CYBA (cytochrome b-245 alpha chain)

Gene

• Entrez ID: 1535
• Gene name: Cytochrome b-245 alpha chain
• Gene symbol: CYBA
• Synonyms (NCBI Gene): CGD4, p22-PHOX
• Chromosome: 16
• Chromosome location: 16q24.2
• Summary: Cytochrome b is comprised of a light chain (alpha) and a heavy chain (beta). This gene encodes the light, alpha subunit which has been proposed as a primary component of the microbicidal oxidase system of phagocytes. Mutations in this gene are associated

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs4673	A>G,T	Benign, likely-pathogenic	Missense variant, coding sequence variant
rs28941476	C>T	Pathogenic	Missense variant, coding sequence variant
rs104894510	T>C	Pathogenic	Coding sequence variant, missense variant
rs104894511	G>A	Pathogenic	Coding sequence variant, stop gained
rs104894513	C>T	Pathogenic	Coding sequence variant, missense variant
rs104894514	G>A,T	Not-provided, pathogenic	Synonymous variant, coding sequence variant, missense variant
rs104894515	G>T	Pathogenic	Downstream transcript variant, coding sequence variant, genic downstream transcript variant, missense variant
rs114610092	C>A,T	Conflicting-interpretations-of-pathogenicity, likely-benign	Genic downstream transcript variant, downstream transcript variant, coding sequence variant, missense variant, stop gained
rs119103269	C>A,T	Pathogenic	Downstream transcript variant, coding sequence variant, genic downstream transcript variant, missense variant
rs179363890	A>G	Pathogenic	Coding sequence variant, missense variant
rs179363892	G>A,C	Not-provided, pathogenic	Coding sequence variant, missense variant
rs377055239	G>A,C,T	Conflicting-interpretations-of-pathogenicity	Intron variant
rs779809359	G>A,C	Pathogenic	Coding sequence variant, stop gained, synonymous variant
rs1352931329	G>-,GG	Pathogenic	Coding sequence variant, frameshift variant
rs1439134665	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs1567607736	G>-	Pathogenic	Coding sequence variant, downstream transcript variant, genic downstream transcript variant, frameshift variant
rs1567608830	CACCGAGAGCCTGGGG>-	Likely-pathogenic	Intron variant, coding sequence variant, splice acceptor variant
rs1567608853	G>C	Pathogenic	Intron variant
rs1567609091	C>T	Pathogenic	Splice donor variant
rs1597374562	G>-	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT046446	hsa-miR-15b-5p	CLASH	23622248
MIRT044553	hsa-miR-320a	CLASH	23622248

