA	17336907
GO:0061098	Process	Positive regulation of protein tyrosine kinase activity	IEA
GO:2000145	Process	Regulation of cell motility	TAS

Other IDs

• MIM: 142445
• HGNC: 7997
• e!Ensembl: ENSG00000157168

Protein

• UniProt ID: Q02297
• Protein name: Pro-neuregulin-1, membrane-bound isoform (Pro-NRG1) [Cleaved into: Neuregulin-1 (Acetylcholine receptor-inducing activity) (ARIA) (Breast cancer cell differentiation factor p45) (Glial growth factor) (Heregulin) (HRG) (Neu differentiation factor) (Sensory
• Protein function: Direct ligand for ERBB3 and ERBB4 tyrosine kinase receptors. Concomitantly recruits ERBB1 and ERBB2 coreceptors, resulting in ligand-stimulated tyrosine phosphorylation and activation of the ERBB receptors. The multiple isoforms perform diverse
• PDB: 1HAE, 1HAF, 1HRE, 1HRF, 3U7U, 7MN5, 7MN6, 7MN8, 7SJL, 8U4I, 8U4L
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF07679	I-set	37 → 129	Immunoglobulin I-set domain	Domain
  PF00008	EGF	182 → 220	EGF-like domain	Domain
  PF02158	Neuregulin	267 → 622	Neuregulin intracellular region	Disordered

• Tissue specificity: TISSUE SPECIFICITY: Type I isoforms are the predominant forms expressed in the endocardium. Isoform alpha is expressed in breast, ovary, testis, prostate, heart, skeletal muscle, lung, placenta liver, kidney, salivary gland, small intestine and brain, but
• Sequence:

  MSERKEGRGKGKGKKKERGSGKKPESAAGSQSPALPPRLKEMKSQESAAGSKLVLRCETS
  SEYSSLRFKWFKNGNELNRKNKPQNIKIQKKPGKSELRINKASLADSGEYMCKVISKLGN
  DSASANITIVESNEIITGMPASTEGAYVSSESPIRISVSTEGANTSSSTSTSTTGTSHLV
  KCAEKEKTFCVNGGECFMVKDLSNPSRYLCKCQPGFTGARCTENVPMKVQNQEKAEELYQ
  KRVLTITGICIALLVVGIMCVVAYCKTKKQRKKLHDRLRQSLRSERNNMMNIANGPHHPN
  PPPENVQLVNQYVSKNVISSEHIVEREAETSFSTSHYTSTAHHSTTVTQTPSHSWSNGHT
  ESILSESHSVIVMSSVENSRHSSPTGGPRGRLNGTGGPRECNSFLRHARETPDSYRDSPH
  SERYVSAMTTPARMSPVDFHTPSSPKSPPSEMSPPVSSMTVSMPSMAVSPFMEEERPLLL
  VTPPRLREKKFDHHPQQFSSFHHNPAHDSNSLPASPLRIVEDEEYETTQEYEPAQEPVKK
  LANSRRAKRTKPNGHIANRLEVDSNTSSQSSNSESETEDERVGEDTPFLGIQNPLAASLE
  ATPAFRLADSRTNPAGRFSTQEEIQARLSSVIANQDPIAV

• Sequence length: 640

Pathways

KEGG:

EGFR tyrosine kinase inhibitor resistance
ErbB signaling pathway
Amyotrophic lateral sclerosis

Reactome:

Signaling by ERBB2
Signaling by ERBB4
SHC1 events in ERBB2 signaling
PI3K events in ERBB4 signaling
SHC1 events in ERBB4 signaling
PIP3 activates AKT signaling
GRB7 events in ERBB2 signaling
Downregulation of ERBB2:ERBB3 signaling
GRB2 events in ERBB2 signaling
PI3K events in ERBB2 signaling
Constitutive Signaling by Aberrant PI3K in Cancer
RAF/MAP kinase cascade
ERBB2 Regulates Cell Motility
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
ERBB2 Activates PTK6 Signaling
Downregulation of ERBB2 signaling
Signaling by ERBB2 KD Mutants
Signaling by ERBB2 TMD/JMD mutants

