Early onset or syndromic epilepsy
Gene: UNC13B
I agree with Zornitza Stark (Australian Genomics) that the evidence for the association of UNC13B to epilepsy is conflicting and the evidence for pathogenicity of several variants is limited.
In addition, this gene has not yet been associated with any relevant phenotypes in OMIM or in Gene2Phenotype.Created: 4 May 2023, 5 p.m. | Last Modified: 4 May 2023, 5 p.m.
Panel Version: 4.25
Phenotypes
partial epilepsy, MONDO:0005384
Publications
No OMIM human disease association. Gene encodes a presynaptic protein Munc13-2 highly expressed in the brain (predominantly cerebral cortex).
Variant interpretation data in human epilepsy cohort somewhat conflicting and restricted to a single study. Wang et al, Brain, 2021 - trio-based whole-exome sequencing identified UNC13B in 12 individuals affected by partial epilepsy and/or febrile seizures from 8 unrelated families. Identified:
x1 de novo nonsense variant, absent in gnomad, damaging in silicos
x1 de novo splice site, absent in gnomad, damaging in silicos
x1 splice site variant present in unaffected mother (low frequency in gnomad)
x2 compound het in one individual - more severe phenotype postulated (x1 variant present in contro cohortl, the other variant present in low frequency in gnomad)
x1 missense variant - in Han Chinese major depressive disorders study, not in gnomad
x1 missense variant - highly conserved residue, not in gnomad
x2 other missense variant - highly conserved residue, low frequency in gnomad
Latter 4 missense variants cosegregated with affected individuals in the families
In Drosophila, seizure rate and duration were increased by Unc13b knockdown compared to wild-type flies, but these effects were less pronounced than in sodium voltage-gated channel alpha subunit 1 (Scn1a) knockdown Drosophila
De novo UNC13B variants previously reported in bipolar disorder and autism spectrum disorder
Sources: LiteratureCreated: 11 Oct 2021, 9:51 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Epilepsy
Publications
Phenotypes for gene: UNC13B were changed from partial epilepsy, MONDO:0005384 to partial epilepsy, MONDO:0005384
Phenotypes for gene: UNC13B were changed from Epilepsy to partial epilepsy, MONDO:0005384
Publications for gene: UNC13B were set to 33876820; 35380625
Publications for gene: UNC13B were set to 33876820; 35380625
Publications for gene: UNC13B were set to 33876820
Gene: unc13b has been classified as Red List (Low Evidence).
Gene: unc13b has been classified as Red List (Low Evidence).
Gene: unc13b has been classified as Red List (Low Evidence).
gene: UNC13B was added gene: UNC13B was added to Genetic epilepsy syndromes. Sources: Literature Mode of inheritance for gene: UNC13B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: UNC13B were set to 33876820 Phenotypes for gene: UNC13B were set to Epilepsy Review for gene: UNC13B was set to RED