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001666	Process	Response to hypoxia	IEA
GO:0001725	Component	Stress fiber	IEA
GO:0001938	Process	Positive regulation of endothelial cell proliferation	IEA
GO:0003106	Process	Negative regulation of glomerular filtration by angiotensin	IEA
GO:0005515	Function	Protein binding	IPI	3305576, 11733522, 15824103, 16326715, 16460309, 17126813, 17140397, 17803994, 22808130, 23957209, 35031518
GO:0005737	Component	Cytoplasm	IEA
GO:0005768	Component	Endosome	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	TAS
GO:0005886	Component	Plasma membrane	IDA	17140397
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	NAS	27048830
GO:0005886	Component	Plasma membrane	TAS
GO:0005925	Component	Focal adhesion	IEA
GO:0006801	Process	Superoxide metabolic process	IEA
GO:0006801	Process	Superoxide metabolic process	IMP	1763037, 2243141
GO:0006954	Process	Inflammatory response	IMP	2243141
GO:0009055	Function	Electron transfer activity	IDA	12042318
GO:0009055	Function	Electron transfer activity	TAS	2243141
GO:0009410	Process	Response to xenobiotic stimulus	IEA
GO:0014823	Process	Response to activity	IEA
GO:0014895	Process	Smooth muscle hypertrophy	IEA
GO:0014895	Process	Smooth muscle hypertrophy	ISS
GO:0016020	Component	Membrane	HDA	19946888
GO:0016020	Component	Membrane	IEA
GO:0016175	Function	Superoxide-generating NAD(P)H oxidase activity	IEA
GO:0016175	Function	Superoxide-generating NAD(P)H oxidase activity	IMP	1763037
GO:0016324	Component	Apical plasma membrane	IEA
GO:0016491	Function	Oxidoreductase activity	IEA
GO:0017004	Process	Cytochrome complex assembly	IDA	7938008
GO:0017124	Function	SH3 domain binding	IPI	7938008
GO:0020037	Function	Heme binding	IEA
GO:0030141	Component	Secretory granule	TAS	12005167
GO:0030307	Process	Positive regulation of cell growth	IEA
GO:0030425	Component	Dendrite	IEA
GO:0030670	Component	Phagocytic vesicle membrane	TAS
GO:0031667	Process	Response to nutrient levels	IEA
GO:0032755	Process	Positive regulation of interleukin-6 production	IDA	22423966
GO:0032760	Process	Positive regulation of tumor necrosis factor production	IDA	22423966
GO:0032930	Process	Positive regulation of superoxide anion generation	IEA
GO:0034137	Process	Positive regulation of toll-like receptor 2 signaling pathway	IDA	22423966
GO:0035579	Component	Specific granule membrane	TAS
GO:0042554	Process	Superoxide anion generation	IBA
GO:0042554	Process	Superoxide anion generation	IDA	38355798
GO:0042554	Process	Superoxide anion generation	IEA
GO:0042554	Process	Superoxide anion generation	IMP	2243141
GO:0043020	Component	NADPH oxidase complex	IBA
GO:0043020	Component	NADPH oxidase complex	IDA	3305576, 22423966, 36241643, 36413210, 38355798
GO:0043020	Component	NADPH oxidase complex	IEA
GO:0043020	Component	NADPH oxidase complex	IMP	1763037
GO:0043020	Component	NADPH oxidase complex	NAS	24598074
GO:0043025	Component	Neuronal cell body	IEA
GO:0045087	Process	Innate immune response	IEA
GO:0045087	Process	Innate immune response	IMP	2243141
GO:0045087	Process	Innate immune response	ISS
GO:0045730	Process	Respiratory burst	IMP	2243141
GO:0045730	Process	Respiratory burst	NAS	27048830
GO:0045777	Process	Positive regulation of blood pressure	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0046982	Function	Protein heterodimerization activity	IPI	12042318
GO:0048661	Process	Positive regulation of smooth muscle cell proliferation	IEA
GO:0050665	Process	Hydrogen peroxide biosynthetic process	IEA
GO:0050665	Process	Hydrogen peroxide biosynthetic process	ISS
GO:0050766	Process	Positive regulation of phagocytosis	IDA	22423966
GO:0051279	Process	Regulation of release of sequestered calcium ion into cytosol	IEA
GO:0051649	Process	Establishment of localization in cell	IEA
GO:0070254	Process	Mucus secretion	IEA
GO:0070257	Process	Positive regulation of mucus secretion	IEA
GO:0070555	Process	Response to interleukin-1	IEA
GO:0070821	Component	Tertiary granule membrane	TAS
GO:0071260	Process	Cellular response to mechanical stimulus	IEA
GO:0071333	Process	Cellular response to glucose stimulus	IEA
GO:0071356	Process	Cellular response to tumor necrosis factor	IEA
GO:0071480	Process	Cellular response to gamma radiation	IEA
GO:0072593	Process	Reactive oxygen species metabolic process	IEA
GO:0097038	Component	Perinuclear endoplasmic reticulum	IEA
GO:1900426	Process	Positive regulation of defense response to bacterium	IDA	22423966
GO:1903428	Process	Positive regulation of reactive oxygen species biosynthetic process	IDA	22423966
GO:1904044	Process	Response to aldosterone	IEA
GO:1904385	Process	Cellular response to angiotensin	IEA
GO:1904628	Process	Cellular response to phorbol 13-acetate 12-myristate	IEA
GO:1904845	Process	Cellular response to L-glutamine	IEA

Other IDs

• MIM: 608508
• HGNC: 2577
• e!Ensembl: ENSG00000051523

Protein

• UniProt ID: P13498
• Protein name: Cytochrome b-245 light chain (Cytochrome b(558) alpha chain) (Cytochrome b558 subunit alpha) (Neutrophil cytochrome b 22 kDa polypeptide) (Superoxide-generating NADPH oxidase light chain subunit) (p22 phagocyte B-cytochrome) (p22-phox) (p22phox)
• Protein function: Subunit of NADPH oxidase complexes that is required for the NADPH oxidase activity that generates, in various cell types, superoxide from molecular oxygen utilizing NADPH as an electron donor (PubMed:15824103, PubMed:17140397, PubMed:38355798).
• PDB: 1WLP, 7U8G, 7YXW, 8GZ3, 8KEI, 8WEJ, 8X2L
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF05038	Cytochrom_B558a	2 → 193	Cytochrome Cytochrome b558 alpha-subunit	Family

• Sequence:

  MGQIEWAMWANEQALASGLILITGGIVATAGRFTQWYFGAYSIVAGVFVCLLEYPRGKRK
  KGSTMERWGQKYMTAVVKLFGPFTRNYYVRAVLHLLLSVPAGFLLATILGTACLAIASGI
  YLLAAVRGEQWTPIEPKPRERPQIGGTIKQPPSNPPPRPPAEARKKPSEEEAAVAAGGPP
  GGPQVNPIPVTDEVV