Associated diseases

Causal
Disease term	Disease name	dbSNP ID	References
Arthritis	Juvenile arthritis	rs1594890601, rs1594882933, rs184370809, rs776489319, rs1594883470	19565504
Breast cancer	Malignant neoplasm of breast	rs587776547, rs1137887, rs137853007, rs587776650, rs80359351, rs80359714, rs121917783, rs104886456, rs121964878, rs80359874, rs80357868, rs80357508, rs387906843, rs80357569, rs80358158, rs80357524, rs80357115, rs80357945, rs80357729, rs80357609, rs80357259, rs80357981, rs80358063, rs80357389, rs80356862, rs80359876, rs80357580, rs80358053, rs80358089, rs80187739, rs397507241, rs80358069, rs80357590, rs80357284, rs80357941, rs80359261, rs80359272, rs80359276, rs276174813, rs80358474, rs80359316, rs1555282969, rs80359388, rs80359499, rs80359505, rs80359520, rs80359526, rs80359533, rs56253082, rs80358824, rs80359554, rs80359636, rs80359651, rs80359659, rs80359011, rs80359012, rs80359013, rs80359718, rs397507410, rs81002812, rs80359730, rs80359152, rs80359159, rs397507419, rs28897759, rs80359211, rs80359775, rs397514577, rs397507584, rs80358435, rs80358456, rs80359340, rs80359343, rs80359365, rs80358579, rs397507670, rs80358593, rs80359406, rs80359444, rs80359454, rs276174853, rs276174854, rs80359483, rs80359537, rs80358815, rs80358843, rs80359558, rs80359560, rs80359594, rs80358893, rs28897743, rs397507900, rs397507906, rs397507918, rs80358971, rs80358981, rs397507941, rs80359030, rs80359035, rs41293511, rs397507396, rs81002806, rs80359112, rs397508006, rs81002893, rs45580035, rs80359760, rs397508051, rs80359772, rs4987049, rs80359777, rs80357770, rs397508867, rs62625303, rs397508874, rs80357506, rs80357287, rs273898674, rs80358042, rs80358083, rs80357058, rs41286296, rs80357960, rs80356945, rs80357223, rs386134270, rs80358116, rs80357856, rs80357424, rs397509050, rs80357485, rs80357966, rs397509067, rs80357310, rs80356866, rs80357260, rs80357437, rs80358023, rs80358086, rs80357133, rs80356993, rs80357997, rs80357239, rs80357227, rs397509243, rs80356969, rs80356959, rs63750617, rs63751319, rs587779315, rs200640585, rs398122546, rs80357543, rs398122687, rs80359328, rs398122779, rs398122783, rs62517194, rs80358029, rs515726060, rs180177103, rs180177111, rs180177133, rs587776527, rs180177135, rs180177136, rs515726117, rs587779813, rs587779909, rs587780024, rs587780100, rs28909982, rs121908698, rs180177100, rs587780210, rs587780240, rs587780639, rs587781269, rs587781353, rs587781471, rs587781658, rs587781697, rs587781730, rs587781894, rs587781948, rs587782005, rs587782011, rs200928781, rs587781558, rs370228071, rs587782245, rs587782401, rs180177110, rs587782504, rs72552322, rs587782531, rs587782620, rs587782680, rs587782774, rs587782818, rs730881411, rs730881389, rs564652222, rs397507768, rs587776419, rs730881868, rs730881940, rs56383036, rs758972589, rs201089102, rs730881348, rs786202608, rs786201886, rs786203318, rs786203775, rs786203714, rs786202033, rs750621215, rs786203884, rs786203650, rs772821016, rs863224521, rs864622223, rs864622655, rs375699023, rs876659572, rs768362387, rs876659535, rs876658957, rs483353072, rs876659435, rs267608041, rs876661113, rs730881369, rs878853535, rs772228129, rs878855122, rs760551339, rs80359596, rs397509222, rs886039630, rs886039683, rs886040828, rs587781799, rs886040374, rs886040649, rs397507967, rs878854957, rs886040043, rs1057517589, rs1060502769, rs866380588, rs863224765, rs1064793243, rs747563556, rs1555074976, rs1064795885, rs753961188, rs1064794708, rs869312772, rs1064793887, rs1131690820, rs1135401928, rs1135401868, rs1135401859, rs1553370324, rs397507630, rs1555283160, rs1555283251, rs1555283262, rs1555283361, rs1555286298, rs1555288462, rs886040950, rs1555289566, rs776323117, rs80357123, rs1555579627, rs1555580697, rs80358054, rs1555593302, rs1328985852, rs763470424, rs1555139694, rs878854697, rs1555461217, rs1555461765, rs774684620, rs766416564, rs1554558613, rs1305740166, rs1555461460, rs1555461407, rs1555461586, rs1555567202, rs1555607022, rs1555069815, rs1442299125, rs1474786480, rs1555084947, rs1555457867, rs141087784, rs1482641121, rs1564830522, rs1565469955, rs1565503137, rs864622613, rs755263466, rs757679199, rs1593903166, rs1597801649, rs1603293306, rs879253880, rs80358754, rs1597062038, rs45494092, rs1603275367, rs887358871, rs1597091518, rs1966967065, rs1064793049, rs2082872908, rs2085078278, rs2072475243	19617202
