OPTN

optineurin

Basic information

Region (hg38): 10:13099448-13138308

Previous symbols: [ "GLC1E" ]

Links

ENSG00000123240 ∙ NCBI:10133 ∙ OMIM:602432 ∙ HGNC:17142 ∙ Uniprot:Q96CV9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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 (Supportive), mode of inheritance: AD
• amyotrophic lateral sclerosis type 12 (Strong), mode of inheritance: AR
• 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: CGD

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 ClinVar and linked to the OPTN gene.

• not provided (117 variants)
• Inborn genetic diseases (66 variants)
• Amyotrophic lateral sclerosis type 12 (65 variants)
• Primary open angle glaucoma (64 variants)
• Primary open angle glaucoma;Glaucoma 1, open angle, E;Amyotrophic lateral sclerosis type 12 (60 variants)
• Primary open angle glaucoma;Amyotrophic lateral sclerosis type 12;Glaucoma 1, open angle, E (42 variants)
• Amyotrophic lateral sclerosis type 12;Glaucoma 1, open angle, E;Primary open angle glaucoma (34 variants)
• Glaucoma 1, open angle, E;Primary open angle glaucoma;Amyotrophic lateral sclerosis type 12 (34 variants)
• Amyotrophic lateral sclerosis type 12;Primary open angle glaucoma;Glaucoma 1, open angle, E (26 variants)
• Glaucoma 1, open angle, E;Amyotrophic lateral sclerosis type 12;Primary open angle glaucoma (16 variants)
• not specified (15 variants)
• OPTN-related condition (10 variants)
• Motor neuron disease (4 variants)
• Amyotrophic Lateral Sclerosis, Recessive (4 variants)
• Glaucoma 1, open angle, E (3 variants)
• Amyotrophic lateral sclerosis (3 variants)
• OPTN-Related Disorders (3 variants)
• Amyotrophic lateral sclerosis type 12;Primary open angle glaucoma;Glaucoma, normal tension, susceptibility to (2 variants)
• Amyotrophic lateral sclerosis type 10 (1 variants)
• Glaucoma, normal tension, susceptibility to (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	50	1	54
missense	1	3	123	2	2	131
nonsense	5	2	3			10
start loss						0
frameshift	9	9	1			19
inframe indel			1			1
splice donor/acceptor (+/-2bp)		8	1			9
splice region			16	2	1	19
non coding			23	50	42	115
Total	15	22	155	102	45

Highest pathogenic variant AF is 0.0000460

Variants in OPTN

This is a list of pathogenic ClinVar variants found in the OPTN region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-13100081-C-T		Primary open angle glaucoma • Amyotrophic Lateral Sclerosis, Recessive	Likely benign (Jun 14, 2016)
10-13100082-G-T		Primary open angle glaucoma • Amyotrophic lateral sclerosis type 12	Uncertain significance (Jan 13, 2018)
10-13100087-G-T		Primary open angle glaucoma • Amyotrophic lateral sclerosis type 12	Benign (Jan 12, 2018)
10-13100127-G-T		Primary open angle glaucoma • Amyotrophic lateral sclerosis type 12	Uncertain significance (Jan 13, 2018)
10-13100153-T-C		Amyotrophic lateral sclerosis type 12 • Primary open angle glaucoma	Benign (Jan 13, 2018)
10-13100192-C-A		Amyotrophic lateral sclerosis type 12 • Primary open angle glaucoma	Benign (Jan 12, 2018)
10-13100194-G-T		Amyotrophic lateral sclerosis type 12 • Primary open angle glaucoma	Uncertain significance (Jan 13, 2018)
10-13100211-C-G		Amyotrophic lateral sclerosis type 12 • Primary open angle glaucoma	Benign (Jan 12, 2018)
10-13100216-C-A		Primary open angle glaucoma • Amyotrophic lateral sclerosis type 12	Uncertain significance (Jan 13, 2018)
10-13100251-G-A		Amyotrophic lateral sclerosis type 12 • Primary open angle glaucoma	Benign (Jan 13, 2018)
10-13100282-C-G		Primary open angle glaucoma • Amyotrophic lateral sclerosis type 12	Uncertain significance (Jan 13, 2018)
10-13100294-G-A		Primary open angle glaucoma • Amyotrophic lateral sclerosis type 12	Uncertain significance (Apr 27, 2017)
10-13100315-A-G		Primary open angle glaucoma • Amyotrophic lateral sclerosis type 12	Benign/Likely benign (Jan 12, 2018)
10-13108781-C-T			Likely benign (May 29, 2019)
10-13108850-T-C			Likely benign (Mar 17, 2019)
10-13108903-T-TGCGC			Benign (Sep 14, 2019)
10-13108909-T-C			Benign (Aug 18, 2019)
10-13108910-G-GCACA			Benign (Aug 15, 2019)
10-13108910-G-GCACACA			Benign (Mar 10, 2020)
10-13108910-G-GCGCACACA			Likely benign (Oct 30, 2019)
10-13109036-A-G			Likely benign (Mar 19, 2019)
10-13109114-A-G		Amyotrophic lateral sclerosis type 12 • Primary open angle glaucoma	Uncertain significance (Jan 15, 2018)
10-13109124-T-A		Primary open angle glaucoma;Amyotrophic lateral sclerosis type 12;Glaucoma 1, open angle, E	Uncertain significance (Jul 13, 2023)
10-13109129-C-T		Primary open angle glaucoma;Amyotrophic lateral sclerosis type 12;Glaucoma 1, open angle, E	Uncertain significance (Dec 11, 2023)
10-13109136-C-G		Glaucoma 1, open angle, E;Primary open angle glaucoma;Amyotrophic lateral sclerosis type 12	Uncertain significance (Jan 02, 2018)

GnomAD

Source: gnomAD

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: dbNSFP

• 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