KARS1 (lysyl-tRNA synthetase 1)

Gene

• Entrez ID: 3735
• Gene name: Lysyl-tRNA synthetase 1
• Gene symbol: KARS1
• Synonyms (NCBI Gene): CMTRIB, DEAPLE, DFNB89, KARS, KARS2, KRS, LEPID
• Chromosome: 16
• Chromosome location: 16q23.1
• Summary: Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. Lysyl-tRNA synthetase is a homodimer localized to the cytoplasm which belongs to the class II family of tRNA synthetases. It has been shown to be a target

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs77573084	G>A	Conflicting-interpretations-of-pathogenicity, benign-likely-benign	Coding sequence variant, missense variant
rs149772470	C>T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, missense variant
rs201650281	G>A	Likely-pathogenic, pathogenic	Missense variant, coding sequence variant
rs267607194	A>T	Pathogenic	Missense variant, coding sequence variant, 5 prime UTR variant
rs377697859	C>A,T	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Intron variant
rs397514745	A>G	Pathogenic	Missense variant, 5 prime UTR variant, coding sequence variant
rs397514746	C>T	Pathogenic	Missense variant, coding sequence variant
rs587776688	->AA	Pathogenic	Frameshift variant, 5 prime UTR variant, coding sequence variant
rs772410450	A>C	Pathogenic	Coding sequence variant, missense variant
rs778748895	C>A,T	Pathogenic	Coding sequence variant, missense variant
rs1415687857	G>A	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs1555512658	G>A	Pathogenic	Missense variant, coding sequence variant
rs1567498374	G>-,GG	Pathogenic	Coding sequence variant, frameshift variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000049	Function	TRNA binding	IBA
GO:0000049	Function	TRNA binding	IEA
GO:0000049	Function	TRNA binding	NAS	10952987
GO:0000166	Function	Nucleotide binding	IEA
GO:0002276	Process	Basophil activation involved in immune response	IBA
GO:0002276	Process	Basophil activation involved in immune response	IEA
GO:0002276	Process	Basophil activation involved in immune response	IGI	19524539
GO:0002863	Process	Positive regulation of inflammatory response to antigenic stimulus	IDA	15851690
GO:0003676	Function	Nucleic acid binding	IEA
GO:0003877	Function	ATP:ADP adenylyltransferase activity	IBA
GO:0003877	Function	ATP:ADP adenylyltransferase activity	IDA	23159739
GO:0004812	Function	Aminoacyl-tRNA ligase activity	IEA
GO:0004824	Function	Lysine-tRNA ligase activity	IBA
GO:0004824	Function	Lysine-tRNA ligase activity	IDA	9278442, 10952987, 23159739
GO:0004824	Function	Lysine-tRNA ligase activity	IEA
GO:0005515	Function	Protein binding	IPI	16189514, 21220307, 21536907, 21900206, 21988832, 22386318, 23159739, 24212136, 24312579, 24983501, 25416956, 29997244, 31116475, 32296183, 32814053, 33961781
GO:0005524	Function	ATP binding	IEA
GO:0005576	Component	Extracellular region	IEA
GO:0005615	Component	Extracellular space	IDA	15851690
GO:0005634	Component	Nucleus	IDA	23159739
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IEA
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA	10952987
GO:0005739	Component	Mitochondrion	IEA
GO:0005759	Component	Mitochondrial matrix	TAS
GO:0005829	Component	Cytosol	IDA	19289464, 23159739
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA
GO:0005886	Component	Plasma membrane	IEA
GO:0006412	Process	Translation	IEA
GO:0006418	Process	TRNA aminoacylation for protein translation	IEA
GO:0006430	Process	Lysyl-tRNA aminoacylation	IBA
GO:0006430	Process	Lysyl-tRNA aminoacylation	IDA	9278442, 10952987, 23159739
GO:0006430	Process	Lysyl-tRNA aminoacylation	IEA
GO:0008033	Process	TRNA processing	NAS	10952987
GO:0010165	Process	Response to X-ray	IEA
GO:0015966	Process	Diadenosine tetraphosphate biosynthetic process	IBA
GO:0015966	Process	Diadenosine tetraphosphate biosynthetic process	IDA	23159739
GO:0015966	Process	Diadenosine tetraphosphate biosynthetic process	IEA
GO:0015966	Process	Diadenosine tetraphosphate biosynthetic process	IGI	19524539
GO:0016020	Component	Membrane	IEA
GO:0016597	Function	Amino acid binding	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0016874	Function	Ligase activity	IEA
GO:0017101	Component	Aminoacyl-tRNA synthetase multienzyme complex	IBA
GO:0017101	Component	Aminoacyl-tRNA synthetase multienzyme complex	IDA	19131329
GO:0017101	Component	Aminoacyl-tRNA synthetase multienzyme complex	IEA
GO:0042802	Function	Identical protein binding	IPI	18272479, 21536907, 24212136
GO:0042803	Function	Protein homodimerization activity	IPI	23159739
GO:0043032	Process	Positive regulation of macrophage activation	IBA
GO:0043032	Process	Positive regulation of macrophage activation	IDA	15851690
GO:0045893	Process	Positive regulation of DNA-templated transcription	IEA
GO:0045893	Process	Positive regulation of DNA-templated transcription	IGI	19524539
GO:0070371	Process	ERK1 and ERK2 cascade	IEA
GO:0070371	Process	ERK1 and ERK2 cascade	IGI	19524539

