Structural eye disease

Gene: TBK1

Red List (low evidence)

TBK1 copy number variants (mostly duplications, triplications) are associated with 1-2% of normal tension glaucoma (NTG). PMID 21447600 (2011) identified heterozygous chromosome 12q14 duplications encompassing TBK1 that segregated with autosomal dominant NTG in two unrelated pedigrees. Affected individuals had early adult-onset disease. Expression and localisation studies supported a TBK1 dosage mechanism. Among 274 glaucoma patients, no SNVs identified showed enrichment in patients vs unaffected controls. No evidence for congenital/developmental glaucoma, anterior segment malformation, or other structural eye disease phenotypes was reported.

In a juvenile/ early-onset glaucoma registry cohort, no cases of congenital/developmental or childhood-onset glaucoma were found to be driven by TBK1 copy number variation; two TBK1-positive cases with onset at mean 30 years (range 25-38) years were identified, both with an NTG phenotype with normal intraocular pressure (IOP) (PMID 33892047 (2021)).

PMID 28984711 (2018) described a series of NTG patients with duplication or triplication of TBK1. Mean age of onset in duplication carriers (n=11) was 38.7 ± 7.4 years and 33.8 ± 14.1 years for Triplication carriers (n=7).

Evidence supports a role for TBK1 dosage in the development of adult/ early-onset NTG. No convincing evidence supports a causative link with congenital/developmental glaucoma or structural eye disease, thus a red rating is recommended.

This gene has not yet been associated with relevant phenotypes in OMIM or Gene2Phenotype.

Created: 30 Jul 2026, 2:59 p.m. | Last Modified: 30 Jul 2026, 2:59 p.m.

Panel Version: 5.7

Mode of inheritance
Other

Phenotypes
low tension glaucoma (MONDO:0006837); juvenile open angle glaucoma (MONDO:0020367)

Publications

• 21447600
• 33892047
• 28984711

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Green List (high evidence)

Autosomal dominant juvenile and adult-onset normal tension and open angle glaucoma. More than 3 families reported. PMID 2774031 reports a family with juvenile normal tension glaucoma from 13 years of age, who have subsequently been reported to have a TBK1 dominant variant (PMID 34536459).
Sources: Literature

Created: 17 Jun 2026, 1:50 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Juvenile open angle glaucoma; Juvenile normal tension glaucoma; HP:0001087 developmental glaucoma; HP:0012108 open angle glaucoma; HP:0000501 glaucoma

Publications

• PMID: 21447600
• 31563868
• 33892047
• 2774031