OTX2 (orthodenticle homeobox 2)

Gene

• Entrez ID: 5015
• Gene name: Orthodenticle homeobox 2
• Gene symbol: OTX2
• Synonyms (NCBI Gene): CPHD6, MCOPS5
• Chromosome: 14
• Chromosome location: 14q22.3
• Summary: This gene encodes a member of the bicoid subfamily of homeodomain-containing transcription factors. The encoded protein acts as a transcription factor and plays a role in brain, craniofacial, and sensory organ development. The encoded protein also influen

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs104894464	G>A,C	Pathogenic	Stop gained, coding sequence variant, non coding transcript variant, missense variant
rs104894465	A>G,T	Pathogenic	Stop gained, coding sequence variant, synonymous variant, non coding transcript variant
rs147896150	C>G,T	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant, non coding transcript variant
rs370761964	T>C	Pathogenic	Coding sequence variant, non coding transcript variant, missense variant
rs397514463	C>A	Pathogenic	Coding sequence variant, stop gained, non coding transcript variant
rs773157352	G>A,T	Pathogenic	Intron variant, stop gained, coding sequence variant, synonymous variant
rs786205224	C>T	Pathogenic, likely-pathogenic	Intron variant, coding sequence variant, missense variant
rs786205873	->GC	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs786205874	G>-	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs786205879	G>C	Pathogenic	Stop gained, non coding transcript variant, coding sequence variant
rs786205884	G>-	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs886043793	G>T	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs1064795810	G>T	Likely-pathogenic	Intron variant, missense variant, coding sequence variant
rs1555350156	GTTG>-	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs1555350163	C>A	Likely-pathogenic	Non coding transcript variant, coding sequence variant, stop gained
rs1555350223	->G	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs1555350254	G>T	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1555350397	ACA>CC	Likely-pathogenic	Coding sequence variant, intron variant, frameshift variant
rs1566622571	C>-	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs1566623121	->AG	Pathogenic	Non coding transcript variant, coding sequence variant, frameshift variant
rs1566623392	T>A	Pathogenic	Non coding transcript variant, coding sequence variant, missense variant
rs1566624472	GGGCAAGTTGATTTTC>-	Pathogenic	Coding sequence variant, intron variant, frameshift variant
rs1594952007	T>-	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1594952111	C>-	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT025137	hsa-miR-181a-5p	Microarray	17612493
MIRT734581	hsa-miR-183-3p	Immunofluorescence, qRT-PCR	31885884
MIRT1208293	hsa-miR-2276	CLIP-seq
MIRT1208294	hsa-miR-3143	CLIP-seq
MIRT1208295	hsa-miR-4272	CLIP-seq
MIRT1208296	hsa-miR-4772-3p	CLIP-seq
MIRT1208297	hsa-miR-377	CLIP-seq
MIRT1208298	hsa-miR-4704-3p	CLIP-seq
MIRT2288165	hsa-miR-3158-5p	CLIP-seq
MIRT2288166	hsa-miR-3194-3p	CLIP-seq
MIRT2288167	hsa-miR-4427	CLIP-seq
MIRT2288168	hsa-miR-4680-3p	CLIP-seq
MIRT2288169	hsa-miR-4760-5p	CLIP-seq
MIRT2288170	hsa-miR-510	CLIP-seq
MIRT2288171	hsa-miR-512-5p	CLIP-seq
MIRT2288172	hsa-miR-548b-3p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	ISA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	12559959
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IEA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	12559959, 20530484
GO:0003677	Function	DNA binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IEA
GO:0005515	Function	Protein binding	IPI	20530484, 32296183, 32814053
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	24399192
GO:0005634	Component	Nucleus	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0007411	Process	Axon guidance	IDA	16267555
GO:0008190	Function	Eukaryotic initiation factor 4E binding	TAS	15705863
GO:0008589	Process	Regulation of smoothened signaling pathway	TAS	15705863
GO:0030426	Component	Growth cone	IDA	16267555
GO:0030900	Process	Forebrain development	TAS	15705863
GO:0030901	Process	Midbrain development	TAS	15705863
GO:0032991	Component	Protein-containing complex	IDA	20530484
GO:0040019	Process	Positive regulation of embryonic development	ISS
