PNKP (polynucleotide kinase 3'-phosphatase)

Gene

• Entrez ID: 11284
• Gene name: Polynucleotide kinase 3'-phosphatase
• Gene symbol: PNKP
• Synonyms (NCBI Gene): AOA4, CMT2B2, EIEE10, MCSZ, PNK
• Chromosome: 19
• Chromosome location: 19q13.33
• Summary: This locus represents a gene involved in DNA repair. In response to ionizing radiation or oxidative damage, the protein encoded by this locus catalyzes 5` phosphorylation and 3` dephosphorylation of nucleic acids. Mutations at this locus have been associa

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs3739173	G>A	Uncertain-significance, conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs3739200	->G	Conflicting-interpretations-of-pathogenicity	Intron variant
rs34472250	C>G,T	Likely-benign, uncertain-significance, conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs75203375	C>G	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, synonymous variant
rs115259839	G>A,C	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Coding sequence variant, missense variant
rs116192442	G>A	Benign-likely-benign, likely-benign, conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs142143566	C>T	Benign, likely-benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs144284975	G>A,C	Benign, likely-benign, conflicting-interpretations-of-pathogenicity	Missense variant, synonymous variant, coding sequence variant
rs145904995	C>T	Uncertain-significance, likely-benign, conflicting-interpretations-of-pathogenicity, benign-likely-benign	Synonymous variant, coding sequence variant
rs151180981	G>A	Benign, likely-benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs199919568	A>C,G	Conflicting-interpretations-of-pathogenicity	Splice donor variant
rs201503405	G>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance	Missense variant, coding sequence variant
rs267606956	C>A,T	Pathogenic	Missense variant, coding sequence variant, stop gained
rs267606957	G>A,C	Pathogenic	Missense variant, coding sequence variant
rs371834726	C>T	Likely-benign, conflicting-interpretations-of-pathogenicity, uncertain-significance	Intron variant
rs372148913	G>A	Likely-pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs372404688	G>A	Likely-pathogenic	Coding sequence variant, stop gained
rs374745816	G>A	Likely-benign, conflicting-interpretations-of-pathogenicity	Intron variant
rs375781731	G>A	Pathogenic	Coding sequence variant, stop gained
rs376854895	C>G,T	Conflicting-interpretations-of-pathogenicity, likely-benign, uncertain-significance, benign, likely-pathogenic	Missense variant, coding sequence variant
rs532550120	C>G,T	Conflicting-interpretations-of-pathogenicity, likely-benign, uncertain-significance	Coding sequence variant, missense variant, synonymous variant
rs539286945	G>A,C	Pathogenic	Stop gained, coding sequence variant, missense variant
rs571119317	G>A	Benign, conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs587784365	->GTCGATGGCGACCCGTT	Pathogenic	Frameshift variant, coding sequence variant
rs587784366	TACCTGGCGC>-	Pathogenic-likely-pathogenic, likely-pathogenic, pathogenic	Intron variant, coding sequence variant, splice donor variant
rs730882224	->GTCGATGGCGACCCGTT	Likely-pathogenic	Frameshift variant, coding sequence variant
rs747244348	G>A	Conflicting-interpretations-of-pathogenicity, likely-benign	Synonymous variant, coding sequence variant
rs750550558	->TT	Likely-pathogenic	Intron variant
rs752902474	AGGAGGGGGGTCAGGGG>-,AGGAGGGGGGTCAGGGGAGGAGGGGGGTCAGGGG	Pathogenic	Intron variant
rs756746191	G>C	Pathogenic	Coding sequence variant, missense variant
rs760249644	->CTACCTGGCGCGGCTCGCG	Likely-benign, conflicting-interpretations-of-pathogenicity	Coding sequence variant, intron variant, splice donor variant
rs764379536	CTCGCGGCGTCTGG>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs766530579	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs767645983	T>G	Pathogenic	Splice acceptor variant
rs768847609	->GACC	Pathogenic	Coding sequence variant, frameshift variant
rs772727116	C>T	Pathogenic	Coding sequence variant, stop gained
rs786203983	C>A	Uncertain-significance, pathogenic	Missense variant, coding sequence variant
rs786205207	GGT>-	Likely-pathogenic, pathogenic	Coding sequence variant, inframe deletion
rs794727920	G>A	Conflicting-interpretations-of-pathogenicity, likely-benign	Synonymous variant, coding sequence variant
rs796052850	G>A	Pathogenic	Coding sequence variant, stop gained
rs796052859	->A	Likely-pathogenic, pathogenic	Coding sequence variant, stop gained
rs796052860	TCGCGGC>-,TCGCGGCTCGCGGC	Likely-pathogenic, pathogenic	Frameshift variant, coding sequence variant
rs796052861	->ACCTGGCG	Pathogenic	Splice donor variant, coding sequence variant
rs796052862	->CTCGG	Pathogenic	Frameshift variant, coding sequence variant
rs796052863	TGT>-	Likely-pathogenic	Coding sequence variant, inframe deletion
rs879255541	->C	Likely-pathogenic	Frameshift variant, coding sequence variant
rs886037744	->CGGCT	Pathogenic	Frameshift variant, coding sequence variant
rs959497903	C>A,T	Likely-pathogenic	Splice donor variant
rs1057518102	C>T	Likely-pathogenic	Splice donor variant
rs1057520630	C>G,T	Pathogenic	Splice donor variant
rs1064794452	TC>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1131691883	GAGCTCGAAGCCGG>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1247055716	C>A	Pathogenic	Splice donor variant
rs1338672803	A>C,G	Likely-pathogenic	Missense variant, coding sequence variant
rs1389034284	->A	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1555810849	CTGGCGCGGCTC>-,CTGGCGCGGCTCCCTGGCGCGGCTC	Uncertain-significance, likely-pathogenic	Coding sequence variant, splice donor variant
rs1555810891	->GGGCTGTCTCACACGTGGTCACACAGCGCTGCCAGGAGCCTAGCGTGTC	Likely-pathogenic	Coding sequence variant, stop gained, inframe indel
rs1568659036	GCTCGCGGCGTCTGGGTTTGTGTTGTCGATGGCGACCCGTTTCCCTTGCTTCAGGGCTGTCTCACACGTGGTCACACAGCGCTGCCAGG>-	Pathogenic	Frameshift variant, coding sequence variant
rs1568660279	T>C	Likely-pathogenic	Splice acceptor variant
rs1568662343	G>A	Likely-pathogenic	Coding sequence variant, stop gained
rs1568663209	G>-	Pathogenic	Frameshift variant, coding sequence variant
rs1600416052	->GTTGTCGATGGCGACCC	Pathogenic	Frameshift variant, coding sequence variant
rs1600423552	C>-	Likely-pathogenic	Frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT029605	hsa-miR-26b-5p	Microarray	19088304