Breast carcinoma	Breast Carcinoma	rs80359671, rs11540652, rs28934575, rs28897672, rs137886232, rs193922376, rs80357783, rs80359306, rs80359405, rs80359507, rs80359598, rs80358429, rs397507683, rs397515636, rs80359451, rs397507859, rs80359709, rs80359742, rs80359205, rs80357627, rs80357004, rs80357571, rs80357767, rs80357653, rs80358086, rs80357608, rs28897696, rs41293465, rs146650273, rs63751017, rs63750617, rs63750726, rs63750199, rs63749848, rs398122618, rs398122653, rs397509211, rs80357791, rs121912666, rs587778541, rs121908698, rs536907995, rs587781302, rs140342925, rs587781506, rs587782652, rs587782849, rs587783057, rs139770721, rs374950566, rs786202800, rs863224451, rs377153250, rs747727055, rs876658804, rs780001540, rs760815829, rs878854926, rs775248597, rs886040658, rs886040192, rs786203523, rs886040319, rs397508006, rs587782011, rs1060502772, rs1555461727, rs1553333072, rs1114167702, rs1257401983, rs886040950, rs1060502759, rs774684620, rs142947311, rs1555580883, rs748513310, rs376170600, rs863224499, rs1593909229, rs748453607, rs1294578913, rs1574737047, rs1593909960, rs2081922847, rs2082559544, rs2053694038	19617202
Dermatitis	Contact Dermatitis	rs61816761, rs150597413, rs138726443, rs201356558, rs149484917, rs372754256, rs747301529, rs567795279, rs745915174	25724174
Hirschsprung disease	Hirschsprung Disease	rs76262710, rs75996173, rs77316810, rs75076352, rs76534745, rs76764689, rs76449634, rs377767412, rs193922699, rs75030001, rs606231342, rs1553540620, rs759944122, rs1057519322, rs1057519323, rs1057519052, rs1588873476, rs1588866040, rs1838178869	25310821, 19196962, 22974608, 27702942
Hypothyroidism	Hypothyroidism	rs869320723, rs121908862, rs121908863, rs121908865, rs121908866, rs121908867, rs121908870, rs121908871, rs121908872, rs2140110277, rs121908881, rs121908884, rs121908885, rs786205080, rs1586182912, rs121917847, rs104893655, rs104893657, rs104893658, rs104893659, rs104893660, rs104893656, rs121917719, rs786204790, rs189261858, rs879255608, rs868197660, rs879255609, rs1586744173, rs1586182837, rs771222349, rs1587618417, rs1601844140, rs760832986, rs780982673, rs1603336347, rs1691155605	27182965
Lung carcinoma	Non-Small Cell Lung Carcinoma	rs1805076, rs121909071, rs121913530, rs112445441, rs121913529, rs121913535, rs121913297, rs121913279, rs104886003, rs397516975, rs11554290, rs121913364, rs121913351, rs121913369, rs121913355, rs121912470, rs121913273, rs121913281, rs121913348, rs727503093, rs121913353, rs397516890, rs397516896, rs121913378, rs397516897, rs397516977, rs397516978, rs397516979, rs397516980, rs397516981, rs397516982, rs121913240, rs17851045, rs397517086, rs121913428, rs397517094, rs397517098, rs397517106, rs121913465, rs397517108, rs397517111, rs397517112, rs397517114, rs397517116, rs1554350366, rs397517127, rs397517200, rs397517202, rs121913283, rs121913370, rs121913357, rs727503106, rs121913238, rs727503108, rs397517040, rs397516976, rs1555618025, rs1057519729, rs1584238193	31326317
Lung adenocarcinoma	Adenocarcinoma of lung (disorder)	rs28934576, rs121913530, rs397516975, rs587776805, rs121913469, rs121913364, rs121913351, rs121913366, rs397516896, rs397516977, rs397516981, rs397517127, rs121913344, rs727504233, rs121913370, rs760043106, rs1057519788, rs1131692238, rs1131692237, rs1554350382	28604730, 31326317
Lung cancer	Malignant neoplasm of lung	rs121913530, rs121913529, rs878855122, rs1057519784, rs770315135	28604730
Marfan syndrome	Mammary Carcinoma, Human	rs137854456, rs137854457, rs267606796, rs137854458, rs137854459, rs137854460, rs137854470, rs137854471, rs267606797, rs137854461, rs137854462, rs137854463, rs869025419, rs137854464, rs137854465, rs137854466, rs137854467, rs387906547, rs387906548, rs137854469, rs137854473, rs1131692050, rs112989722, rs137854474, rs137854476, rs140593, rs1555395819, rs137854478, rs137854479, rs137854480, rs137854481, rs137854482, rs137854483, rs137854484, rs137854485, rs112289537, rs193922181, rs193922182, rs193922185, rs140603, rs193922187, rs193922188, rs193921256, rs112660651, rs193922193, rs193922194, rs193922197, rs193922198, rs193922199, rs193922203, rs193922204, rs193922205, rs193922206, rs111401431, rs193922207, rs113871