GO:0040036	Process	Regulation of fibroblast growth factor receptor signaling pathway	TAS	15705863
GO:0045893	Process	Positive regulation of DNA-templated transcription	ISS
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	12559959, 20530484
GO:0065003	Process	Protein-containing complex assembly	IDA	20530484
GO:0071542	Process	Dopaminergic neuron differentiation	IGI	19951692
GO:0071542	Process	Dopaminergic neuron differentiation	TAS	24431302
GO:0090009	Process	Primitive streak formation	ISS
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536
GO:2000543	Process	Positive regulation of gastrulation	ISS

Other IDs

• MIM: 600037
• HGNC: 8522
• e!Ensembl: ENSG00000165588

Protein

• UniProt ID: P32243
• Protein name: Homeobox protein OTX2 (Orthodenticle homolog 2)
• Protein function: Transcription factor probably involved in the development of the brain and the sense organs. Can bind to the bicoid/BCD target sequence (BTS): 5'-TCTAATCCC-3'.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00046	Homeodomain	39 → 95	Homeodomain	Domain
  PF03529	TF_Otx	153 → 234	Otx1 transcription factor	Family

• Sequence:

  MMSYLKQPPYAVNGLSLTTSGMDLLHPSVGYPATPRKQRRERTTFTRAQLDVLEALFAKT
  RYPDIFMREEVALKINLPESRVQVWFKNRRAKCRQQQQQQQNGGQNKVRPAKKKTSPARE
  VSSESGTSGQFTPPSSTSVPTIASSSAPVSIWSPASISPLSDPLSTSSSCMQRSYPMTYT
  QASGYSQGYAGSTSYFGGMDCGSYLTPMHHQLPGPGATLSPMGTNAVTSHLNQSPASLST
  QGYGASSLGFNSTTDCLDYKDQTASWKLNFNADCLDYKDQTSSWKFQVL

• Sequence length: 289

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
Anophthalmia	Pathogenic	rs2503896318, rs2503895810, rs1555350254	RCV002291337 RCV002291338 RCV000616304	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Anophthalmia-microphthalmia syndrome	Pathogenic; Likely pathogenic	rs758119168, rs2139528859, rs2139528560, rs2503894370, rs2503896952, rs2503908103, rs2503896126, rs2503898831, rs2503907718, rs754929157, rs2503896661, rs2503898578, rs397514463, rs1555350223, rs1566622642, rs1594952158, rs1891902224, rs1891900408	RCV001387780 RCV001931395 RCV001950991 RCV002856764 RCV002870678 RCV003026661 RCV003027041 RCV003057151 RCV003530680 RCV003646251 RCV003646451 RCV003646448 RCV001857357 RCV003530088 RCV000705232 RCV000795211 RCV001045026 RCV001215981	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Leber congenital amaurosis	Pathogenic	rs2139528052	RCV001591810	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
OTX2-related disorder	Pathogenic; Likely pathogenic	rs747279627, rs2503896787, rs2503897056, rs2503908217, rs2503907965	RCV004725665 RCV004545865 RCV003397199 RCV004529277 RCV004542637	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Pituitary hormone deficiency, combined, 6	Pathogenic	rs370761964	RCV000022923	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Syndromic microphthalmia type 5	Pathogenic; Likely pathogenic	rs2139528313, rs2139527991, rs2139529394, rs786205884, rs104894464, rs786205224, rs747279627, rs786205873, rs786205874, rs104894465, rs1246931412, rs1566623121, rs786205879, rs1566624472, rs397514463, rs1566623392, rs1555350223, rs1555350156, rs1566622571, rs1594952111, rs1594952007	RCV001542487 RCV001775384 RCV001806358 RCV000170470 RCV000170471 RCV000170472 RCV003153234 RCV000010123 RCV000010124 RCV000010125 RCV000010126 RCV003985210 RCV000022924 RCV000022925 RCV000022926 RCV000022927 RCV000022928 RCV000594111 RCV000656394 RCV000680055 RCV000824976 RCV001002701	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
46,XY partial gonadal dysgenesis	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANOPHTHALMOS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ANXIETY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATTENTION DEFICIT HYPERACTIVITY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BUTTERFLY-SHAPED PIGMENT DYSTROPHY	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BUTTERFLY-SHAPED PIGMENTARY MACULAR DYSTROPHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLOBOMATOUS MICROPHTHALMIA	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED PITUITARY HORMONE DEFICIENCIES, GENETIC FORM	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED PITUITARY HORMONE DEFICIENCIES, GENETIC FORMS	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED PITUITARY HORMONE DEFICIENCY	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED PITUITARY HORMONE DEFICIENCY GENETIC FORM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Combined Pituitary Hormone Deficiency, Dominant	Uncertain significance; Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital hypothyroidism	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETIC NEPHROPATHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MACULAR DYSTROPHY, PATTERNED, 1	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Male infertility with azoospermia or oligozoospermia due to single gene mutation	Conflicting classifications of pathogenicity	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
MEDULLOBLASTOMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microcephaly	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROPHTHALMIA, SYNDROMIC 5	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MICROPHTHALMOS CO-OCCURRENT WITH CONGENITAL OCULAR COLOBOMA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NANOPHTHALMOS	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NYSTAGMUS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OPTIC ATROPHY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OTX2-Related Syndromic Microphthalmia	Uncertain significance; Benign; Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PANHYPOPITUITARISM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PATTERNED MACULAR DYSTROPHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PREECLAMPSIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Retinal dystrophy	Benign; Likely benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RETINITIS PIGMENTOSA 1	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEPTO-OPTIC DYSPLASIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEPTO-OPTIC DYSPLASIA SPECTRUM	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SEPTOOPTIC DYSPLASIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SUBSTANCE ABUSE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Syndromic Microphthalmia, Dominant	Uncertain significance; Conflicting classifications of pathogenicity; 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
Adenocarcinoma	Adenocarcinoma	BEFREE	28348423, 30882801		★☆☆☆☆ Found in Text Mining only
Adenocarcinoma of lung (disorder)	Lung adenocarcinoma	BEFREE	30928384		★☆☆☆☆ Found in Text Mining only
Adrenocorticotropic hormone (ACTH) deficiency (disorder)	Adrenocorticotropic Hormone Deficiency	BEFREE	27299576		★☆☆☆☆ Found in Text Mining only
Adult Hodgkin Lymphoma	Hodgkin Lymphoma	BEFREE	26406991, 26473286		★☆☆☆☆ Found in Text Mining only
Adult Medulloblastoma	Medulloblastoma	BEFREE	11015565, 15705863, 15705891, 16462208, 20028867, 21047732, 21964830, 22016811, 22558385, 22986744, 23179372, 23523800, 24816892, 25198066, 25473003, 25859932, 26398939, 28213356, 28401018, 28844926, 29377567, 29490009, 30100614, 30797919		★☆☆☆☆ Found in Text Mining only
Adult Medulloblastoma	Medulloblastoma	CTD_human_DG	19270706		★☆☆☆☆ Found in Text Mining only
Age related macular degeneration	Age-related macular degeneration	BEFREE	27660103, 28988713		★☆☆☆☆ Found in Text Mining only
Agenesis of corpus callosum	Agenesis Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Agnathia-holoprosencephaly-situs inversus syndrome	Agnathia-Holoprosencephaly-Situs Inversus Syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Amaurosis congenita of Leber type 1	Leber congenital amaurosis	Pubtator	40294858	Associate	★☆☆☆☆ Found in Text Mining only
Amaurosis congenita of Leber, type 1	Leber congenital amaurosis	BEFREE	19956411		★☆☆☆☆ Found in Text Mining only
Anaplasia	Anaplasia	BEFREE	28988713		★☆☆☆☆ Found in Text Mining only
Aniridia	Aniridia	BEFREE	17406642		★☆☆☆☆ Found in Text Mining only
Anophthalmia with pulmonary hypoplasia	Anophthalmia	Pubtator	20486942, 22204637	Associate	★☆☆☆☆ Found in Text Mining only
Anophthalmos	Syndromic microphthalmia	BEFREE	15846561, 18628516, 18781617, 18854396, 19397404, 20396904, 20486942, 21203406, 23103883, 25342853, 26130484, 27299576, 27378064, 29178648, 30268123		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Anophthalmos	Syndromic microphthalmia	LHGDN	18781617		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Anophthalmos	Anophthalmia	Pubtator	20486942, 21203406, 22204637, 25457163, 26130484, 30268123	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Anophthalmos	Syndromic microphthalmia	CLINVAR_DG	29178648		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Anophthalmos	Syndromic microphthalmia	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Anxiety	Anxiety Disorder	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atrophy	Atrophy	Pubtator	40294858	Stimulate	★☆☆☆☆ Found in Text Mining only
