OTX2 orthodenticle homeobox 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: OTX2provided by HGNC
Official Full Name: orthodenticle homeobox 2provided by HGNC
Primary source: HGNC:HGNC:8522
See related: Ensembl:ENSG00000165588 MIM:600037; AllianceGenome:HGNC:8522
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CPHD6; MCOPS5
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 influences the proliferation and differentiation of dopaminergic neuronal progenitor cells during mitosis. Mutations in this gene cause syndromic microphthalmia 5 (MCOPS5) and combined pituitary hormone deficiency 6 (CPHD6). This gene is also suspected of having an oncogenic role in medulloblastoma. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Pseudogenes of this gene are known to exist on chromosomes two and nine. [provided by RefSeq, Jul 2012]
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: 14q22.3

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (56799905..56810479, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (51005697..51016270, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (57266623..57277197, complement)

Chromosome 14 - NC_000014.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The OTX2 Gene Induces Tumor Growth and Triggers Leptomeningeal Metastasis by Regulating the mTORC2 Signaling Pathway in Group 3 Medulloblastomas.
Title: The OTX2 Gene Induces Tumor Growth and Triggers Leptomeningeal Metastasis by Regulating the mTORC2 Signaling Pathway in Group 3 Medulloblastomas.
OTX2 duplications: a recurrent cause of oculo-auriculo-vertebral spectrum.
Title: OTX2 duplications: a recurrent cause of oculo-auriculo-vertebral spectrum.
Genetic alterations of TP53 and OTX2 indicate increased risk of relapse in WNT medulloblastomas: "it's a numbers game"-implications for WNT medulloblastoma dose-reduction clinical trials.
Title: Genetic alterations of TP53 and OTX2 indicate increased risk of relapse in WNT medulloblastomas: "it's a numbers game"-implications for WNT medulloblastoma dose-reduction clinical trials.
The LHX2-OTX2 transcriptional regulatory module controls retinal pigmented epithelium differentiation and underlies genetic risk for age-related macular degeneration.
Title: The LHX2-OTX2 transcriptional regulatory module controls retinal pigmented epithelium differentiation and underlies genetic risk for age-related macular degeneration.
Identification of a novel de novo variant in OTX2 in a patient with congenital microphthalmia using targeted next-generation sequencing followed by prenatal diagnosis.
Title: Identification of a novel de novo variant in OTX2 in a patient with congenital microphthalmia using targeted next-generation sequencing followed by prenatal diagnosis.
An OTX2 Gene Mutation Causing a More Severe Retinal Phenotype in a Female RPGR Mutation Carrier.
Title: An OTX2 Gene Mutation Causing a More Severe Retinal Phenotype in a Female RPGR Mutation Carrier.
OTX2 regulates CFTR expression during endoderm differentiation and occupies 3' cis-regulatory elements.
Title: OTX2 regulates CFTR expression during endoderm differentiation and occupies 3' cis-regulatory elements.
Otx2b mutant zebrafish have pituitary, eye and mandible defects that model mammalian disease.
Title: Otx2b mutant zebrafish have pituitary, eye and mandible defects that model mammalian disease.
Congenital pituitary hypoplasia model demonstrates hypothalamic OTX2 regulation of pituitary progenitor cells.
Title: Congenital pituitary hypoplasia model demonstrates hypothalamic OTX2 regulation of pituitary progenitor cells.
Authors found that the function of DMBX1 was dependent on p21 (CDKN1A), a key regulator of G1/S cell cycle progression. Co-IP assay revealed that DMBX1 directly bound to another homeobox transcription factor, OTX2. ChIP and luciferase reporter assay confirmed that OTX2 directly interacted with the promoter region of p21 to enhance its transcription, and DMBX1 repressed OTX2-mediated transcription of p21.
Title: DMBX1 promotes tumor proliferation and regulates cell cycle progression via repressing OTX2-mediated transcription of p21 in lung adenocarcinoma cell.

Submit: New GeneRIF Correction See all GeneRIFs (81)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Anophthalmia-microphthalmia syndrome MedGen: C5680330 GeneReviews: Not available	Compare labs
Pituitary hormone deficiency, combined, 6 MedGen: C3151440 OMIM: 613986 GeneReviews: Not available	Compare labs
Syndromic microphthalmia type 5 MedGen: C1864690 OMIM: 610125 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2020-09-08) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2020-09-08) ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Otx2 (e-PCR), detects polymorphism
- UniSTS:530694

A005E27 (e-PCR)
- UniSTS:11037

OTX2_1019 (e-PCR)
- UniSTS:277547

OTX2_V273 (e-PCR)
- UniSTS:277547

Otx2 (e-PCR), detects polymorphism
- UniSTS:516143

Otx2 (e-PCR), detects polymorphism
- UniSTS:516144

SHGC-153881 (e-PCR)
- UniSTS:177972

Otx2 (e-PCR), detects polymorphism
- UniSTS:238144

PMC304098P1 (e-PCR)
- UniSTS:272520

RH68366 (e-PCR)
- UniSTS:18887

PMC263842P1 (e-PCR)
- UniSTS:272330

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables eukaryotic initiation factor 4E binding	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sequence-specific double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in axon guidance	IDA Inferred from Direct Assay more info	PubMed
involved_in dopaminergic neuron differentiation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in dopaminergic neuron differentiation	TAS Traceable Author Statement more info	PubMed
involved_in forebrain development	TAS Traceable Author Statement more info	PubMed
involved_in midbrain development	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of embryonic development	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of gastrulation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in primitive streak formation	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein-containing complex assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of fibroblast growth factor receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in regulation of smoothened signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in chromatin	ISA Inferred from Sequence Alignment more info
located_in growth cone	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: homeobox protein OTX2

