Structural eye disease

Gene: EFEMP1

Green List (high evidence)

Comment on list classification: There is sufficient evidence available for the association of monoallelic EFEMP1 variants with glaucoma, which fits into the scope of this panel. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 18 Jul 2025, 11:59 a.m. | Last Modified: 18 Jul 2025, 11:59 a.m.

Panel Version: 4.12

As reviewed by Cassandra Smith, there are at least five different monoallelic variants reported in several unrelated patients with open-angle glaucoma. There is also functional evidence available for variants reported in PMIDs: 34923728 & 38083999, showing protein aggregation.

The ClinGen Glaucoma and Neuro-Ophthalmology expert panel has classified the association of EFEMP1 gene to open-angle glaucoma (MONDO:0005338) as 'Moderate'. More information can be found in https://search.clinicalgenome.org/CCID:008636.

This gene has been associated with open angle glaucoma phenotype in OMIM (MIM #611276), but not yet in Gene2Phenotype.

Created: 18 Jul 2025, 11:57 a.m. | Last Modified: 18 Jul 2025, 11:57 a.m.

Panel Version: 4.9

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Glaucoma 1, open angle, H, OMIM:611276

Green List (high evidence)

PMID: 34923728 - Three families segregating heterozygous EFEMP1 variants associated with glaucoma - either missense variants or stop lost. Functional study shows protein aggregation

PMID: 38083999 - Met59Leu segregating with disease in two families, plus other variants identified in sporadic cases. Functional analysis showed protein aggregation.

PMID: 32476818 - stop loss variant identified in family with glaucoma

Created: 28 Dec 2024, 1:48 p.m. | Last Modified: 28 Dec 2024, 1:48 p.m.

Panel Version: 4.1

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Publications

• PMID: 34923728
• 38083999
• 32476818

Red List (low evidence)

retinal gene, can't find any evidence that it is associated with structural eye disease

Created: 19 Jun 2019, 3:32 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Doyne honeycomb degeneration of retina; 126600

Red List (low evidence)

Submitted on behalf of Professor Nicola Ragge (Wessex and West Midlands GLH). retinal gene, can't find any evidence that it is associated with structural eye disease

Created: 17 Apr 2019, 3:30 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Doyne honeycomb degeneration of retina, 126600