SLC6A11

protein-coding

solute carrier family 6 member 11, the group of Solute carrier family 6

Gene summary

The protein encoded by this gene is a sodium-dependent transporter that uptakes gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, which ends the GABA neurotransmission. Defects in this gene may result in epilepsy, behavioral problems, or intellectual problems. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

MANE transcript

NM_014229.3

Inheritance

—

ClinVar variants

U:77B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr3:10,816,201-10,940,714

External References & Databases

Ensembl (ENSG00000132164)

Transcript & Mutation Effects

hg38 • Region Span ~124.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLC6A11 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 74

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014229.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	3 clinvar	4
missense			77 clinvar	2 clinvar	1 clinvar	80
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	77	3	4	84

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014229.3	RefSeq	NP_055044.1	14	MANE Select
ENST00000254488.7	Ensembl	ENSP00000254488.2	14	MANE Select
NM_001317406.3	RefSeq	NP_001304335.1	4	Standard
ENST00000454147.1	Ensembl	ENSP00000404120.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Benzodiazepine Pathway, Pharmacodynamics
GABAergic synapse - Homo sapiens (human)
Nuclear Receptors Meta-Pathway
NRF2 pathway
GABA receptor Signaling

Biological Process

brain development
gamma-aminobutyric acid transport
response to drug
transmembrane transport

Molecular Function

gamma-aminobutyric acid:sodium symporter activity
neurotransmitter binding

Cellular Component

cytoplasm
plasma membrane
integral component of membrane
neuron projection
GABA-ergic synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000254488
Coding exons: 14
Length: 124535
Individuals with no LoFs: 125713
Homozygous LoFs: 0
Heterozygous LoFs: 35
Defined: 125748
p: 0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.56	227	365	0.623	0.0000203	4126
Missense (PolyPhen)		79	177.14	0.44598		1963
Synonymous	-0.542	159	151	1.06	0.00000927	1228
Loss of Function	3.15	13	32.3	0.402	0.00000148	374

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00037	0.00037	rare
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Terminates the action of GABA by its high affinity sodium-dependent reuptake into presynaptic terminals.;

Recessive Scores

pRec: 0.143

Intolerance Scores

LoFtool: 0.367
RVIS EVS: -0.44
RVIS percentile EVS: 24.53

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.150

Gene Damage Prediction

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