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Relevance to Autism

A rare CNV in the SLC4A10 gene has been identified with autism in AGRE, NIMH and additional cohorts (Sebat et al., 2007). In addition, a rare translocation involving the SLC4A10 gene has been identified with epilepsy and cognitive impairment in a patient (Gurnett et al., 2008). More recently, biallelic variants in the SLC4A10 gene have been found to cause an autosomal recessive neurodevelopmental disorder in which a subset of affected individuals presented with autistic features or stereotypy (Fasham et al., 2023; Maroofian et al., 2024).

Molecular Function

inorganic anion exchanger activity

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Strong association of de novo copy number mutations with autism.
ASD
Support
SLC4A10 mutation causes a neurological disorder associated with impaired GABAergic transmission
Neurodevelopmental disorder with hypotonia and cha
Stereotypy, epilepsy/seizures
Support
Integrating de novo and inherited variants in 42
ASD
Support
Whole-Genome Sequencing of Cytogenetically Balanced Chromosome Translocations Identifies Potentially Pathological Gene Disruptions and Highlights t...
ASD, ID
Highly Cited
A SCL4A10 gene product maps selectively to the basolateral plasma membrane of choroid plexus epithelial cells.
Recent Recommendation
Biallelic variants in SLC4A10 encoding a sodium-dependent bicarbonate transporter lead to a neurodevelopmental disorder
Neurodevelopmental disorder with hypotonia and cha
Autistic features, epilepsy/seizures
Recent Recommendation
Disruption of sodium bicarbonate transporter SLC4A10 in a patient with complex partial epilepsy and mental retardation.
Epilepsy
MR
Recent Recommendation
Mice with targeted Slc4a10 gene disruption have small brain ventricles and show reduced neuronal excitability.
Recent Recommendation
Sodium coupled bicarbonate transporters in the kidney, an update.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN234R001 
 translocation 
  
  
 De novo 
  
  
 GEN234R002 
 copy_number_loss 
  
  
 De novo 
  
 Simplex 
 GEN234R003 
 translocation 
  
  
 De novo 
  
  
 GEN234R004 
 splice_site_variant 
 c.577+1G>T 
  
 De novo 
  
  
 GEN234R005 
 missense_variant 
 c.1195G>T 
 p.Val399Leu 
 De novo 
  
  
 GEN234R006 
 missense_variant 
 c.1366C>G 
 p.Pro456Ala 
 De novo 
  
  
 GEN234R007 
 frameshift_variant 
 c.1570del 
 p.Val524SerfsTer16 
 De novo 
  
  
 GEN234R008 
 frameshift_variant 
 c.1570del 
 p.Val524SerfsTer16 
 De novo 
  
 Simplex 
 GEN234R009 
 splice_site_variant 
 c.767-2A>G 
  
 Familial 
 Maternal 
 Multiplex 
 GEN234R010a 
 copy_number_loss 
  
  
 Familial 
 Both parents 
 Multiplex 
 GEN234R011a 
 stop_gained 
 c.2269C>T 
 p.Arg757Ter 
 Familial 
 Both parents 
 Simplex 
 GEN234R012a 
 splice_site_variant 
 c.2863-2A>C 
  
 Familial 
 Both parents 
 Multiplex 
 GEN234R013a 
 stop_gained 
 c.2619G>A 
 p.Trp873Ter 
 Familial 
 Both parents 
 Extended multiplex 
 GEN234R014a 
 missense_variant 
 c.1730A>T 
 p.Lys577Met 
 Familial 
 Both parents 
 Multiplex 
 GEN234R014b 
 missense_variant 
 c.3308A>T 
 p.Asn1103Ile 
 Familial 
 Both parents 
 Multiplex 
 GEN234R015a 
 missense_variant 
 c.2894C>T 
 p.Pro965Leu 
 Familial 
 Both parents 
 Multiplex 
 GEN234R016a 
 missense_variant 
 c.1864C>T 
 p.Arg622Trp 
 Familial 
 Maternal 
 Simplex 
 GEN234R016b 
 missense_variant 
 c.1052G>C 
 p.Arg351Thr 
 De novo 
  
 Simplex 
 GEN234R017a 
 missense_variant 
 c.2162A>G 
 p.Tyr721Cys 
 Familial 
 Both parents 
 Multiplex 
 GEN234R018a 
 missense_variant 
 c.667C>T 
 p.His223Tyr 
 Familial 
 Both parents 
 Multiplex 
 GEN234R019a 
 splice_site_variant 
 c.81+2T>C 
  
 Familial 
 Both parents 
 Multiplex 
 GEN234R020a 
 missense_variant 
 c.2118G>T 
 p.Leu706Phe 
 Familial 
 Maternal 
 Simplex 
 GEN234R020b 
 missense_variant 
 c.1612C>T 
 p.Arg538Cys 
 Familial 
 Paternal 
 Simplex 

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
2
Duplication
 1
 
2
Duplication
 1
 
2
Deletion
 1
 
2
Deletion
 1
 
2
Deletion-Duplication
 7
 
2
Deletion
 3
 
2
Deletion
 1
 
2
Deletion-Duplication
 19
 
2
Deletion
 5
 

Model Summary

lc4a10 is involved in the control of neuronal pH and excitability and may contribute to the secretion of cerebrospinal fluid.