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0003684	Function	Damaged DNA binding	NAS	10446193
GO:0003690	Function	Double-stranded DNA binding	TAS	10446193
GO:0003824	Function	Catalytic activity	IEA
GO:0004519	Function	Endonuclease activity	NAS	10446192
GO:0005515	Function	Protein binding	IPI	15385968, 16189514, 19155274, 21637298, 25416956, 25609649, 26496610, 28514442, 32296183, 32814053, 33961781, 38225382
GO:0005524	Function	ATP binding	IEA
GO:0005524	Function	ATP binding	NAS	10446192
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	10446193
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005694	Component	Chromosome	IEA
GO:0005730	Component	Nucleolus	IDA
GO:0006261	Process	DNA-templated DNA replication	NAS	10446192
GO:0006281	Process	DNA repair	IBA
GO:0006281	Process	DNA repair	IEA
GO:0006281	Process	DNA repair	IGI	10446192
GO:0006287	Process	Base-excision repair, gap-filling	TAS
GO:0006289	Process	Nucleotide-excision repair	TAS	10446193
GO:0006303	Process	Double-strand break repair via nonhomologous end joining	IDA	15385968, 28453785
GO:0006974	Process	DNA damage response	IEA
GO:0006979	Process	Response to oxidative stress	IDA	10446192
GO:0009314	Process	Response to radiation	NAS	10446193
GO:0009314	Process	Response to radiation	TAS	10446192
GO:0016020	Component	Membrane	HDA	19946888
GO:0016301	Function	Kinase activity	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0017076	Function	Purine nucleotide binding	NAS	10446193
GO:0032206	Process	Positive regulation of telomere maintenance	IMP	21531765
GO:0035861	Component	Site of double-strand break	IDA	28453785
GO:0035861	Component	Site of double-strand break	IEA
GO:0046403	Function	Polynucleotide 3'-phosphatase activity	IBA
GO:0046403	Function	Polynucleotide 3'-phosphatase activity	IDA	10446192, 10446193
GO:0046403	Function	Polynucleotide 3'-phosphatase activity	IEA
GO:0046403	Function	Polynucleotide 3'-phosphatase activity	TAS
GO:0046404	Function	ATP-dependent polydeoxyribonucleotide 5'-hydroxyl-kinase activity	IBA
GO:0046404	Function	ATP-dependent polydeoxyribonucleotide 5'-hydroxyl-kinase activity	IDA	10446193
GO:0046404	Function	ATP-dependent polydeoxyribonucleotide 5'-hydroxyl-kinase activity	IEA
GO:0051734	Function	ATP-dependent polynucleotide 5'-hydroxyl-kinase activity	IEA
GO:2001034	Process	Positive regulation of double-strand break repair via nonhomologous end joining	IMP	12032095

