SLC6A4

solute carrier family 6 member 4, the group of Solute carrier family 6

Basic information

Region (hg38): 17:30194319-30236002

Previous symbols: [ "HTT", "OCD1" ]

Links

ENSG00000108576 ∙ NCBI:6532 ∙ OMIM:182138 ∙ HGNC:11050 ∙ Uniprot:P31645 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism spectrum disorder (Disputed Evidence), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC6A4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC6A4 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			8	7		15
missense			28	2		30
nonsense						0
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			3	1	1	5
non coding			59	13	6	78
Total	0	1	96	22	6

Variants in SLC6A4

This is a list of pathogenic ClinVar variants found in the SLC6A4 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-30194565-T-C		Behavior disorder	Uncertain significance (Jan 13, 2018)
17-30194625-A-G		Behavior disorder	Uncertain significance (Jan 13, 2018)
17-30195008-C-G		Behavior disorder	Likely benign (Jan 12, 2018)
17-30195138-A-C		Behavior disorder	Uncertain significance (Jan 13, 2018)
17-30195229-C-T		Behavior disorder	Uncertain significance (Jan 12, 2018)
17-30195409-T-C		Behavior disorder	Likely benign (Jan 13, 2018)
17-30195486-C-T		Behavior disorder	Uncertain significance (Jan 13, 2018)
17-30195499-G-A		Behavior disorder	Benign (Jan 12, 2018)
17-30195620-G-A		Behavior disorder	Uncertain significance (Jan 13, 2018)
17-30195753-T-C		Behavior disorder	Likely benign (Jan 12, 2018)
17-30195961-C-T		Behavior disorder	Uncertain significance (Jan 13, 2018)
17-30196044-C-G		Behavior disorder	Uncertain significance (Jan 15, 2018)
17-30196067-T-C		Behavior disorder	Benign (Jan 12, 2018)
17-30196068-G-A		Behavior disorder	Benign (Jan 13, 2018)
17-30196103-T-C		Behavior disorder	Benign (Jan 12, 2018)
17-30196264-C-G		Behavior disorder	Uncertain significance (Mar 30, 2018)
17-30196296-C-A		Behavior disorder	Benign (Jan 13, 2018)
17-30196344-G-A		Behavior disorder	Uncertain significance (Jan 13, 2018)
17-30196362-C-T		Behavior disorder	Uncertain significance (Jan 13, 2018)
17-30196364-AT-A		Behavior disorder	Uncertain significance (Jun 14, 2016)
17-30196364-A-AT		Behavior disorder	Uncertain significance (Jun 14, 2016)
17-30196371-T-G		Behavior disorder	Uncertain significance (Jan 13, 2018)
17-30196437-G-A		Behavior disorder	Uncertain significance (Jan 12, 2018)
17-30196523-A-G		Behavior disorder	Uncertain significance (Jan 13, 2018)
17-30196556-A-G		Behavior disorder	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC6A4	protein_coding	protein_coding	ENST00000401766	13	41684

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.246	0.754	125731	0	17	125748	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.93	272	378	0.720	0.0000224	4107
Missense in Polyphen		94	159.7	0.58859		1854
Synonymous	0.517	147	155	0.947	0.0000102	1263
Loss of Function	4.12	8	33.8	0.236	0.00000173	359

