TJP2 (tight junction protein 2)

Gene

• Entrez ID: 9414
• Gene name: Tight junction protein 2
• Gene symbol: TJP2
• Synonyms (NCBI Gene): C9DUPq21.11, DFNA51, DUP9q21.11, FHCA1, PFIC4, X104, ZO2
• Chromosome: 9
• Chromosome location: 9q21.11
• Summary: This gene encodes a zonula occluden that is a member of the membrane-associated guanylate kinase homolog family. The encoded protein functions as a component of the tight junction barrier in epithelial and endothelial cells and is necessary for proper ass

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121918299	T>C	Pathogenic	Coding sequence variant, missense variant
rs138241615	C>T	Conflicting-interpretations-of-pathogenicity, likely-benign	Coding sequence variant, missense variant
rs138509345	C>A,T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs139314808	G>A	Pathogenic	Coding sequence variant, missense variant
rs141496493	C>G,T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs149911553	C>G,T	Conflicting-interpretations-of-pathogenicity, likely-benign, uncertain-significance	Missense variant, coding sequence variant
rs184519036	C>T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant, intron variant
rs191634088	G>A,C	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant, intron variant
rs199641113	C>T	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs200222645	G>A	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs200415824	A>T	Conflicting-interpretations-of-pathogenicity, likely-benign	Intron variant
rs530810462	C>G,T	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs587777518	GCCT>-	Pathogenic	Coding sequence variant, frameshift variant
rs587777519	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs587777520	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs587777521	A>G	Pathogenic	Splice acceptor variant
rs745427593	G>A	Likely-benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs746830415	C>T	Pathogenic	Stop gained, coding sequence variant
rs748671901	C>T	Pathogenic	Stop gained, coding sequence variant
rs749009273	C>T	Pathogenic	Stop gained, coding sequence variant, intron variant
rs750625862	G>T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs764379398	C>A,G,T	Pathogenic	Coding sequence variant, synonymous variant, missense variant, stop gained
rs771690686	A>-	Pathogenic	Coding sequence variant, frameshift variant
rs776869985	T>-,TT	Pathogenic	Coding sequence variant, frameshift variant
rs777460754	C>G,T	Pathogenic	Coding sequence variant, missense variant, stop gained
rs781334233	->G	Pathogenic	Coding sequence variant, frameshift variant
rs786205659	G>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs864321695	G>T	Pathogenic	Intron variant, splice acceptor variant
rs864321697	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs886041948	->CCTCA	Likely-pathogenic, pathogenic	Coding sequence variant, frameshift variant
rs886042381	T>A	Pathogenic	Coding sequence variant, stop gained
rs928915940	C>T	Pathogenic, uncertain-significance	Coding sequence variant, stop gained
rs1057518679	T>-	Pathogenic	Coding sequence variant, frameshift variant
rs1060499649	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1182781290	C>G,T	Pathogenic	Stop gained, coding sequence variant, missense variant
rs1251192873	C>G,T	Pathogenic	Missense variant, coding sequence variant, stop gained