Auriculo-condylar syndrome	Auriculocondylar syndrome	BEFREE	22577225		★☆☆☆☆ Found in Text Mining only
Autistic Disorder	Autism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Bilateral microphthalmos	Microphthalmos	BEFREE	23103883		★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar Disorder	BEFREE	17541950		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bipolar Disorder	Bipolar Disorder	LHGDN	17541950		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bipolar Disorder	Bipolar Disorder	PSYGENET_DG	17541950		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Branchio-Oto-Renal Syndrome	Branchiootorenal Syndrome	BEFREE	18666230		★☆☆☆☆ Found in Text Mining only
Branchiootic syndrome	Branchiootic syndrome	Pubtator	18666230	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	22581028		★☆☆☆☆ Found in Text Mining only
Bulbo-Spinal Atrophy, X-Linked	Bulbospinal Atrophy, X-Linked	BEFREE	29377567		★☆☆☆☆ Found in Text Mining only
Butterfly-shaped pigment dystrophy	Macular dystrophy, patterned	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Butterfly-shaped pigmentary macular dystrophy	Macular dystrophy, patterned	ORPHANET_DG	25293953		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Carcinoma	Carcinoma	BEFREE	28348423, 30882801		★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	HPO_DG			★☆☆☆☆ Found in Text Mining only
Childhood Medulloblastoma	Medulloblastoma	BEFREE	11015565, 15705863, 15705891, 16462208, 20028867, 21047732, 21964830, 22016811, 22558385, 22986744, 23179372, 23523800, 24816892, 25198066, 25473003, 25859932, 26398939, 28213356, 28401018, 28844926, 29377567, 29490009, 30100614, 30797919		★☆☆☆☆ Found in Text Mining only
Childhood Medulloblastoma	Medulloblastoma	CTD_human_DG	19270706		★☆☆☆☆ Found in Text Mining only
Chromosome 17q21.31 Deletion Syndrome	17q21.31 Deletion Syndrome	BEFREE	29588463		★☆☆☆☆ Found in Text Mining only
Chronic granulomatous disease	Granulomatous Disease	BEFREE	28575744		★☆☆☆☆ Found in Text Mining only
Coloboma	Coloboma	Pubtator	26130484	Associate	★☆☆☆☆ Found in Text Mining only
Combined pituitary hormone deficiencies, genetic forms	Pituitary Hormone Deficiency	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Combined Pituitary Hormone Deficiency	Combined pituitary hormone deficiency	Pubtator	18728160, 32796691	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital absence of mandible	Mandibular aplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital anomaly of brain	Brain malformation	BEFREE	30268123		★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of penis	Congenital Hypoplasia Of Penis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital ocular coloboma (disorder)	Congenital ocular coloboma	LHGDN	18781617		★☆☆☆☆ Found in Text Mining only
Congenital ocular coloboma (disorder)	Congenital ocular coloboma	BEFREE	24859618		★☆☆☆☆ Found in Text Mining only
Congenital ocular coloboma (disorder)	Congenital ocular coloboma	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital small ears	Microtia	GENOMICS_ENGLAND_DG	9174161		★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cyclocephaly	Cyclocephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cystic Fibrosis	Cystic fibrosis	Pubtator	21177983	Stimulate	★☆☆☆☆ Found in Text Mining only
Depression in children	Mental Depression	BEFREE	30089883		★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	30089883		★☆☆☆☆ Found in Text Mining only
Desmoplastic Medulloblastoma	Medulloblastoma	CTD_human_DG	19270706		★☆☆☆☆ Found in Text Mining only
Dextrocardia with situs inversus	Dextrocardia	BEFREE	28844926		★☆☆☆☆ Found in Text Mining only
Diabetes Insipidus	Diabetes Insipidus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Disorder of eye	Disorder Of Eye	BEFREE	18637741, 19641633		★☆☆☆☆ Found in Text Mining only
