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Relevance to Autism

To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. Exploratory analyses examining specific sub-groups of the AGP discovery cohort and a smaller replication cohort from AGRE identified two SNPs within the ST8SIA2 gene with strong association signals for the verbal sub-group (Anney et al., 2010).

Molecular Function

The protein encoded by this gene is a type II membrane protein that is thought to catalyze the transfer of sialic acid from CMP-sialic acid to N-linked oligosaccharides and glycoproteins. The encoded protein may be found in the Golgi apparatus and may be involved in the production of polysialic acid, a modulator of the adhesive properties of neural cell adhesion molecule (NCAM1). This protein is a member of glycosyltransferase family 29.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
A genome-wide scan for common alleles affecting risk for autism.
ASD
Support
Mutations in Human Accelerated Regions Disrupt Cognition and Social Behavior.
ASD
Support
Effects of intronic single nucleotide polymorphisms (iSNPs) of a polysialyltransferase, ST8SIA2 gene found in psychiatric disorders on its gene pro...
Support
Characterization of a 520 kb deletion on chromosome 15q26.1 including ST8SIA2 in a patient with behavioral disturbance, autism spectrum disorder, a...
ASD
Epilepsy
Support
Identification of sialyltransferase 8B as a generalized susceptibility gene for psychotic and mood disorders on chromosome 15q25-26.
BPD
SCZ
Support
Positive association between SIAT8B and schizophrenia in the Chinese Han population.
SCZ
Support
Association between polymorphisms in the promoter region of the sialyltransferase 8B (SIAT8B) gene and schizophrenia.
SCZ
Support
Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
ASD
Recent Recommendation
Differential effect of disease-associated ST8SIA2 haplotype on cerebral white matter diffusion properties in schizophrenia and healthy controls.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN420R001 
 copy_number_loss 
  
  
 Unknown 
 Not maternal 
 Multi-generational 
 GEN420R002 
 intergenic_variant 
 delT 
  
  
  
 Unknown 
 GEN420R003 
 intergenic_variant 
 A>G 
  
  
  
 Unknown 
 GEN420R004 
 intergenic_variant 
 A>G 
  
  
  
 Unknown 
 GEN420R005 
 intergenic_variant 
 T>C 
  
  
  
 Unknown 
 GEN420R006 
 splice_site_variant 
 c.99-1G>T 
  
 Familial 
 Paternal 
 Multiplex 

Common

Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
 GEN419C001 
 intron_variant 
 rs3784730 
 c.549-738A>G;c.486-738A>G 
 Minor allele G 
 Discovery: Autism Genome Project (AGP); Combined: AGP and AGRE cohorts 
 Discovery & Combined 
 GEN419C002 
 intron_variant 
 rs2045268 
 c.842+1488C>T;c.779+1488C>T 
 Minor allele A 
 Autism Genome Project (AGP) 
 Discovery & Combined 
 GEN419C003 
 upstream_gene_variant 
 rs4586379 
  
 G/A 
 Australian BPD case-control cohort (n=385) 
 Discovery 
 GEN419C004 
 intron_variant 
 rs11074070 
 c.99-6453T>G;c.99-10651T>G 
 C/A 
 Australian BPD case-control cohort (n=385) 
 Discovery 
 GEN419C005 
 intron_variant 
 rs3784735 
 c.161+1988A>C;c.99-2148A>C 
 C/A 
 Australian BPD case-control cohort (n=385) 
 Discovery 
 GEN419C006 
 intron_variant 
 rs2168351 
 c.548+1882A>G;c.485+1882A>G 
 G/A 
 Australian BPD case-control cohort (n=385) 
 Discovery 
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
15
Duplication
 66
  construct
15
Duplication
 1
 
15
Duplication
 1
 
15
Duplication
 1
 
15
Duplication
 1
 
15
Deletion-Duplication
 27
 
15
Duplication
 1
 

Model Summary

ST8Sia-II-deficient mice exhibited higher exploratory drive and reduced behavioral responses to Pavlovian fear conditioning.