• Sequence length: 195

Pathways

KEGG:

Phagosome
Osteoclast differentiation
Neutrophil extracellular trap formation
NOD-like receptor signaling pathway
Leukocyte transendothelial migration
Prion disease
Leishmaniasis
Chemical carcinogenesis - reactive oxygen species
Diabetic cardiomyopathy
Lipid and atherosclerosis
Fluid shear stress and atherosclerosis

Reactome:

ROS and RNS production in phagocytes
Cross-presentation of particulate exogenous antigens (phagosomes)
Detoxification of Reactive Oxygen Species
VEGFA-VEGFR2 Pathway
RHO GTPases Activate NADPH Oxidases
Neutrophil degranulation
WNT5:FZD7-mediated leishmania damping

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
Chronic granulomatous disease	Likely pathogenic; Pathogenic	rs1191361764, rs1352931329, rs1272232395, rs104894514, rs104894515, rs104894511, rs28941476, rs1567608830, rs779809359, rs771926427, rs179363892, rs179363894, rs113932941, rs747774702	RCV001826131 RCV001831390 RCV005429377 RCV001731273 RCV000208600 RCV001826407 RCV001274006 RCV003317353 RCV001830682 RCV004526773 RCV001271457 RCV004526610 RCV001828796 RCV001828951	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
CYBA-related disorder	Likely pathogenic; Pathogenic	rs179363892, rs1439134665	RCV003893090 RCV004757277	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Granulomatous disease, chronic, autosomal recessive, cytochrome b-negative	Pathogenic; Likely pathogenic	rs1284271131, rs905944088, rs2142873834, rs2142875237, rs1445023836, rs1191361764, rs1352931329, rs2142877263, rs1272232395, rs1326361967, rs758709616, rs179363892, rs2142883490, rs1907355667, rs104894513, rs104894514, rs104894515, rs1567609091, rs104894511, rs28941476, rs1907271302, rs119103269, rs2507528036, rs2507533402, rs2507521330, rs983116270, rs2507529918, rs111571762, rs2507541256, rs2507533282, rs2507533269, rs2507541496, rs1246768740, rs1907299746, rs1344198103, rs1907352884, rs1567608830, rs1567608853, rs1439134665, rs779809359, rs1597374562, rs771926427, rs179363894, rs535897564, rs763678131, rs1907272370, rs113932941, rs747774702	RCV001335108 RCV001377368 RCV001377396 RCV001378333 RCV001379559 RCV001377848 RCV001384757 RCV001383797 RCV002015070 RCV001975164 RCV001864543 RCV002036378 RCV001975001 RCV002001450 RCV000002346 RCV000002347 RCV000002348 RCV000002350 RCV000002352 RCV000002353 RCV000002354 RCV000002355 RCV003064361 RCV003064363 RCV002754998 RCV002736564 RCV002876405 RCV002966868 RCV003021493 RCV003498167 RCV003499993 RCV003498480 RCV003604268 RCV003602901 RCV003603018 RCV003603771 RCV003821216 RCV003842991 RCV003867025 RCV003990745 RCV002536414 RCV000757944 RCV000757945 RCV001384756 RCV000818649 RCV000805167 RCV000796683 RCV000687649 RCV003497833 RCV001069145 RCV001580564 RCV001211585 RCV001225987 RCV001225583 RCV001240485	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Polyglandular autoimmune syndrome, type 1	Likely pathogenic; Pathogenic	rs179363894	RCV004542731	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ASTHMA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATHEROSCLEROSIS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC ISCHEMIC HEART DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC OBSTRUCTIVE AIRWAY DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY ARTERIOSCLEROSIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CORONARY HEART DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CYBA POLYMORPHISM	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETES MELLITUS, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETES MELLITUS, NON-INSULIN-DEPENDENT	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETES MELLITUS, TYPE 2	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ESSENTIAL HYPERTENSION	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GRANULOMATOUS DISEASE, CHRONIC	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GRANULOMATOUS DISEASE, CHRONIC, AUTOSOMAL RECESSIVE, 4	—	Disgenet, HPO Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Granulomatous disease, chronic, X-linked	Likely benign	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
HEART DISEASES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEPATOMEGALY	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSION	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSIVE DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KIDNEY FAILURE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