Disorder of eye	Disorder Of Eye	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	BEFREE	18628516, 30268123		★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dwarfism Pituitary	Pituitary dwarfism	Pubtator	19956411, 36714562	Associate	★☆☆☆☆ Found in Text Mining only
Dysgnathia complex	Dysgnathia Complex	BEFREE	22577225		★☆☆☆☆ Found in Text Mining only
Dysgnathia complex	Dysgnathia Complex	ORPHANET_DG	22577225		★☆☆☆☆ Found in Text Mining only
Dysgnathia complex	Dysgnathia complex	Pubtator	32100971, 36553536	Associate	★☆☆☆☆ Found in Text Mining only
Dysmorphic features	Dysmorphic Features	CLINVAR_DG	18728160, 22577225, 24167467		★☆☆☆☆ Found in Text Mining only
Dysostoses	Dysostoses	BEFREE	27378064		★☆☆☆☆ Found in Text Mining only
Dyssomnias	Dyssomnia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ectopic anterior pituitary gland	Ectopic anterior pituitary gland	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ependymoma	Ependymoma	BEFREE	29909548		★☆☆☆☆ Found in Text Mining only
Esophageal Atresia	Esophageal Atresia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Eye Abnormalities	Eye abnormalities	Pubtator	19641633, 22234157	Associate	★☆☆☆☆ Found in Text Mining only
Eye Diseases	Eye disease	Pubtator	19641633, 19956411	Associate	★☆☆☆☆ Found in Text Mining only
Familial Glucocorticoid Deficiency 1	Glucocorticoid deficiency	Pubtator	18728160	Associate	★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	BEFREE	18781617		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Goldenhar Syndrome	Goldenhar Syndrome	BEFREE	18666230, 24816892		★☆☆☆☆ Found in Text Mining only
Goldenhar Syndrome	Goldenhar syndrome	Pubtator	18666230	Associate	★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	30268123	Associate	★☆☆☆☆ Found in Text Mining only
Hearing Loss Sensorineural	Hearing loss	Pubtator	25457163	Associate	★☆☆☆☆ Found in Text Mining only
Hemiplegia/hemiparesis	Hemiplegia/hemiparesis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hodgkin Disease	Hodgkin Disease	BEFREE	26406991, 26473286		★☆☆☆☆ Found in Text Mining only
Hodgkin Disease	Hodgkin disease	Pubtator	26406991, 26473286	Associate	★☆☆☆☆ Found in Text Mining only
Holoprosencephaly	Holoprosencephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Horizontal Nystagmus	Horizontal nystagmus	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Hyperplasia	Hyperplasia	Pubtator	21177983	Stimulate	★☆☆☆☆ Found in Text Mining only
Hypoglycemia	Hypoglycemia	Pubtator	18728160	Associate	★☆☆☆☆ Found in Text Mining only
Hypoglycemia	Hypoglycemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypogonadotropic hypogonadism	Hypogonadotropic Hypogonadism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypohidrosis	Hypohidrosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypopituitarism	Hypopituitarism	BEFREE	27299576, 30959475		★☆☆☆☆ Found in Text Mining only
Hypoplasia of the optic nerve	Hypoplasia Of The Optic Nerve	BEFREE	22715480		★☆☆☆☆ Found in Text Mining only
Hypoplasia of the optic nerve	Hypoplasia Of The Optic Nerve	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	30268123		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	30268123	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Isolated microphthalmia-anophthalmia-coloboma	Isolated Microphthalmia-Anophthalmia-Coloboma	Orphanet			★☆☆☆☆ Found in Text Mining only
Isolated somatotropin deficiency	Isolated Somatotropin Deficiency	BEFREE	18628516, 20396904, 26974134		★☆☆☆☆ Found in Text Mining only
Jaw Abnormalities	Jaw Abnormalities	CTD_human_DG	12183386		★☆☆☆☆ Found in Text Mining only
Kallmann Syndrome	Kallmann Syndrome	ORPHANET_DG	21396578, 24802313		★☆☆☆☆ Found in Text Mining only
Leber Congenital Amaurosis	Leber Congenital Amaurosis	BEFREE	15846561, 17406642, 19956411		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Leber Congenital Amaurosis	Leber congenital amaurosis	Pubtator	19956411	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Macular Degeneration	Macular degeneration	Pubtator	22259223, 29204067	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of brain	Brain Neoplasms	BEFREE	21964830		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	22581028		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	17522332, 25575132, 28213356		★☆☆☆☆ Found in Text Mining only
Mastocytosis Cutaneous	Mastocytosis	Pubtator	32752121	Associate	★☆☆☆☆ Found in Text Mining only
