SLC6A5

solute carrier family 6 member 5, the group of Solute carrier family 6

Basic information

Region (hg38): 11:20599594-20659285

Previous symbols: [ "NET1" ]

Links

ENSG00000165970 ∙ NCBI:9152 ∙ OMIM:604159 ∙ HGNC:11051 ∙ Uniprot:Q9Y345 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyperekplexia 1 (Definitive), mode of inheritance: AR
• hyperekplexia 3 (Strong), mode of inheritance: AR
• hereditary hyperekplexia (Supportive), mode of inheritance: AD
• hyperekplexia 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperekplexia 3	AR	Neurologic	Neonates are at risk of sudden death from apnea/aspiration, and surveillance, as well as primary prevention with medical treatments (eg, clonazepam) may be beneficial	Neurologic	1334371; 1355335; 16751771; 22753417; 22700964; 20301437

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC6A5 gene.

• Hyperekplexia 3 (22 variants)
• not provided (3 variants)
• Inborn genetic diseases (1 variants)
• Exaggerated startle response (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC6A5 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	187	10	198
missense	1	7	288	16	11	323
nonsense	11	3	1			15
start loss						0
frameshift	9	3	1			13
inframe indel		1	3			4
splice donor/acceptor (+/-2bp)	3	7	1		1	12
splice region			14	28	2	44
non coding			8	72	51	131
Total	24	21	303	275	73

Highest pathogenic variant AF is 0.0000460

Variants in SLC6A5

This is a list of pathogenic ClinVar variants found in the SLC6A5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-20599632-G-T		Hyperekplexia	Likely benign (Jun 14, 2016)
11-20599640-C-T		Hyperekplexia	Benign (May 15, 2021)
11-20599671-A-G		Hyperekplexia	Uncertain significance (Jun 14, 2016)
11-20599676-G-T		Hyperekplexia 3	Likely pathogenic (Jul 25, 2022)
11-20599680-GTGTT-G		Hyperekplexia 3	Likely benign (May 17, 2022)
11-20599683-T-A		Hyperekplexia 3	Likely benign (Oct 09, 2022)
11-20599690-T-C		Hyperekplexia 3	Likely benign (Nov 04, 2023)
11-20599691-T-A		Hyperekplexia 3	Likely benign (Dec 22, 2022)
11-20599693-T-G		Hyperekplexia 3	Likely benign (Jul 21, 2023)
11-20599695-C-T		Hyperekplexia 3	Likely benign (May 21, 2021)
11-20600917-A-C			Benign (May 17, 2021)
11-20600983-C-A			Benign (May 26, 2021)
11-20601059-A-G			Benign (May 17, 2021)
11-20601114-A-G		Hyperekplexia 3	Likely benign (Aug 24, 2022)
11-20601116-A-C		Hyperekplexia 3	Likely benign (Oct 09, 2023)
11-20601117-T-C		Hyperekplexia 3	Likely benign (Oct 16, 2023)
11-20601118-T-C		Hyperekplexia 3	Conflicting classifications of pathogenicity (Jan 04, 2024)
11-20601120-T-G		Hyperekplexia 3	Uncertain significance (Aug 24, 2021)
11-20601121-G-GCTC		Hyperekplexia 3	Likely benign (Nov 01, 2022)
11-20601134-C-A		Hyperekplexia 3	Pathogenic/Likely pathogenic (Nov 19, 2023)
11-20601143-C-T		Hyperekplexia 3	Likely benign (Apr 25, 2021)
11-20601146-G-A		Hyperekplexia 3	Likely benign (Aug 28, 2023)
11-20601152-G-A		Hyperekplexia 3	Uncertain significance (Jul 28, 2021)
11-20601153-A-C		Hyperekplexia 3	Uncertain significance (Nov 08, 2022)
11-20601156-A-T		Hyperekplexia 3	Pathogenic (Apr 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC6A5	protein_coding	protein_coding	ENST00000525748	16	59886

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.98e-15	0.643	125680	0	68	125748	0.000270

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0941	442	436	1.01	0.0000237	5160
Missense in Polyphen		118	130.86	0.90176		1593
Synonymous	-1.99	210	176	1.19	0.0000108	1592
Loss of Function	1.72	28	39.7	0.705	0.00000196	443

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000820	0.000820
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000298	0.000290
Middle Eastern	0.0000544	0.0000544
South Asian	0.000425	0.000425
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Terminates the action of glycine by its high affinity sodium-dependent reuptake into presynaptic terminals. May be responsible for the termination of neurotransmission at strychnine-sensitive glycinergic synapses. {ECO:0000269|PubMed:10381548, ECO:0000269|PubMed:10606742, ECO:0000269|PubMed:9845349}.
• Pathway: Nuclear Receptors Meta-Pathway;NRF2 pathway;Amine compound SLC transporters;Transport of bile salts and organic acids, metal ions and amine compounds;SLC-mediated transmembrane transport;Transport of small molecules;Na+/Cl- dependent neurotransmitter transporters (Consensus)

Recessive Scores

• pRec: 0.122

Intolerance Scores

• loftool: 0.692
• rvis_EVS: 0.78
• rvis_percentile_EVS: 87.26

Haploinsufficiency Scores

• pHI: 0.287
• hipred: N
• hipred_score: 0.277

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.829

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc6a5
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); 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); skeleton phenotype; growth/size/body region phenotype; craniofacial phenotype; muscle phenotype

Gene ontology

• Biological process: chemical synaptic transmission;synaptic transmission, glycinergic;glycine import across plasma membrane
• Cellular component: plasma membrane;integral component of membrane;glycinergic synapse;integral component of presynaptic membrane
• Molecular function: glycine:sodium symporter activity;metal ion binding