HERC1 (HECT and RLD domain containing E3 ubiquitin protein ligase family member 1)

Gene

• Entrez ID: 8925
• Gene name: HECT and RLD domain containing E3 ubiquitin protein ligase family member 1
• Gene symbol: HERC1
• Synonyms (NCBI Gene): MDFPMR, p532, p619
• Chromosome: 15
• Chromosome location: 15q22.31
• Summary: This gen encodes a member of the HERC protein family. This protein stimulates guanine nucleotide exchange on ARF1 and Rab proteins. This protein may be involved in membrane transport processes. [provided by RefSeq, Mar 2012]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs80203202	C>T	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs753780877	G>A,C	Pathogenic	Stop gained, genic downstream transcript variant, coding sequence variant, missense variant
rs757749585	G>A	Likely-pathogenic	Genic downstream transcript variant, stop gained, coding sequence variant
rs769677823	C>G,T	Pathogenic	Missense variant, genic downstream transcript variant, coding sequence variant
rs797045141	T>G	Pathogenic, likely-pathogenic	Splice acceptor variant
rs879253786	C>T	Pathogenic	Coding sequence variant, stop gained
rs1064794786	C>T	Likely-pathogenic	Stop gained, coding sequence variant
rs1064796508	A>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1085307759	C>T	Likely-pathogenic	Stop gained, coding sequence variant, genic downstream transcript variant
rs1131691853	G>A	Likely-pathogenic	Stop gained, coding sequence variant
rs1555404908	GG>T	Likely-pathogenic	Genic downstream transcript variant, coding sequence variant, frameshift variant
rs1555417272	C>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1595819527	T>-	Likely-pathogenic	Coding sequence variant, genic downstream transcript variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT050724	hsa-miR-18a-5p	CLASH	23622248
MIRT048986	hsa-miR-92a-3p	CLASH	23622248
MIRT048986	hsa-miR-92a-3p	CLASH	23622248
MIRT042828	hsa-miR-324-3p	CLASH	23622248
MIRT041520	hsa-miR-193b-3p	CLASH	23622248
MIRT037896	hsa-miR-455-3p	CLASH	23622248
MIRT1044285	hsa-miR-1303	CLIP-seq
MIRT1044286	hsa-miR-4420	CLIP-seq
MIRT1044287	hsa-miR-4698	CLIP-seq
MIRT1044288	hsa-miR-4705	CLIP-seq
MIRT1044289	hsa-miR-4735-5p	CLIP-seq
MIRT1044290	hsa-miR-501-3p	CLIP-seq
MIRT1044291	hsa-miR-502-3p	CLIP-seq
MIRT1044292	hsa-miR-522	CLIP-seq
MIRT1044293	hsa-miR-548ac	CLIP-seq
MIRT1044294	hsa-miR-548ae	CLIP-seq
MIRT1044295	hsa-miR-548aj	CLIP-seq
MIRT1044296	hsa-miR-548am	CLIP-seq
MIRT1044297	hsa-miR-548d-3p	CLIP-seq
MIRT1044298	hsa-miR-548x	CLIP-seq
MIRT1044299	hsa-miR-548z	CLIP-seq
MIRT1044300	hsa-miR-767-5p	CLIP-seq
MIRT1044285	hsa-miR-1303	CLIP-seq
MIRT2545635	hsa-miR-2116	CLIP-seq
MIRT2545636	hsa-miR-299-5p	CLIP-seq
MIRT2545637	hsa-miR-3129-3p	CLIP-seq
MIRT2545638	hsa-miR-3187-3p	CLIP-seq
MIRT2545639	hsa-miR-374a	CLIP-seq
MIRT2545640	hsa-miR-374b	CLIP-seq
MIRT2545641	hsa-miR-409-3p	CLIP-seq
MIRT2545642	hsa-miR-4529-5p	CLIP-seq
MIRT2545643	hsa-miR-4677-5p	CLIP-seq
MIRT1044288	hsa-miR-4705	CLIP-seq
MIRT1044289	hsa-miR-4735-5p	CLIP-seq
MIRT2545644	hsa-miR-4781-3p	CLIP-seq
MIRT1044293	hsa-miR-548ac	CLIP-seq
MIRT1044294	hsa-miR-548ae	CLIP-seq
MIRT1044295	hsa-miR-548aj	CLIP-seq
MIRT1044296	hsa-miR-548am	CLIP-seq
MIRT1044297	hsa-miR-548d-3p	CLIP-seq
MIRT1044298	hsa-miR-548x	CLIP-seq
MIRT1044299	hsa-miR-548z	CLIP-seq
MIRT2545645	hsa-miR-663b	CLIP-seq
MIRT1044285	hsa-miR-1303	CLIP-seq
MIRT2545637	hsa-miR-3129-3p	CLIP-seq
MIRT2545638	hsa-miR-3187-3p	CLIP-seq
MIRT2545639	hsa-miR-374a	CLIP-seq
MIRT2545640	hsa-miR-374b	CLIP-seq
MIRT2545642	hsa-miR-4529-5p	CLIP-seq
MIRT1044288	hsa-miR-4705	CLIP-seq
MIRT1044289	hsa-miR-4735-5p	CLIP-seq
MIRT1044293	hsa-miR-548ac	CLIP-seq
MIRT1044294	hsa-miR-548ae	CLIP-seq
MIRT1044295	hsa-miR-548aj	CLIP-seq
MIRT1044296	hsa-miR-548am	CLIP-seq
MIRT1044297	hsa-miR-548d-3p	CLIP-seq
MIRT1044298	hsa-miR-548x	CLIP-seq
MIRT1044299	hsa-miR-548z	CLIP-seq
MIRT2545645	hsa-miR-663b	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004842	Function	Ubiquitin-protein transferase activity	IEA
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	IEA
GO:0005085	Function	Guanyl-nucleotide exchange factor activity	TAS	8861955
GO:0005737	Component	Cytoplasm	IEA
GO:0005737	Component	Cytoplasm	TAS	8861955
GO:0005794	Component	Golgi apparatus	IEA
GO:0005794	Component	Golgi apparatus	TAS	8861955
GO:0005829	Component	Cytosol	IEA
GO:0006914	Process	Autophagy	IEA
GO:0007420	Process	Brain development	IEA
GO:0010467	Process	Gene expression	IEA
GO:0010507	Process	Negative regulation of autophagy	IEA
GO:0016020	Component	Membrane	IEA
GO:0016567	Process	Protein ubiquitination	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0021702	Process	Cerebellar Purkinje cell differentiation	IEA
GO:0022038	Process	Corpus callosum development	IEA
GO:0030282	Process	Bone mineralization	IEA
GO:0031175	Process	Neuron projection development	IEA
GO:0046849	Process	Bone remodeling	IEA
GO:0050885	Process	Neuromuscular process controlling balance	IEA
GO:0061630	Function	Ubiquitin protein ligase activity	IEA