Medulloblastoma	Medulloblastoma	BEFREE	11015565, 15705863, 15705891, 16462208, 17522332, 20028867, 21047732, 21964830, 22016811, 22558385, 22986744, 23179372, 23523800, 24816892, 25198066, 25473003, 25859932, 26398939, 28213356, 28401018, 28844926, 29377567, 29490009, 30100614, 30797919		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Medulloblastoma	Medulloblastoma	LHGDN	15705863		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Medulloblastoma	Medulloblastoma	CTD_human_DG	19270706		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Medulloblastoma	Medulloblastoma	Pubtator	19893048, 21047732, 22016811, 25198066, 26398939, 28213356, 31996670, 36131014, 36181537, 36273157, 36749287	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Medullomyoblastoma	Medullomyoblastoma	CTD_human_DG	19270706		★☆☆☆☆ Found in Text Mining only
Medullomyoblastoma	Medullomyoblastoma	BEFREE	22986744		★☆☆☆☆ Found in Text Mining only
Melanotic medulloblastoma	Medulloblastoma	CTD_human_DG	19270706		★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	30089883		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	25457163	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microcornea	Microcornea	HPO_DG			★☆☆☆☆ Found in Text Mining only
Microglossia	Microglossia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Microphthalmia Syndromic 6	Microphthalmia	Pubtator	20486942	Associate	★☆☆☆☆ Found in Text Mining only
MICROPHTHALMIA, ISOLATED 1	Microphthalmia	ORPHANET_DG	24033328		★☆☆☆☆ Found in Text Mining only
Microphthalmia, Syndromic 3	Syndromic microphthalmia	BEFREE	20486942		★☆☆☆☆ Found in Text Mining only
Microphthalmia, Syndromic 5	Syndromic microphthalmia	ORPHANET_DG	15846561, 20396904		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microphthalmia, Syndromic 5	Syndromic microphthalmia	GENOMICS_ENGLAND_DG	15846561, 18628516, 18781617, 19965921, 9174161		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microphthalmia, Syndromic 5	Syndromic microphthalmia	UNIPROT_DG	15846561, 19956411, 20396904, 22577225, 24167467, 25293953		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microphthalmia, Syndromic 5	Syndromic microphthalmia	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microphthalmia, Syndromic 5	Syndromic microphthalmia	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microphthalmos	Microphthalmos	BEFREE	17406642, 18781617, 19397404, 20486942, 21203406, 22577225, 23103883, 24859618, 25542770, 26974134, 27299576, 27378064, 28388256, 30181649, 30268123, 30773800		★☆☆☆☆ Found in Text Mining only
Microphthalmos	Microphthalmos	Pubtator	20486942, 22204637, 25457163, 26130484, 30268123	Associate	★☆☆☆☆ Found in Text Mining only
Microphthalmos	Microphthalmos	HPO_DG			★☆☆☆☆ Found in Text Mining only
Microphthalmos co-occurrent with congenital ocular coloboma	Microphthalmos Co-Occurrent With Congenital Ocular Coloboma	BEFREE	21203406		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Microphthalmos, Autosomal Recessive	Microphthalmos	ORPHANET_DG	24033328		★☆☆☆☆ Found in Text Mining only
Microstomia	Microstomia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mucocutaneous Lymph Node Syndrome	Kawasaki disease	BEFREE	29377567		★☆☆☆☆ Found in Text Mining only
Multiple congenital anomalies	Multiple Congenital Anomalies	CLINVAR_DG	18728160, 22577225, 24167467		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	15705891, 16462208, 19686387, 20028867, 21047732, 22558385, 25198066, 26397460, 26398939, 28025236, 28213356, 30882801		★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nystagmus	Nystagmus	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Obesity	Obesity	HPO_DG			★☆☆☆☆ Found in Text Mining only
Optic Nerve Aplasia, Bilateral	Optic nerve aplasia	BEFREE	22645276		★☆☆☆☆ Found in Text Mining only
Osteopenia	Osteopenia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Osteoporosis of vertebrae	Osteoporosis of vertebrae	HPO_DG			★☆☆☆☆ Found in Text Mining only
Otocephaly	Otocephaly	BEFREE	22198066, 22577225, 25589041		★☆☆☆☆ Found in Text Mining only
Otocephaly	Otocephaly	ORPHANET_DG	22577225		★☆☆☆☆ Found in Text Mining only
Panhypopituitarism	Panhypopituitarism	BEFREE	18728160, 18854396, 22715480, 27299576, 30773800		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Panhypopituitarism	Panhypopituitarism	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Papilloma	Papilloma	BEFREE	25575132		★☆☆☆☆ Found in Text Mining only