rs1278244243	T>C	Likely-pathogenic	Splice donor variant
rs1554660803	CG>-	Pathogenic	Coding sequence variant, frameshift variant
rs1554662952	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs1554664852	G>T	Pathogenic	Splice donor variant
rs1554667607	C>T	Likely-pathogenic	Coding sequence variant, stop gained
rs1563915664	->A	Pathogenic	Coding sequence variant, frameshift variant
rs1563948951	C>T	Pathogenic	Coding sequence variant, stop gained
rs1588080674	A>C	Pathogenic	Splice acceptor variant
rs1588080680	G>A	Pathogenic	Splice acceptor variant
rs1588081022	T>G	Likely-pathogenic	Missense variant, coding sequence variant
rs1588117076	T>C	Likely-pathogenic	Missense variant, coding sequence variant
rs1588127136	G>A	Pathogenic	Splice acceptor variant
rs1588135086	T>G	Likely-pathogenic	Intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT002718	hsa-miR-124-3p	Microarray	15685193
MIRT006684	hsa-miR-203a-3p	qRT-PCR, Western blot	22101077
MIRT016495	hsa-miR-193b-3p	Microarray	20304954
MIRT002718	hsa-miR-124-3p	Microarray	18668037
MIRT002718	hsa-miR-124-3p	Microarray	15685193
MIRT024740	hsa-miR-215-5p	Microarray	19074876
MIRT025356	hsa-miR-34a-5p	Proteomics	21566225
MIRT025356	hsa-miR-34a-5p	Proteomics	21566225
MIRT025356	hsa-miR-34a-5p	Proteomics	21566225
MIRT026686	hsa-miR-192-5p	Microarray	19074876
MIRT1425830	hsa-miR-129-5p	CLIP-seq
MIRT1425831	hsa-miR-3122	CLIP-seq
MIRT1425832	hsa-miR-3157-3p	CLIP-seq
MIRT1425833	hsa-miR-3689a-3p	CLIP-seq
MIRT1425834	hsa-miR-3689c	CLIP-seq
MIRT1425835	hsa-miR-3913-5p	CLIP-seq
MIRT1425836	hsa-miR-4735-5p	CLIP-seq
MIRT1425837	hsa-miR-874	CLIP-seq
MIRT1425838	hsa-miR-938	CLIP-seq
MIRT1425839	hsa-miR-1297	CLIP-seq
MIRT1425840	hsa-miR-132	CLIP-seq
MIRT1425841	hsa-miR-1587	CLIP-seq
MIRT1425842	hsa-miR-1910	CLIP-seq
MIRT1425843	hsa-miR-212	CLIP-seq
MIRT1425844	hsa-miR-26a	CLIP-seq
MIRT1425845	hsa-miR-26b	CLIP-seq
MIRT1425846	hsa-miR-342-3p	CLIP-seq
MIRT1425847	hsa-miR-345	CLIP-seq
MIRT1425848	hsa-miR-3651	CLIP-seq
MIRT1425849	hsa-miR-3663-3p	CLIP-seq
MIRT1425850	hsa-miR-4256	CLIP-seq
MIRT1425851	hsa-miR-4461	CLIP-seq
MIRT1425852	hsa-miR-4465	CLIP-seq
MIRT1425853	hsa-miR-4662a-5p	CLIP-seq
MIRT1425854	hsa-miR-4674	CLIP-seq
MIRT1425855	hsa-miR-494	CLIP-seq
MIRT1425856	hsa-miR-498	CLIP-seq
MIRT1425857	hsa-miR-635	CLIP-seq
MIRT2127609	hsa-miR-124	CLIP-seq
MIRT2127610	hsa-miR-1273d	CLIP-seq
MIRT2127611	hsa-miR-128	CLIP-seq
MIRT1425840	hsa-miR-132	CLIP-seq
MIRT2127612	hsa-miR-148a	CLIP-seq
MIRT2127613	hsa-miR-148b	CLIP-seq
MIRT2127614	hsa-miR-152	CLIP-seq
MIRT2127615	hsa-miR-1909	CLIP-seq
MIRT1425842	hsa-miR-1910	CLIP-seq
MIRT1425843	hsa-miR-212	CLIP-seq
MIRT2127616	hsa-miR-3130-5p	CLIP-seq
MIRT2127617	hsa-miR-320e	CLIP-seq
MIRT2127618	hsa-miR-3714	CLIP-seq
MIRT2127619	hsa-miR-3915	CLIP-seq
MIRT2127620	hsa-miR-3928	CLIP-seq
MIRT2127621	hsa-miR-4477a	CLIP-seq
MIRT2127622	hsa-miR-4482	CLIP-seq
MIRT2127623	hsa-miR-4493	CLIP-seq
MIRT2127624	hsa-miR-4635	CLIP-seq
MIRT2127625	hsa-miR-4668-5p	CLIP-seq
MIRT1425855	hsa-miR-494	CLIP-seq
MIRT2127626	hsa-miR-506	CLIP-seq
MIRT2127627	hsa-miR-642b	CLIP-seq
MIRT2349333	hsa-miR-105	CLIP-seq
MIRT2127609	hsa-miR-124	CLIP-seq
MIRT2127610	hsa-miR-1273d	CLIP-seq
MIRT2127611	hsa-miR-128	CLIP-seq
MIRT1425840	hsa-miR-132	CLIP-seq
MIRT2349334	hsa-miR-137	CLIP-seq
MIRT2127612	hsa-miR-148a	CLIP-seq
