SLC6A1

solute carrier family 6 member 1, the group of Solute carrier family 6

Basic information

Region (hg38): 3:10992186-11039247

Links

ENSG00000157103 ∙ NCBI:6529 ∙ OMIM:137165 ∙ HGNC:11042 ∙ Uniprot:P30531 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• epilepsy with myoclonic atonic seizures (Strong), mode of inheritance: AD
• epilepsy with myoclonic atonic seizures (Strong), mode of inheritance: AD
• myoclonic-astatic epilepsy (Supportive), mode of inheritance: Unknown
• epilepsy with myoclonic atonic seizures (Definitive), mode of inheritance: AD
• epilepsy with myoclonic atonic seizures (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myoclonic-atonic epilepsy	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	25865495

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC6A1 gene.

• Epilepsy_with_myoclonic_atonic_seizures (784 variants)
• not_provided (269 variants)
• Inborn_genetic_diseases (124 variants)
• SLC6A1-related_disorder (38 variants)
• not_specified (17 variants)
• Intellectual_disability (8 variants)
• Seizure (6 variants)
• Neurodevelopmental_delay (3 variants)
• Neurodevelopmental_disorder (2 variants)
• Global_developmental_delay (2 variants)
• See_cases (2 variants)
• SLC6A1-related_neurodevelopmental_disorder (2 variants)
• Developmental_and_epileptic_encephalopathy_94 (1 variants)
• Self-limited_epilepsy_with_centrotemporal_spikes (1 variants)
• Autism_spectrum_disorder (1 variants)
• Marfanoid_habitus_and_intellectual_disability (1 variants)
• Autosomal_dominant_epilepsy (1 variants)
• SLC6A1-related_neurodevelopmental_condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC6A1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003042.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	7	195	9	212
missense	26	77	291	69	22	485
nonsense	24	5				29
start loss	1					1
frameshift	29	8	5			42
splice donor/acceptor (+/-2bp)	9	15	1			25
Total	89	106	304	264	31

Highest pathogenic variant AF is 0.000012396766

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC6A1	protein_coding	protein_coding	ENST00000287766	14	46524

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000670	123129	0	1	123130	0.00000406

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.18	144	370	0.389	0.0000217	3926
Missense in Polyphen		21	145.69	0.14414		1586
Synonymous	-0.958	170	155	1.10	0.0000102	1176
Loss of Function	5.05	1	31.7	0.0316	0.00000144	340

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000899	0.00000899
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Terminates the action of GABA by its high affinity sodium-dependent reuptake into presynaptic terminals.
• Disease: DISEASE: Myoclonic-atonic epilepsy (MAE) [MIM:616421]: A form of epilepsy characterized by myoclonic-atonic and absence seizures, appearing in early childhood. Patients have delayed development before the onset of seizures and show varying degrees of intellectual disability following seizure onset. {ECO:0000269|PubMed:25865495}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Benzodiazepine Pathway, Pharmacodynamics;GABAergic synapse - Homo sapiens (human);Nuclear Receptors Meta-Pathway;NRF2 pathway;Monoamine Transport;Amine compound SLC transporters;Transport of bile salts and organic acids, metal ions and amine compounds;SLC-mediated transmembrane transport;Transport of small molecules;Neuronal System;Urea cycle and metabolism of arginine, proline, glutamate, aspartate and asparagine;Na+/Cl- dependent neurotransmitter transporters;Reuptake of GABA;GABA synthesis, release, reuptake and degradation;Neurotransmitter release cycle;Transmission across Chemical Synapses (Consensus)

Recessive Scores

• pRec: 0.240

Intolerance Scores

• rvis_EVS: -0.36
• rvis_percentile_EVS: 29.16

Haploinsufficiency Scores

• pHI: 0.189
• hipred: Y
• hipred_score: 0.851
• ghis: 0.575

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.836

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Slc6a1
• Phenotype: taste/olfaction phenotype; growth/size/body region phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: chemical synaptic transmission;learning;response to toxic substance;response to sucrose;response to lead ion;positive regulation of gamma-aminobutyric acid secretion;response to purine-containing compound;negative regulation of synaptic transmission, GABAergic;response to estradiol;response to cocaine;protein homooligomerization;response to calcium ion;gamma-aminobutyric acid import;transmembrane transport
• Cellular component: plasma membrane;cell surface;membrane;integral component of membrane;axon;neuron projection;GABA-ergic synapse;integral component of postsynaptic membrane;integral component of presynaptic membrane
• Molecular function: gamma-aminobutyric acid:sodium symporter activity;protein binding;neurotransmitter binding;metal ion binding