Other IDs

• MIM: 605109
• HGNC: 4867
• e!Ensembl: ENSG00000103657

Protein

• UniProt ID: Q15751
• Protein name: Probable E3 ubiquitin-protein ligase HERC1 (EC 2.3.2.26) (HECT domain and RCC1-like domain-containing protein 1) (HECT-type E3 ubiquitin transferase HERC1) (p532) (p619)
• Protein function: Involved in membrane trafficking via some guanine nucleotide exchange factor (GEF) activity and its ability to bind clathrin. Acts as a GEF for Arf and Rab, by exchanging bound GDP for free GTP. Binds phosphatidylinositol 4,5-bisphosphate, which
• PDB: 4O2W, 4QT6
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00415	RCC1	476 → 526	Regulator of chromosome condensation (RCC1) repeat	Repeat
  PF00415	RCC1	529 → 576	Regulator of chromosome condensation (RCC1) repeat	Repeat
  PF00415	RCC1	579 → 629	Regulator of chromosome condensation (RCC1) repeat	Repeat
  PF00415	RCC1	683 → 733	Regulator of chromosome condensation (RCC1) repeat	Repeat
  PF00622	SPRY	2072 → 2190	SPRY domain	Family
  PF00400	WD40	3417 → 3456	WD domain, G-beta repeat	Repeat
  PF00400	WD40	3737 → 3781	WD domain, G-beta repeat	Repeat
  PF00415	RCC1	4100 → 4149	Regulator of chromosome condensation (RCC1) repeat	Repeat
  PF00415	RCC1	4152 → 4201	Regulator of chromosome condensation (RCC1) repeat	Repeat
  PF00415	RCC1	4206 → 4254	Regulator of chromosome condensation (RCC1) repeat	Repeat
  PF00415	RCC1	4309 → 4358	Regulator of chromosome condensation (RCC1) repeat	Repeat
  PF00632	HECT	4534 → 4843	HECT-domain (ubiquitin-transferase)	Domain

• Tissue specificity: TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:8861955}.
• Sequence:

  MATMIPPVKLKWLEHLNSSWITEDSESIATREGVAVLYSKLVSNKEVVPLPQQVLCLKGP
  QLPDFERESLSSDEQDHYLDALLSSQLALAKMVCSDSPFAGALRKRLLVLQRVFYALSNK
  YHDKGKVKQQQHSPESSSGSADVHSVSERPRSSTDALIEMGVRTGLSLLFALLRQSWMMP
  VSGPGLSLCNDVIHTAIEVVSSLPPLSLANESKIPPMGLDCLSQVTTFLKGVTIPNSGAD
  TLGRRLASELLLGLAAQRGSLRYLLEWIEMALGASAVVHTMEKGKLLSSQEGMISFDCFM
  TILMQMRRSLGSSADRSQWREPTRTSDGLCSLYEAALCLFEEVCRMASDYSRTCASPDSI
  QTGDAPIVSETCEVYVWGSNSSHQLVEGTQEKILQPKLAPSFSDAQTIEAGQYCTFVIST
  DGSVRACGKGSYGRLGLGDSNNQSTLKKLTFEPHRSIKKVSSSKGSDGHTLAFTTEGEVF
  SWGDGDYGKLGHGNSSTQKYPKLIQGPLQGKVVVCVSAGYRHSAAVTEDGELYTWGEGDF
  GRLGHGDSNSRNIPTLVKDISNVGEVSCGSSHTIALSKDGRTVWSFGGGDNGKLGHGDTN
  RVYKPKVIEALQGMFIRKVCAGSQSSLALTSTGQVYAWGCGACLGCGSSEATALRPKLIE
  ELAATRIVDVSIGDSHCLALSHDNEVYAWGNNSMGQCGQGNSTGPITKPKKVSGLDGIAI
  QQISAGTSHSLAWTALPRDRQVVAWHRPYCVDLEESTFSHLRSFLERYCDKINSEIPPLP
  FPSSREHHSFLKLCLKLLSNHLALALAGGVATSILGRQAGPLRNLLFRLMDSTVPDEIQE
  VVIETLSVGATMLLPPLRERMELLHSLLPQGPDRWESLSKGQRMQLDIILTSLQDHTHVA
  SLLGYSSPSDAADLSSVCTGYGNLSDQPYGTQSCHPDTHLAEILMKTLLRNLGFYTDQAF
  GELEKNSDKFLLGTSSSENSQPAHLHELLCSLQKQLLAFCHINNISENSSSVALLHKHLQ
  LLLPHATDIYSRSANLLKESPWNGSVGEKLRDVIYVSAAGSMLCQIVNSLLLLPVSVARP
  LLSYLLDLLPPLDCLNRLLPAADLLEDQELQWPLHGGPELIDPAGLPLPQPAQSWVWLVD
  LERTIALLIGRCLGGMLQGSPVSPEEQDTAYWMKTPLFSDGVEMDTPQLDKCMSCLLEVA
  LSGNEEQKPFDYKLRPEIAVYVDLALGCSKEPARSLWISMQDYAVSKDWDSATLSNESLL
  DTVSRFVLAALLKHTNLLSQACGESRYQPGKHLSEVYRCVYKVRSRLLACKNLELIQTRS
  SSRDRWISENQDSADVDPQEHSFTRTIDEEAEMEEQAERDREEGHPEPEDEEEEREHEVM
  TAGKIFQCFLSAREVARSRDRDRMNSGAGSGARADDPPPQSQQERRVSTDLPEGQDVYTA
  ACNSVIHRCALLILGVSPVIDELQKRREEGQLQQPSTSASEGGGLMTRSESLTAESRLVH
  TSPNYRLIKSRSESDLSQPESDEEGYALSGRRNVDLDLAASHRKRGPMHSQLESLSDSWA
  RLKHSRDWLCNSSYSFESDFDLTKSLGVHTLIENVVSFVSGDVGNAPGFKEPEESMSTSP