References

Type
Title
Author, Year
Primary
Sialyltransferase ST8Sia-II assembles a subset of polysialic acid that directs hippocampal axonal targeting and promotes fear behavior.
Additional
Schizophrenia-like phenotype of polysialyltransferase ST8SIA2-deficient mice.
Additional
Amygdala GluN2B-NMDAR dysfunction is critical in abnormal aggression of neurodevelopmental origin induced by St8sia2 deficiency.

M_ST8SIA2_1_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Targeted deletion of exon 4 of St8sia2 gene.
Allele Type: Targeted (Deletion)
Strain of Origin: C57BL/6
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Reported

M_ST8SIA2_2_KD

Model Type: Genetic
Model Genotype: Other
Mutation: 10 microgram short hairpin RNA or control GFP was injected into the amygdala by polyethylene mediated gene delivery during early postnatal period (P2). Control mice were injected with a scrambled plasmid. As the St8sia2 gene is developmentally downregulat
Allele Type: Targeted (Deletion)
Strain of Origin: C57BL/6J
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: 30089788

M_ST8SIA2_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity1
Increased
Description: Increased activity as measured by increased distance traveled
Exp Paradigm: Open field test; rearing activity
 Open field test
 12-16 weeks
Synapse density: excitatory3
Decreased
Description: Mutants show smaller excitatory synapses compared with controls. mutants show reduced expression of glun2b along with weakened glutamatergic synapses.
Exp Paradigm: NA
 Electron microscopy
 Adult
Brain morphology2
Increased
Description: St8sia2 null mice show an enlargement of lateral ventricles relative to wildtype littermates. ( brain morphology was highly variable in st8sia2 null mice)
Exp Paradigm: NA
 Histology
 2-4 months
Neuroreceptor levels: glutamate receptors: nmda receptors3
Decreased
Description: Mutants show decreased protein levels of glun2b compared with controls.
Exp Paradigm: NA
 Immunohistochemistry
 Adult
Brain morphology2
Decreased
Description: St8sia2 null mice show a marked decrease in the volume of the thalamus and internal capsule compared to wild type littermates. (brain morphology was highly variable in st8sia2 null mice)
Exp Paradigm: NA
 Histology
 2-4 months
Thalamic morphology2
Abnormal
Description: St8sia2 null mice have disorganized patterns of parallel fibers in the reticular thalamic nucleus with a significant decrease on levels of vglut2, compared to littermate controls. level of vglut1 was similar to littermate controls
Exp Paradigm: Lysates from frontal cortex were used to determine levels of vglut1 and vglut2-immunohistochemistry
 Immunohistochemistry
 3 months
Neuroreceptor levels: glutamate receptors: nmda receptors3
Decreased
Description: Mutants show decreased mrna levels of nmdar subunits glun2a and glun2b compared with wildtype.
Exp Paradigm: NA
 Quantitative pcr (qrt-pcr)
 Adult
Brain development2
Decreased
Description: A reduction in polysia is detected in the forebrain lysates of st8sia2 embryos, compared to littermate controls.
Exp Paradigm: NA
 Western blot
 Unreported
Thalamic morphology2
Abnormal
Description: St8sia2 null mice have disorganized patterns of parallel fibers in the reticular thalamic nucleus with a significant decrease on levels of vglut2, compared to littermate controls. level of vglut1 was similar to littermate controls
Exp Paradigm: Lysates from frontal cortex were used to determine levels of vglut1 and vglut2- western blot
 Western blot
 3 months
Dendritic architecture: spine morphology3
Abnormal
Description: Mutants show more thin and less mushroom like spines than control mice.
Exp Paradigm: Syn-gfp-wpre lentivirus were infused in the amygdala to visualize synaptic morphology.
 Immunohistochemistry
 Adult
Brain cytoarchitecture1
Abnormal
Description: Abnormal brain cytoarchitecture: mistargeting of hippocampal infrapyramidal mossy fibers and mossy fibers along ventral side of granule cell layer association with ectopic synapses
Exp Paradigm: Timm's staining on hippocampal slices
 Timm's sulfide silver staining for metals
 2 weeks, adult
Synaptic plasticity: post-tetanic potentiation (ptp)3
Decreased
Description: Mutants show a decrease in effectivity of tetanic stimulation on the level of synaptic ltp compared with controls that showed robust ltp of epsps upon pairing tetanic stimulation with postsynaptic depolarization which was prevented by nmdar blockade with