KIDNEY FAILURE, CHRONIC	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER CIRRHOSIS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER CIRRHOSIS, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MYOCARDIAL ISCHEMIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OLIGODENDROGLIOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Very early onset inflammatory bowel disease	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute Coronary Syndrome	Coronary Syndrome	BEFREE	25990054		★☆☆☆☆ Found in Text Mining only
Adrenal Cortical Adenoma	Adrenocortical adenoma	BEFREE	19625761		★☆☆☆☆ Found in Text Mining only
Aggressive Periodontitis	Aggressive Periodontitis	BEFREE	16899095		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	35954209	Associate	★☆☆☆☆ Found in Text Mining only
Alzheimer Disease, Late Onset	Alzheimer disease	BEFREE	26000926		★☆☆☆☆ Found in Text Mining only
Anthracosis	Anthracosis	BEFREE	30654669		★☆☆☆☆ Found in Text Mining only
Arteriosclerosis	Arteriosclerosis	BEFREE	11023926, 11133215, 11914250, 12547880, 13130177, 15078863, 16788250, 19126404, 21622150, 21777168, 22268370, 29948131, 31266015		★☆☆☆☆ Found in Text Mining only
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	33145364	Associate	★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	LHGDN	18672803, 18716406		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Asthma	Asthma	BEFREE	18716406, 28510479		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atherosclerosis	Atherosclerosis	BEFREE	11023926, 11133215, 11914250, 12547880, 13130177, 15078863, 16788250, 19126404, 21622150, 21777168, 22268370, 29948131, 31266015		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atherosclerosis	Atherosclerosis	LHGDN	12547880, 17684442, 18158642		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atherosclerosis	Atherosclerosis	Pubtator	16788250, 17620958, 21622150, 33851807	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atherosclerosis	Atherosclerosis	CTD_human_DG	20720404		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autosomal Recessive Chronic Granulomatous Disease	Granulomatous disease	BEFREE	18422995, 19292887, 2243141		★☆☆☆☆ Found in Text Mining only
Autosomal Recessive Chronic Granulomatous Disease	Granulomatous disease	CTD_human_DG	2243141		★☆☆☆☆ Found in Text Mining only
B-Cell Lymphomas	B-Cell Lymphoma	BEFREE	29861101, 30605065		★☆☆☆☆ Found in Text Mining only
Brain Infarction	Brain Infarction	BEFREE	17880563		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	21792883, 30310735		★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	27740521	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	37643785	Associate	★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular Diseases	BEFREE	10754002, 17880563, 18184111, 21045268, 21622150, 22011848, 22357521, 22613645, 22919264, 29783161		★☆☆☆☆ Found in Text Mining only
Cardiovascular Diseases	Cardiovascular disease	Pubtator	15255799, 21045268, 21622150, 22919264	Associate	★☆☆☆☆ Found in Text Mining only
Carotid Atherosclerosis	Carotid Atherosclerosis	BEFREE	12547880, 22932942		★☆☆☆☆ Found in Text Mining only
Cerebral Aneurysm	Cerebral Aneurysm	BEFREE	13130177		★☆☆☆☆ Found in Text Mining only
Cerebral Infarction	Ischemic stroke	Pubtator	21963893	Associate	★☆☆☆☆ Found in Text Mining only
Cerebrovascular accident	Stroke	BEFREE	17880563, 30850755		★☆☆☆☆ Found in Text Mining only
Cerebrovascular accident	Stroke	LHGDN	17880563, 18158642, 18799874		★☆☆☆☆ Found in Text Mining only
Cerebrovascular Disorders	Cerebrovascular Disorders	BEFREE	10754002, 13130177, 18799874, 25619262		★☆☆☆☆ Found in Text Mining only
cervical cancer	Cervical Cancer	BEFREE	25307973		★☆☆☆☆ Found in Text Mining only
Cervix carcinoma	Cervix carcinoma	BEFREE	25307973		★☆☆☆☆ Found in Text Mining only