Other IDs

• MIM: 605610
• HGNC: 9154
• e!Ensembl: ENSG00000039650

Protein

• UniProt ID: Q96T60
• Protein name: Bifunctional polynucleotide phosphatase/kinase (DNA 5'-kinase/3'-phosphatase) (Polynucleotide kinase-3'-phosphatase) [Includes: Polynucleotide 3'-phosphatase (EC 3.1.3.32) (2'(3')-polynucleotidase); Polynucleotide 5'-hydroxyl-kinase (EC 2.7.1.78)]
• Protein function: Plays a key role in the repair of DNA damage, functioning as part of both the non-homologous end-joining (NHEJ) and base excision repair (BER) pathways (PubMed:10446192, PubMed:10446193, PubMed:15385968, PubMed:20852255, PubMed:28453785). Throug
• PDB: 2BRF, 2W3O
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF17913	FHA_2	10 → 107	FHA domain	Domain
  PF08645	PNK3P	166 → 328	Polynucleotide kinase 3 phosphatase	Family
  PF13671	AAA_33	367 → 407		Domain
  PF13671	AAA_33	399 → 489		Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in many tissues with highest expression in spleen and testis, and lowest expression in small intestine (PubMed:10446192). Expressed in higher amount in pancreas, heart and kidney and at lower levels in brain, lung and liver (
• Sequence:

  MGEVEAPGRLWLESPPGGAPPIFLPSDGQALVLGRGPLTQVTDRKCSRTQVELVADPETR
  TVAVKQLGVNPSTTGTQELKPGLEGSLGVGDTLYLVNGLHPLTLRWEETRTPESQPDTPP
  GTPLVSQDEKRDAELPKKRMRKSNPGWENLEKLLVFTAAGVKPQGKVAGFDLDGTLITTR
  SGKVFPTGPSDWRILYPEIPRKLRELEAEGYKLVIFTNQMSIGRGKLPAEEFKAKVEAVV
  EKLGVPFQVLVATHAGLYRKPVTGMWDHLQEQANDGTPISIGDSIFVGDAAGRPANWAPG
  RKKKDFSCADRLFALNLGLPFATPEEFFLKWPAAGFELPAFDPRTVSRSGPLCLPESRAL
  LSASPEVVVAVGFPGAGKSTFLKKHLVSAGYVHVNRDTLGSWQRCVTTCETALKQGKRVA
  IDNTNPDAASRARYVQCARAAGVPCRCFLFTATLEQARHNNRFREMTDSSHIPVSDMVMY
  GYRKQFEAPTLAEGFSAILEIPFRLWVEPRLGRLYCQFSEG

• Sequence length: 521

Pathways

KEGG:

Base excision repair

Reactome:

APEX1-Independent Resolution of AP Sites via the Single Nucleotide Replacement Pathway