References

Type
Title
Author, Year
Primary
Mice with targeted Slc4a10 gene disruption have small brain ventricles and show reduced neuronal excitability.

M_SLC4A10_1_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: loxP/Cre mediated deletion of exon 12 of the Slc4a10 gene which leads to a frameshift and a premature termination codon in exon 13.
Allele Type: Targeted (Knock-out)
Strain of Origin: 129/SvJ
Genetic Background: C57B/L6
ES Cell Line: R1
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_SLC4A10_1_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Brain anatomy1
Abnormal
Description: Drastically reduced apical microvilli; enlarged lateral intercellular spaces; aberrant placement of chroid plexus near the walls of ventricles
Exp Paradigm: Histological and electron microscopy analysis
 Histology
 Unreported
Brain anatomy1
Abnormal
Description: Drastically decreased volume of ventricles; no change in apparent diffusion coefficient (adc) value
Exp Paradigm: Mri volumetry for brain ventricle volume, brain water content, and adc maps
 Magnetic resonance imaging (mri)
 Unreported
Network excitability1
Decreased
Description: Decreased frequency of interictal-like events; decreased rebound increase in network event frequency after washout
Exp Paradigm: In vitro 4-aminopyridine (4-ap) model with field potential recordings from ca3 stratum pyramidale networks
 Field potential recordings
 Unreported
Seizures1
Increased
Description: Increased latency until onset of generalized seizures
Exp Paradigm: Susceptibility to seizure induced by hyperthermia (febrile seizures)
 Observation of hyperthermia induced seizures
 P10
Seizures1
Increased
Description: Increased latency until onset of myoclonic jerks; no progression to generalized seizures; decreased mortality due to seizures
Exp Paradigm: Susceptiblity to chemically induced seizures using 40 mg/kg pentylenetetrazole (ptz)
 Observation of chemically induced seizures
 Unreported
Blood volume and ph1
Abnormal
Description: Decreased rate of phi recovery; decreased alkaline overshoot; no change in baseline ph
Exp Paradigm: Bcecf fluorescence imaging of brain slices exposed to acid shift with 20mm propionate in bath solution
 Fluorescence microscopy
 8-12 weeks
Blood volume and ph1
Decreased
Description: Decreased na+ -dependent recovery of phi in the presence of bicarbonate
Exp Paradigm: Recovery of isolated clusters of choroid plexus epithelial cells' ph from acid-loading
 Fluorescence microscopy
 Unreported
Mortality/lethality1
Increased
Description: Increased lethality around weaning
Exp Paradigm: General observations
 General observations
 2 months
Developmental trajectory1
Abnormal
Description: Abnormal diet: soft food diet from 2 weeks
Exp Paradigm: General observations
 General observations
 2 weeks
Protein expression level evidence1
Decreased
Description: Absence of slc4a10 protein in choroid plexus, cortex, olfactory bulb, cerebellum, brainstem, and spinal cord
Exp Paradigm: Slc4a10 protein expression
 Immunohistochemistry
 Unreported
Protein expression level evidence1
Decreased
Description: Absence of slc4a10 protein in brain tissue
Exp Paradigm: Slc4a10 protein expression
 Western blot
 Unreported
Spatial reference memory1
 No change
 Morris water maze test
 3-4 months
General locomotor activity1
 No change
 Light-dark exploration test
 3-4 months
Motor coordination and balance1
 No change
 Accelerating rotarod test
 3-4 months
Brain morphology1
 No change
 Histology
 6 months
Startle response: acoustic stimulus1
 No change
 Acoustic startle reflex test
 3-4 months
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Maternal behavior, Physiological parameters, Repetitive behavior, Social behavior





Download SLC4A10's Cytoscape file

Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
UBC ubiquitin C 7316 P63279 diGly proteomics
Kim W , et al. 2011
Rbfox1 RNA binding protein, fox-1 homolog (C. elegans) 1 268859 Q9JJ43 HITS-CLIP
Weyn-Vanhentenryck SM , et al. 2014
Slc9a3r1 solute carrier family 9 (sodium/hydrogen exchanger), member 3 regulator 1 26941 P70441 IP/WB
Lee YS , et al. 2006

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