  QASIIAMEQQQLRAELRLEALHQILVLLSGMEEKGSISLAGSRLSSGFQSSTLLTSVRLQ
  FLAGCFGLGTVGHTGGKGESGRLHHYQDGIRAAKRNIQIEIQVAVHKIYQQLSATLERAL
  QANKHHIEAQQRLLLVTVFALSVHYQPVDVSLAISTGLLNVLSQLCGTDTMLGQPLQLLP
  KTGVSQLSTALKVASTRLLQILAITTGTYADKLSPKVVQSLLDLLCSQLKNLLSQTGVLH
  MASFGEGEQEDGEEEEKKVDSSGETEKKDFRAALRKQHAAELHLGDFLVFLRRVVSSKAI
  QSKMASPKWTEVLLNIASQKCSSGIPLVGNLRTRLLALHVLEAVLPACESGVEDDQMAQI
  VERLFSLLSDCMWETPIAQAKHAIQIKEKEQEIKLQKQGELEEEDENLPIQEVSFDPEKA
  QCCLVENGQILTHGSGGKGYGLASTGVTSGCYQWKFYIVKENRGNEGTCVGVSRWPVHDF
  NHRTTSDMWLYRAYSGNLYHNGEQTLTLSSFTQGDFITCVLDMEARTISFGKNGEEPKLA
  FEDVDAAELYPCVMFYSSNPGEKVKICDMQMRGTPRDLLPGDPICSPVAAVLAEATIQLI
  RILHRTDRWTYCINKKMMERLHKIKICIKESGQKLKKSRSVQSREENEMREEKESKEEEK
  GKHTRHGLADLSELQLRTLCIEVWPVLAVIGGVDAGLRVGGRCVHKQTGRHATLLGVVKE
  GSTSAKVQWDEAEITISFPTFWSPSDTPLYNLEPCEPLPFDVARFRGLTASVLLDLTYLT
  GVHEDMGKQSTKRHEKKHRHESEEKGDVEQKPESESALDMRTGLTSDDVKSQSTTSSKSE
  NEIASFSLDPTLPSVESQHQITEGKRKNHEHMSKNHDVAQSEIRAVQLSYLYLGAMKSLS
  ALLGCSKYAELLLIPKVLAENGHNSDCASSPVVHEDVEMRAALQFLMRHMVKRAVMRSPI
  KRALGLADLERAQAMIYKLVVHGLLEDQFGGKIKQEIDQQAEESDPAQQAQTPVTTSPSA
  SSTTSFMSSSLEDTTTATTPVTDTETVPASESPGVMPLSLLRQMFSSYPTTTVLPTRRAQ
  TPPISSLPTSPSDEVGRRQSLTSPDSQSARPANRTALSDPSSRLSTSPPPPAIAVPLLEM
  GFSLRQIAKAMEATGARGEADAQNITVLAMWMIEHPGHEDEEEPQSGSTADSRPGAAVLG
  SGGKSNDPCYLQSPGDIPSADAAEMEEGFSESPDNLDHTENAASGSGPSARGRSAVTRRH
  KFDLAARTLLARAAGLYRSVQAHRNQSRREGISLQQDPGALYDFNLDEELEIDLDDEAME
  AMFGQDLTSDNDILGMWIPEVLDWPTWHVCESEDREEVVVCELCECSVVSFNQHMKRNHP
  GCGRSANRQGYRSNGSYVDGWFGGECGSGNPYYLLCGTCREKYLAMKTKSKSTSSERYKG
  QAPDLIGKQDSVYEEDWDMLDVDEDEKLTGEEEFELLAGPLGLNDRRIVPEPVQFPDSDP
  LGASVAMVTATNSMEETLMQIGCHGSVEKSSSGRITLGEQAAALANPHDRVVALRRVTAA
  AQVLLARTMVMRALSLLSVSGSSCSLAAGLESLGLTDIRTLVRLMCLAAAGRAGLSTSPS