Other IDs

• MIM: 601421
• HGNC: 6215
• e!Ensembl: ENSG00000065427

Protein

• UniProt ID: Q15046
• Protein name: Lysine--tRNA ligase (EC 2.7.7.-) (EC 6.1.1.6) (Lysyl-tRNA synthetase) (LysRS)
• Protein function: Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA (PubMed:18029264, PubMed:18272479, Pub
• PDB: 3BJU, 4DPG, 4YCU, 4YCW, 6CHD, 6ILD, 6ILH, 7EA9, 8HYR, 8XP4, 9DOW, 9DPA, 9DPB, 9DPL
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01336	tRNA_anti-codon	126 → 206	OB-fold nucleic acid binding domain	Domain
  PF00152	tRNA-synt_2	222 → 574	tRNA synthetases class II (D, K and N)	Domain

• Sequence:

  MAAVQAAEVKVDGSEPKLSKNELKRRLKAEKKVAEKEAKQKELSEKQLSQATAAATNHTT
  DNGVGPEEESVDPNQYYKIRSQAIHQLKVNGEDPYPHKFHVDISLTDFIQKYSHLQPGDH
  LTDITLKVAGRIHAKRASGGKLIFYDLRGEGVKLQVMANSRNYKSEEEFIHINNKLRRGD
  IIGVQGNPGKTKKGELSIIPYEITLLSPCLHMLPHLHFGLKDKETRYRQRYLDLILNDFV
  RQKFIIRSKIITYIRSFLDELGFLEIETPMMNIIPGGAVAKPFITYHNELDMNLYMRIAP
  ELYHKMLVVGGIDRVYEIGRQFRNEGIDLTHNPEFTTCEFYMAYADYHDLMEITEKMVSG
  MVKHITGSYKVTYHPDGPEGQAYDVDFTPPFRRINMVEELEKALGMKLPETNLFETEETR
  KILDDICVAKAVECPPPRTTARLLDKLVGEFLEVTCINPTFICDHPQIMSPLAKWHRSKE
  GLTERFELFVMKKEICNAYTELNDPMRQRQLFEEQAKAKAAGDDEAMFIDENFCTALEYG
  LPPTAGWGMGIDRVAMFLTDSNNIKEVLLFPAMKPEDKKENVATTDTLESTTVGTSV

• Sequence length: 597

Pathways

KEGG:

Aminoacyl-tRNA biosynthesis

Reactome:

Cytosolic tRNA aminoacylation
Mitochondrial tRNA aminoacylation

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
Abnormal cerebral white matter morphology	Likely pathogenic; Pathogenic	rs201650281	RCV000681462	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Abnormal pyramidal sign	Likely pathogenic; Pathogenic	rs201650281	RCV000681462	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Autosomal recessive nonsyndromic hearing loss 89	Pathogenic; Likely pathogenic	rs1299524768, rs201650281, rs760134437, rs778748895	RCV002204554 RCV000986183 RCV004555374 RCV000986182	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Charcot-Marie-Tooth disease recessive intermediate B	Likely pathogenic; Pathogenic	rs201650281, rs267607194, rs587776688	RCV003147413 RCV000008647 RCV000008648	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Congenital sensorineural hearing impairment	Likely pathogenic; Pathogenic	rs201650281	RCV000681462	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Deafness, congenital, and adult-onset progressive leukoencephalopathy	Likely pathogenic; Pathogenic	rs201650281, rs1555512658, rs778748895	RCV001293662 RCV001293660 RCV001293658	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Global developmental delay	Likely pathogenic; Pathogenic	rs2151809445, rs1567498374	RCV002226985 RCV000678489	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hearing loss, autosomal recessive	Likely pathogenic; Pathogenic	rs201650281	RCV004699121	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hypotonia	Pathogenic	rs1567498374	RCV000678489	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
KARS-related disorder	Likely pathogenic; Pathogenic	rs201650281	RCV001265601	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
KARS1-related disorder	Likely pathogenic; Pathogenic	rs201650281, rs1431954464, rs2507056779, rs761527468	RCV001526444 RCV004527905 RCV004536823 RCV004531073	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Lactic acidosis	Pathogenic	rs1567498374	RCV000678489	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
LEUKOENCEPHALOPATHY, PROGRESSIVE, INFANTILE-ONSET, WITH DEAFNESS	Likely pathogenic; Pathogenic	rs201650281, rs778748895, rs1567498374, rs768349236, rs2082153181	RCV001293661 RCV001293659 RCV001293663 RCV001293665 RCV001293666	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Leukoencephalopathy, progressive, infantile-onset, with or without deafness	Likely pathogenic; Pathogenic	rs201650281, rs1299184638, rs2507556167, rs2507056779, rs1370913867, rs774447299, rs761527468, rs770522582	RCV002463662 RCV003223482 RCV003323263 RCV005254809 RCV003322806 RCV002463798 RCV001293656 RCV001293657	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Microcephaly	Likely pathogenic	rs2151809445	RCV002226985	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Nystagmus	Likely pathogenic	rs2151809445	RCV002226985	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Optic neuropathy	Likely pathogenic; Pathogenic	rs201650281	RCV000681462	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Progressive cerebellar ataxia	Likely pathogenic; Pathogenic	rs201650281	RCV000681462	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Seizure	Likely pathogenic	rs2151809445	RCV002226985	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Sensorineural hearing loss disorder	Pathogenic	rs1567498374	RCV000678489	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
AUTOSOMAL RECESSIVE INTERMEDIATE CHARCOT-MARIE-TOOTH DISEASE TYPE B	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL RECESSIVE ISOLATED SENSORINEURAL DEAFNESS TYPE DFNB	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Charcot-Marie-Tooth disease	Benign; Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
CHARCOT-MARIE-TOOTH DISEASE, RECESSIVE INTERMEDIATE B	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL SENSORINEURAL HEARING LOSS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEAFNESS, AUTOSOMAL RECESSIVE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEAFNESS, AUTOSOMAL RECESSIVE 89	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEJERINE-SOTTAS DISEASE	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EARLY ONSET PROGRESSIVE LEUKOENCEPHALOPATHY- CENTRAL NERVOUS SYSTEM CALCIFICATION- HEARING LOSS-VISUAL IMPAIRMENT SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EARLY-ONSET PROGRESSIVE LEUKOENCEPHALOPATHY-CENTRAL NERVOUS SYSTEM CALCIFICATION-DEAFNESS-VISUAL IMPAIRMENT SYNDROME	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hearing impairment	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
HEREDITARY MOTOR AND SENSORY NEUROPATHIES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEREDITARY MOTOR AND SENSORY NEUROPATHY, TYPES I-IV	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTROPHIC NEUROPATHY OF INFANCY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Leukodystrophy	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonsyndromic genetic hearing loss	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PERONEAL MUSCULAR ATROPHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ROUSSY-LEVY SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SENSORINEURAL HEARING LOSS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SENSORINEURAL HEARING LOSS OF BILATERAL EARS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	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