094, rs111671429, rs193922216, rs193922219, rs193922220, rs193922223, rs193922224, rs193922225, rs193922226, rs193922227, rs193922228, rs193922230, rs193922235, rs147195031, rs193922236, rs193922239, rs193922240, rs193922241, rs193922246, rs397514558, rs398122934, rs397515753, rs397515754, rs397515755, rs397515756, rs397515757, rs113812345, rs397515758, rs397515759, rs397515762, rs25403, rs397515765, rs397515766, rs397515767, rs397515768, rs397515769, rs397515770, rs397515771, rs25404, rs397515773, rs397515774, rs397515775, rs397515776, rs397515778, rs397515779, rs397515781, rs112202622, rs397515782, rs397515784, rs397515785, rs397515786, rs397515788, rs397515789, rs397515790, rs397515791, rs397515792, rs397515793, rs397515794, rs397515797, rs397515798, rs397515799, rs397515801, rs397515802, rs397515803, rs397515804, rs397515805, rs397515808, rs397515810, rs397515811, rs397515812, rs111231312, rs267606798, rs397515814, rs113905529, rs397515816, rs397515817, rs397515818, rs397515819, rs397515820, rs363853, rs113249837, rs397515821, rs111929350, rs397515823, rs397515824, rs113086760, rs397515825, rs397515826, rs397515827, rs363807, rs397515828, rs397515829, rs397515830, rs397515831, rs397515833, rs111687884, rs113080385, rs397515834, rs397515836, rs113001196, rs397515840, rs397515845, rs397515846, rs397515847, rs397515848, rs397515851, rs397515852, rs397515853, rs397515854, rs111856492, rs397515859, rs397515861, rs397515863, rs397515864, rs397515865, rs397515866, rs397515867, rs137854855, rs199474693, rs587782944, rs587782947, rs587782948, rs672601352, rs876658120, rs727504651, rs727503054, rs727504315, rs727504411, rs727503057, rs727504454, rs200309328, rs363811, rs727504410, rs363821, rs727504347, rs727505006, rs727505110, rs730880356, rs727505269, rs727503058, rs727504421, rs730880107, rs730880104, rs730880103, rs730880102, rs730880101, rs730880106, rs730880100, rs730880105, rs730880099, rs112645512, rs730880108, rs730880098, rs730880097, rs794728321, rs794728283, rs794728280, rs794728336, rs794728272, rs794728160, rs794728271, rs794728270, rs794728319, rs794728262, rs794728251, rs76702162, rs794728335, rs794728334, rs794728246, rs763091520, rs794728333, rs794728237, rs761857514, rs794728234, rs140630, rs794728231, rs794728228, rs794728225, rs794728308, rs794728216, rs794728221, rs763449629, rs201058219, rs794728210, rs794728208, rs794728206, rs794728199, rs794728195, rs794728194, rs794728193, rs794728190, rs1555399381, rs794728176, rs1555399968, rs113422242, rs794728326, rs794728166, rs794728325, rs794728165, rs794728162, rs794728213, rs869025417, rs112642323, rs869025416, rs869025415, rs869025424, rs869025423, rs869025414, rs869025422, rs869025413, rs869025412, rs869025411, rs869025418, rs869025426, rs869025406, rs869025421, rs869025425, rs869025404, rs869025420, rs869025403, rs398122833, rs876657645, rs878853686, rs878853676, rs886038919, rs886038795, rs187553035, rs886038869, rs886038949, rs886038967, rs886038976, rs886038848, rs886038940, rs886038877, rs886039038, rs886038817, rs886038963, rs886039036, rs886038797, rs886039550, rs886041482, rs1057517855, rs1057518912, rs1057518973, rs1057519502, rs1057521100, rs1057521102, rs1057518881, rs1057520617, rs1057521101, rs1555394445, rs369058466, rs1060501069, rs1060501031, rs778966916, rs1060501043, rs1555397663, rs1060501017, rs1060501094, rs1060501065, rs1555393848, rs1555394151, rs1060501051, rs1060501013, rs1060501054, rs1060501048, rs1060501089, rs1060501039, rs1555398160, rs1060501022, rs1060501024, rs1060501086, rs1060501058, rs1060501036, rs1060501100, rs1060501042, rs1060501059, rs1555397743, rs1060501021, rs1060501027, rs1060501096, rs1060501038, rs1060501050, rs1064794130, rs112118237, rs1064793980, rs1064793118, rs1064793636, rs1064794282, rs1064793559, rs1085307921, rs1085308004, rs1085307468, rs112907302, rs1131691479, rs1131691373, rs1131691467, rs1131691938, rs1131691311, rs1131691806, rs1131691317, rs1555393827, rs363804, rs1555397738, rs1555399144, rs1555400274, rs1555394195, rs1555398836, rs113543334, rs1555399825, rs1555394626, rs1555395256, rs1555395257, rs1555396427, rs1555397548, rs1555398173, rs1555404803, rs1232880706, rs1555393825, rs1555394567, rs1555396998, rs1555394928, rs1555397203, rs112375043, rs1555397720, rs