Chronic granulomatous disease	Granulomatous Disease	BEFREE	10068684, 10479485, 10759707, 10914676, 12073015, 16937026, 1763037, 18422995, 18625437, 20167518, 20407811, 22924696, 27048830, 27222152, 27666509, 28941186, 29132304, 31364312, 7517218, 7938008, 8168815, 8245781, 8615831, 9338608		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Chronic granulomatous disease	Granulomatous Disease	LHGDN	12073015		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Chronic granulomatous disease	Granulomatous Disease	CLINVAR_DG	20167518		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Chronic granulomatous disease	Granulomatous Disease	CTD_human_DG	2243141		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Chronic granulomatous disease	Granulomatous Disease	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Chronic kidney disease stage 5	Kidney Disease	BEFREE	16215641, 21045268, 25862415, 26607824, 26627442		★☆☆☆☆ Found in Text Mining only
Chronic Kidney Diseases	Kidney Disease	BEFREE	24033955		★☆☆☆☆ Found in Text Mining only
Chronic Obstructive Airway Disease	Chronic Obstructive Pulmonary Disease	BEFREE	20080081, 28729471		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chronic Obstructive Airway Disease	Chronic Obstructive Pulmonary Disease	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chronic Obstructive Airway Disease	Chronic Obstructive Pulmonary Disease	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cognition Disorders	Cognition disorder	Pubtator	21902598	Associate	★☆☆☆☆ Found in Text Mining only
Colitis Ulcerative	Ulcerative colitis	Pubtator	25599773	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	15865106		★☆☆☆☆ Found in Text Mining only
Conn Adenoma	Conn Adenoma	BEFREE	19625761		★☆☆☆☆ Found in Text Mining only
Coronary Arteriosclerosis	Coronary Arteriosclerosis	BEFREE	10440830, 10469162, 10488959, 10510050, 10865844, 11133215, 12037698, 12639216, 12877653, 16788250, 16923427, 17627182, 18239158, 18324526, 20100625, 21777168, 22613645, 24039708, 24345348, 24392120, 24415302, 27314008, 28474233, 9445163		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary Artery Disease	Coronary artery disease	BEFREE	10440830, 10469162, 10488959, 10510050, 10865844, 10996353, 11133215, 11530961, 12037698, 12639216, 14709372, 16788250, 16923427, 17627182, 18239158, 18324526, 18327409, 20100625, 20512451, 21136016, 21777168, 22613645, 23040216, 24039708, 24345348, 24392120, 24415302, 27314008, 28474233, 30296872, 9445163		★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	Pubtator	15255799, 16788250, 24477591, 27314008, 36421822	Associate	★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	LHGDN	16293794, 16788250, 16923427, 18327409		★☆☆☆☆ Found in Text Mining only
Coronary Artery Vasospasm	Coronary Artery Vasospasm	BEFREE	15172469		★☆☆☆☆ Found in Text Mining only
Coronary Disease	Coronary artery disease	Pubtator	20581851, 34883250	Associate	★☆☆☆☆ Found in Text Mining only
Coronary heart disease	Coronary Heart Disease	BEFREE	10440830, 10469162, 10488959, 10510050, 10583446, 10865844, 11133215, 12037698, 12639216, 16788250, 16923427, 17627182, 18239158, 18324526, 20100625, 21777168, 22613645, 24039708, 24345348, 24392120, 24415302, 24933031, 27314008, 28474233, 9445163		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary heart disease	Coronary Heart Disease	LHGDN	17383305, 18324526		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Coronary Stenosis	Coronary Stenosis	LHGDN	16788250		★☆☆☆☆ Found in Text Mining only
Coronary Stenosis	Coronary stenosis	Pubtator	16788250	Associate	★☆☆☆☆ Found in Text Mining only
Coronary Vasospasm	Coronary vasospasm	Pubtator	16998253	Associate	★☆☆☆☆ Found in Text Mining only
Crohn Disease	Crohn disease	Pubtator	29454792	Associate	★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	LHGDN	18077487		★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	BEFREE	23922196		★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	16759310, 19118408, 21622150, 26607824		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes mellitus	Pubtator	12226552, 21622150	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	16759310, 19118408, 21622150, 22268370, 26607824		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 1	Diabetes mellitus, type 1	Pubtator	21962117	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	21622150, 23701472, 33851807, 34883250	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Insulin-Dependent	Diabetes Mellitus	BEFREE	14578247, 14679084, 21962117, 25862415, 26607824, 29924645		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	12547880, 16358232, 16759310, 16922713, 21237524, 21622150, 22932942, 23701472, 24156725, 24621175, 26130419		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	CTD_human_DG	15531508		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Diabetic Nephropathies	Diabetic neuropathy	Pubtator	21962117, 33161510	Associate	★☆☆☆☆ Found in Text Mining only