Exp Paradigm: NA
 Whole-cell patch clamp
 NA
Epsp-spike relationship3
Decreased
Description: Mutants show reduction in nmdar-mediated output at cortical synapses compared with controls, as measured by input-output curves of glutamatergic currents.
Exp Paradigm: NA
 Whole-cell patch clamp
 NA
Synaptic neuroreceptor ratio (nmdar/ampar) dependent transmission
Decreased
Description: Mutants show increase of ampa/nmda ratio at the cortical input compared with controls.
Exp Paradigm: Synaptic responses were evoked at cortical inputs, through stimulation of the external
 Whole-cell patch clamp
 NA
Neuroreceptor activity3
Decreased
Description: Mutants show decreased sensitivity of nmdar currents to the glun2b blocker cp-101606, compared with controls, indicating a reduced contribution of glun2b to the synaptic population of nmdars.
Exp Paradigm: NA
 Whole-cell patch clamp
 NA
Neuronal activation3
Decreased
Description: Mutants subjected to resident-intruder test show decreased phospho-erk activation in neurons of the medial. basal and central but not lateral amygdala compared with controls, indicating decrease in neuronal activation. mutants subjected to fear conditioni
Exp Paradigm: NA
 Immunohistochemistry
 Adult
Repetitive digging3
Decreased
Description: Mutants bury fewer marbles compared to controls.
Exp Paradigm: NA
 Marble-burying test
 12 weeks
Taste2
Abnormal
Description: St8sia2 null mice showed no preference for the sucrose solution, whereas littermate controls shows a clear preference for it. however, in a taste aversion test, st8si2 null mice chose to drink tap water over 0.1m hcl, indicating that taste processing in general is not affected in this group
Exp Paradigm: Tested the preference for sucrose solution to water and for tap water to 0.1 m hcl.
 Sucrose preference test
 2-4 months
Sensorimotor gating2
Decreased
Description: Pre pulse inhibition is significantly decreased in st8sia2 null mice compared to littermate controls.
Exp Paradigm: NA
 Prepulse inhibition
 2-4 months
Aggression3
Increased
Description: Mutants showi increased aggressiveness toward juvenile and female conspecific mice compared with controls.
Exp Paradigm: NA
 Reciprocal social interaction test
 13 weeks
Aggression3
Increased
Description: Mutants show decreased latency to attack male intruder, increased number of bites in vulnerable parts of the male intruder and increased numbers of attacks on the male intruder while the intruder was submissive, compared with controls.
Exp Paradigm: NA
 Resident-intruder test
 13 weeks
Anxiety3
Decreased
Description: Mutants show decreased anxiety levels as they spend more time in the anxiogenic open arms compared with controls.
Exp Paradigm: NA
 Elevated plus maze test
 12 weeks
Anxiety3
Decreased
Description: Mutants show decreased anxiety levels as they spend more time in the anxiogenic center of the open field compared with controls.
Exp Paradigm: NA
 Open field test
 12 weeks
Cued or contextual fear conditioning: passive avoidance1
Abnormal
Description: Abnormal passive avoidance behavior demonstrated by failure to increase latency to enter dark chamber
Exp Paradigm: Open field test
 Open field test
 12-16 weeks
Spatial working memory2
Abnormal
Description: While both groups of mice performed above chance, the performance of st8si2 null mice was significantly worse than that of littermate controls during the whole period of testing
Exp Paradigm: Delayed alternation with food reward, food deprivation to 85% of weight.
 T-maze test
 2-4 months
Cued or contextual fear conditioning: memory of cue3
Decreased
Description: Mutants show no change in freezing response during the training phase but show decreased freezing when the acoustic conditional stimulus was presented in a new context during tone test, compared with controls.
Exp Paradigm: NA
 Fear conditioning test
 14 weeks
Spatial working memory2
Decreased
Description: St8si2 null mice improved their performance in the eight arm maze over training, similar to littermate controls. however, st8sia2 null mice made significantly more revisiting errors compared to controls. latencies to obtain food pellets was the same between genotypes
Exp Paradigm: Eight arm radial maze
 Radial maze test
 2-4 months
Cued or contextual fear conditioning1
Abnormal
Description: Abnormal response to cued and contextual version of fear conditioning