140599, rs1555399150, rs1555400373, rs1555405041, rs1555395229, rs1555397671, rs775417975, rs1555398774, rs1555399368, rs1555394904, rs1555395987, rs1555397424, rs1555398377, rs1555398835, rs1555401011, rs1555405043, rs1555394580, rs1555397404, rs1555398511, rs1555395826, rs1555399372, rs1555399821, rs1555399836, rs1555400063, rs363810, rs1555397655, rs1555395756, rs1555395742, rs1555393844, rs112550005, rs1555395002, rs1555395658, rs765387131, rs1555396429, rs1555396835, rs1555397014, rs1555397016, rs778710767, rs1555397557, rs1555397704, rs140648, rs1555398406, rs1555398681, rs1555399257, rs1555399361, rs1555399764, rs1555405056, rs1555393510, rs1555395980, rs1555396789, rs1555399094, rs1555399378, rs1555399816, rs1555395645, rs371097218, rs1555398278, rs1555394238, rs1555396418, rs1206813753, rs1555399271, rs1555405044, rs113544411, rs1555395663, rs1555397216, rs1555398989, rs1555399149, rs1555401670, rs1555395001, rs1445085747, rs1555393538, rs1555393565, rs1404133653, rs1555394450, rs1555394581, rs1555394633, rs1555394900, rs1555395189, rs1555395261, rs1052480459, rs1555395480, rs1555395670, rs363806, rs1555395820, rs1555396419, rs1555396765, rs1296209846, rs794728233, rs1555396853, rs1555396863, rs1555397197, rs1555397204, rs1555397212, rs1555397713, rs1555397736, rs1555398139, rs1555398144, rs1555398409, rs1555398510, rs1555398520, rs1555398524, rs1555398667, rs1555399089, rs1555399482, rs1555399763, rs1555401002, rs794728323, rs1555393508, rs1555393514, rs1555393525, rs1555393532, rs1555393653, rs1555393657, rs1555393824, rs1555393831, rs112196241, rs1555393847, rs1555393862, rs1555393863, rs1555393866, rs113935744, rs1555393882, rs1555393886, rs1555393889, rs1555394138, rs1555394144, rs1555394146, rs1555394148, rs1555394149, rs1555394152, rs1555394153, rs1555394189, rs1555394197, rs1555394206, rs1555394212, rs1555394218, rs1555394220, rs1555394235, rs1555394245, rs1555394246, rs1057520728, rs1555394390, rs1555394391, rs537570299, rs1555394397, rs1555394398, rs1555394399, rs1555394402, rs1555394407, rs1555394412, rs1555394435, rs1555394436, rs1555394441, rs1555394556, rs1555394557, rs1555394559, rs1555394561, rs1555394570, rs397515844, rs1555394571, rs1555394574, rs1555394579, rs1555394582, rs534811966, rs111588631, rs1555394628, rs1555394629, rs1555394630, rs1555394631, rs1555394641, rs1555394644, rs1555394647, rs1555394756, rs886051245, rs1555394775, rs1555394776, rs1555394777, rs1555394779, rs1555394780, rs1555394783, rs1555394901, rs1555394906, rs1555394925, rs794728253, rs886039158, rs1555395013, rs1555395187, rs1555395188, rs1555395203, rs1555395205, rs363815, rs1246984265, rs794728245, rs1555395263, rs1555395267, rs1555395456, rs1555395475, rs1555395482, rs1555395638, rs1555395641, rs1555395648, rs1555395653, rs1555395659, rs111239111, rs1555395745, rs1555395747, rs1555395753, rs1555395757, rs1555395766, rs1555395767, rs1555395843, rs1555395846, rs1555395849, rs1555395978, rs1555395981, rs1555395984, rs1555395989, rs1555395990, rs1260109901, rs1555396186, rs1555396188, rs1555396198, rs1555396199, rs1555396201, rs1555396202, rs1555396205, rs1555396213, rs1555396424, rs1555396426, rs1555396428, rs1555396435, rs1555396630, rs1555396635, rs1555396636, rs1555396639, rs1555396757, rs1555396769, rs1555396838, rs1555396844, rs140627, rs1555396858, rs1555396990, rs1555396991, rs1555396993, rs769588424, rs1555397022, rs1555397024, rs1555397160, rs1555397174, rs1555397176, rs1555397193, rs1555397209, rs1555397210, rs1555397214, rs1060501076, rs113082854, rs113693945, rs111978932, rs1555397403, rs1555397419, rs1555397420, rs1555397421, rs1555397536, rs1555397537, rs1555397540, rs1555397542, rs1555397543, rs1555397545, rs1555397546, rs1555397670, rs1555397692, rs1555397718, rs1555397723, rs1555397744, rs113393517, rs1555398148, rs1555398152, rs1555398174, rs1555398176, rs1555398179, rs1555398282, rs1555398287, rs1555398380, rs1555398394, rs1555398397, rs1555398401, rs1555398404, rs1555398407, rs1555398413, rs1555398501, rs1555398508, rs1555398512, rs1555398513, rs1555398515, rs1555398521, rs794728205, rs1555398527, rs1555398551, rs1060501075, rs1555398566, rs1555398572, rs1555398580, rs1555398582, rs140597, rs1555398622, rs1555398624, rs1555398625, rs112547596, rs1555398627, rs1555398633, rs1555398637, rs1555398642, rs778867355, rs1555398648, rs1555398659, rs1293095681, rs1060501040, rs987202268, rs1555398672, rs1555398673, rs1555398677, rs1555398793, rs1555398803, rs1555398811, rs1555398826, rs1555398833, rs1555398974, rs1555398981, rs778900586, rs1555398988, rs1555398994, rs1555398995, rs1555398996, rs1555399093, rs869025405, rs1555399101, rs1555399146, rs1555399160, rs1555399162, rs1555399164, rs1555399165, rs1555399193, rs1555399195, rs1555399202, rs1555399204, rs1555399206, rs201778577, rs1555399210, rs1555399214, rs1555399270, rs1555399273, rs1555399281, rs1555399371, rs1555399385, rs1555399477, rs1555399484, rs1555399761, rs1555399775, rs1555399802, rs1555399804, rs1555399837, rs1555399840, rs1555399940, rs1555399944, rs1555399949, rs1555399953, rs1555399954, rs1555399955, rs1555399959, rs1555399962, rs1555399963, rs1060501041, rs1555399974, rs1555399976, rs1555399977, rs1555400049, rs794728172, rs1555400062, rs1555400064, rs1555400066, rs1555400267, rs1555400268, rs1555400278, rs794728168, rs1555400279, rs1156747241, rs1555400288, rs1555400371, rs1555400372, rs1555400379, rs1555400385, rs587782943, rs1555400387, rs1555400406, rs1439533354, rs746201757, rs1555400595, rs1555400603, rs1555400604, rs1555400606, rs1555400609, rs752010116, rs1555400612, rs1555400616, rs1555401004, rs1555401005, rs146348130, rs1555401667, rs1555401671, rs1555401676, rs1555401679, rs1555401687, rs1555401689, rs1555401695, rs1555401697, rs1555401701, rs1555404799, rs1555404800, rs200295020, rs1555404810, rs1555404820, rs1555405031, rs1555405039, rs1555405045, rs1555405530, rs794728292, rs1555405533, rs1555405536, rs1555405537, rs111764111, rs1555405658, rs1555405664, rs774371494, rs1555405673, rs1555407399, rs1555407414, rs1555407423, rs1555407429, rs886041536, rs1555404806, rs1566911709, rs1566913974, rs1566894226, rs1566895223, rs1566897376, rs1566902526, rs1566915277, rs1566897374, rs1566897420, rs1566891655, rs1346043320, rs1566922396, rs1566891706, rs1566894783, rs1566913670, rs1555394196, rs1566891454, rs1566891406, rs1566891404, rs1566895262, rs1566891645, rs1566895225, rs1566896114, rs1566898399, rs1566904011, rs1566906537, rs1566908956, rs1566909766, rs1566919599, rs1566937712, rs1566915335, rs1566891675, rs1566904526, rs1566906506, rs1566900540, rs1566894230, rs1555395206, rs1566891797, rs1597512576, rs1597523873, rs1597581001, rs1597516325, rs1057524757, rs1597506641, rs1597520781, rs1597593695, rs1597529829, rs1597520625, rs1597579923, rs1597531796, rs1008275504, rs1597567249, rs1597569265, rs1597652471, rs1597516347, rs1597577114, rs1597633163, rs1597519658, rs1597593852, rs1597516501, rs1566913982, rs1555393859, rs1597513708, rs368978109, rs1480832655, rs1597520683, rs1597522390, rs1597522553, rs1597529748, rs1597533707, rs1597537815, rs1597545309, rs1597545836, rs1597563234, rs1597563280, rs1597564359, rs772108557, rs1597568968, rs1597574236, rs1597574308, rs1597577975, rs193922179, rs1597581005, rs1597593736, rs1597623670, rs1597625734, rs1597631662, rs113604459, rs1597633183, rs1597633219, rs1597518951, rs1555394781, rs1597525871, rs1597526073, rs1597569159, rs1597569536, rs1597563934, rs1597545199, rs1364210063, rs1597552583, rs1597520619, rs1597540854, rs1597591602, rs1597569551, rs1597548716, rs1597553721, rs112728248, rs1597537858, rs1597517935, rs1597540907, rs1597552388, rs1597591643, rs1597529841, rs1597506547, rs1597509836, rs1597529686, rs1566897404, rs1597533713, rs1597543486, rs1597545257, rs1597545345, rs1597548672, rs1597562812, rs1597563287, rs1597571391, rs1555400052, rs1597583989, rs363852, rs1597547226, rs363808, rs974604498, rs2043595650, rs2043526284, rs2042997306, rs1555397195, rs886039054, rs1555397213, rs2042873946	19617202
Papillary thyroid carcinoma	Papillary thyroid carcinoma	rs751409106	28703219
Schizophrenia	Schizophrenia	rs13447324, rs387906932, rs387906933, rs863223354, rs863223355, rs776061422, rs863223349, rs748809996, rs759748655, rs863223353, rs863223350, rs863223356, rs781821239, rs863223348, rs863223346, rs863223347, rs863223351, rs863223352, rs61734270, rs797045205, rs869312829, rs869312830, rs770913157, rs869312832, rs869312831, rs781720548, rs1262969313	17333138, 17460065, 20582876, 12145742, 20701826, 22440650, 17905522, 25944848, 20561508

