OPTN
optineurin
Basic information
Region (hg38): 10:13099449-13138308
Previous symbols: [ "GLC1E" ]
Links
Phenotypes
GenCC
Source:
- amyotrophic lateral sclerosis type 12 (Strong), mode of inheritance: AR
- amyotrophic lateral sclerosis type 12 (Strong), mode of inheritance: Semidominant
- glaucoma 1, open angle, E (Limited), mode of inheritance: AD
- amyotrophic lateral sclerosis type 12 (Strong), mode of inheritance: AR
- amyotrophic lateral sclerosis (Supportive), mode of inheritance: AD
- amyotrophic lateral sclerosis type 12 (Strong), mode of inheritance: AR
- amyotrophic lateral sclerosis type 12 (Strong), mode of inheritance: AD
- glaucoma 1, open angle, E (Strong), mode of inheritance: AD
- amyotrophic lateral sclerosis type 12 (Definitive), mode of inheritance: Semidominant
- glaucoma, normal tension, susceptibility to (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Glaucoma, normal tension, susceptibility to; Glaucoma primary open angle | AD | Ophthalmologic; Pharmacogenomic | Open-angle glaucoma is typically asymptomatic until late stages, when irreversible nerve damage has already taken place; Agents that may contribute to glaucoma should be avoided | Neurologic; Ophthalmologic | 11834836; 17389490; 20428114; 21613650; 21644038; 21730848; 22708870; 22402017; 23062601; 21852022; 21802176 |
ClinVar
This is a list of variants' phenotypes submitted to
- Amyotrophic_lateral_sclerosis_type_12 (335 variants)
- Primary_open_angle_glaucoma (328 variants)
- Glaucoma_1,_open_angle,_E (316 variants)
- not_provided (114 variants)
- Inborn_genetic_diseases (92 variants)
- OPTN-related_disorder (62 variants)
- not_specified (15 variants)
- Motor_neuron_disease (4 variants)
- Amyotrophic_lateral_sclerosis (3 variants)
- Amyotrophic_Lateral_Sclerosis,_Recessive (2 variants)
- Frontotemporal_dementia (1 variants)
- Glaucoma,_normal_tension,_susceptibility_to (1 variants)
- Amyotrophic_lateral_sclerosis_type_10 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the OPTN gene is commonly pathogenic or not. These statistics are base on transcript: NM_001008212.2. 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 | 74 | 80 | ||||
| missense | 201 | 218 | ||||
| nonsense | 10 | 20 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 14 | 15 | 31 | |||
| splice donor/acceptor (+/-2bp) | 13 | |||||
| Total | 29 | 37 | 212 | 81 | 4 |
Highest pathogenic variant AF is 0.0000706358
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| OPTN | protein_coding | protein_coding | ENST00000378748 | 13 | 38843 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 5.91e-18 | 0.0130 | 125603 | 2 | 143 | 125748 | 0.000577 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.622 | 267 | 297 | 0.898 | 0.0000156 | 3833 |
| Missense in Polyphen | 64 | 78.608 | 0.81417 | 1090 | ||
| Synonymous | -0.601 | 123 | 115 | 1.07 | 0.00000647 | 1038 |
| Loss of Function | 0.428 | 28 | 30.6 | 0.916 | 0.00000140 | 395 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000850 | 0.000850 |
| Ashkenazi Jewish | 0.00367 | 0.00368 |
| East Asian | 0.0000546 | 0.0000544 |
| Finnish | 0.0000925 | 0.0000924 |
| European (Non-Finnish) | 0.000625 | 0.000580 |
| Middle Eastern | 0.0000546 | 0.0000544 |
| South Asian | 0.000131 | 0.000131 |
| Other | 0.00163 | 0.00147 |
dbNSFP
Source:
- Function
