Table 3.
Brain disorders associated with SLCs. Examples of brain disorders in SLC knockout/overexpression mice/rats, or mice/rats models of human disease in which SLCs are modified are shown. Human brain disorders caused by SLC gene dysfunction are also shown. Data on human disorders were retrieved from omim.org.
| SLCs | Brain disorders in mouse/rat | Human brain disorders caused by SLC gene dysfunction |
|---|---|---|
| SLC1A1/EAAT3 | obsessive-compulsive disorder, schizophrenia | Dicarboxylicamino aciduria (glutamate-aspartate transport defect) |
| SLC1A2/EAAT2 | Epilepsy | Epileptic encephalopathy |
| SLC1A3/EAAT1 | Alzheimer's disease | Episodic ataxia |
| SLC1A4/ASCT1 | Schizophrenia | Epileptic encephalopathy, developmental delay, microcephaly and hypomyelination, severe intellectual disability |
| SLC1A5/ASCT2 | Schizophrenia | No |
| SLC1A6/EAAT4 | No | Hypoxia, ischemia |
| SLC2A1/GLUT1 | Epilepsy and metabolic dysfunction | Glucose transporter type 1 deficiency syndrome, intractable infantile seizures, complex motor disorder, intellectual impairment, low CSF glucose (hypoglycorrhachia), microcephaly |
| SLC2A4/GLUT4 | Impaired glucose tolerance, decreased insulin sensitivity | No |
| SLC4A10/NBCn2 | Small brain ventricles, reduced neuronal excitability | Epilepsy, mental retardation |
| SLC5A7/CHT | No | Attention-deficit hyperactivity disorder |
| SLC6A1/GAT1 | Epilepsy | Myoclonic-atonic epilepsy |
| SLC6A3/DAT | Attention-deficit/hyperactivity disorder, Parkinson's disease | Dopamine transporter deficiency syndrome, parkinsonism-dystonia |
| SLC6A4/ 5-HTT | Anxiety | Obsessive-compulsive disorder, anxiety-related personality traits, bipolar affective disorder, alcoholism, migraine with aura, sudden infant death, pulmonary hypertension |
| SLC6A5/GlyT2 | Hyperekplexia | Hyperekplexia |
| SLC6A8/CrT | Cognitive deficits | Cerebral creatine deficiency syndrome |
| SLC6A9/GlyT1 | Epilepsy, schizophrenia | Glycine encephalopathy |
| SLC6A11/GAT3 | Epilepsy | Intellectual disability, epilepsy and stereotypic behavior |
| SLC6A12/BGT1 | No | Epilepsy |
| SLC6A15/v7-3 | Depression | Major depression |
| SLC6A17/NTT4 | No | Autosomal recessive intellectual disability |
| SLC7A3/CAT3 | No | Autism spectrum disorder |
| SLC7A5/LAT1 | Glioma | Autism spectrum disorder |
| SLC8A1/NCX1 | No | No |
| SLC8A2/NCX2 | Glioblastoma, cerebral ischemia | No |
| SLC8A3/NCX3 | Cerebral ischemia | No |
| SLC9A1/NHE1 | Glioma | Cerebellar ataxia, Lichtenstein-Knorr syndrome |
| SLC9A6/NHE6 | Christianson syndrome | Mental retardation, X-linked syndromic, christianson type |
| SLC9A7/NHE7 | No | Nonsyndromic X-linked intellectual disability |
| SLC9A9/NHE9 | Autism | Autism susceptibility 16, attention-deficit/hyperactivity disorder |
| SLC10A4/P4 | cognitive impairments | no |
| SLC11A2/DCT1 | Parkinson's disease | No |
| SLC12A2/NKCC1 | Stroke, epilepsy | Epilepsy |
| SLC12A5/KCC2 | Epilepsy | Epilepsy |
| SLC12A6/KCC3 | Hypertension | Andermann syndrome |
| SLC13A5/NaCT | No | Kohlschütter-Tönz syndrome, epilepsy |
| SLC16A2/MCT8 | No | Severe psychomotor disability of unknown etiology, Allan-Herndon-Dudley syndrome |