MIRT2127613	hsa-miR-148b	CLIP-seq
MIRT2127614	hsa-miR-152	CLIP-seq
MIRT2127615	hsa-miR-1909	CLIP-seq
MIRT2349335	hsa-miR-194	CLIP-seq
MIRT2349336	hsa-miR-208a	CLIP-seq
MIRT2349337	hsa-miR-208b	CLIP-seq
MIRT1425843	hsa-miR-212	CLIP-seq
MIRT2349338	hsa-miR-23a	CLIP-seq
MIRT2349339	hsa-miR-23b	CLIP-seq
MIRT2349340	hsa-miR-23c	CLIP-seq
MIRT2127616	hsa-miR-3130-5p	CLIP-seq
MIRT2349341	hsa-miR-3148	CLIP-seq
MIRT2349342	hsa-miR-3163	CLIP-seq
MIRT2127617	hsa-miR-320e	CLIP-seq
MIRT1425846	hsa-miR-342-3p	CLIP-seq
MIRT1425847	hsa-miR-345	CLIP-seq
MIRT2349343	hsa-miR-3617	CLIP-seq
MIRT2349344	hsa-miR-3647-3p	CLIP-seq
MIRT2349345	hsa-miR-3658	CLIP-seq
MIRT2127618	hsa-miR-3714	CLIP-seq
MIRT2127619	hsa-miR-3915	CLIP-seq
MIRT2127620	hsa-miR-3928	CLIP-seq
MIRT1425850	hsa-miR-4256	CLIP-seq
MIRT2349346	hsa-miR-4282	CLIP-seq
MIRT2127621	hsa-miR-4477a	CLIP-seq
MIRT2127622	hsa-miR-4482	CLIP-seq
MIRT2127623	hsa-miR-4493	CLIP-seq
MIRT2127624	hsa-miR-4635	CLIP-seq
MIRT2127625	hsa-miR-4668-5p	CLIP-seq
MIRT2349347	hsa-miR-4774-5p	CLIP-seq
MIRT1425855	hsa-miR-494	CLIP-seq
MIRT2349348	hsa-miR-499-5p	CLIP-seq
MIRT2127626	hsa-miR-506	CLIP-seq
MIRT2349349	hsa-miR-548ac	CLIP-seq
MIRT2349350	hsa-miR-548ae	CLIP-seq
MIRT2349351	hsa-miR-548aj	CLIP-seq
MIRT2349352	hsa-miR-548am	CLIP-seq
MIRT2349353	hsa-miR-548d-3p	CLIP-seq
MIRT2349354	hsa-miR-548x	CLIP-seq
MIRT2349355	hsa-miR-548z	CLIP-seq
MIRT2349356	hsa-miR-641	CLIP-seq
MIRT2127627	hsa-miR-642b	CLIP-seq
MIRT2349357	hsa-miR-802	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004385	Function	GMP kinase activity	TAS	8824195
GO:0005515	Function	Protein binding	IPI	15975580, 18823282, 22665060, 23885123
GO:0005634	Component	Nucleus	IDA	20868367
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA	11090614
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0005912	Component	Adherens junction	IEA
GO:0005923	Component	Bicellular tight junction	IBA
GO:0005923	Component	Bicellular tight junction	IDA	22006950, 23885123
GO:0005923	Component	Bicellular tight junction	IEA
GO:0016020	Component	Membrane	IEA
GO:0019904	Function	Protein domain specific binding	IPI	23885123
GO:0030674	Function	Protein-macromolecule adaptor activity	IDA	23885123
GO:0034109	Process	Homotypic cell-cell adhesion	IDA	21679692
GO:0035633	Process	Maintenance of blood-brain barrier	NAS	30280653
GO:0044291	Component	Cell-cell contact zone	IDA	21679692
GO:0045216	Process	Cell-cell junction organization	IBA
GO:0045296	Function	Cadherin binding	HDA	25468996
GO:0046037	Process	GMP metabolic process	IEA
GO:0046710	Process	GDP metabolic process	IEA
GO:0050839	Function	Cell adhesion molecule binding	IBA
GO:0050892	Process	Intestinal absorption	IMP	23885123
GO:0070160	Component	Tight junction	IEA
GO:0070161	Component	Anchoring junction	IEA
GO:0090557	Process	Establishment of endothelial intestinal barrier	IBA
GO:0090557	Process	Establishment of endothelial intestinal barrier	IMP	23885123
GO:0090559	Process	Regulation of membrane permeability	IMP	23885123
GO:0098609	Process	Cell-cell adhesion	IBA
GO:0150105	Process	Protein localization to cell-cell junction	IBA
GO:1905605	Process	Positive regulation of blood-brain barrier permeability	IBA
GO:1905605	Process	Positive regulation of blood-brain barrier permeability	IMP	19148554
GO:1990782	Function	Protein tyrosine kinase binding	IPI	21679692