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acoustic Neuroma	Acoustic Neuroma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Adult type dermatomyositis	Dermatomyositis	BEFREE	30275047		★☆☆☆☆ Found in Text Mining only
Anemia	Anemia	Pubtator	29875423	Associate	★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Autoimmune Diseases	BEFREE	30275047		★☆☆☆☆ Found in Text Mining only
Autosomal recessive intermediate Charcot-Marie-Tooth disease type B	Charcot-Marie-Tooth Disease	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autosomal recessive non-syndromic sensorineural deafness type DFNB	Non-Syndromic Sensorineural Deafness	Orphanet			★☆☆☆☆ Found in Text Mining only
Autosomal Recessive Parkinsonism	Parkinsonian disease	BEFREE	22296644		★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	33084231	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	29029422, 31050289		★☆☆☆☆ Found in Text Mining only
Cardiomyopathies	Cardiomyopathy	BEFREE	30252186		★☆☆☆☆ Found in Text Mining only
Cardiomyopathies	Cardiomyopathy	Pubtator	33260297	Associate	★☆☆☆☆ Found in Text Mining only
Charcot-Marie-Tooth Disease	Charcot-Marie-Tooth Disease	BEFREE	20920668		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
CHARCOT-MARIE-TOOTH DISEASE, RECESSIVE INTERMEDIATE B	Charcot-Marie-Tooth Disease	ORPHANET_DG	20920668		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHARCOT-MARIE-TOOTH DISEASE, RECESSIVE INTERMEDIATE B	Charcot-Marie-Tooth Disease	UNIPROT_DG	20920668		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHARCOT-MARIE-TOOTH DISEASE, RECESSIVE INTERMEDIATE B	Charcot-Marie-Tooth Disease	GENOMICS_ENGLAND_DG	20920668, 23768514, 25330800, 27604308, 28496994, 8812440		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHARCOT-MARIE-TOOTH DISEASE, RECESSIVE INTERMEDIATE B	Charcot-Marie-Tooth Disease	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHARCOT-MARIE-TOOTH DISEASE, RECESSIVE INTERMEDIATE B	Charcot-Marie-Tooth Disease	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon Carcinoma	Colon Carcinoma	BEFREE	30188867		★☆☆☆☆ Found in Text Mining only
Congenital sensorineural hearing loss	Congenital Sensorineural Hearing Loss	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Deafness	Deafness	Pubtator	30737337, 32048449	Associate	★☆☆☆☆ Found in Text Mining only
DEAFNESS, AUTOSOMAL RECESSIVE 89	Deafness	GENOMICS_ENGLAND_DG	20920668, 23768514, 25330800, 27604308, 28496994, 8812440		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEAFNESS, AUTOSOMAL RECESSIVE 89	Deafness	UNIPROT_DG	23768514, 28887846		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEAFNESS, AUTOSOMAL RECESSIVE 89	Deafness	CLINVAR_DG	23768514		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEAFNESS, AUTOSOMAL RECESSIVE 89	Deafness	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dermatomyositis	Dermatomyositis	BEFREE	30275047		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	33478492	Associate	★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	GENOMICS_ENGLAND_DG	25330800, 28496994		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Global developmental delay	Developmental Delay	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Global developmental delay	Developmental Delay	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hearing Loss	Hearing loss	Pubtator	33478492, 35106950	Associate	★☆☆☆☆ Found in Text Mining only
Hearing Loss Sensorineural	Hearing loss	Pubtator	31116475, 33260297, 33942428	Associate	★☆☆☆☆ Found in Text Mining only
Heart Failure	Heart failure	Pubtator	33478492	Associate	★☆☆☆☆ Found in Text Mining only
Hypertension Portal	Portal hypertension	Pubtator	33478492	Associate	★☆☆☆☆ Found in Text Mining only
