Optic neuropathy

Gene: ALPK1

Green List (high evidence)

ALPK1 variants have been associated with ROSAH syndrome (OMIM:614979) and as strong Gen2Phen gene for the same condition. To date, 20 patients from 12 unrelated families carry NM_025144.4(ALPK1):c.710C>T (p.Thr237Met)(PMID: 30967659; 31939038; 35868845) and one case negative for this variant carried: ALPK1(NM_025144.4):c.761A>G (p.Tyr254Cys)(PMID: 35868845). These variants are in the ligand binding domain of ALPK1 and have a gain-of-function action, resulting in enhanced NF-κB activation in transfected cells and fibroblasts from patients with ROSAH syndrome (PMID: 35868845).

Created: 15 Aug 2023, 2:29 p.m. | Last Modified: 15 Aug 2023, 2:29 p.m.

Panel Version: 4.11

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 8 Mar 2022, 10:41 a.m. | Last Modified: 8 Mar 2022, 10:41 a.m.

Panel Version: 2.60

Comment on list classification: New gene added by Neringa Jurkute (MD). This gene is associated with a phenotype in OMIM and Gene2Phenotype (Strong). There is enough evidence to support a gene-disease assocation. This gene should be rated Green at the next review.

Created: 7 Dec 2021, 10:40 a.m. | Last Modified: 7 Dec 2021, 10:40 a.m.

Panel Version: 2.53

Green List (high evidence)

Recurrent variant has been reported in affected individuals from 9 unrelated families. Affected individuals shared overlapping phenotype with retinal changes, chronic disc swelling observed in majority of cases.

OMIM: 614979
PMID: 30967659; 31053777; 31939038; 34159509
Sources: Literature, Research, Other

Created: 6 Dec 2021, 4:03 p.m. | Last Modified: 6 Dec 2021, 4:09 p.m.

Panel Version: 2.51

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Retinopathy; Optic disc swelling; Splenomegaly; Pancytopenia; Headaches; ocular inflammation.

Publications

• PMID: 30967659
• 31053777
• 31939038
• 34159509

Mode of pathogenicity
Other