Other IDs

• MIM: 607709
• HGNC: 11828
• e!Ensembl: ENSG00000119139

Protein

• UniProt ID: Q9UDY2
• Protein name: Tight junction protein 2 (Tight junction protein ZO-2) (Zona occludens protein 2) (Zonula occludens protein 2)
• Protein function: Plays a role in tight junctions and adherens junctions (By similarity). Acts as a positive regulator of RANKL-induced osteoclast differentiation, potentially via mediating downstream transcriptional activity (By similarity). {ECO:0000250|UniProt
• PDB: 2OSG, 3E17
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00595	PDZ	33 → 117	PDZ domain	Domain
  PF00595	PDZ	298 → 382	PDZ domain	Domain
  PF00595	PDZ	510 → 589	PDZ domain	Domain
  PF07653	SH3_2	608 → 667	Variant SH3 domain	Domain
  PF00625	Guanylate_kin	767 → 878	Guanylate kinase	Domain

• Tissue specificity: TISSUE SPECIFICITY: This protein is found in epithelial cell junctions. Isoform A1 is abundant in the heart and brain. Detected in brain and skeletal muscle. It is present almost exclusively in normal tissues. Isoform C1 is expressed at high level in the
• Sequence:

  MPVRGDRGFPPRRELSGWLRAPGMEELIWEQYTVTLQKDSKRGFGIAVSGGRDNPHFENG
  ETSIVISDVLPGGPADGLLQENDRVVMVNGTPMEDVLHSFAVQQLRKSGKVAAIVVKRPR
  KVQVAALQASPPLDQDDRAFEVMDEFDGRSFRSGYSERSRLNSHGGRSRSWEDSPERGRP
  HERARSRERDLSRDRSRGRSLERGLDQDHARTRDRSRGRSLERGLDHDFGPSRDRDRDRS
  RGRSIDQDYERAYHRAYDPDYERAYSPEYRRGARHDARSRGPRSRSREHPHSRSPSPEPR
  GRPGPIGVLLMKSRANEEYGLRLGSQIFVKEMTRTGLATKDGNLHEGDIILKINGTVTEN
  MSLTDARKLIEKSRGKLQLVVLRDSQQTLINIPSLNDSDSEIEDISEIESNRSFSPEERR
  HQYSDYDYHSSSEKLKERPSSREDTPSRLSRMGATPTPFKSTGDIAGTVVPETNKEPRYQ
  EDPPAPQPKAAPRTFLRPSPEDEAIYGPNTKMVRFKKGDSVGLRLAGGNDVGIFVAGIQE
  GTSAEQEGLQEGDQILKVNTQDFRGLVREDAVLYLLEIPKGEMVTILAQSRADVYRDILA
  CGRGDSFFIRSHFECEKETPQSLAFTRGEVFRVVDTLYDGKLGNWLAVRIGNELEKGLIP
  NKSRAEQMASVQNAQRDNAGDRADFWRMRGQRSGVKKNLRKSREDLTAVVSVSTKFPAYE
  RVLLREAGFKRPVVLFGPIADIAMEKLANELPDWFQTAKTEPKDAGSEKSTGVVRLNTVR
  QIIEQDKHALLDVTPKAVDLLNYTQWFPIVIFFNPDSRQGVKTMRQRLNPTSNKSSRKLF
  DQANKLKKTCAHLFTATINLNSANDSWFGSLKDTIQHQQGEAVWVSEGKMEGMDDDPEDR
  MSYLTAMGADYLSCDSRLISDFEDTDGEGGAYTDNELDEPAEEPLVSSITRSSEPVQHEE
  SIRKPSPEPRAQMRRAASSDQLRDNSPPPAFKPEPPKAKTQNKEESYDFSKSYEYKSNPS
  AVAGNETPGASTKGYPPPVAAKPTFGRSILKPSTPIPPQEGEEVGESSEEQDNAPKSVLG
  KVKIFEKMDHKARLQRMQELQEAQNARIEIAQKHPDIYAVPIKTHKPDPGTPQHTSSRPP
  EPQKAPSRPYQDTRGSYGSDAEEEEYRQQLSEHSKRGYYGQSARYRDTEL

• Sequence length: 1190

Pathways

KEGG:

Tight junction
Vibrio cholerae infection

Reactome:

Signaling by Hippo
Apoptotic cleavage of cell adhesion proteins

Associated diseases

Evidence Score:

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

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Autosomal dominant nonsyndromic hearing loss 51	Pathogenic	rs756322608	RCV004585138	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Cholestasis, progressive familial intrahepatic, 4	Pathogenic; Likely pathogenic	rs1830481830, rs2133314949, rs2133456150, rs1225374015, rs587777519, rs587777520, rs587777521, rs2538580998, rs121918299, rs1830959398, rs2538448383, rs864321695, rs776869985, rs864321697, rs886041948, rs2538590798, rs766748789, rs2538518655, rs760746355, rs1830470553, rs1358228134, rs2538557576, rs1057518679, rs1060499649, rs1554667607, rs1554660803, rs771690686, rs928915940, rs1182781290, rs1588081022, rs777460754, rs1251192873, rs1588117076, rs748671901, rs139314808, rs749009273, rs1588080674, rs1588080680, rs1588127136, rs1588135086, rs749237210, rs1830379007	RCV001332517 RCV001564054 RCV001706958 RCV002272498 RCV000128571 RCV000128572 RCV000128573 RCV002284005 RCV005406721 RCV002470294 RCV003492776 RCV000203578 RCV000203571 RCV000203574 RCV000984952 RCV003388678 RCV003492887 RCV003492888 RCV003492889 RCV003986035 RCV004556896 RCV004585202 RCV000415040 RCV000449597 RCV005899813 RCV000505572 RCV003492118 RCV000993663 RCV000855542 RCV000993652 RCV000993661 RCV000993657 RCV000993653 RCV000993660 RCV000993655 RCV000993656 RCV000993662 RCV000993659 RCV000993654 RCV000993658 RCV001250178 RCV001250179	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Hypercholanemia, familial 1	Pathogenic; Likely pathogenic	rs587777520, rs121918299, rs928915940	RCV003992193 RCV000003041 RCV003987702	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Melnick-Fraser syndrome	Likely pathogenic; Pathogenic	rs139314808	RCV001375126	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
TJP2-related disorder	Likely pathogenic; Pathogenic	rs1178833797, rs1060499649, rs771690686, rs746830415	RCV003904331 RCV003422418 RCV005223026 RCV003892676	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDER	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTISM SPECTRUM DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL DOMINANT ISOLATED SENSORINEURAL DEAFNESS TYPE DFNA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL DOMINANT NONSYNDROMIC HEARING LOSS	—	GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autosomal recessive nonsyndromic hearing loss 4	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BRANCHIO-OTO-RENAL SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHOLESTASIS, INTRAHEPATIC	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHOLESTASIS, PROGRESSIVE FAMILIAL INTRAHEPATIC 4	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEAFNESS, AUTOSOMAL DOMINANT 51	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
FAMILIAL HYPERCHOLANEMIA	—	CTD, Orphanet CTD, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial pancreatic carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Conflicting classifications of pathogenicity; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hearing impairment	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
HEARING LOSS	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERCHOLANEMIA, FAMILIAL	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTRAHEPATIC CHOLESTASIS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lymphoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MIGRAINE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-ALCOHOLIC FATTY LIVER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonsyndromic Hearing Loss, Dominant	Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Primary biliary cholangitis	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS TYPE 4	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma of pancreas	Pancreatic adenocarcinoma	BEFREE	10360833		★☆☆☆☆ Found in Text Mining only
Autosomal dominant non-syndromic sensorineural deafness type DFNA	Non-Syndromic Sensorineural Deafness	Orphanet			★☆☆☆☆ Found in Text Mining only
Bile acid synthesis defect congenital 1	Congenital bile acid synthesis defect	Pubtator	32089630, 32636225, 38090248	Associate	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	22193974	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	37995182	Inhibit	★☆☆☆☆ Found in Text Mining only
Carcinoma	Carcinoma	BEFREE	10495427		★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	32089630	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma in Situ	Carcinoma in situ	Pubtator	17217619	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	36966163	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	17585317	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	37240145	Inhibit	★☆☆☆☆ Found in Text Mining only
