Paroxysmal central nervous system disorders
Gene: ALPK1
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, 2:27 p.m. | Last Modified: 15 Aug 2023, 2:30 p.m.
Panel Version: 3.6
Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.Created: 15 Aug 2023, 1:56 p.m. | Last Modified: 15 Aug 2023, 1:56 p.m.
Panel Version: 3.5
ALPK1 is associated with ROSAH syndrome, which commonly include episodic migraine or other headaches.
Sources: LiteratureCreated: 18 Jul 2023, 6:14 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
ROSAH syndrome
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Publications for gene: ALPK1 were set to 30967659; 31939038; 35868845
Tag Q3_23_promote_green tag was added to gene: ALPK1. Tag Q3_23_MOI tag was added to gene: ALPK1.
Gene: alpk1 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: ALPK1 were changed from ROSAH syndrome to ROSAH syndrome, OMIM:614979; optic nerve edema-splenomegaly syndrome, MONDO:0013999
Publications for gene: ALPK1 were set to 30967659; 31939038
Publications for gene: ALPK1 were set to PMID: 30967659
gene: ALPK1 was added gene: ALPK1 was added to Paroxysmal central nervous system disorders. Sources: Literature Mode of inheritance for gene: ALPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ALPK1 were set to PMID: 30967659 Phenotypes for gene: ALPK1 were set to ROSAH syndrome Mode of pathogenicity for gene: ALPK1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: ALPK1 was set to GREEN