OTX2
orthodenticle homeobox 2, the group of PRD class homeoboxes and pseudogenes
Basic information
Region (hg38): 14:56799905-56816693
Links
Phenotypes
GenCC
Source:
- syndromic microphthalmia type 5 (Definitive), mode of inheritance: AD
- syndromic microphthalmia type 5 (Strong), mode of inheritance: AD
- pituitary hormone deficiency, combined, 6 (Moderate), mode of inheritance: AD
- syndromic microphthalmia type 5 (Moderate), mode of inheritance: AD
- septooptic dysplasia (Supportive), mode of inheritance: AD
- isolated anophthalmia-microphthalmia syndrome (Supportive), mode of inheritance: AD
- combined pituitary hormone deficiencies, genetic form (Supportive), mode of inheritance: AD
- patterned macular dystrophy (Supportive), mode of inheritance: AD
- syndromic microphthalmia type 5 (Supportive), mode of inheritance: AD
- syndromic microphthalmia type 5 (Strong), mode of inheritance: AD
- pituitary hormone deficiency, combined, 6 (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Pituitary hormone deficiency, combined 6; Microphthalmia, syndromic 5; Retinal dystrophy, early-onset, and pituitary dysfunction | AD | Endocrine; Genitourinary | Hormone replacement therapy can be effective, as individuals may have multiple pituitary insufficiency (eg, manifesting with hypothyroidism, growth hormone, gonadotropin, and cortisol deficiency) | Endocrine; Genitourinary; Neurologic; Ophthalmologic | 15846561; 18628516; 18728160; 18781617; 19956411; 18854396; 19965921; 20396904; 20486942; 20494911; 21353197; 22198066; 24859618; 25293953; 25589041 |
ClinVar
This is a list of variants' phenotypes submitted to
- Anophthalmia-microphthalmia_syndrome (163 variants)
- not_provided (62 variants)
- Syndromic_microphthalmia_type_5 (36 variants)
- Inborn_genetic_diseases (28 variants)
- Pituitary_hormone_deficiency,_combined,_6 (20 variants)
- OTX2-related_disorder (10 variants)
- Retinal_dystrophy (10 variants)
- not_specified (10 variants)
- OTX2-Related_Syndromic_Microphthalmia (10 variants)
- Syndromic_Microphthalmia,_Dominant (6 variants)
- Anophthalmia (3 variants)
- Combined_Pituitary_Hormone_Deficiency,_Dominant (2 variants)
- Optic_atrophy (2 variants)
- Intellectual_disability (1 variants)
- Microcephaly (1 variants)
- 46,XY_partial_gonadal_dysgenesis (1 variants)
- Anxiety (1 variants)
- Horizontal_nystagmus (1 variants)
- Phonophobia (1 variants)
- Leber_congenital_amaurosis (1 variants)
- Hypotelorism (1 variants)
- Male_infertility_with_azoospermia_or_oligozoospermia_due_to_single_gene_mutation (1 variants)
- Protruding_ear (1 variants)
- Pointed_chin (1 variants)
- Hypertonia (1 variants)
- Nystagmus (1 variants)
- Low-set_ears (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the OTX2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000021728.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 47 | 50 | ||||
| missense | 127 | 150 | ||||
| nonsense | 14 | 20 | ||||
| start loss | 0 | |||||
| frameshift | 26 | 33 | ||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 45 | 17 | 135 | 56 | 1 |
Highest pathogenic variant AF is 0.00022798772
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| OTX2 | protein_coding | protein_coding | ENST00000339475 | 3 | 9773 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.923 | 0.0765 | 124669 | 0 | 3 | 124672 | 0.0000120 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.05 | 123 | 160 | 0.768 | 0.00000780 | 1908 |
| Missense in Polyphen | 19 | 54.266 | 0.35013 | 658 | ||
| Synonymous | -0.0999 | 65 | 64.0 | 1.02 | 0.00000311 | 616 |
| Loss of Function | 3.03 | 1 | 12.6 | 0.0792 | 6.56e-7 | 140 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00 | 0.00 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000981 | 0.0000981 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- 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'. {ECO:0000269|PubMed:22715480}.;
- Disease
- DISEASE: Microphthalmia, syndromic, 5 (MCOPS5) [MIM:610125]: Patients manifest unilateral or bilateral microphthalmia/clinical anophthalmia and variable additional features including pituitary dysfunction, coloboma, microcornea, cataract, retinal dystrophy, hypoplasia or agenesis of the optic nerve, agenesis of the corpus callosum, developmental delay, joint laxity, hypotonia, and seizures. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. {ECO:0000269|PubMed:15846561, ECO:0000269|PubMed:20396904, ECO:0000269|PubMed:22577225, ECO:0000269|PubMed:24167467}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Pituitary hormone deficiency, combined, 6 (CPHD6) [MIM:613986]: Combined pituitary hormone deficiency is defined as the impaired production of growth hormone and one or more of the other five anterior pituitary hormones. CPHD6 patients manifest neonatal hypoglycemia, and deficiencies of growth hormone, thyroid-stimulating hormone, luteinizing hormone, follicle stimulating hormone and adrenocorticotropic hormone. {ECO:0000269|PubMed:18728160, ECO:0000269|PubMed:22715480}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Retinal dystrophy, early-onset, with or without pituitary dysfunction (RDEOP) [MIM:610125]: An autosomal dominant ocular disease characterized by pattern dystrophy of the retinal pigment epithelium, and photoreceptor degeneration. Mild developmental anomalies include optic nerve head dysplasia, microcornea, and Rathke's cleft cyst. Some patients manifest pituary dysfunction. {ECO:0000269|PubMed:19956411, ECO:0000269|PubMed:25293953}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- TP53 Network;Endoderm Differentiation;Dopaminergic Neurogenesis
(Consensus)
Recessive Scores
- pRec
- 0.344
Intolerance Scores
- loftool
- 0.0813
- rvis_EVS
- -0.38
- rvis_percentile_EVS
- 27.42
Haploinsufficiency Scores
- pHI
- 0.933
- hipred
- Y
- hipred_score
- 0.851
- ghis
- 0.609
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.796
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Otx2
- Phenotype
- taste/olfaction phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; digestive/alimentary phenotype; muscle phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; pigmentation phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; embryo phenotype; skeleton phenotype; vision/eye phenotype;
Zebrafish Information Network
- Gene name
- otx2b
- Affected structure
- ceratobranchial cartilage
- Phenotype tag
- abnormal
- Phenotype quality
- shortened
Gene ontology
- Biological process
- axon guidance;regulation of smoothened signaling pathway;forebrain development;midbrain development;positive regulation of embryonic development;regulation of fibroblast growth factor receptor signaling pathway;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;protein-containing complex assembly;dopaminergic neuron differentiation;primitive streak formation;positive regulation of gastrulation
- Cellular component
- nucleus;growth cone;protein-containing complex
- Molecular function
- RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;protein binding;eukaryotic initiation factor 4E binding