Hypertrophic Cardiomyopathy	Hypertrophic cardiomyopathy	BEFREE	27891585		★☆☆☆☆ Found in Text Mining only
Hypertrophic obstructive cardiomyopathy	Hypertrophic cardiomyopathy	BEFREE	27891585		★☆☆☆☆ Found in Text Mining only
Hypothyroidism	Hypothyroidism	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	GENOMICS_ENGLAND_DG	25330800, 28496994		★☆☆☆☆ Found in Text Mining only
Intracranial Arteriovenous Malformations	Intracranial arteriovenous malformation	Pubtator	40551197	Associate	★☆☆☆☆ Found in Text Mining only
KUFOR-RAKEB SYNDROME	Kufor-Rakeb Syndrome	BEFREE	22296644		★☆☆☆☆ Found in Text Mining only
LEOPARD Syndrome	Leopard syndrome	Pubtator	33478492	Associate	★☆☆☆☆ Found in Text Mining only
Leukodystrophy	Leukodystrophy	BEFREE	30715177		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Leukodystrophy Metachromatic	Metachromatic leukodystrophy	Pubtator	30737337, 33260297, 33942428	Associate	★☆☆☆☆ Found in Text Mining only
Leukoencephalopathy	Leukoencephalopathy	BEFREE	28887846, 29615062		★☆☆☆☆ Found in Text Mining only
Lung Diseases	Lung disease	Pubtator	29875423	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	29029422, 31050289		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	26891990, 30188867		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	30188867		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	28394346		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	BEFREE	27891585		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Microcephaly	Microcephaly	Pubtator	33260297, 33478492	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Mitochondrial Diseases	Mitochondrial Diseases	BEFREE	23596069		★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	30737337, 33260297, 33478492	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	30188867		★☆☆☆☆ Found in Text Mining only
Nervous System Diseases	Nervous system disease	Pubtator	33942428	Associate	★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	29029422		★☆☆☆☆ Found in Text Mining only
Nonsyndromic Deafness	Nonsyndromic Deafness	CLINGEN_DG	14975237, 23768514, 28887846		★☆☆☆☆ Found in Text Mining only
Nonsyndromic Deafness	Nonsyndromic Deafness	BEFREE	27891585, 31116475		★☆☆☆☆ Found in Text Mining only
Optic Neuropathy	Optic Neuropathy	BEFREE	31116475		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Optic Neuropathy	Optic Neuropathy	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ovarian Dysgenesis 2	Ovarian dysgenesis	Pubtator	30737337	Associate	★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Nervous System Diseases	BEFREE	20920668		★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Peripheral nervous system disease	Pubtator	20920668, 33260297	Associate	★☆☆☆☆ Found in Text Mining only
Peripheral Neuropathy	Peripheral Neuropathy	BEFREE	20920668		★☆☆☆☆ Found in Text Mining only
Polymyositis	Polymyositis	BEFREE	30275047		★☆☆☆☆ Found in Text Mining only
Polyneuropathy	Polyneuropathy	BEFREE	27891585		★☆☆☆☆ Found in Text Mining only
Prion Diseases	Prion disease	Pubtator	25149502	Associate	★☆☆☆☆ Found in Text Mining only
Progressive cerebellar ataxia	Cerebellar Ataxia	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Secondary malignant neoplasm of colon and/or rectum	Colorectal Neoplasms	BEFREE	19549774		★☆☆☆☆ Found in Text Mining only
Seizures	Seizures	Pubtator	31618474, 33942428	Associate	★☆☆☆☆ Found in Text Mining only
Seminoma	Seminoma	Pubtator	36713456	Associate	★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	BEFREE	28887846, 30252186		★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	31315917	Associate	★☆☆☆☆ Found in Text Mining only