Paragangliomas 3	Paraganglioma	Pubtator	31996670	Associate	★☆☆☆☆ Found in Text Mining only
Pituitary dwarfism	Pituitary dwarfism	BEFREE	20396904, 22715480		★☆☆☆☆ Found in Text Mining only
Pituitary dwarfism	Pituitary dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pituitary Hormone Deficiency, Combined, 1	Pituitary Hormone Deficiency	ORPHANET_DG	18728160		★☆☆☆☆ Found in Text Mining only
PITUITARY HORMONE DEFICIENCY, COMBINED, 6	Pituitary Hormone Deficiency	UNIPROT_DG	18728160, 22715480		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
PITUITARY HORMONE DEFICIENCY, COMBINED, 6	Pituitary Hormone Deficiency	GENOMICS_ENGLAND_DG	19965921, 26416826		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
PITUITARY HORMONE DEFICIENCY, COMBINED, 6	Pituitary Hormone Deficiency	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Pituitary stalk interruption syndrome	Pituitary Stalk Interruption Syndrome	BEFREE	23199197, 27917547		★☆☆☆☆ Found in Text Mining only
Polydactyly	Polydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Proliferative vitreoretinopathy	Proliferative Vitreoretinopathy	BEFREE	24227910		★☆☆☆☆ Found in Text Mining only
Retinal Degeneration	Retinal degeneration	Pubtator	22259223	Associate	★☆☆☆☆ Found in Text Mining only
Retinal Diseases	Retinal Diseases	BEFREE	23761884, 25293953		★☆☆☆☆ Found in Text Mining only
Retinal Diseases	Retinal detachment	Pubtator	40294858	Associate	★☆☆☆☆ Found in Text Mining only
Retinal Dystrophies	Retinal Dystrophy	BEFREE	19956411		★☆☆☆☆ Found in Text Mining only
Retinal Dystrophies	Retinal Dystrophy	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Retinal Dystrophies	Retinal Dystrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Retinitis Pigmentosa	Retinitis Pigmentosa	BEFREE	15846561, 28988713		★☆☆☆☆ Found in Text Mining only
Retinoblastoma	Retinoblastoma	BEFREE	19686387, 26397460, 28861107		★☆☆☆☆ Found in Text Mining only
Retinoblastoma	Retinoblastoma	Pubtator	19686387, 24509483	Associate	★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	17541950, 28620275		★☆☆☆☆ Found in Text Mining only
SCHIZOPHRENIA 15	Schizophrenia	BEFREE	17541950		★☆☆☆☆ Found in Text Mining only
Sclerocornea	Sclerocornea	BEFREE	26130484		★☆☆☆☆ Found in Text Mining only
Secondary hypothyroidism	Hypothyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Seizures	Seizures	Pubtator	19956411, 25457163	Associate	★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Septo-Optic Dysplasia	Septo-Optic Dysplasia	ORPHANET_DG	21396578, 24802313		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Septo-Optic Dysplasia	Septo-Optic Dysplasia	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Septo-optic dysplasia spectrum	Septo-Optic Dysplasia	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Situs inversus totalis	Situs Inversus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sleep Disorders	Sleep Disorders	HPO_DG			★☆☆☆☆ Found in Text Mining only
Somatotropin deficiency	Somatotropin Deficiency	BEFREE	26974134		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma	Carcinoma	BEFREE	22143938		★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	31903890	Associate	★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	36740995	Associate	★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Subfertility	Subfertility	BEFREE	30261489, 30739114		★☆☆☆☆ Found in Text Mining only
Subfertility, Female	Subfertility	BEFREE	30739114		★☆☆☆☆ Found in Text Mining only
Syndromic microphthalmia type 5	Syndromic Microphthalmia	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Syndromic microphthalmia type 5	Syndromic Microphthalmia	BEFREE	28388256		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Synotus	Synotus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Variegate Porphyria	Variegate Porphyria	BEFREE	31026452		★☆☆☆☆ Found in Text Mining only
Velopharyngeal Insufficiency	Velopharyngeal Insufficiency	BEFREE	25589041		★☆☆☆☆ Found in Text Mining only
Vision Disorders	Visual disorder	Pubtator	19956411	Associate	★☆☆☆☆ Found in Text Mining only
Vitreoretinopathy Proliferative	Vitreoretinopathy	Pubtator	24227910	Associate	★☆☆☆☆ Found in Text Mining only