Unknown
Disease term	Disease name	Evidence	References	Source
Asthma	Childhood asthma		17611496	ClinVar
Chronic obstructive pulmonary disease	Chronic Obstructive Airway Disease		26634245	ClinVar
Congestive heart failure	Congestive heart failure		19801490	ClinVar
Heart failure	Heart failure, Left-Sided Heart Failure, Heart Failure, Right-Sided		19801490	ClinVar
Mental depression	Mental Depression, Depressive disorder, Unipolar Depression, Major Depressive Disorder		17449450, 19204725, 25944848	ClinVar
Myocardial infarction	Myocardial Failure		19801490	ClinVar
Mental Depression	Mental Depression			GWAS
Hirschsprung Disease	Hirschsprung Disease			GWAS
Metabolic Syndrome	Metabolic Syndrome			GWAS
Gout	Gout			GWAS
Cleft Lip With Or Without Cleft Palate	Cleft Lip With Or Without Cleft Palate			GWAS
Rheumatic Heart Disease	Rheumatic Heart Disease			GWAS
Insomnia	Insomnia			GWAS

Associations from Text Mining
Disease Name	Relationship Type	References
Adenocarcinoma	Associate	26837769, 35322195
Adenocarcinoma Mucinous	Associate	26837769, 33839364, 33947695
Adenocarcinoma of Lung	Associate	26134228, 26486077, 26845116, 27770508, 29858224, 33839363, 35029906, 36096509
Adenoma	Associate	25562676
Alzheimer Disease	Associate	22739235, 32337953, 32690068, 37061663
Astrocytoma	Associate	15812817
Attention Deficit Disorder with Hyperactivity	Associate	30415889
Autism Spectrum Disorder	Associate	22952857, 30415889
Behcet Syndrome	Associate	23625463
Bipolar Disorder	Associate	19127563, 19449332, 20435087, 21232925, 22590542, 24865593, 27063557
Brain Damage Chronic	Associate	19733651
Brain Diseases	Associate	21876540
Brain Neoplasms	Associate	37423059
Breast Neoplasms	Associate	19110721, 20625696, 23991224, 24112719, 25492965, 26885614, 30988082, 32618109, 32788048, 33413557, 33692466, 33839363, 36424660
Breast Neoplasms	Inhibit	19802002, 22939885
Bursitis	Associate	21232925
Calcinosis Cutis	Associate	34747541
Carcinogenesis	Associate	33839363, 35135829, 38219288
Carcinoma Hepatocellular	Associate	31944381
Carcinoma Medullary	Associate	7992839
Carcinoma Non Small Cell Lung	Associate	26134228, 30914778, 30988082, 34132450, 35135829, 36096509, 37164276, 37678511
Carcinoma Renal Cell	Associate	30988082, 33858375
Cerebral Palsy	Associate	19733651
Cholangiocarcinoma	Associate	35986087
Cockayne Syndrome	Associate	31980658
Cognitive Dysfunction	Associate	32690068
Colorectal Neoplasms	Associate	30988082, 32852072, 35321516, 35748788, 36394757, 37164276
Congenital Hereditary and Neonatal Diseases and Abnormalities	Associate	36443333
Conversion Disorder	Associate	30415889
Coronary Artery Disease	Associate	31956140
Cystic Fibrosis	Associate	35922154
Depressive Disorder	Associate	22590542
Depressive Disorder Major	Associate	21745728, 37061663
Developmental Disabilities	Associate	19733651
Diabetic Cardiomyopathies	Associate	31956140
Disruptive Impulse Control and Conduct Disorders	Associate	32710539
Down Syndrome	Associate	31819021
Endocardial Cushion Defects	Associate	31819021
Epilepsy	Associate	28273943
Esophagitis	Associate	37164276
Fibrosarcoma	Associate	26269601
Fragile X Syndrome	Associate	12950170
Gallbladder Neoplasms	Associate	30988082
Gastrointestinal Diseases	Associate	18852951
Gastrointestinal Neoplasms	Associate	35400204
Glioblastoma	Associate	31844032, 34054873
Glioma	Associate	15812817, 34054873, 34284546
