TMPRSS6 (transmembrane serine protease 6)

Gene

• Entrez ID: 164656
• Gene name: Transmembrane serine protease 6
• Gene symbol: TMPRSS6
• Synonyms (NCBI Gene): IRIDA, MT2
• Chromosome: 22
• Chromosome location: 22q12.3
• Summary: The protein encoded by this gene is a type II transmembrane serine proteinase that is found attached to the cell surface. The encoded protein may be involved in matrix remodeling processes in the liver. Alternative splicing results in multiple transcript

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs137853119	C>T	Pathogenic	Coding sequence variant, missense variant
rs137853120	C>T	Pathogenic	Coding sequence variant, missense variant
rs137853121	G>T	Pathogenic	Coding sequence variant, stop gained
rs137853122	A>C	Pathogenic	Coding sequence variant, stop gained
rs137853123	G>A	Pathogenic-likely-pathogenic	Coding sequence variant, stop gained
rs267607121	G>T	Pathogenic	Coding sequence variant, missense variant
rs387907018	C>T	Pathogenic	Missense variant, coding sequence variant
rs767094129	CC>-,C,CCC	Pathogenic	Frameshift variant, coding sequence variant
rs775869554	G>A	Pathogenic	Coding sequence variant, stop gained
rs786205058	C>T	Pathogenic	Splice donor variant
rs786205059	C>G	Pathogenic	Splice donor variant
rs786205060	->GGGG	Pathogenic	Frameshift variant, coding sequence variant
rs869320724	->GC	Pathogenic	Frameshift variant, coding sequence variant
rs1384933966	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs1569024289	G>C	Pathogenic	Coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT030016	hsa-miR-26b-5p	Microarray	19088304
MIRT721887	hsa-miR-6798-5p	HITS-CLIP	19536157
MIRT721886	hsa-miR-6742-3p	HITS-CLIP	19536157
MIRT721885	hsa-miR-1266-5p	HITS-CLIP	19536157
MIRT721884	hsa-miR-4518	HITS-CLIP	19536157
MIRT721883	hsa-miR-661	HITS-CLIP	19536157
MIRT721882	hsa-miR-2861	HITS-CLIP	19536157
MIRT721881	hsa-miR-6772-5p	HITS-CLIP	19536157
MIRT721880	hsa-miR-4455	HITS-CLIP	19536157
MIRT721879	hsa-miR-609	HITS-CLIP	19536157
MIRT721878	hsa-miR-4417	HITS-CLIP	19536157
MIRT721877	hsa-miR-4265	HITS-CLIP	19536157
MIRT721876	hsa-miR-4296	HITS-CLIP	19536157
MIRT721875	hsa-miR-4322	HITS-CLIP	19536157
MIRT721887	hsa-miR-6798-5p	HITS-CLIP	19536157
MIRT721886	hsa-miR-6742-3p	HITS-CLIP	19536157
MIRT721885	hsa-miR-1266-5p	HITS-CLIP	19536157
MIRT721884	hsa-miR-4518	HITS-CLIP	19536157
MIRT721883	hsa-miR-661	HITS-CLIP	19536157
MIRT721882	hsa-miR-2861	HITS-CLIP	19536157
MIRT721881	hsa-miR-6772-5p	HITS-CLIP	19536157
MIRT721880	hsa-miR-4455	HITS-CLIP	19536157
MIRT721879	hsa-miR-609	HITS-CLIP	19536157
MIRT721878	hsa-miR-4417	HITS-CLIP	19536157
MIRT721877	hsa-miR-4265	HITS-CLIP	19536157
MIRT721876	hsa-miR-4296	HITS-CLIP	19536157
MIRT721875	hsa-miR-4322	HITS-CLIP	19536157
MIRT1441176	hsa-miR-1179	CLIP-seq
MIRT1441177	hsa-miR-1291	CLIP-seq
MIRT1441178	hsa-miR-296-5p	CLIP-seq
MIRT1441179	hsa-miR-3173-5p	CLIP-seq
MIRT1441180	hsa-miR-338-3p	CLIP-seq