Names: orthodenticle homolog 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008204.2 RefSeqGene

Range

11215..21789

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_718

mRNA and Protein(s)

NM_001270523.2 → NP_001257452.1 homeobox protein OTX2 isoform b

See identical proteins and their annotated locations for NP_001257452.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an in-frame segment of the coding region, compared to variant 1, and, compared to isoform a, encodes a shorter isoform (b). Variants 2-4 encode the same protein (isoform b).

Source sequence(s)

AB593058, AL161757, BC032579, CV812961

Consensus CDS

CCDS41960.1

UniProtKB/Swiss-Prot

B2RAN5, P32243, Q6GTV3, Q9HAW3, Q9P2R1

UniProtKB/TrEMBL

F1T0D0

Related

ENSP00000343819.5, ENST00000339475.10

Conserved Domains (2) summary

pfam00046
Location:42 → 94

Homeobox; Homeobox domain

pfam03529
Location:155 → 234

TF_Otx; Otx1 transcription factor
NM_001270524.2 → NP_001257453.1 homeobox protein OTX2 isoform b

See identical proteins and their annotated locations for NP_001257453.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR and lacks an in-frame segment of the coding region, compared to variant 1, and, compared to isoform a, encodes a shorter isoform (b). Variants 2-4 encode the same protein (isoform b).

Source sequence(s)

AB593058, AK314271, AL161757, BC032579

Consensus CDS

CCDS41960.1

UniProtKB/Swiss-Prot

B2RAN5, P32243, Q6GTV3, Q9HAW3, Q9P2R1

UniProtKB/TrEMBL

F1T0D0

Related

ENSP00000452336.1, ENST00000555006.5

Conserved Domains (2) summary

pfam00046
Location:42 → 94

Homeobox; Homeobox domain

pfam03529
Location:155 → 234

TF_Otx; Otx1 transcription factor
NM_001270525.2 → NP_001257454.1 homeobox protein OTX2 isoform a

See identical proteins and their annotated locations for NP_001257454.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR, compared to variant 1, and encodes the longer isoform (a). Variants 1 and 5 encode the same protein (isoform a).

Source sequence(s)

AB593056, AL161757, BC032579, BU176852

Consensus CDS

CCDS9728.1

UniProtKB/TrEMBL

F1T0D0, F1T0D1

Related

ENSP00000451357.2, ENST00000554845.2

Conserved Domains (2) summary

pfam00046
Location:50 → 102

Homeobox; Homeobox domain

pfam03529
Location:163 → 242

TF_Otx; Otx1 transcription factor
NM_021728.4 → NP_068374.1 homeobox protein OTX2 isoform a

See identical proteins and their annotated locations for NP_068374.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (a). Variants 1 and 5 encode the same protein (isoform a).

Source sequence(s)

AB593058, AL161757, BC032579

Consensus CDS

CCDS9728.1

UniProtKB/TrEMBL

F1T0D0, F1T0D1

Related

ENSP00000500115.1, ENST00000672264.2

Conserved Domains (2) summary

pfam00046
Location:50 → 102

Homeobox; Homeobox domain

pfam03529
Location:163 → 242

TF_Otx; Otx1 transcription factor
NM_172337.3 → NP_758840.1 homeobox protein OTX2 isoform b

See identical proteins and their annotated locations for NP_758840.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and lacks an in-frame segment of the coding region, compared to variant 1, and, compared to isoform a, encodes a shorter isoform (b). Variants 2-4 encode the same protein (isoform b).

Source sequence(s)

AB593056, AB593057, AL161757, BC032579

Consensus CDS

CCDS41960.1

UniProtKB/Swiss-Prot

B2RAN5, P32243, Q6GTV3, Q9HAW3, Q9P2R1

UniProtKB/TrEMBL

F1T0D0

Related

ENSP00000386185.3, ENST00000408990.8

Conserved Domains (2) summary

pfam00046
Location:42 → 94

Homeobox; Homeobox domain

pfam03529
Location:155 → 234

TF_Otx; Otx1 transcription factor

RNA

NR_073034.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (6) lacks an exon in the coding region, compared to variant 1, which results in a frameshift and early stop codon. The transcript is sufficiently abundant to represent as a RefSeq record; however, the predicted protein is not represented because the product is significantly truncated.

Source sequence(s)

AL161757, BC032579, DB294481
NR_073036.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (7) differs in the 5' UTR and lacks an exon in the coding region, compared to variant 1, which results in a frameshift and early stop codon. The transcript is sufficiently abundant to represent as a RefSeq record; however, the predicted protein is not represented because the product is significantly truncated.

Source sequence(s)

AB593056, AL161757, BC032579