  AMASTSERSRGGHSKANKPISCLAYLSTAVGCLASNAPSAAKLLVQLCTQNLISAATGVN
  LTTVDDSIQRKFLPSFLRGIAEENKLVTSPNFVVTQALVALLADKGAKLRPNYDKSEVEK
  KGPLELANALAACCLSSRLSSQHRQWAAQQLVRTLAAHDRDNQTTLQTLADMGGDLRKCS
  FIKLEAHQNRVMTCVWCNKKGLLATSGNDGTIRVWNVTKKQYSLQQTCVFNRLEGDAEES
  LGSPSDPSFSPVSWSISGKYLAGALEKMVNIWQVNGGKGLVDIQPHWVSALAWPEEGPAT
  AWSGESPELLLVGRMDGSLGLIEVVDVSTMHRRELEHCYRKDVSVTCIAWFSEDRPFAVG
  YFDGKLLLGTKEPLEKGGIVLIDAHKDTLISMKWDPTGHILMTCAKEDSVKLWGSISGCW
  CCLHSLCHPSIVNGIAWCRLPGKGSKLQLLMATGCQSGLVCVWRIPQDTTQTNVTSAEGW
  WEQESNCQDGYRKSSGAKCVYQLRGHITPVRTVAFSSDGLALVSGGLGGLMNIWSLRDGS
  VLQTVVIGSGAIQTTVWIPEVGVAACSNRSKDVLVVNCTAEWAAANHVLATCRTALKQQG
  VLGLNMAPCMRAFLERLPMMLQEQYAYEKPHVVCGDQLVHSPYMQCLASLAVGLHLDQLL
  CNPPVPPHHQNCLPDPASWNPNEWAWLECFSTTIKAAEALTNGAQFPESFTVPDLEPVPE
  DELVFLMDNSKWINGMDEQIMSWATSRPEDWHLGGKCDVYLWGAGRHGQLAEAGRNVMVP
  AAAPSFSQAQQVICGQNCTFVIQANGTVLACGEGSYGRLGQGNSDDLHVLTVISALQGFV
  VTQLVTSCGSDGHSMALTESGEVFSWGDGDYGKLGHGNSDRQRRPRQIEALQGEEVVQMS
  CGFKHSAVVTSDGKLFTFGNGDYGRLGLGNTSNKKLPERVTALEGYQIGQVACGLNHTLA
  VSADGSMVWAFGDGDYGKLGLGNSTAKSSPQKIDVLCGIGIKKVACGTQFSVALTKDGHV
  YTFGQDRLIGLPEGRARNHNRPQQIPVLAGVIIEDVAVGAEHTLALASNGDVYAWGSNSE
  GQLGLGHTNHVREPTLVTGLQGKNVRQISAGRCHSAAWTAPPVPPRAPGVSVPLQLGLPD
  TVPPQYGALREVSIHTVRARLRLLYHFSDLMYSSWRLLNLSPNNQNSTSHYNAGTWGIVQ
  GQLRPLLAPRVYTLPMVRSIGKTMVQGKNYGPQITVKRISTRGRKCKPIFVQIARQVVKL
  NASDLRLPSRAWKVKLVGEGADDAGGVFDDTITEMCQELETGIVDLLIPSPNATAEVGYN
  RDRFLFNPSACLDEHLMQFKFLGILMGVAIRTKKPLDLHLAPLVWKQLCCVPLTLEDLEE
  VDLLYVQTLNSILHIEDSGITEESFHEMIPLDSFVGQSADGKMVPIIPGGNSIPLTFSNR
  KEYVERAIEYRLHEMDRQVAAVREGMSWIVPVPLLSLLTAKQLEQMVCGMPEISVEVLKK
  VVRYREVDEQHQLVQWFWHTLEEFSNEERVLFMRFVSGRSRLPANTADISQRFQIMKVDR
  PYDSLPTSQTCFFQLRLPPYSSQLVMAERLRYAINNCRSIDMDNYMLSRNVDNAEGSDTD
  Y