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 the nervous system	Pathogenic; Likely pathogenic	rs267606956, rs587784365, rs768847609	RCV001813953 RCV001813954 RCV001814226	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ataxia - oculomotor apraxia type 4	Pathogenic; Likely pathogenic	rs1477525034, rs982113263, rs786203983, rs886037744, rs1555810613, rs786205207, rs587784365, rs756746191	RCV001335536 RCV002497869 RCV000167523 RCV000167524 RCV000167525 RCV000170438 RCV000167521 RCV000853401	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia	Likely pathogenic; Pathogenic	rs587784366	RCV000825541	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Cerebellar atrophy	Likely pathogenic	rs730882224	RCV000162138	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Charcot-Marie-Tooth disease type 2B2	Likely pathogenic; Pathogenic	rs982113263, rs786205207, rs796052862, rs2122334749, rs1247055716	RCV002497869 RCV001093540 RCV001814094 RCV003990465 RCV001328605	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Developmental and epileptic encephalopathy, 12	Likely pathogenic; Pathogenic	rs1391913873, rs2122319491, rs1337771339, rs1163218519, rs2074810148, rs1057520630, rs149614720, rs138249970, rs766419491, rs2122315348, rs1413085852, rs965965834, rs1309576866, rs2122333424, rs1170743406, rs1600414549, rs982113263, rs1247055716, rs746413622, rs762003634, rs2122329109, rs587784366, rs786203983, rs893076827, rs786205207, rs1245431420, rs780627462, rs267606956, rs587784365, rs1433969585, rs2074810318, rs796052862, rs796052860, rs772727116, rs796052850, rs796052859, rs2514636093, rs752902474, rs2514631082, rs780834499, rs1409975594, rs766239881, rs1183620642, rs2514644262, rs1415935726, rs1243918665, rs2514631912, rs763027558, rs2074764232, rs1233430749, rs916130044, rs2514638711, rs1568660169, rs751675183, rs2074766866, rs1057518102, rs372404688, rs539286945, rs1131691883, rs764379536, rs766530579, rs768847609, rs1568659036, rs1568663209, rs1366190965, rs2074784617, rs745505490, rs2074757362, rs1246416070, rs2074756863, rs1568658916, rs2074777487	RCV001379489 RCV001389015 RCV001384335 RCV001381085 RCV001384137 RCV002541158 RCV001970322 RCV001923081 RCV002027658 RCV002037658 RCV001950872 RCV001943423 RCV001899543 RCV001994753 RCV001890349 RCV002035465 RCV002037963 RCV002036262 RCV001946592 RCV001992260 RCV001951493 RCV001070856 RCV000648410 RCV003526220 RCV001226527 RCV002607730 RCV003108614 RCV002512794 RCV000706286 RCV002676527 RCV002715283 RCV001387495 RCV003638640 RCV001857632 RCV005055689 RCV000550810 RCV002801539 RCV000798839 RCV002893882 RCV003005461 RCV003002797 RCV003034787 RCV003036041 RCV003525515 RCV003525844 RCV003525753 RCV003527119 RCV003526805 RCV003527540 RCV003639001 RCV003639756 RCV003639927 RCV003639869 RCV003640281 RCV003813968 RCV003857160 RCV001378231 RCV001231907 RCV000821367 RCV003114620 RCV001376960 RCV002532707 RCV000704636 RCV005092093 RCV000812409 RCV000807769 RCV001860590 RCV001059979 RCV001043154 RCV001058986 RCV001224000 RCV001217975 RCV001212535 RCV001214794 RCV001240620 RCV001880168	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Global developmental delay	Likely pathogenic	rs730882224	RCV000162138	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual disability	Pathogenic	rs587784365	RCV001257702	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Microcephaly, seizures, and developmental delay	Pathogenic; Likely pathogenic	rs2122319422, rs982113263, rs762003634, rs587784366, rs786203983, rs2514633587, rs786205207, rs267606956, rs587784365, rs267606957, rs752902474, rs770344860, rs1247055716, rs1600416052, rs2514637165, rs2514644062	RCV001731174 RCV002497869 RCV003339880 RCV000147346 RCV001813762 RCV002470636 RCV000500375 RCV000005119 RCV000005120 RCV000005121 RCV000194165 RCV003340935 RCV000502084 RCV000995611 RCV001255835 RCV001255766	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Nonpapillary renal cell carcinoma	Pathogenic	rs767645983	RCV005892190	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ovarian serous cystadenocarcinoma	Likely pathogenic; Pathogenic	rs1057520630	RCV005922457	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