Cholangiocarcinoma	Cholangiocarcinoma	Pubtator	34211100	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholestasis	Cholestasis	BEFREE	30250217		★☆☆☆☆ Found in Text Mining only
Cholestasis Intrahepatic	Intrahepatic cholestasis	Pubtator	32089630	Associate	★☆☆☆☆ Found in Text Mining only
Cholestasis of pregnancy	Cholestasis of pregnancy	BEFREE	28924228		★☆☆☆☆ Found in Text Mining only
Cholestasis progressive familial intrahepatic 1	Cholelithiasis	Pubtator	30658709, 32089630	Associate	★☆☆☆☆ Found in Text Mining only
Cholestasis, progressive familial intrahepatic 1	Intrahepatic cholestasis	BEFREE	29238877, 30658709		★☆☆☆☆ Found in Text Mining only
Cholestasis, progressive familial intrahepatic 4	Cholestasis	CLINVAR_DG	24614073		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholestasis, progressive familial intrahepatic 4	Cholestasis	ORPHANET_DG	24614073		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholestasis, progressive familial intrahepatic 4	Cholestasis	GENOMICS_ENGLAND_DG	24752540		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholestasis, progressive familial intrahepatic 4	Cholestasis	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholestatic liver disease	Cholestatic liver disease	BEFREE	24614073, 30658709		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	23612256		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	28493909		★☆☆☆☆ Found in Text Mining only
Ductal Breast Carcinoma	Breast Carcinoma	BEFREE	10495427		★☆☆☆☆ Found in Text Mining only
Ductal Carcinoma	Ductal Carcinoma	BEFREE	10495427		★☆☆☆☆ Found in Text Mining only
Familial hypercholanemia	Hypercholanemia	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Friedreich Ataxia	Friedreich Ataxia	BEFREE	7485155		★☆☆☆☆ Found in Text Mining only
FRIEDREICH ATAXIA 1	Friedreich Ataxia	BEFREE	7485155		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	18796682	Associate	★☆☆☆☆ Found in Text Mining only
Hypercholanemia, Familial	Hypercholanemia	BEFREE	12704386		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypercholanemia, Familial	Hypercholanemia	ORPHANET_DG	12704386		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypercholanemia, Familial	Hypercholanemia	UNIPROT_DG	12704386		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypercholanemia, Familial	Hypercholanemia	GENOMICS_ENGLAND_DG	24752540		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypercholanemia, Familial	Hypercholanemia	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypercholanemia, Familial	Hypercholanemia	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hyperlipoproteinemia Type IIa	Hyperlipoproteinemia	BEFREE	12704386		★☆☆☆☆ Found in Text Mining only
Hypertension Portal	Portal hypertension	Pubtator	32089630	Associate	★☆☆☆☆ Found in Text Mining only
Intrahepatic Cholestasis	Intrahepatic Cholestasis	CTD_human_DG	24614073		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intrahepatic Cholestasis	Intrahepatic Cholestasis	BEFREE	31696999		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intrahepatic Cholestasis	Intrahepatic Cholestasis	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intrahepatic Cholestasis of Pregnancy	Intrahepatic cholestasis of pregnancy	Pubtator	28924228, 32942997	Associate	★☆☆☆☆ Found in Text Mining only
leukemia	Leukemia	BEFREE	27764235		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver Diseases	Liver disease	Pubtator	30658709, 32089630, 32636225	Associate	★☆☆☆☆ Found in Text Mining only
Liver Failure	Liver failure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	37240145	Inhibit	★☆☆☆☆ Found in Text Mining only
Myopia	Myopia	GWASCAT_DG	27182965		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	23612256		★☆☆☆☆ Found in Text Mining only
Nonsyndromic Deafness	Nonsyndromic Deafness	CLINGEN_DG	18172007, 18616530, 20602916, 24752540, 24853665, 26668150		★☆☆☆☆ Found in Text Mining only
Nonsyndromic Deafness	Nonsyndromic Deafness	BEFREE	20602916		★☆☆☆☆ Found in Text Mining only
Osteoporosis	Osteoporosis	Pubtator	26668150	Associate	★☆☆☆☆ Found in Text Mining only
Portal Hypertension	Portal Hypertension	HPO_DG			★☆☆☆☆ Found in Text Mining only
Progressive familial intrahepatic cholestasis type 4	Intrahepatic Cholestasis	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Progressive intrahepatic cholestasis (disorder)	Intrahepatic Cholestasis	BEFREE	29238877, 30658709		★☆☆☆☆ Found in Text Mining only
Rhinitis Allergic	Rhinitis	Pubtator	35480562	Associate	★☆☆☆☆ Found in Text Mining only
Rickets	Rickets	HPO_DG			★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	33721374	Associate	★☆☆☆☆ Found in Text Mining only