Retinal 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, 2:28 p.m. | Last Modified: 15 Aug 2023, 2:28 p.m.
Panel Version: 4.24
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; 34159509Created: 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
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
Six unrelated families reported with same recurrent missense variant c.710C>T, (p.Thr237Met). Pancytopaenia and recurrent infections present in some.
Sources: Expert listCreated: 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
Variants in this GENE are reported as part of current diagnostic practice
Publications for gene: ALPK1 were set to 30967659; 31939038; 31053777; 34159509
Tag for-review was removed from gene: ALPK1. Tag Q4_21_NHS_review was removed from gene: ALPK1.
Source Expert Review Green was added to ALPK1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q4_21_NHS_review tag was added to gene: ALPK1.
Publications for gene: ALPK1 were set to 30967659; 31939038
Gene: alpk1 has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: ALPK1.
Phenotypes for gene: ALPK1 were changed from ROSAH syndrome; retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache to ROSAH syndrome, OMIM:614979
gene: ALPK1 was added gene: ALPK1 was added to Retinal disorders. Sources: Expert list Mode of inheritance for gene: ALPK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ALPK1 were set to 30967659; 31939038 Phenotypes for gene: ALPK1 were set to ROSAH syndrome; retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache Review for gene: ALPK1 was set to GREEN gene: ALPK1 was marked as current diagnostic