PNKP-related disorder	Likely pathogenic; Pathogenic	rs982113263, rs587784366, rs760131892, rs752902474, rs1212228078, rs1247055716, rs2074784617	RCV004579583 RCV004700470 RCV004539747 RCV003335190 RCV003995126 RCV004535608 RCV004536078	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Primary microcephaly	Likely pathogenic	rs730882224	RCV000162138	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Seizure	Pathogenic	rs587784365	RCV005401280	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Abnormal cerebral morphology	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Adrenocortical carcinoma, hereditary	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATAXIA-OCULOMOTOR APRAXIA 4	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATAXIA-OCULOMOTOR APRAXIA TYPE 4	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2B2	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHARCOT-MARIE-TOOTH DISEASE, TYPE 2B2	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL MICROCEPHALY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL NEUROLOGIC ANOMALIES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 12	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEVELOPMENTAL DISABILITIES	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DNA REPAIR-DEFICIENCY DISORDERS	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EARLY INFANTILE DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EARLY INFANTILE EPILEPTIC ENCEPHALOPATHY WITH SUPPRESSION BURSTS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EPILEPSY, PYRIDOXINE-DEPENDENT	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Epileptic encephalopathy	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GENETIC DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GOUT	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEART FAILURE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Benign; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	-; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microcephaly	Conflicting classifications of pathogenicity	ClinVar CTD, Disgenet CTD, Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Pyridoxine-dependent epilepsy	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEIZURES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acquired Kyphoscoliosis	Acquired Kyphoscoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Adenoma	Adenoma	BEFREE	18414202		★☆☆☆☆ Found in Text Mining only
Amyotrophic Lateral Sclerosis	Amyotrophic lateral sclerosis	Pubtator	32005289	Associate	★☆☆☆☆ Found in Text Mining only
Apraxia oculomotor Cogan type	Apraxia	Pubtator	35326432	Associate	★☆☆☆☆ Found in Text Mining only
Ataxia	Ataxia	Pubtator	25728773, 27165045, 30039206	Associate	★☆☆☆☆ Found in Text Mining only
Ataxia Telangiectasia	Ataxia Telangiectasia	BEFREE	25590633, 30994454		★☆☆☆☆ Found in Text Mining only
ATAXIA, EARLY-ONSET, WITH OCULOMOTOR APRAXIA AND HYPOALBUMINEMIA	Ataxia-oculomotor apraxia	BEFREE	25728773, 28552035, 29498415		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
ATAXIA, EARLY-ONSET, WITH OCULOMOTOR APRAXIA AND HYPOALBUMINEMIA	Ataxia-oculomotor apraxia	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Ataxia, Spinocerebellar	Spinocerebellar Ataxia	BEFREE	27470939		★☆☆☆☆ Found in Text Mining only
ATAXIA-OCULOMOTOR APRAXIA 4	Ataxia-Oculomotor Apraxia	ORPHANET_DG	25728773		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATAXIA-OCULOMOTOR APRAXIA 4	Ataxia-Oculomotor Apraxia	CLINVAR_DG	25728773		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATAXIA-OCULOMOTOR APRAXIA 4	Ataxia-Oculomotor Apraxia	UNIPROT_DG	25728773		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATAXIA-OCULOMOTOR APRAXIA 4	Ataxia-Oculomotor Apraxia	GENOMICS_ENGLAND_DG	25728773, 30039206		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATAXIA-OCULOMOTOR APRAXIA 4	Ataxia-Oculomotor Apraxia	BEFREE	29498415		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATAXIA-OCULOMOTOR APRAXIA 4	Ataxia-Oculomotor Apraxia	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ataxia-oculomotor apraxia type 4	Ataxia-Oculomotor Apraxia	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Autistic behavior	Autism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autosomal Recessive Primary Microcephaly	Primary microcephaly	Pubtator	34697416	Associate	★☆☆☆☆ Found in Text Mining only
Benign Hereditary Chorea	Benign Hereditary Chorea	BEFREE	30956058		★☆☆☆☆ Found in Text Mining only
Brain Neoplasms	Brain neoplasms	Pubtator	35354845	Associate	★☆☆☆☆ Found in Text Mining only
Cerebellar atrophy	Cerebellar atrophy	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Cerebellar atrophy	Cerebellar atrophy	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Cerebellar Diseases	Cerebellar diseases	Pubtator	32980744, 35326432	Associate	★☆☆☆☆ Found in Text Mining only
Charcot-Marie-Tooth Disease	Charcot-Marie-Tooth Disease	BEFREE	30039206, 31110700		★☆☆☆☆ Found in Text Mining only
Charcot-Marie-Tooth disease type 2B2	Charcot-Marie-Tooth Disease	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Charcot-Marie-Tooth disease, Type 2B2	Charcot-Marie-Tooth disease	BEFREE	30039206		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Child Development Deviations	Development Disorder	CTD_human_DG	20118933		★☆☆☆☆ Found in Text Mining only