Diabetic Nephropathy	Diabetic Nephropathy	BEFREE	14578247, 14747204, 16358232, 21962117, 25041504, 25862415, 28457704		★☆☆☆☆ Found in Text Mining only
Diabetic Nephropathy	Diabetic Nephropathy	LHGDN	14747204, 17336700		★☆☆☆☆ Found in Text Mining only
Diabetic Polyneuropathies	Diabetic polyneuropathy	BEFREE	26130419		★☆☆☆☆ Found in Text Mining only
Diffuse Large B-Cell Lymphoma	Diffuse Lymphoma	BEFREE	19448608		★☆☆☆☆ Found in Text Mining only
Dystonic Disorders	Dystonia	Pubtator	19279361	Associate	★☆☆☆☆ Found in Text Mining only
Dystrophia myotonica 2	Myotonic dystrophy	BEFREE	26130419		★☆☆☆☆ Found in Text Mining only
Eclampsia	Eclampsia	BEFREE	12037698		★☆☆☆☆ Found in Text Mining only
Eczema	Eczema	HPO_DG			★☆☆☆☆ Found in Text Mining only
Endometrial Neoplasms	Endometrial neoplasm	Pubtator	37322935	Associate	★☆☆☆☆ Found in Text Mining only
Essential Hypertension	Hypertension	BEFREE	15210651, 16794479, 17620958		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Essential Hypertension	Hypertension	Pubtator	17620958, 23701472	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Fabry Disease	Fabry disease	Pubtator	30261035	Associate	★☆☆☆☆ Found in Text Mining only
Fatty Liver Disease	Fatty Liver	BEFREE	30087027		★☆☆☆☆ Found in Text Mining only
Fibrosis, Liver	Liver Fibrosis	CTD_human_DG	25226513		★☆☆☆☆ Found in Text Mining only
Gastritis	Gastritis	BEFREE	19089790		★☆☆☆☆ Found in Text Mining only
Gingivitis	Gingivitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glaucoma	Glaucoma	BEFREE	22919264		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	34646273	Associate	★☆☆☆☆ Found in Text Mining only
Glomerulonephritis	Glomerulonephritis	Pubtator	26627442	Associate	★☆☆☆☆ Found in Text Mining only
Granulomatosis	Granulomatosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Granulomatous Disease Chronic	Granulomatous disease	Pubtator	10627478, 10706888, 10759707, 10910929, 1332032, 1415254, 1763037, 18422995, 22924696, 28356734, 28830888, 29132304, 30506560, 31364312, 33717137, 33746979, 35842407, 36122532, 36705996, 7517218, 7919388, 7949143, 8083361, 8182143, 8245781, 8615831	Associate	★☆☆☆☆ Found in Text Mining only
Granulomatous Disease, Chronic, Autosomal Recessive, Cytochrome B-Negative	Granulomatous Disease	GENOMICS_ENGLAND_DG	10759707, 27537055		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Granulomatous Disease, Chronic, Autosomal Recessive, Cytochrome B-Negative	Granulomatous Disease	UNIPROT_DG	10759707, 10910929, 10914676, 1415254, 1763037, 18422995, 2243141, 23910690, 7964505, 8168815		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Granulomatous Disease, Chronic, Autosomal Recessive, Cytochrome B-Negative	Granulomatous Disease	CLINVAR_DG	10759707, 10910929, 19292887		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Granulomatous Disease, Chronic, Autosomal Recessive, Cytochrome B-Negative	Granulomatous Disease	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Granulomatous Disease, Chronic, X-Linked	Granulomatous Disease	CTD_human_DG	2243141		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Granulomatous Disease, Chronic, X-Linked	Granulomatous Disease	BEFREE	29132304		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Heart Diseases	Heart Diseases	CTD_human_DG	16330681		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Heart Diseases	Heart disease	Pubtator	23576480	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Heart Diseases	Heart Diseases	BEFREE	27048830		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
High altitude pulmonary edema	High Altitude Pulmonary Edema	BEFREE	14561241, 21973220		★☆☆☆☆ Found in Text Mining only
Hodgkin Disease	Hodgkin disease	Pubtator	24376854	Associate	★☆☆☆☆ Found in Text Mining only
Hypercholesterolemia	Hypercholesterolemia	BEFREE	12639216, 14709372, 17627182, 21777168		★☆☆☆☆ Found in Text Mining only
Hypercholesterolemia	Hypercholesterolemia	LHGDN	17627182		★☆☆☆☆ Found in Text Mining only
Hyperglycemia	Hyperglycemia	BEFREE	24936444		★☆☆☆☆ Found in Text Mining only
