Mitochondrial disorders
Gene: SLC25A36
Comment on list classification: As reviewed by Hannah Knight, there is sufficient evidence available for the association of this gene with green rating in the next GMS review.Created: 12 Dec 2023, 9:32 a.m. | Last Modified: 12 Dec 2023, 9:32 a.m.
Panel Version: 4.127
Solute carrier family 25 member 36 (SLC25A36) is a known mitochondrial pyrimidine nucleotide carrier in humans.
PMID:34576089 - A 12-year-old patient was reported with hypothyroidism, hyperinsulinism, hyperammonemia, chronical obstipation, short stature, along with language and general developmental delay and was identified with a homozygous variant in SLC25A36 gene (c.803dupT/ p.Ser269llefs*35). Functional analysis of mutant SLC25A36 protein in proteoliposomes showed a virtually abolished transport activity. Immunoblotting results suggest that the mutant SLC25A36 protein in the patient undergoes fast degradation. Supplementation with uridine lead to some improvement in clinical course.
PMID:34971397 - Two siblings were reported with hyperinsulinism, hypoglycemia and hyperammonemia from early infancy with homozygous SLC25A36 variant (c.284 + 3 A > T). Functional studies support loss of function mechanism.
This gene has been associated with relevant phenotypes in OMIM (MIM #620211), but not in Gene2Phenotype.
PMID:36695547 - The same homozygous variant (c.284 + 3 A > T) was reported in four individuals of two Bedouin Israeli related families. They had hyperinsulinism, hyperammonemia, borderline low birth weight, tonic-clonic seizures commencing around 6 months of age, yet normal intellect and no significant other morbidities.
This gene has been associated with relevant phenotypes in OMIM (MIM #620211), but not in Gene2Phenotype.Created: 12 Dec 2023, 9:29 a.m. | Last Modified: 12 Dec 2023, 9:29 a.m.
Panel Version: 4.125
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Hyperinsulinemic hypoglycemia, familial, 8, OMIM:620211
Publications
More than three cases reported in past three years
PMID: 34576089 (2021) - first case, a 12-year-old patient with hypothyroidism, hyperinsulinism, hyperammonemia, chronical obstipation, short stature, along with language and general developmental delay. Homozygous frameshift variant identified c.803dupT, p.Ser269llefs*35
PMID: 34971397 (2022) - two siblings with homozygous splice site variant
PMID: 36695547 (2023) - four individuals of two Bedouin Israeli related families - same homozygous splice site variant identified
Sources: LiteratureCreated: 4 Dec 2023, 2:36 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Hyperinsulinemic hypoglycemia, familial, 8
Publications
Gene: slc25a36 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: SLC25A36 were changed from Hyperinsulinemic hypoglycemia, familial, 8 to Hyperinsulinemic hypoglycemia, familial, 8, OMIM:620211
Tag Q4_23_promote_green tag was added to gene: SLC25A36. Tag Q4_23_NHS_review tag was added to gene: SLC25A36.
gene: SLC25A36 was added gene: SLC25A36 was added to Mitochondrial disorders. Sources: Literature Mode of inheritance for gene: SLC25A36 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC25A36 were set to 34576089; 34971397; 36695547 Phenotypes for gene: SLC25A36 were set to Hyperinsulinemic hypoglycemia, familial, 8 Review for gene: SLC25A36 was set to GREEN