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 3 (Strong), mode of inheritance: AR
• hyperekplexia 3 (Strong), mode of inheritance: AR
• hereditary hyperekplexia (Supportive), mode of inheritance: AD
• hyperekplexia 3 (Strong), mode of inheritance: AD
• hyperekplexia 3 (Strong), mode of inheritance: AR
• hyperekplexia 3 (Definitive), 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 (736 variants)
• Inborn_genetic_diseases (122 variants)
• not_provided (53 variants)
• Hyperekplexia (34 variants)
• SLC6A5-related_disorder (15 variants)
• not_specified (4 variants)
• Exaggerated_startle_response (2 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. These statistics are base on transcript: NM_000004211.5. 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			2	234	5	241
missense	7	13	322	31	5	378
nonsense	14	4	1			19
start loss						0
frameshift	13	4	1			18
splice donor/acceptor (+/-2bp)	3	13	2		1	19
Total	37	34	328	265	11

Highest pathogenic variant AF is 0.000054575605

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
		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

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

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