Hypertension	Hypertension	Pubtator	15671602, 17620958, 19516159, 21884584, 24339896, 27314008	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypertensive disease	Hypertension	LHGDN	11910303, 12729892, 16115038, 17336700, 17620958, 18158642		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypertensive disease	Hypertension	BEFREE	14965315, 15210651, 15671602, 16026320, 16794479, 17314996, 17336700, 19043982, 19516159, 20798523, 22268370, 23701472, 24339896, 24349292, 24573492, 25787042, 27314008, 28729471		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypertensive disease	Hypertension	CTD_human_DG	16685210, 17324946, 20505675		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypertrophy Left Ventricular	Left ventricular disease	Pubtator	27314008	Associate	★☆☆☆☆ Found in Text Mining only
Hyperuricemia	Hyperuricemia	BEFREE	15135268, 15172469		★☆☆☆☆ Found in Text Mining only
Hypocholesterolemia	Hypocholesterolemia	BEFREE	21042717		★☆☆☆☆ Found in Text Mining only
Hypoxia	Hypoxia	Pubtator	30367082	Associate	★☆☆☆☆ Found in Text Mining only
Idiopathic Pulmonary Fibrosis	Idiopathic pulmonary fibrosis	Pubtator	40294812	Associate	★☆☆☆☆ Found in Text Mining only
Immune System Diseases	Immune system disease	Pubtator	35482138	Associate	★☆☆☆☆ Found in Text Mining only
Immunologic Deficiency Syndromes	Immunologic Deficiency Syndromes	HPO_DG			★☆☆☆☆ Found in Text Mining only
Inflammatory abnormality of the eye	Inflammatory abnormality of the eye	BEFREE	26415877		★☆☆☆☆ Found in Text Mining only
Inflammatory abnormality of the eye	Inflammatory abnormality of the eye	HPO_DG			★☆☆☆☆ Found in Text Mining only
Inflammatory Bowel Disease 25 Autosomal Recessive	Inflammatory bowel disease	Pubtator	30709874	Associate	★☆☆☆☆ Found in Text Mining only
Inflammatory Bowel Diseases	Inflammatory bowel disease	Pubtator	30709874, 39273699	Associate	★☆☆☆☆ Found in Text Mining only
Insulin Resistance	Diabetes mellitus, type 2	Pubtator	12226552	Associate	★☆☆☆☆ Found in Text Mining only
Intracranial Aneurysm	Intracranial Aneurysm	BEFREE	13130177, 30226557		★☆☆☆☆ Found in Text Mining only
Intrahepatic Cholangiocarcinoma	Intrahepatic Cholangiocarcinoma	BEFREE	25307973		★☆☆☆☆ Found in Text Mining only
Ischemic stroke	Ischemic Stroke	BEFREE	17880563, 21082491, 23684671		★☆☆☆☆ Found in Text Mining only
Kidney Diseases	Kidney Disease	BEFREE	14747204, 16358232, 16922713, 21962117		★☆☆☆☆ Found in Text Mining only
Kidney Diseases	Kidney disease	Pubtator	21962117	Associate	★☆☆☆☆ Found in Text Mining only
Kidney Failure	Kidney Failure	BEFREE	21045268, 26627442		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Kidney Failure	Kidney Failure	CTD_human_DG	23325087		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Kidney Failure Chronic	Kidney failure	Pubtator	21045268, 26627442	Associate	★☆☆☆☆ Found in Text Mining only
Kidney Failure, Acute	Kidney Failure	BEFREE	17151330		★☆☆☆☆ Found in Text Mining only
Kidney Failure, Chronic	Kidney Failure	BEFREE	16215641, 21045268, 25862415, 26607824, 26627442		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Kidney Failure, Chronic	Kidney Failure	LHGDN	16215641		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Kidney Failure, Chronic	Kidney Failure	CTD_human_DG	19420110		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Left Ventricular Hypertrophy	Left Ventricular Hypertrophy	BEFREE	17314996		★☆☆☆☆ Found in Text Mining only
leukemia	Leukemia	LHGDN	16754784		★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	22807997	Associate	★☆☆☆☆ Found in Text Mining only
Lip and Oral Cavity Carcinoma	Lip and Oral Cavity Carcinoma	BEFREE	28498554		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	27740521		★☆☆☆☆ Found in Text Mining only
Liver Cirrhosis	Liver Cirrhosis	CTD_human_DG	25226513		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Low Tension Glaucoma	Low Tension Glaucoma	BEFREE	22919264		★☆☆☆☆ Found in Text Mining only
Lung diseases	Lung Diseases	BEFREE	30654669		★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus, Discoid	Lupus Erythematosus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus, Systemic	Lupus Erythematosus	BEFREE	19965945		★☆☆☆☆ Found in Text Mining only
Lymphadenitis	Lymphadenitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lymphoma, Non-Hodgkin	Non-Hodgkin lymphoma	BEFREE	17149600, 20215507		★☆☆☆☆ Found in Text Mining only
Lymphoma, Non-Hodgkin, Familial	Lymphoma	BEFREE	20215507		★☆☆☆☆ Found in Text Mining only
Macular Degeneration	Macular degeneration	Pubtator	31485293	Stimulate	★☆☆☆☆ Found in Text Mining only