- FUNCTION: Plays an important role in the maintenance of the Golgi complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8 (PubMed:27534431). Links myosin VI to the Golgi complex and plays an important role in Golgi ribbon formation (PubMed:27534431). Plays a role in the activation of innate immune response during viral infection. Mechanistically, recruits TBK1 at the Golgi apparatus, promoting its trans-phosphorylation after RLR or TLR3 stimulation (PubMed:27538435). In turn, activated TBK1 phosphorylates its downstream partner IRF3 to produce IFN-beta. Plays a neuroprotective role in the eye and optic nerve. May act by regulating membrane trafficking and cellular morphogenesis via a complex that contains Rab8 and hungtingtin (HD). Mediates the interaction of Rab8 with the probable GTPase-activating protein TBC1D17 during Rab8-mediated endocytic trafficking, such as of transferrin receptor (TFRC/TfR); regulates Rab8 recruitment to tubules emanating from the endocytic recycling compartment. Autophagy receptor that interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family; targets ubiquitin-coated bacteria (xenophagy), such as cytoplasmic Salmonella enterica, and appears to function in the same pathway as SQSTM1 and CALCOCO2/NDP52. {ECO:0000269|PubMed:11834836, ECO:0000269|PubMed:15837803, ECO:0000269|PubMed:20085643, ECO:0000269|PubMed:20174559, ECO:0000269|PubMed:21617041, ECO:0000269|PubMed:22854040, ECO:0000269|PubMed:27534431, ECO:0000269|PubMed:27538435}.;
- Disease
- DISEASE: Glaucoma 1, open angle, E (GLC1E) [MIM:137760]: A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. {ECO:0000269|PubMed:11834836, ECO:0000269|PubMed:12939304, ECO:0000269|PubMed:14597044, ECO:0000269|PubMed:15226658, ECO:0000269|PubMed:15326130, ECO:0000269|PubMed:15557444, ECO:0000269|PubMed:17389490, ECO:0000269|PubMed:20085643, ECO:0000269|PubMed:22854040, ECO:0000269|PubMed:23669351, ECO:0000269|PubMed:24752605}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Glaucoma, normal pressure (NPG) [MIM:606657]: A primary glaucoma characterized by intraocular pression consistently within the statistically normal population range. {ECO:0000269|PubMed:15370540}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Amyotrophic lateral sclerosis 12 (ALS12) [MIM:613435]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5- 10% of the cases. {ECO:0000269|PubMed:20428114, ECO:0000269|PubMed:27534431}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Mitophagy - animal - Homo sapiens (human);Vesicle-mediated transport;TBC/RABGAPs;Membrane Trafficking;Regulation of PLK1 Activity at G2/M Transition;Rab regulation of trafficking;G2/M Transition;Mitotic G2-G2/M phases;Cell Cycle;Cell Cycle, Mitotic;Optineurin and Myosin Phosphatase Negatively Regulate PLK1
(Consensus)
Recessive Scores
- pRec
- 0.220
Intolerance Scores
- loftool
- 0.0731
- rvis_EVS
- -0.58
- rvis_percentile_EVS
- 18.72
Haploinsufficiency Scores
- pHI
- 0.128
- hipred
- Y
- hipred_score
- 0.515
- ghis
- 0.568
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.978
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Optn
- Phenotype
- homeostasis/metabolism 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);
Zebrafish Information Network
- Gene name
- optn
- Affected structure
- neuron
- Phenotype tag
- abnormal
- Phenotype quality
- decreased speed
Gene ontology
- Biological process
- G2/M transition of mitotic cell cycle;negative regulation of receptor recycling;autophagy;Golgi organization;signal transduction;cell death;positive regulation of autophagy;protein localization to Golgi apparatus;cellular response to unfolded protein;Golgi to plasma membrane protein transport;negative regulation of I-kappaB kinase/NF-kappaB signaling;innate immune response;defense response to Gram-negative bacterium;parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization;Golgi ribbon formation;positive regulation of xenophagy
- Cellular component
- Golgi membrane;nucleus;nucleoplasm;cytoplasm;autophagosome;Golgi apparatus;trans-Golgi network;cytosol;perinuclear region of cytoplasm;recycling endosome membrane
- Molecular function
- protein binding;protein C-terminus binding;Rab GTPase binding;protein binding, bridging;polyubiquitin modification-dependent protein binding;identical protein binding;metal ion binding;K63-linked polyubiquitin modification-dependent protein binding