MIRT1441181	hsa-miR-3689d	CLIP-seq
MIRT1441182	hsa-miR-4252	CLIP-seq
MIRT1441183	hsa-miR-4310	CLIP-seq
MIRT1441184	hsa-miR-4459	CLIP-seq
MIRT1441185	hsa-miR-4663	CLIP-seq
MIRT1441186	hsa-miR-541	CLIP-seq
MIRT1441187	hsa-miR-654-5p	CLIP-seq
MIRT1441188	hsa-miR-665	CLIP-seq
MIRT1441176	hsa-miR-1179	CLIP-seq
MIRT1441180	hsa-miR-338-3p	CLIP-seq
MIRT1441182	hsa-miR-4252	CLIP-seq
MIRT1441183	hsa-miR-4310	CLIP-seq
MIRT1441185	hsa-miR-4663	CLIP-seq
MIRT1441176	hsa-miR-1179	CLIP-seq
MIRT1441182	hsa-miR-4252	CLIP-seq
MIRT2353191	hsa-miR-4492	CLIP-seq
MIRT2353192	hsa-miR-4498	CLIP-seq
MIRT1441185	hsa-miR-4663	CLIP-seq
MIRT2353193	hsa-miR-762	CLIP-seq
MIRT1441176	hsa-miR-1179	CLIP-seq
MIRT1441182	hsa-miR-4252	CLIP-seq
MIRT1441183	hsa-miR-4310	CLIP-seq
MIRT1441185	hsa-miR-4663	CLIP-seq
MIRT2646818	hsa-miR-34a	CLIP-seq
MIRT2646819	hsa-miR-34c-5p	CLIP-seq
MIRT2646820	hsa-miR-3684	CLIP-seq
MIRT2646821	hsa-miR-449a	CLIP-seq
MIRT2646822	hsa-miR-449b	CLIP-seq
MIRT2646823	hsa-miR-4646-3p	CLIP-seq
MIRT2646824	hsa-miR-4671-5p	CLIP-seq
MIRT2646818	hsa-miR-34a	CLIP-seq
MIRT2646819	hsa-miR-34c-5p	CLIP-seq
MIRT2646820	hsa-miR-3684	CLIP-seq
MIRT2646821	hsa-miR-449a	CLIP-seq
MIRT2646822	hsa-miR-449b	CLIP-seq
MIRT2646823	hsa-miR-4646-3p	CLIP-seq
MIRT2646824	hsa-miR-4671-5p	CLIP-seq
MIRT2693590	hsa-miR-765	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IEA
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	ISS
GO:0004222	Function	Metalloendopeptidase activity	TAS
GO:0004252	Function	Serine-type endopeptidase activity	IEA
GO:0005515	Function	Protein binding	IPI	18976966, 19357398, 32814053
GO:0005615	Component	Extracellular space	IDA	25156943
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA	19357398
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0006508	Process	Proteolysis	IEA
GO:0006879	Process	Intracellular iron ion homeostasis	IEA
GO:0006879	Process	Intracellular iron ion homeostasis	ISS
GO:0008233	Function	Peptidase activity	IEA
GO:0008236	Function	Serine-type peptidase activity	IBA
GO:0008236	Function	Serine-type peptidase activity	IEA
GO:0016020	Component	Membrane	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0022617	Process	Extracellular matrix disassembly	TAS
GO:0030509	Process	BMP signaling pathway	IEA
GO:0030514	Process	Negative regulation of BMP signaling pathway	IEA
GO:0030574	Process	Collagen catabolic process	TAS
GO:0033619	Process	Membrane protein proteolysis	IMP	25156943
GO:0045892	Process	Negative regulation of DNA-templated transcription	IEA
GO:0045892	Process	Negative regulation of DNA-templated transcription	IMP	25156943
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	ISS
GO:0060586	Process	Multicellular organismal-level iron ion homeostasis	IEA
GO:0060586	Process	Multicellular organismal-level iron ion homeostasis	IEA
GO:0060586	Process	Multicellular organismal-level iron ion homeostasis	IMP	18408718
GO:0097264	Process	Self proteolysis	IMP	25156943