Child Development Disorders, Specific	Development Disorder	CTD_human_DG	20118933		★☆☆☆☆ Found in Text Mining only
Choreoathetosis	Choreoathetosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Chromosome Instability Syndromes	Chromosome Instability Syndromes	CTD_human_DG	20118933		★☆☆☆☆ Found in Text Mining only
Clonic Seizures	Clonic Seizures	CTD_human_DG	20118933		★☆☆☆☆ Found in Text Mining only
Clumsiness - motor delay	Motor delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	29277765		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	35271294	Associate	★☆☆☆☆ Found in Text Mining only
Complex partial seizures	Seizure	CTD_human_DG	20118933		★☆☆☆☆ Found in Text Mining only
Congenital exomphalos	Congenital Exomphalos	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital kyphoscoliosis	Congenital kyphoscoliosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital microcephaly	Congenital Microcephaly	BEFREE	30195441, 31436889		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Developmental Disabilities	Development Disorder	CTD_human_DG	20118933		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Developmental Disabilities	Developmental disability	Pubtator	22508754, 25728773, 32980744, 37916443	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Developmental regression	Developmental regression	HPO_DG			★☆☆☆☆ Found in Text Mining only
DNA Repair-Deficiency Disorders	DNA Repair-Deficiency Disorders	CTD_human_DG	20118933		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dyscalculia	Dyscalculia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dyskinetic syndrome	Dyskinetic Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dyslexia	Dyslexia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dyssomnias	Dyssomnia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Early infantile epileptic encephalopathy	Epileptic encephalopathy	Orphanet			★☆☆☆☆ Found in Text Mining only
Early infantile epileptic encephalopathy with suppression bursts	Epileptic Encephalopathy	ORPHANET_DG	20118933		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Edema	Edema	Pubtator	27165045	Associate	★☆☆☆☆ Found in Text Mining only
Epileptic drop attack	Hypotonic seizures	CTD_human_DG	20118933		★☆☆☆☆ Found in Text Mining only
Epileptic drop attack	Hypotonic seizures	HPO_DG			★☆☆☆☆ Found in Text Mining only
Epileptic encephalopathy	Epileptic encephalopathy	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 12	Epileptic encephalopathy	CLINVAR_DG	20118933, 22508754, 23224214, 25558065, 25728773		★☆☆☆☆ Found in Text Mining only
Episodic Ataxia	Episodic Ataxia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Febrile Convulsions	Febrile seizures	HPO_DG			★☆☆☆☆ Found in Text Mining only
Fleck corneal dystrophy	Fleck Corneal Dystrophy	BEFREE	29661558		★☆☆☆☆ Found in Text Mining only
Focal seizures, afebril	Focal Seizures	HPO_DG			★☆☆☆☆ Found in Text Mining only
Generalized clonic seizures	Clonic Seizures	HPO_DG			★☆☆☆☆ Found in Text Mining only
Generalized seizures	Seizure	CTD_human_DG	20118933		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	35354845	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	35354845	Associate	★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	BEFREE	20118933, 31436889		★★★★☆ 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)
Huntington Disease	Huntington Disease	BEFREE	30994454		★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Jacksonian Seizure	Jacksonian Seizure	CTD_human_DG	20118933		★☆☆☆☆ Found in Text Mining only
Machado-Joseph Disease	Machado-Joseph Disease	BEFREE	25590633, 25633985		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	28922417		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	29277765		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	BEFREE	20118933, 27125728, 27232581, 27470939, 28821613, 30956058, 31436889		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Microcephaly	Microcephaly	CTD_human_DG	20118933		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Microcephaly	Microcephaly	Pubtator	20118933, 22508754, 25728773, 28821613, 30039206, 32504494, 32980744, 34697416, 35354845, 35412344, 37916443	Associate	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Microcephaly	Microcephaly	HPO_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