Exp Paradigm: Cued and contextual fear test assay
 Fear conditioning test
 12-16 weeks
Object recognition memory2
Decreased
Description: Both short and long-term recognition memory is impaired in the st8sia2 null mice.
Exp Paradigm: Short and long term memory analyzed. habituation to two similar objects on day 1. introduction to a new object, replaced by one of the old objects, 2 hrs and 24 hrs later.
 Novel object recognition test
 2-4 months
Cell adhesion3
Decreased
Description: Mutants show decreased transcript levels of the glutamatergic cell adhesion molecule, ncam, transcript compared with controls.
Exp Paradigm: NA
 Quantitative pcr (qrt-pcr)
 Adult
Targeted expression3
Decreased
Description: Mutants show reduction in st8sia2 transcript in the amygdala compared to controls. wildtype controls show peak expression of st8sia2 at p5 and decay from p15 onwards.
Exp Paradigm: NA
 Quantitative pcr (qrt-pcr)
 P4
Protein expression level evidence1
Decreased
Description: Decreased polysialic acid (psa) expression in olfactory bulb and
Exp Paradigm: Psa expression
 Western blot
 8 weeks
Circadian rhythm1
 No change
 NA
 12-16 weeks
Cardiovascular development and function1
 No change
 Heart rate measurement
 12-16 weeks
Cardiovascular development and function1
 No change
 Blood pressure measurement
 12-16 weeks
General characteristics1
 No change
 General observations
 12-16 weeks
Acute stress response3
 No change
 Resident-intruder test
 Adult
Spatial learning1
 No change
 Morris water maze test
 12-16 weeks
Gene expression3
 No change
 Quantitative pcr (qrt-pcr)
 P4
Protein expression level evidence1
 No change
 Western blot
 8 weeks
General locomotor activity3
 No change
 Novel cage test
 12 weeks
General locomotor activity2
 No change
 NA
 Unreported
Grip strength1
 No change
 Grip strength test
 12-16 weeks
Motor coordination and balance1
 No change
 Accelerating rotarod test
 12-16 weeks
Brain cytoarchitecture1
 No change
 NA
 Unreported
Brain morphology1
 No change
 Histology
 Unreported
Brain morphology2
 No change
 Histology
 2-4 months
Neuronal number: excitatory neurons3
 No change
 Immunohistochemistry
 Adult
Neuronal number: inhibitory neurons3
 No change
 Immunohistochemistry
 Adult
Neuroreceptor levels: glutamate receptors: nmda receptors3
 No change
 Immunohistochemistry
 Adult
Neuroreceptor levels: glutamate receptors: nmda receptors3
 No change
 Quantitative pcr (qrt-pcr)
 Adult
Synapse density3
 No change
 Immunohistochemistry
 Adult
Synapse density: inhibitory3
 No change
 Electron microscopy
 Adult
Action potential property: firing rate3
 No change
 Whole-cell patch clamp
 5-8 weeks
Epsp-spike relationship3
 No change
 Whole-cell patch clamp
 NA
Membrane potential3
 No change
 Whole-cell patch clamp
 5-8 weeks
Miniature post synaptic current amplitude: excitatory3
 No change
 Whole-cell patch clamp
 NA
Miniature post synaptic current amplitude: inhibitory3
 No change
 Whole-cell patch clamp
 5-8 weeks
Miniature post synaptic current frequency: inhibitory3
 No change
 Whole-cell patch clamp
 5-8 weeks
Neuronal activation3
 No change
 Immunohistochemistry
 Adult
Presynaptic function: paired-pulse facilitation3
 No change
 Paired-pulse ratio
 1-2 weeks, 4-5 weeks, 8-11 weeks, 11-18 weeks
Synaptic neuroreceptor ratio (nmdar/ampar) dependent transmission
 No change
 Whole-cell patch clamp
 NA
Synaptic plasticity1
 No change
 Whole-cell patch clamp
 5-6 months
Synaptic transmission1
 No change
 Western blot
 Unreported
Homeostasis1
 No change
 Ph/blood gas analyzer and thermometer
 12-16 weeks
Respiratory function1
 No change
 Respiration rate and pattern analysis
 12-16 weeks
Respiratory function1
 No change
 Diffusing capacity of the lung for carbon monoxide (dlco) measurement
 12-16 weeks
Pain or nociception3
 No change
 Hot plate test
 12 weeks
Pain or nociception1
 No change
 Hot plate test
 12-16 weeks
Pain or nociception1
 No change
 Tail flick test
 12-16 weeks
Startle response: acoustic stimulus3
 No change
 Acoustic startle reflex test
 15 weeks
Startle response: acoustic stimulus1
 No change
 Acoustic startle reflex test
 12-16 weeks
Social approach3
 No change
 Three-chamber social approach test
 13 weeks
Social approach3
 No change
 Resident-intruder test
 13 weeks
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Maternal behavior, Molecular profile, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Social behavior

