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

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Anophthalmia	Pathogenic	rs2503896318, rs2503895810, rs1555350254	RCV002291337 RCV002291338 RCV000616304
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
Leber congenital amaurosis	Pathogenic	rs2139528052	RCV001591810
OTX2-related disorder	Pathogenic; Likely pathogenic	rs747279627, rs2503896787, rs2503897056, rs2503908217, rs2503907965	RCV004725665 RCV004545865 RCV003397199 RCV004529277 RCV004542637
Pituitary hormone deficiency, combined, 6	Pathogenic	rs370761964	RCV000022923
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

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
46,XY partial gonadal dysgenesis	Conflicting classifications of pathogenicity	rs199761861	RCV002254530
Combined Pituitary Hormone Deficiency, Dominant	Uncertain significance; Likely benign; Conflicting classifications of pathogenicity	rs886050558, rs886050560, rs3215889, rs534764707	RCV000287317 RCV000347171 RCV000399305 RCV000346482
Congenital hypothyroidism	Uncertain significance	rs376333965	RCV006442762
Male infertility with azoospermia or oligozoospermia due to single gene mutation	Conflicting classifications of pathogenicity	rs199761861	RCV003991583
Microcephaly	Uncertain significance	rs758228717	RCV001252757
OTX2-Related Syndromic Microphthalmia	Uncertain significance; Benign; Likely benign; Conflicting classifications of pathogenicity	rs376333965, rs171978, rs886050558, rs371958059, rs886050560, rs57390094, rs775857186, rs34537598, rs199799627, rs3215889, rs142727455, rs886050559, rs886050556, rs747916036, rs28757218, rs886050561, rs534764707	RCV002260548 RCV000265380 RCV000281553 RCV000262277 RCV000383120 RCV000388150 RCV000393648 RCV000387640 RCV000290304 RCV000280280 RCV000368520 RCV000310510 RCV000408269 RCV000367675 RCV000389637 RCV000287641 RCV000335384 RCV000284540
Retinal dystrophy	Benign; Likely benign; Uncertain significance; Conflicting classifications of pathogenicity	rs171978, rs886050558, rs371958059, rs886050560, rs57390094, rs886050555, rs886050557, rs138197536, rs3215889, rs142727455, rs199799627, rs886050556, rs747916036, rs28757218, rs886050561, rs534764707, rs199761861, rs768857621, rs1892049835	RCV000375013 RCV000378345 RCV000302223 RCV000284028 RCV000330159 RCV000289031 RCV000326073 RCV000343098 RCV000338659 RCV000406892 RCV000341742 RCV000315292 RCV000332721 RCV000332140 RCV000299082 RCV000376817 RCV004818099 RCV001073772 RCV001074938
Syndromic Microphthalmia, Dominant	Uncertain significance; Conflicting classifications of pathogenicity; Benign; Likely benign	rs886050558, rs371958059, rs886050560, rs57390094, rs886050555, rs775857186, rs886050557, rs34537598, rs199799627, rs138197536, rs3215889, rs142727455, rs886050559, rs747916036, rs534764707	RCV000321280 RCV000359343 RCV000339037 RCV000386973 RCV000347428 RCV000297593 RCV000268781 RCV000295747 RCV000348735 RCV000284506 RCV000351598 RCV000311619 RCV000323416 RCV000353670 RCV000400816

Associations from Text Mining
Disease Name	Relationship Type	References
Adenocarcinoma	Associate	22143938
Allergic Fungal Sinusitis	Associate	21177983
Amaurosis congenita of Leber type 1	Associate	40294858
Anophthalmia with pulmonary hypoplasia	Associate	20486942, 22204637
Anophthalmos	Associate	20486942, 21203406, 22204637, 25457163, 26130484, 30268123
Atrophy	Stimulate	40294858
Branchio Oto Renal Syndrome	Associate	18666230
Branchiootic syndrome	Associate	18666230
Chorioretinitis	Associate	25457163
Coloboma	Associate	26130484
Combined Pituitary Hormone Deficiency	Associate	18728160, 32796691
Cone Rod Dystrophies	Associate	29204067
Cystic Fibrosis	Stimulate	21177983
Dwarfism Pituitary	Associate	19956411, 36714562
Dysgnathia complex	Associate	32100971, 36553536
Esthesioneuroblastoma Olfactory	Associate	28348423
Eye Abnormalities	Associate	19641633, 22234157
Eye Diseases	Associate	19641633, 19956411
Familial Glucocorticoid Deficiency 1	Associate	18728160
Genetic Diseases Inborn	Associate	30268123
Goldenhar Syndrome	Associate	18666230
Growth Disorders	Associate	30268123
Hearing Loss Sensorineural	Associate	25457163
Hodgkin Disease	Associate	26406991, 26473286
Hyperplasia	Stimulate	21177983
Hypoglycemia	Associate	18728160
Infections	Associate	36740995
Infratentorial Neoplasms	Associate	29909548
Intellectual Disability	Associate	30268123
Leber Congenital Amaurosis	Associate	19956411
Macular Degeneration	Associate	22259223, 29204067
Mastocytosis Cutaneous	Associate	32752121
Medulloblastoma	Associate	19893048, 21047732, 22016811, 25198066, 26398939, 28213356, 31996670, 36131014, 36181537, 36273157, 36749287
Microcephaly	Associate	25457163
Microphthalmia Syndromic 6	Associate	20486942
Microphthalmos	Associate	20486942, 22204637, 25457163, 26130484, 30268123
Neoplasms	Associate	20233874, 21047732, 25198066, 26398939, 28348423, 36273157
Neoplastic Syndromes Hereditary	Associate	29204067
Night Blindness	Associate	19956411, 40294858
Paragangliomas 3	Associate	31996670
Photophobia	Associate	40294858
Pituitary Diseases	Associate	18728160, 19956411, 29204067, 30268123, 31845906
Respiratory System Abnormalities	Associate	20486942
Retinal Degeneration	Associate	22259223
Retinal Diseases	Associate	40294858
Retinal Dystrophies	Associate	19956411, 29204067
Retinoblastoma	Associate	19686387, 24509483
Seizures	Associate	19956411, 25457163
Sinonasal undifferentiated carcinoma	Associate	28348423
Squamous Cell Carcinoma of Head and Neck	Associate	31903890
Stomach Neoplasms	Associate	36740995
Vision Disorders	Associate	19956411
Vitreoretinopathy Proliferative	Associate	24227910
Wolff Parkinson White Syndrome	Associate	20486942