Other IDs

• MIM: 609862
• HGNC: 16517
• e!Ensembl: ENSG00000187045

Protein

• UniProt ID: Q8IU80
• Protein name: Transmembrane protease serine 6 (EC 3.4.21.-) (Matriptase-2)
• Protein function: Membrane-bound serine protease (PubMed:18976966, PubMed:20518742, PubMed:25156943, PubMed:25588876). Through the cleavage of cell surface hemojuvelin (HJV), a regulator of the expression of the iron absorption-regulating hormone hepicidin/HAMP,
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01390	SEA	86 → 192	SEA domain	Family
  PF00057	Ldl_recept_a	490 → 525	Low-density lipoprotein receptor domain class A	Repeat
  PF00057	Ldl_recept_a	529 → 566	Low-density lipoprotein receptor domain class A	Repeat
  PF00089	Trypsin	577 → 806	Trypsin	Domain

• Sequence:

  MLLLFHSKRMPVAEAPQVAGGQGDGGDGEEAEPEGMFKACEDSKRKARGYLRLVPLFVLL
  ALLVLASAGVLLWYFLGYKAEVMVSQVYSGSLRVLNRHFSQDLTRRESSAFRSETAKAQK
  MLKELITSTRLGTYYNSSSVYSFGEGPLTCFFWFILQIPEHRRLMLSPEVVQALLVEELL
  STVNSSAAVPYRAEYEVDPEGLVILEASVKDIAALNSTLGCYRYSYVGQGQVLRLKGPDH
  LASSCLWHLQGPKDLMLKLRLEWTLAECRDRLAMYDVAGPLEKRLITSVYGCSRQEPVVE
  VLASGAIMAVVWKKGLHSYYDPFVLSVQPVVFQACEVNLTLDNRLDSQGVLSTPYFPSYY
  SPQTHCSWHLTVPSLDYGLALWFDAYALRRQKYDLPCTQGQWTIQNRRLCGLRILQPYAE
  RIPVVATAGITINFTSQISLTGPGVRVHYGLYNQSDPCPGEFLCSVNGLCVPACDGVKDC
  PNGLDERNCVCRATFQCKEDSTCISLPKVCDGQPDCLNGSDEEQCQEGVPCGTFTFQCED
  RSCVKKPNPQCDGRPDCRDGSDEEHCDCGLQGPSSRIVGGAVSSEGEWPWQASLQVRGRH
  ICGGALIADRWVITAAHCFQEDSMASTVLWTVFLGKVWQNSRWPGEVSFKVSRLLLHPYH
  EEDSHDYDVALLQLDHPVVRSAAVRPVCLPARSHFFEPGLHCWITGWGALREGGPISNAL
  QKVDVQLIPQDLCSEVYRYQVTPRMLCAGYRKGKKDACQGDSGGPLVCKALSGRWFLAGL
  VSWGLGCGRPNYFGVYTRITGVISWIQQVVT

• Sequence length: 811

Pathways

Reactome:

Collagen degradation
Degradation of the extracellular matrix

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
Abnormality of metabolism/homeostasis	Likely pathogenic	rs2146038092	RCV001814410	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Iron-refractory iron deficiency anemia	Likely pathogenic; Pathogenic	rs2146057214, rs869320724, rs767094129, rs786205058, rs786205059, rs137853119, rs137853120, rs137853121, rs1384933966, rs137853122, rs137853123, rs786205060, rs267607121, rs776912815, rs918426003, rs387907018	RCV001730052 RCV000001464 RCV000001465 RCV000001466 RCV000001467 RCV000001468 RCV001375845 RCV000001470 RCV000001471 RCV000001472 RCV001375844 RCV000001474 RCV000001475 RCV002810026 RCV005356520 RCV000023787	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Microcytic anemia	Likely pathogenic; Pathogenic	rs137853120, rs137853123, rs1569024289, rs775869554, rs1927509977, rs1930010425	RCV000001469 RCV000001473 RCV000754711 RCV000770971 RCV001250722 RCV001250721	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
TMPRSS6-related disorder	Likely pathogenic	rs137853120, rs137853121, rs2517768538	RCV004755696 RCV003952335 RCV003403018	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ANEMIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANEMIA, IRON-DEFICIENCY	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
IRON METABOLISM DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OTHER SPECIFIED IRON DEFICIENCY ANEMIAS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
POLYCYTHEMIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
3 beta-Hydroxysteroid dehydrogenase deficiency	3 beta-hydroxysteroid dehydrogenase deficiency	BEFREE	12050213		★☆☆☆☆ Found in Text Mining only
AMYOTROPHIC LATERAL SCLEROSIS 1	Lateral Sclerosis	BEFREE	11298796		★☆☆☆☆ Found in Text Mining only
Androgen-Insensitivity Syndrome	Androgen-Insensitivity Syndrome	BEFREE	21480980, 25257530, 27314307		★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	BEFREE	19377077, 21622652, 22323359, 22509377, 23433094, 24319154, 24904115, 25557470, 29498084		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Anemia	Anemia	Pubtator	23433094, 25557470, 30984307, 34444942	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Anemia Hemolytic	Hemolytic anemia	Pubtator	22509377, 24175968	Associate	★☆☆☆☆ Found in Text Mining only
Anemia hypochromic microcytic	Hypochromic microcytic anemia	Pubtator	18596229	Associate	★☆☆☆☆ Found in Text Mining only
Anemia Iron Deficiency	Iron deficiency anemia	Pubtator	18408718, 18596229, 18603562, 19357398, 19818657, 20713458, 20966077, 21873547, 22581667, 23319530, 24782651, 24867957, 25557470, 25588876, 28447549, 28460265, 29194702, 32446932, 34444942, 34780475, 39582459	Associate	★☆☆☆☆ Found in Text Mining only
beta Thalassemia	Beta thalassemia	Pubtator	23144979	Associate	★☆☆☆☆ Found in Text Mining only
Beta thalassemia intermedia	beta Thalassemia	BEFREE	25425686, 29498084		★☆☆☆☆ Found in Text Mining only
Bladder Neoplasm	Bladder Neoplasm	BEFREE	11270423		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	16533768, 23649491, 9694254		★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	30135444	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of bladder	Bladder carcinoma	BEFREE	11270423		★☆☆☆☆ Found in Text Mining only
Celiac Disease	Celiac disease	BEFREE	29194702		★☆☆☆☆ Found in Text Mining only
Celiac Disease	Celiac disease	Pubtator	29194702, 34444942	Associate	★☆☆☆☆ Found in Text Mining only
Childhood Acute Lymphoblastic Leukemia	Lymphoblastic Leukemia	BEFREE	25085015		★☆☆☆☆ Found in Text Mining only
Chronic Disease	Chronic disease	Pubtator	23433094	Associate	★☆☆☆☆ Found in Text Mining only
Colitis	Colitis	BEFREE	24452846		★☆☆☆☆ Found in Text Mining only
