Retinal disorders

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, 2:28 p.m. | Last Modified: 15 Aug 2023, 2:28 p.m.

Panel Version: 4.24

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

Created: 6 Dec 2021, 4:06 p.m. | Last Modified: 6 Dec 2021, 4:08 p.m.

Panel Version: 2.236

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Retinal dystrophy; optic disc swelling; splenomegaly; headaches; ocular inflammation

Publications

• 30967659
• 31053777
• 31939038
• 34159509

Mode of pathogenicity
Other

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

Created: 8 Mar 2022, 10:06 a.m. | Last Modified: 8 Mar 2022, 10:06 a.m.

Panel Version: 2.243

Comment on publications: Added new publication (PMID:31053777;34159509).

Created: 7 Dec 2021, 10:32 a.m. | Last Modified: 7 Dec 2021, 10:32 a.m.

Panel Version: 2.239

Comment on list classification: New gene added by Zornitza Stark. This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. There is enough evidence to support a gene-disease association; therefore, this gene has been given an Amber rating and should be promoted to Green at the next review.

Created: 6 Jan 2021, 1:19 p.m. | Last Modified: 6 Jan 2021, 1:19 p.m.

Panel Version: 2.50

Green List (high evidence)

Six unrelated families reported with same recurrent missense variant c.710C>T, (p.Thr237Met). Pancytopaenia and recurrent infections present in some.
Sources: Expert list

Created: 10 Oct 2020, 5:26 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
ROSAH syndrome; retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache

Publications

• 30967659
• 31939038

Variants in this GENE are reported as part of current diagnostic practice