OPTN

Chr 10ADAR

optineurin

Also known as: ALS12, FIP2, GLC1E, HIP7, HYPL, NRP, TFIIIA-INTP

NCBI Gene: 10133 ENSG00000123240 UniProt: Q96CV9 OMIM: 602432

Optineurin functions in membrane trafficking, vesicle trafficking, autophagy, and apoptosis regulation through interactions with RAB8, huntingtin, and transcription factors. Mutations cause autosomal dominant normal-tension glaucoma, primary open-angle glaucoma, and amyotrophic lateral sclerosis type 12 with or without frontotemporal dementia, as well as autosomal recessive forms of these conditions. The pathogenic mechanism involves disruption of cellular trafficking pathways and dysregulated apoptosis.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes the coiled-coil containing protein optineurin. Optineurin may play a role in normal-tension glaucoma and adult-onset primary open angle glaucoma. Optineurin interacts with adenovirus E3-14.7K protein and may utilize tumor necrosis factor-alpha or Fas-ligand pathways to mediate apoptosis, inflammation or vasoconstriction. Optineurin may also function in cellular morphogenesis and membrane trafficking, vesicle trafficking, and transcription activation through its interactions with the RAB8, huntingtin, and transcription factor IIIA proteins. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Glaucoma, normal tension, susceptibility to}MIM #606657

Amyotrophic lateral sclerosis 12 with or without frontotemporal dementiaMIM #613435

ADAR

Glaucoma 1, open angle, EMIM #137760

UniProtGlaucoma, normal pressure

Clinical highlights

Gene–disease validity (ClinGen)

Active trials

338

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

Multiple*

Mechanism· predicted

📖

GeneReview available — OPTN

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in OPTN?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

713 rare PASS variants

Rare truncating (LoF)

1 in 1,000

136 rare PASS variants

Rare synonymous (reference)

1 in 120

299 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for OPTN. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 150	1 in 1,100
South Asian	~43k	1 in 70	1 in 1,700
Remaining (unassigned)	~30k	1 in 100	1 in 720
European (Finnish)	~27k	1 in 250	1 in 2,200
Admixed American	~22k	1 in 110	1 in 720
African / African American	~21k	1 in 75	1 in 1,600
East Asian	~20k	1 in 95	≈ 1 in 5,000
Ashkenazi Jewish	~13k	1 in 590	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 78	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 12 of 13 coding exons well covered in gnomAD exomes; exon 11 marginal. Genomes: all 13.? see exons ↓