Coronary Artery Disease	Coronary artery disease	Pubtator	28684612	Associate	★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	19708722, 21353709		★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	29136618, 29464840		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	29136618, 29464840		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes mellitus	Pubtator	36585034	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	22301935, 22815867	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	22301935, 23798576, 29637854		★☆☆☆☆ Found in Text Mining only
Down Syndrome	Down Syndrome	BEFREE	31540037		★☆☆☆☆ Found in Text Mining only
Endometrial Carcinoma	Endometrial carcinoma	BEFREE	28382516		★☆☆☆☆ Found in Text Mining only
Fabry Disease	Fabry disease	Pubtator	36140670	Associate	★☆☆☆☆ Found in Text Mining only
Fatty Liver Disease	Fatty Liver	BEFREE	28051796		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	27898674	Associate	★☆☆☆☆ Found in Text Mining only
Glycogen Storage Disease XII	Glycogen storage disease	Pubtator	33887194	Associate	★☆☆☆☆ Found in Text Mining only
Hamartoma Syndrome, Multiple	Hamartoma	BEFREE	29194702		★☆☆☆☆ Found in Text Mining only
Heart Diseases	Heart disease	Pubtator	31226389	Associate	★☆☆☆☆ Found in Text Mining only
Hemochromatosis	Hemochromatosis	BEFREE	21355094, 24319154, 28219045, 30536387		★☆☆☆☆ Found in Text Mining only
Hemochromatosis	Hemochromatosis	Pubtator	23433094	Associate	★☆☆☆☆ Found in Text Mining only
HEMOCHROMATOSIS, TYPE 1	Hemochromatosis	BEFREE	21355094, 23468552, 24319154, 25085015, 28219045, 30536387		★☆☆☆☆ Found in Text Mining only
Hepatitis C Chronic	Hepatitis c	Pubtator	37632052	Associate	★☆☆☆☆ Found in Text Mining only
Hereditary hemochromatosis	Hereditary Hemochromatosis	BEFREE	22885719, 23433094, 25976471, 28555756		★☆☆☆☆ Found in Text Mining only
HFE-Associated Hereditary Hemochromatosis	Hemochromatosis	BEFREE	21355094		★☆☆☆☆ Found in Text Mining only
Hodgkin Disease	Hodgkin Disease	BEFREE	9694254		★☆☆☆☆ Found in Text Mining only
Hypercholesterolemia	Hypercholesterolemia	Pubtator	31220083	Associate	★☆☆☆☆ Found in Text Mining only
Hyperferritinemia	Hyperferritinemia	Pubtator	23319530	Associate	★☆☆☆☆ Found in Text Mining only
Hyperinsulinism	Hyperinsulinism	BEFREE	31624901		★☆☆☆☆ Found in Text Mining only
Hyperkeratosis	Hyperkeratosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoxia	Hypoxia	Pubtator	20966077	Stimulate	★☆☆☆☆ Found in Text Mining only
Ichthyoses	Ichthyosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intrahepatic Cholestasis	Intrahepatic Cholestasis	HPO_DG			★☆☆☆☆ Found in Text Mining only
IRIDA syndrome	IRIDA Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Iron deficiency anemia	Iron deficiency anemia	BEFREE	18408718, 18596229, 19386032, 19818657, 20738301, 20966077, 22323359, 22509377, 23319530, 24782651, 25557470, 28447549, 29073189, 29194702, 29928945		★☆☆☆☆ Found in Text Mining only
Iron deficiency anemia	Iron deficiency anemia	CTD_human_DG	18408718, 22169218		★☆☆☆☆ Found in Text Mining only
Iron Metabolism Disorders	Iron Metabolism Disorders	BEFREE	19386032, 30135444		★☆☆☆☆ Found in Text Mining only
Iron Overload	Iron Overload	BEFREE	21355094, 22301935, 23144979, 26762582, 28219045, 28555756, 29498084, 30945556		★☆☆☆☆ Found in Text Mining only
Iron Overload	Iron overload	Pubtator	22301935, 23144979	Associate	★☆☆☆☆ Found in Text Mining only