MICROCEPHALY, SEIZURES, AND DEVELOPMENTAL DELAY	MICROCEPHALY, SEIZURES, AND DEVELOPMENTAL DELAY	GENOMICS_ENGLAND_DG	20118933, 25728773, 30039206		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MICROCEPHALY, SEIZURES, AND DEVELOPMENTAL DELAY	MICROCEPHALY, SEIZURES, AND DEVELOPMENTAL DELAY	UNIPROT_DG	20118933, 27232581		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MICROCEPHALY, SEIZURES, AND DEVELOPMENTAL DELAY	MICROCEPHALY, SEIZURES, AND DEVELOPMENTAL DELAY	BEFREE	23224214, 27232581, 30039206, 30195441, 31436889		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MICROCEPHALY, SEIZURES, AND DEVELOPMENTAL DELAY	MICROCEPHALY, SEIZURES, AND DEVELOPMENTAL DELAY	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
MICROCEPHALY, SEIZURES, AND DEVELOPMENTAL DELAY	MICROCEPHALY, SEIZURES, AND DEVELOPMENTAL DELAY	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Microlissencephaly	Microlissencephaly	CTD_human_DG	20118933		★☆☆☆☆ Found in Text Mining only
Movement Disorders	Movement Disorders	CLINVAR_DG	10446192, 20118933, 23224214, 24965255, 25728773, 27165045, 27232581, 7165045		★☆☆☆☆ Found in Text Mining only
Muscular Dystrophy	Muscular dystrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	29498415		★☆☆☆☆ Found in Text Mining only
nervous system disorder	Nervous System Disorder	BEFREE	20118933, 28922417, 29498415		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	25590633, 32504494, 37061005	Associate	★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	30148840	Inhibit	★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	23224214, 30956058		★☆☆☆☆ Found in Text Mining only
Neurodevelopmental Disorders	Neurodevelopmental Disorders	BEFREE	27232581		★☆☆☆☆ Found in Text Mining only
Neurodevelopmental Disorders	Neurodevelopmental disorder	Pubtator	32504494	Associate	★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	HPO_DG			★☆☆☆☆ Found in Text Mining only
Oculomotor apraxia	Oculomotor apraxia	BEFREE	28552035		★☆☆☆☆ Found in Text Mining only
Oculomotor apraxia	Oculomotor apraxia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Oculovestibuloauditory syndrome	Oculovestibuloauditory Syndrome	BEFREE	28552035		★☆☆☆☆ Found in Text Mining only
Oculovestibuloauditory syndrome	Oculovestibuloauditory Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pachygyria	Pachygyria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Penis agenesis	Penis Agenesis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Peripheral Nervous System Diseases	Nervous System Diseases	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pilocytic Astrocytoma	Astrocytoma	BEFREE	29498415		★☆☆☆☆ Found in Text Mining only
Polyneuropathy	Polyneuropathy	BEFREE	23224214, 29661558, 30956058		★☆☆☆☆ Found in Text Mining only
Precocious Puberty	Precocious puberty	HPO_DG			★☆☆☆☆ Found in Text Mining only
Primary microcephaly	Microcephaly	BEFREE	23587236		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Primary microcephaly	Microcephaly	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Progressive cerebellar ataxia	Cerebellar Ataxia	BEFREE	28552035		★☆☆☆☆ Found in Text Mining only
Progressive distal muscular atrophy	Distal Muscular Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	29320576, 33569050	Associate	★☆☆☆☆ Found in Text Mining only
Quadriplegia	Quadriplegia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Renal Cell Dysplasia	Renal dysplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Renal dysplasia	Renal dysplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Seckel syndrome	Seckel Syndrome	BEFREE	27232581		★☆☆☆☆ Found in Text Mining only
Seizures	Seizures	Pubtator	20118933, 22508754, 25728773, 32504494, 32980744, 34697416, 37916443	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sensorimotor neuropathy	Sensorimotor neuropathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Severe Congenital Microcephaly	Congenital Microcephaly	CTD_human_DG	20118933		★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Single Seizure	Seizure	CTD_human_DG	20118933		★☆☆☆☆ Found in Text Mining only
Sleep Disorders	Sleep Disorders	HPO_DG			★☆☆☆☆ Found in Text Mining only
Spinocerebellar ataxia autosomal recessive 1	Spinocerebellar ataxia	Pubtator	25728773	Associate	★☆☆☆☆ Found in Text Mining only
SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 1	Spinocerebellar Ataxia	BEFREE	25728773, 27125728, 28821613, 30039206, 31436889		★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	28415784	Stimulate	★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Tonic - clonic seizures	Seizure	CTD_human_DG	20118933		★☆☆☆☆ Found in Text Mining only
Tonic - clonic seizures	Seizure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ureterocele	Ureterocele	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ventricular Septal Defects	Ventricular septal defect	HPO_DG			★☆☆☆☆ Found in Text Mining only
Visual seizure	Seizure	CTD_human_DG	20118933		★☆☆☆☆ Found in Text Mining only
West Syndrome	West Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only