Malabsorption Syndrome	Malabsorption Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	21792883, 30310735		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of mouth	Malignant neoplasm of mouth	BEFREE	28498554		★☆☆☆☆ Found in Text Mining only
Malignant tumor of cervix	Cervical Tumor	BEFREE	25307973		★☆☆☆☆ Found in Text Mining only
Mediastinal lymphadenopathy	Mediastinal lymphadenopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	29342889	Associate	★☆☆☆☆ Found in Text Mining only
Metabolic Syndrome	Metabolic syndrome	Pubtator	22396743	Associate	★☆☆☆☆ Found in Text Mining only
Metabolic Syndrome X	Metabolic Syndrome	BEFREE	25888935, 30087027		★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple sclerosis	Pubtator	35073438	Associate	★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis Chronic Progressive	Multiple sclerosis	Pubtator	35073438	Associate	★☆☆☆☆ Found in Text Mining only
MYELODYSPLASTIC SYNDROME	Myelodysplastic Syndrome	BEFREE	12962720		★☆☆☆☆ Found in Text Mining only
Myelodysplastic Syndromes	Myelodysplastic syndrome	Pubtator	24719867	Associate	★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial Infarction	BEFREE	10469162, 16998253, 21136016, 23040216		★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial infarction	Pubtator	15255799, 16998253	Associate	★☆☆☆☆ Found in Text Mining only
Myocardial Ischemia	Myocardial Ischemia	BEFREE	12877653		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Necrosis	Necrosis	Pubtator	23576480	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	28498554		★☆☆☆☆ Found in Text Mining only
Nephrotic Syndrome	Nephrotic syndrome	Pubtator	35173708	Inhibit	★☆☆☆☆ Found in Text Mining only
Neural Tube Defects	Neural tube defect	Pubtator	12962720	Associate	★☆☆☆☆ Found in Text Mining only
Non-alcoholic Fatty Liver Disease	Non-Alcoholic Fatty Liver Disease	BEFREE	30087027, 30298849		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	22268370, 30298849, 31284000		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	Pubtator	24477591, 27765769	Associate	★☆☆☆☆ Found in Text Mining only
Osteoarthritis	Osteoarthritis	Pubtator	38292759	Associate	★☆☆☆☆ Found in Text Mining only
Osteoarthritis, Knee	Knee osteoarthritis	BEFREE	23922196		★☆☆☆☆ Found in Text Mining only
Osteomyelitis	Osteomyelitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Otitis Media	Otitis media	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	21118808	Associate	★☆☆☆☆ Found in Text Mining only
Peripheral Arterial Diseases	Vascular Diseases	BEFREE	22199011		★☆☆☆☆ Found in Text Mining only
Peroxisome Biogenesis Disorder, Complementation Group D	Zellweger Syndrome	BEFREE	29132304		★☆☆☆☆ Found in Text Mining only
Pulmonary Arterial Hypertension	Pulmonary arterial hypertension	Pubtator	15255799, 23701472	Associate	★☆☆☆☆ Found in Text Mining only
Pulmonary Edema	Pulmonary edema	Pubtator	34883250	Associate	★☆☆☆☆ Found in Text Mining only
Refractory anemias	Anemia	BEFREE	29183727		★☆☆☆☆ Found in Text Mining only
Renal Insufficiency	Renal Insufficiency	CTD_human_DG	23325087		★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	BEFREE	29183727		★☆☆☆☆ Found in Text Mining only
Sinusitis	Sinusitis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sleep Apnea Obstructive	Sleep apnea	Pubtator	21872458, 21902598, 31819149	Associate	★☆☆☆☆ Found in Text Mining only
Sleep Apnea, Obstructive	Sleep Apnea	BEFREE	19567155, 21872458, 21902598, 31819149		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma	Carcinoma	BEFREE	28498554		★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	25686830	Associate	★☆☆☆☆ Found in Text Mining only
Status Epilepticus	Status Epilepticus	BEFREE	30983975		★☆☆☆☆ Found in Text Mining only
Systemic Scleroderma	Scleroderma	BEFREE	15530459		★☆☆☆☆ Found in Text Mining only
T-Cell Lymphoma	T-Cell Lymphoma	BEFREE	17149600		★☆☆☆☆ Found in Text Mining only
Tetralogy of Fallot	Tetralogy of Fallot	LHGDN	17445342		★☆☆☆☆ Found in Text Mining only
Ulcerative Colitis	Ulcerative colitis	BEFREE	25599773		★☆☆☆☆ Found in Text Mining only
Uterine Cervical Neoplasms	Uterine neoplasm	Pubtator	25307973	Associate	★☆☆☆☆ Found in Text Mining only
Vascular Diseases	Vascular Diseases	BEFREE	19965945		★☆☆☆☆ Found in Text Mining only
Vascular Diseases	Vascular disease	Pubtator	33851807	Associate	★☆☆☆☆ Found in Text Mining only