Head and Neck Neoplasms	Associate	35461210
Heart Defects Congenital	Associate	31819021
Heart Failure	Associate	23975515, 28235789
Hereditary Breast and Ovarian Cancer Syndrome	Associate	37164276
Hirschsprung Disease	Associate	19196962, 21283760, 21712996, 22589734, 25310821, 25475805, 28256518, 29377512, 29379196, 30180823, 31767031, 34006365, 35443634, 36443333
Hypertrophy Left Ventricular	Associate	25329069
Hypothyroidism	Associate	33600668
Inflammation	Associate	20625696, 28235789
Inflammatory Bowel Diseases	Associate	26764183
Lung Diseases	Associate	27770508
Lung Neoplasms	Associate	17627612, 26134228, 26837769, 28950338, 33839363, 35400204, 36086904
Lymphatic Metastasis	Associate	27342578
Lymphoma Large Cell Anaplastic	Associate	36086904
Male Infertility with Large Headed Multiflagellar Polyploid Spermatozoa	Associate	26662397
Melanoma	Associate	22249266, 26206558, 26269601, 34044811
Melanoma Cutaneous Malignant	Associate	26206558
Mental Disorders	Associate	21232925, 22590542, 24795156
Mood Disorders	Associate	33828235
Multiple Sclerosis	Associate	20625696
Myocardial Ischemia	Inhibit	31956140
Neoplasm Invasiveness	Associate	20193695
Neoplasm Metastasis	Associate	18159252
Neoplasms	Associate	18159252, 21840482, 22249266, 23991224, 24112719, 24237343, 25492965, 26046304, 26269601, 26764183, 26837769, 27342578, 27770508, 28950338, 29858224, 30988082, 32243841, 32852072, 33692466, 33755158, 33839363, 33839364, 33947695, 34054873, 34132450, 35135829, 35367216, 35400204, 35621010, 35876504, 35911687, 36096509, 37164276, 37678511, 38173003, 38219288, 39923761, 7992839
Neoplasms	Inhibit	19802002, 20193695, 30917865
Neoplasms Squamous Cell	Associate	37424047
Neurilemmoma	Associate	23354516
Neurodegenerative Diseases	Inhibit	35008438
Neuroendocrine Tumors	Associate	30988082
Neuroinflammatory Diseases	Associate	32690068
Neurologic Manifestations	Associate	27057274
Neuroma Acoustic	Associate	23776562
Neurotoxicity Syndromes	Inhibit	22739235
Ocular Motility Disorders	Associate	19965935
Ovarian Diseases	Associate	37164276
Ovarian Neoplasms	Associate	30988082, 32243841
Pancreatic Neoplasms	Associate	30988082, 31164372, 33755158, 35135829
Pancreatitis	Associate	37164276
Precancerous Conditions	Associate	33903236
Psychological Distress	Associate	31801286
Psychotic Disorders	Associate	17519028, 18286587
Sarcoma	Associate	30988082, 34747541
Sarcoma Clear Cell	Associate	16867224
Schizophrenia	Associate	17410640, 17519028, 18159252, 18243664, 19118813, 19127563, 19350564, 19449332, 19521112, 19965935, 20435087, 20497232, 20625696, 20713722, 21232925, 21498463, 21745728, 21876540, 22590542, 22952857, 24237343, 24683514, 24865593, 30415889, 30738251, 32690068
Sleep Apnea Obstructive	Associate	25325441
Sleep Apnea Syndromes	Associate	34446064
Speech Disorders	Associate	19350564
Squamous Cell Carcinoma of Head and Neck	Associate	28723928
Stomach Neoplasms	Associate	25583476
Stomach Ulcer	Stimulate	16357062
Stress Disorders Post Traumatic	Associate	31944381
Thyroid Cancer Papillary	Associate	23659773, 25562676, 27342578, 29121253, 29901070, 33551988
Thyroid Neoplasms	Associate	22267200, 24591304, 25562676, 27512836, 28703219, 29901070, 33903625
Thyroiditis Autoimmune	Inhibit	33600668
Trigeminal Neuralgia	Associate	28273943
Urinary Bladder Neoplasms	Associate	21364580, 30988082
Warts	Associate	31892232