| SLC16A4/MCT4 | Glioma | Epilepsy |
| SLC16A7/MCT2 | Epilepsy | Epilepsy |
| SLC17A5/AST | No | Free sialic acid storage diseases |
| SLC17A6/VGLUT2 | Epilepsy | Gnathodiaphyseal dysplasia, tendinosis |
| SLC17A7/VGLUT1 | Depression, Alzheimer's disease | Spinocerebellar Ataxia 27, deafness autosomal dominant 25 |
| SLC17A8/VGLUT3 | anxiety | deafness, autosomal dominant 25 and deafness, autosomal recessive 6 |
| SLC18A2/VMAT2 | Opioid dependence, alcohol and nicotine dependence | Parkinsonism-dystonia, infantile, 2 and brain dopamine-serotonin vesicular transport disease |
| SLC18A3/VAChT | Impaired short-term object recognition memory | Myasthenic syndrome, congenital, 21, presynaptic and presynaptic congenital myasthenic syndromes |
| SLC19A1/RFC1 | No | Ischemic stroke, silent brain infarction |
| SLC19A3/ThTr2 | No | Basal ganglia disease |
| SLC20A2/PiT2 | No | Brain calcification, acute ischemic stroke |
| SLCO1C1/OATP14 | No | Brain-specific hypothyroidism and neurodegeneration |
| SLC22A6/OAT1 | Learning and memory impairment | No |
| SLC22A17/BOCT | No | Deafness, autosomal dominant 53 and deafness, autosomal recessive 5 |
| SLC22A18/ORCTL2 | No | Glioma |
| SLC23A3/SVCT3 | No | Epilepsy |
| SLC24A4/NCKX4 | No | Alzheimer's disease |
| SLC25A4/ANT1 | Bipolar disorder | No |
| SLC25A5/ANT2 | No | Intellectual disability |
| SLC25A12/AGC1 | Hypomyelination and neuronal defects | Epileptic encephalopathy, early infantile, 39 and asperger syndrome |
| SLC25A17/PMP34 | No | Cerebral degeneration |
| SLC25A19/DNC | No | Microcephaly, amish type and thiamine metabolism dysfunction syndrome 4, bilateral striatal necrosis |
| SLC25A22/GC1 | No | Epileptic encephalopathy, early infantile, 3 |
| SLC25A27/UCP4 | No | Multiple sclerosis |
| SLC25A37/MFRN1 | No | Major depressive disorder |
| SLC25A39/CGI69 | No | Childhood absence epilepsy |
| SLC25A42/MECREN | No | Epileptic encephalopathy |
| SLC25A46/HMSN6B | Neurodegeneration | Neuropathy, hereditary motor and sensory, lethal congenital pontocerebellar hypoplasia |
| SLC27A4/FATP4 | No | Autism |
| SLC29A1/ENT1 | Huntington's disease | Huntington's disease |
| SLC29A4/ENT4 | No | Autism |
| SLC30A1/ZNT1 | Ischemic stroke, neonatal seizures | No |
| SLC30A3/ZNT3 | No | Schizophrenia |
| SLC30A4/ZNT4 | No | Alzheimer's disease |
| SLC30A10/ZNT10 | No | Hereditary hypermanganesemia |
| SLC31A1/CTR1 | Manganese-induced neurotoxicity | No |
| SLC32A1/VGAT | Anxiety, epilepsy, excitotoxicity, cortical dysplasia | No |
| SLC33A1/AT1 | Alzheimer's disease | Neurodegeneration |
| SLC35A1/CST | No | Encephalopathy |
| SLC35A3/AMRS | No | Autism spectrum disorder, epilepsy |
| SLC45A1/DNB5 | no | Intellectual developmental disorder with neuropsychiatric features and autosomal recessive non-syndromic intellectual disability |
| SLC52A3/RFVT3 | No | Brown-Vialetto-Van Laere syndrome |
| SLC53A1/XPR1 | No | Brain calcification |
| SLC55A1/LETM1 | No | Epileptic seizures |
| SLC59A1/MFSD2A | blood-brain barrier disruption | Microcephaly |
| SLC62A1/ANKH | No | Seizure |
| SLC65A1/NPC1 | No | Niemann-Pick disease type C |