SLC6A2

solute carrier family 6 member 2, the group of Solute carrier family 6

Basic information

Region (hg38): 16:55655988-55707645

Previous symbols: [ "NET1", "NAT1", "SLC6A5" ]

Links

ENSG00000103546 ∙ NCBI:6530 ∙ OMIM:163970 ∙ HGNC:11048 ∙ Uniprot:P23975 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• postural orthostatic tachycardia syndrome (Supportive), mode of inheritance: AD
• postural orthostatic tachycardia syndrome (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Orthostatic intolerance	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	Endocrine; Neurologic	10684912; 11458707; 12805287

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLC6A2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLC6A2 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				13	3	16
missense			27	4	3	34
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2	1	3
non coding			8	4	3	15
Total	0	0	35	21	9

Variants in SLC6A2

This is a list of pathogenic ClinVar variants found in the SLC6A2 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-55656705-C-A		not specified	Uncertain significance (Feb 21, 2024)
16-55656715-C-A			Likely benign (Jan 18, 2024)
16-55656729-C-T		not specified	Uncertain significance (Sep 16, 2021)
16-55656758-G-C		not specified	Uncertain significance (Jan 17, 2023)
16-55656780-A-G		not specified	Uncertain significance (Jul 06, 2021)
16-55656781-A-C		not specified	Uncertain significance (May 02, 2023)
16-55656805-G-A			Likely benign (Jun 26, 2018)
16-55656811-C-T			Benign (May 21, 2018)
16-55656812-A-T		not specified	Uncertain significance (Aug 02, 2021)
16-55656814-C-T			Likely benign (Apr 04, 2018)
16-55656848-G-T		not specified	Uncertain significance (Dec 04, 2024)
16-55660998-G-C			Benign (Aug 14, 2018)
16-55661256-C-G			Benign (Aug 14, 2018)
16-55669586-C-T		SLC6A2-related disorder	Benign (Dec 31, 2019)
16-55671848-T-G			Likely benign (May 01, 2024)
16-55671873-C-T			Likely benign (Apr 01, 2022)
16-55671909-C-T		SLC6A2-related disorder	Likely benign (May 03, 2019)
16-55671957-C-T			Likely benign (Dec 31, 2019)
16-55672079-C-G		not specified	Uncertain significance (Sep 06, 2022)
16-55672094-C-T		not specified	Uncertain significance (Oct 07, 2024)
16-55672099-C-T		not specified	Uncertain significance (Nov 09, 2021)
16-55672113-C-T			Likely benign (Dec 20, 2017)
16-55672124-A-G		not specified	Uncertain significance (Jan 26, 2023)
16-55672155-G-A			Likely benign (Mar 01, 2018)
16-55672162-G-A		not specified	Uncertain significance (Mar 28, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLC6A2	protein_coding	protein_coding	ENST00000219833	14	50589

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0815	0.918	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.02	254	362	0.701	0.0000218	4094
Missense in Polyphen		89	152.26	0.58454		1750
Synonymous	-1.56	188	163	1.16	0.0000116	1270
Loss of Function	3.76	8	30.4	0.264	0.00000142	344

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000308	0.000246
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000884	0.0000879
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000980	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals. {ECO:0000269|PubMed:2008212}.
• Disease: DISEASE: Orthostatic intolerance (OI) [MIM:604715]: Syndrome characterized by lightheadedness, fatigue, altered mentation and syncope. It is associated with postural tachycardia. Plasma norepinephrine concentration is abnormally high. {ECO:0000269|PubMed:10684912}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Venlafaxine Pathway, Pharmacokinetics;Sympathetic Nerve Pathway (Neuroeffector Junction);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;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;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;Nuclear Receptors Meta-Pathway;NRF2 pathway;Monoamine Transport;Amine compound SLC transporters;Tyrosine metabolism;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: 0.252

Intolerance Scores

• loftool: 0.538
• rvis_EVS: -0.44
• rvis_percentile_EVS: 24.46

Haploinsufficiency Scores

• pHI: 0.210
• hipred: Y
• hipred_score: 0.756
• ghis: 0.465

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.187

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Slc6a2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms 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); 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); 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); 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); growth/size/body region phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: chemical synaptic transmission;monoamine transport;norepinephrine transport;response to pain;dopamine uptake involved in synaptic transmission;norepinephrine uptake;transmembrane transport;neuron cellular homeostasis
• Cellular component: plasma membrane;integral component of plasma membrane;cell surface;membrane;neuronal cell body membrane;presynaptic membrane;neuron projection;membrane raft
• Molecular function: actin binding;neurotransmitter:sodium symporter activity;dopamine:sodium symporter activity;norepinephrine:sodium symporter activity;protein binding;monoamine transmembrane transporter activity;alpha-tubulin binding;metal ion binding;beta-tubulin binding