Iron-Refractory Iron Deficiency Anemia	Anemia	BEFREE	18408718, 18596229, 19357398, 19377077, 19592582, 19708871, 19786206, 20232450, 20713458, 20738301, 21150441, 21355094, 21618415, 21622652, 21643693, 21783390, 22169218, 22509377, 22581667, 23180434, 23319530, 25064705, 25156943, 25425686, 25557470, 25588876, 27120435, 28169443, 28460265, 29927322, 30130276, 30135444, 30594846, 31714439		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Iron-Refractory Iron Deficiency Anemia	Anemia	GENOMICS_ENGLAND_DG	18408718		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Iron-Refractory Iron Deficiency Anemia	Anemia	UNIPROT_DG	18408718, 18603562, 19357398, 19592582, 19708871, 19747362, 20232450, 20704562, 21618415, 22581667, 25156943, 25588876		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Iron-Refractory Iron Deficiency Anemia	Anemia	ORPHANET_DG	19357398, 20232450, 25252070		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Iron-Refractory Iron Deficiency Anemia	Anemia	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Iron-Refractory Iron Deficiency Anemia	Anemia	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Juvenile hemochromatosis	Hemochromatosis	BEFREE	25588876		★☆☆☆☆ Found in Text Mining only
Kidney Diseases	Kidney disease	Pubtator	34437439	Associate	★☆☆☆☆ Found in Text Mining only
Kidney Failure Chronic	Kidney failure	Pubtator	30984307	Associate	★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	30135444		★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus Systemic	Systemic lupus erythematosus	Pubtator	33693920	Associate	★☆☆☆☆ Found in Text Mining only
Major Depressive Disorder	Mental Depression	BEFREE	19708722		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	16533768, 23649491, 9694254		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of endometrium	Endometrial Cancer	BEFREE	28382516		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	18449907, 22858929, 30518272		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of urinary bladder	Urinary bladder cancer	BEFREE	11270423		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	20015002, 22858929, 26862950, 29854276, 30518272		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	BEFREE	11888668, 23238872, 23649491		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	LHGDN	16533768, 17575220		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	19708722, 21353709		★☆☆☆☆ Found in Text Mining only
Microcytic hypochromic anemia (disorder)	Anemia	BEFREE	27120435		★☆☆☆☆ Found in Text Mining only
Microcytic hypochromic anemia (disorder)	Anemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple Sclerosis	BEFREE	26746433		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	23238872, 26862950, 28507478		★☆☆☆☆ Found in Text Mining only
Non-alcoholic Fatty Liver Disease	Non-Alcoholic Fatty Liver Disease	BEFREE	23144979		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	29636509		★☆☆☆☆ Found in Text Mining only
Osteoporosis, Postmenopausal	Osteoporosis	BEFREE	28512916		★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	BEFREE	20110911		★☆☆☆☆ Found in Text Mining only
Periodontal Diseases	Periodontal Diseases	BEFREE	31540037		★☆☆☆☆ Found in Text Mining only
Peripheral Arterial Disease	Peripheral arterial disease	Pubtator	20927387	Associate	★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Nervous System Diseases	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pica Disease	Pica	BEFREE	22265928		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	18449907, 22858929		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic Neoplasms	LHGDN	18449907		★☆☆☆☆ Found in Text Mining only
Recurrent depressive disorder	Mental Depression	BEFREE	21353709		★☆☆☆☆ Found in Text Mining only
Refractory anemias	Anemia	BEFREE	18408718		★☆☆☆☆ Found in Text Mining only
Restless Legs Syndrome	Restless Legs Syndrome	BEFREE	26597663		★☆☆☆☆ Found in Text Mining only
Sleep Disorders	Sleep Disorders	BEFREE	23971978, 28382516		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma	Carcinoma	BEFREE	26862950		★☆☆☆☆ Found in Text Mining only
Thalassemia	Thalassemia	Pubtator	25557470	Associate	★☆☆☆☆ Found in Text Mining only
Triple Negative Breast Neoplasms	Triple Negative Breast Neoplasms	BEFREE	23649491		★☆☆☆☆ Found in Text Mining only