M_ST8SIA2_2_KD

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neuroreceptor levels: glutamate receptors: nmda receptors1
Decreased
Description: Mutants show decreased transcript levels of glun2b compared with controls.
Exp Paradigm: NA
 Quantitative pcr (qrt-pcr)
 P4
Aggression1
Increased
Description: Mutants show increased aggressive behavior through decreased latency to attack, increased bites in vulnerable parts, and increased number of attacks while the intruder is submissive.
Exp Paradigm: NA
 Resident-intruder test
 Adult
Cued or contextual fear conditioning: memory of cue1
Decreased
Description: Mutants show no change in freezing response during the training phase but show decreased freezing when the acoustic conditional stimulus was presented in a new context during tone test 24 hrs later, compared with controls.
Exp Paradigm: NA
 Fear conditioning test
 14 weeks
Metabolite level quantification1
Decreased
Description: Mutants show decrease in polysialic acid levels in the amygdala compared to controls.
Exp Paradigm: NA
 Elisa
 P4
Targeted expression1
Decreased
Description: Mutants show reduction in st8sia2 transcript in the amygdala compared to controls.
Exp Paradigm: NA
 Quantitative pcr (qrt-pcr)
 P4
Size/growth1
 No change
 Body weight measurement
 3 months
Anxiety1
 No change
 Elevated plus maze test
 Adult
Metabolite level quantification1
 No change
 Elisa
 P4
Targeted expression1
 No change
 Quantitative pcr (qrt-pcr)
 P4
Neuroreceptor levels: glutamate receptors: nmda receptors1
 No change
 Quantitative pcr (qrt-pcr)
 P4
Social approach1
 No change
 Three-chamber social approach test
 Adult
 Not Reported: Circadian sleep/wake cycle, Communications, Immune response, Maternal behavior, Motor phenotype, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory

 

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