• Sequence length: 4861

Pathways

KEGG:

Ubiquitin mediated proteolysis

Reactome:

Antigen processing: Ubiquitination & Proteasome degradation

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
HERC1-related disorder	Pathogenic	rs776053920	RCV003901012	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Macrocephaly, dysmorphic facies, and psychomotor retardation	Pathogenic; Likely pathogenic	rs753780877, rs797045141, rs772789325, rs2551273132, rs879253786, rs769677823, rs2551074619, rs2550842376, rs2551285409, rs757446033	RCV000235006 RCV000235008 RCV003140515 RCV003145992 RCV000235009 RCV000235003 RCV003995075 RCV004556028 RCV004587853 RCV001265603	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Megalencephaly with thick corpus callosum, cerebellar atrophy, and intellectual disability	Pathogenic; Likely pathogenic	rs753780877, rs797045141	RCV000186608 RCV000190895	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Adrenocortical carcinoma, hereditary	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION	—	CTD, Disgenet, GWAS catalog CTD, Disgenet, GWAS catalog CTD, Disgenet, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATTENTION DEFICIT HYPERACTIVITY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC OBSTRUCTIVE PULMONARY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DENTAL CARIES	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intellectual disability	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Lung cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAJOR DEPRESSIVE DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Multiple congenital anomalies/dysmorphic syndrome	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neurodevelopmental disorder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEVELOPMENTAL DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEUROTIC DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Papillary renal cell carcinoma type 1	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Premature ovarian insufficiency	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SUBSTANCE ABUSE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thymoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uveal melanoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adult Acute Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	21946537		★☆☆☆☆ Found in Text Mining only
Age related macular degeneration	Age-related macular degeneration	GWASCAT_DG	29346644		★☆☆☆☆ Found in Text Mining only
Agenesis of Corpus Callosum	Corpus callosum agenesis	Pubtator	26153217	Associate	★☆☆☆☆ Found in Text Mining only
Angelman Syndrome	Angelman Syndrome	BEFREE	23065719		★☆☆☆☆ Found in Text Mining only
Arachnodactyly	Arachnodactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial Fibrillation	CTD_human_DG	30061737		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atrial Fibrillation	Atrial Fibrillation	GWASCAT_DG	30061737		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autism Spectrum Disorder	Autism	Pubtator	26290361	Inhibit	★☆☆☆☆ Found in Text Mining only
Autism Spectrum Disorders	Autism Spectrum Disorder	BEFREE	26582266		★☆☆☆☆ Found in Text Mining only
Byzanthine arch palate	High palate	HPO_DG			★☆☆☆☆ Found in Text Mining only
Carcinoma Lobular	Lobular carcinoma	Pubtator	27811364	Associate	★☆☆☆☆ Found in Text Mining only
Cerebellar atrophy	Cerebellar atrophy	BEFREE	26153217		★☆☆☆☆ Found in Text Mining only
Cerebellar Diseases	Cerebellar diseases	Pubtator	26153217	Associate	★☆☆☆☆ Found in Text Mining only
Chronic Obstructive Airway Disease	Chronic Obstructive Pulmonary Disease	GWASCAT_DG	30940143		★☆☆☆☆ Found in Text Mining only
Class III malocclusion	Malocclusion	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	21946537	Associate	★☆☆☆☆ Found in Text Mining only
Congenital anomaly of face	Facial dysmorphism	BEFREE	27108999		★☆☆☆☆ Found in Text Mining only
Exophthalmos	Proptosis	CLINVAR_DG	27108999		★☆☆☆☆ Found in Text Mining only
Exophthalmos	Proptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Frontal bossing	Frontal bossing	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	23065719, 26138117, 26153217, 27108999, 28323226		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Intellectual Disability	Intellectual developmental disorder	Pubtator	26153217	Associate	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Intellectual Disability	Mental retardation	HPO_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Leukemia	Leukemia	Pubtator	21946537	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	31896782	Associate	★☆☆☆☆ Found in Text Mining only
Macrocephaly	Macrocephaly	BEFREE	26153217, 27108999		★☆☆☆☆ Found in Text Mining only
Macrocephaly	Macrocephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
MACROCEPHALY, DYSMORPHIC FACIES, AND PSYCHOMOTOR RETARDATION	Macrocephaly, Dysmorphic Facies, And Psychomotor Retardation	UNIPROT_DG	26138117		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MACROCEPHALY, DYSMORPHIC FACIES, AND PSYCHOMOTOR RETARDATION	Macrocephaly, Dysmorphic Facies, And Psychomotor Retardation	GENOMICS_ENGLAND_DG	26153217, 27108999		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MACROCEPHALY, DYSMORPHIC FACIES, AND PSYCHOMOTOR RETARDATION	Macrocephaly, Dysmorphic Facies, And Psychomotor Retardation	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MACROCEPHALY, DYSMORPHIC FACIES, AND PSYCHOMOTOR RETARDATION	Macrocephaly, Dysmorphic Facies, And Psychomotor Retardation	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Macrotia	Macrotia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Megalencephaly-severe kyphoscoliosis-overgrowth syndrome	Megalencephaly Kyphoscoliosis-Overgrowth Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Mental impairment	Mental Depression	BEFREE	28102468		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	26153217	Associate	★☆☆☆☆ Found in Text Mining only
Paroxysmal atrial fibrillation	Paroxysmal atrial fibrillation	CTD_human_DG	30061737		★☆☆☆☆ Found in Text Mining only
Posteriorly rotated ear	Posteriorly Rotated Ear	HPO_DG			★☆☆☆☆ Found in Text Mining only
Relative macrocephaly	Macrocephaly	CLINVAR_DG	27108999		★☆☆☆☆ Found in Text Mining only
Scoliosis, unspecified	Scoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Seizures Febrile	Seizures	Pubtator	35022648	Associate	★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	BEFREE	26153217, 28323226		★☆☆☆☆ Found in Text Mining only
T-Cell Prolymphocytic Leukemia	T-Cell Prolymphocytic Leukemia	BEFREE	29352181		★☆☆☆☆ Found in Text Mining only