SLC35G1 was identified in an ASD candidate gene in Wang et al., 2023 based on reaching a false discovery rate (FDR) threshold of <0.1 following TADA analysis in both a discovery cohort of 1,141 Chinese ASD probands and a combined cohort consisting of the discovery cohort of Chinese ASD probands and 42,607 ASD probands originally published in Zhou et al., 2022. Wang et al., 2023 also demonstrated that mice harboring a heterozygous deletion of Slc35g1 exhibited defects in interactive social behaviors and increased marble-burying activity compared to wild-type mice. In total, four de novo coding variants in SLC35G1 (two loss-of-function variants and two missense variants) have been reported in ASD probands (Yuen et al., 2017; Zhou et al., 2022; Wang et al., 2023).
Molecular Function
This gene encodes a transmembrane protein which is a member of the drug/metabolite transporter protein superfamily. The encoded protein may play a role in the regulation of calcium levels inside the cell.
Recent analysis has identified SLC35G1 as a new autism spectrum disorder (ASD) candidate gene. In line with this finding, the Slc35g1 knockout mouse model shows numerous deficits in social behavior. Heterozygous male mice exhibit significant decreases in social approach and social memory, with a significant decrease in preference for a novel mouse over a familiar mouse in the three-chamber social approach test. Additionally, the model shows a change in repetitive behaviors, with an increase in the number of marbles buried in the marble-burying test. The model shows no change in anxiety, general locomotor activity, or spatial learning, as demonstrated by results in the elevated plus maze test, the open field test, and the Barnes maze test, respectively.
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
An 8.5kb chromosomal deletion at the Slc35g1 locus in the C57BL/6N genome was achieved by designing two specific guide RNAs (sgRNAs). The two sequences targeting Slc35g1 were in exon 1 and exon 3, with a complete deletion of exon 2.
Allele Type: Knockout
Strain of Origin: C57BL/6N
Genetic Background: C57BL/6N
ES Cell Line: Mutant ES Cell Line: Model Source: Biocytogen
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
An 8.5kb chromosomal deletion at the Slc35g1 locus in the C57BL/6N genome was achieved by designing two specific guide RNAs (sgRNAs). The two sequences targeting Slc35g1 were in exon 1 and exon 3, with a complete deletion of exon 2.
Allele Type: Knockout
Strain of Origin: C57BL/6N
Genetic Background: C57BL/6N
ES Cell Line: Mutant ES Cell Line: Model Source: Biocytogen
Description: Slc35g1 mutant mice exhibited a significant decrease in interaction time with a wildtype stranger mouse (as opposed to an empty cage) compared to wildtype controls, as further exhibited by a decrease in social preference from 40.3% to -1.55%.
Exp Paradigm: stranger mouse (s1) in chamber 1, empty cage (object) in chamber 2
Description: Slc35g1 mutant mice exhibited a significant decrease in the amount of time spent exploring a novel mouse (s2) as opposed to a familiar mouse (s1) compared to wildtype controls, suggesting a deficit in social memory.
Exp Paradigm: familiar mouse in chamber 1 (s1), stranger mouse (s2) in chamber 2