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000178	0.000177
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000705	0.0000703
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner. {ECO:0000269|PubMed:17506858, ECO:0000269|PubMed:18227069, ECO:0000269|PubMed:19270731, ECO:0000269|PubMed:27049939}.
• Pathway: Citalopram Pathway, Pharmacokinetics;Serotonergic synapse - Homo sapiens (human);Selective Serotonin Reuptake Inhibitor Pathway, Pharmacodynamics;Fluoxetine Pathway, Pharmacokinetics;Venlafaxine Pathway, Pharmacokinetics;Levomethadyl Acetate Action Action Pathway;Fluoxetine Action Pathway;Citalopram Action Pathway;Escitalopram Action Pathway;Imipramine Action Pathway;Desipramine Action Pathway;Levallorphan Action Pathway;Dimethylthiambutene Action Pathway;Ethylmorphine Action Pathway;Pentazocine Action Pathway;Naltrexone Action Pathway;Buprenorphine Action Pathway;Alvimopan Action Pathway;Naloxone Action Pathway;Dihydromorphine Action Pathway;Imipramine Metabolism Pathway;Desipramine Metabolism Pathway;Citalopram Metabolism Pathway;Nicotine Action Pathway;Nalbuphine Action Pathway;Ketobemidone Action Pathway;Lidocaine (Local Anaesthetic) Action Pathway;Mepivacaine Action Pathway;Chloroprocaine Action Pathway;Cocaine Action Pathway;Dibucaine Action Pathway;Levobupivacaine Action Pathway;Benzocaine Action Pathway;Bupivacaine Action Pathway;Levorphanol Action Pathway;Propoxyphene Action Pathway;Tramadol Action Action Pathway;Diphenoxylate Action Pathway;Anileridine Action Pathway;Methadone Action Pathway;Oxycodone Action Pathway;Oxybuprocaine Action Pathway;Prilocaine Action Pathway;Procaine Action Pathway;Proparacaine Action Pathway;Ropivacaine Action Pathway;Codeine Action Pathway;Morphine Action Pathway;Heroin Action Pathway;Venlafaxine Metabolism Pathway;Fluoxetine Metabolism Pathway;Alfentanil Action Pathway;Oxymorphone Action Pathway;Hydrocodone Action Pathway;Hydromorphone Action Pathway;Sufentanil Action Pathway;Remifentanil Action Pathway;Fentanyl Action Pathway;Carfentanil Action Pathway;3-Methylthiofentanyl Action Pathway;Methadyl Acetate Action Pathway;Dezocine Action Pathway;Serotonin Transporter Activity;Synaptic Vesicle Pathway;Nuclear Receptors Meta-Pathway;NRF2 pathway;Selective serotonin reuptake inhibitors lead to several adverse outcomes;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Monoamine Transport;Neuronal System;Tryptophan metabolism;Serotonin clearance from the synaptic cleft;Neurotransmitter clearance;Transmission across Chemical Synapses (Consensus)

Recessive Scores

• pRec: 0.559

Intolerance Scores

• loftool: 0.528
• rvis_EVS: -0.6
• rvis_percentile_EVS: 18.06

Haploinsufficiency Scores

• pHI: 0.127
• hipred: Y
• hipred_score: 0.762
• ghis: 0.445

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.803

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc6a4
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); normal 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)

Gene ontology

• Biological process: response to hypoxia;serotonin transport;response to nutrient;memory;circadian rhythm;response to toxic substance;positive regulation of gene expression;positive regulation of serotonin secretion;monoamine transport;negative regulation of cerebellar granule cell precursor proliferation;negative regulation of synaptic transmission, dopaminergic;response to estradiol;social behavior;neurotransmitter biosynthetic process;vasoconstriction;response to drug;sperm ejaculation;negative regulation of neuron differentiation;positive regulation of cell cycle;negative regulation of organ growth;brain morphogenesis;protein complex oligomerization;protein homooligomerization;serotonin uptake;transmembrane transport;cellular response to retinoic acid;cellular response to cGMP;regulation of thalamus size
• Cellular component: cytosol;plasma membrane;integral component of plasma membrane;endosome membrane;endomembrane system;neuron projection;membrane raft;integral component of postsynaptic membrane;integral component of presynaptic membrane;serotonergic synapse
• Molecular function: serotonin:sodium symporter activity;protein binding;monoamine transmembrane transporter activity;myosin binding;syntaxin-1 binding;Rab GTPase binding;cocaine binding;protein homodimerization activity;metal ion binding;nitric-oxide synthase binding;actin filament binding;serotonin binding