SLC6A2 (solute carrier family 6 member 2)

Gene

• Entrez ID: 6530
• Gene name: Solute carrier family 6 member 2
• Gene symbol: SLC6A2
• Synonyms: NAT1, NET, NET1, SLC6A5
• Chromosome: 16
• Chromosome location: 16q12.2
• Summary: This gene encodes a member of the sodium:neurotransmitter symporter family. This member is a multi-pass membrane protein, which is responsible for reuptake of norepinephrine into presynaptic nerve terminals and is a regulator of norepinephrine homeostasis

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121918126	G>A,C,T	Pathogenic	Non coding transcript variant, missense variant, coding sequence variant, 3 prime UTR variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1366302	hsa-miR-1321	CLIP-seq
MIRT1366303	hsa-miR-150	CLIP-seq
MIRT1366304	hsa-miR-19a	CLIP-seq
MIRT1366305	hsa-miR-19b	CLIP-seq
MIRT1366306	hsa-miR-3665	CLIP-seq
MIRT1366307	hsa-miR-3934	CLIP-seq
MIRT1366308	hsa-miR-3944-5p	CLIP-seq
MIRT1366309	hsa-miR-4419a	CLIP-seq
MIRT1366310	hsa-miR-4510	CLIP-seq
MIRT1366311	hsa-miR-4715-3p	CLIP-seq
MIRT1366312	hsa-miR-4739	CLIP-seq
MIRT1366313	hsa-miR-4756-5p	CLIP-seq
MIRT1366314	hsa-miR-485-5p	CLIP-seq
MIRT1366315	hsa-miR-657	CLIP-seq
MIRT1366316	hsa-miR-3074-5p	CLIP-seq
MIRT1366317	hsa-miR-3591-3p	CLIP-seq
MIRT1366318	hsa-miR-3616-3p	CLIP-seq
MIRT1366319	hsa-miR-4685-5p	CLIP-seq
MIRT1366320	hsa-miR-4733-5p	CLIP-seq
MIRT1366321	hsa-miR-4773	CLIP-seq
MIRT1366322	hsa-miR-548a-3p	CLIP-seq
MIRT1366323	hsa-miR-548e	CLIP-seq
MIRT1366324	hsa-miR-548f	CLIP-seq
MIRT1366325	hsa-miR-549	CLIP-seq
MIRT1366326	hsa-miR-198	CLIP-seq
MIRT1366327	hsa-miR-3973	CLIP-seq
MIRT1366328	hsa-miR-520g	CLIP-seq
MIRT1366329	hsa-miR-520h	CLIP-seq
MIRT1366330	hsa-miR-548c-3p	CLIP-seq
MIRT2332369	hsa-miR-23a	CLIP-seq
MIRT2332370	hsa-miR-23b	CLIP-seq
MIRT2332371	hsa-miR-23c	CLIP-seq
MIRT2459859	hsa-miR-1224-3p	CLIP-seq
MIRT2459860	hsa-miR-1224-5p	CLIP-seq
MIRT2459861	hsa-miR-1294	CLIP-seq
MIRT2459862	hsa-miR-3176	CLIP-seq
MIRT2459863	hsa-miR-3922-3p	CLIP-seq
MIRT2459864	hsa-miR-4312	CLIP-seq
MIRT2459865	hsa-miR-4316	CLIP-seq
MIRT2459866	hsa-miR-4751	CLIP-seq
MIRT2459859	hsa-miR-1224-3p	CLIP-seq
MIRT2459860	hsa-miR-1224-5p	CLIP-seq
MIRT2459861	hsa-miR-1294	CLIP-seq
MIRT2459862	hsa-miR-3176	CLIP-seq
MIRT2459863	hsa-miR-3922-3p	CLIP-seq
MIRT2459864	hsa-miR-4312	CLIP-seq
MIRT2459865	hsa-miR-4316	CLIP-seq
MIRT2459866	hsa-miR-4751	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003779	Function	Actin binding	IPI	18331289
GO:0005326	Function	Neurotransmitter transmembrane transporter activity	ISS
GO:0005328	Function	Neurotransmitter:sodium symporter activity	IEA
GO:0005330	Function	Dopamine:sodium symporter activity	IBA	21873635
GO:0005334	Function	Norepinephrine:sodium symporter activity	IBA	21873635
GO:0005334	Function	Norepinephrine:sodium symporter activity	TAS
GO:0005515	Function	Protein binding	IPI	11343649, 17156375, 18331289
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	IBA	21873635
GO:0005887	Component	Integral component of plasma membrane	IEA
GO:0006836	Process	Neurotransmitter transport	ISS
GO:0007268	Process	Chemical synaptic transmission	TAS	2008212
GO:0008504	Function	Monoamine transmembrane transporter activity	IDA	16024787
GO:0008504	Function	Monoamine transmembrane transporter activity	ISS
GO:0009986	Component	Cell surface	IEA
GO:0015844	Process	Monoamine transport	IDA	16024787
GO:0015874	Process	Norepinephrine transport	IBA	21873635
GO:0016020	Component	Membrane	TAS	2008212
GO:0032809	Component	Neuronal cell body membrane	IBA	21873635
GO:0035725	Process	Sodium ion transmembrane transport	IBA	21873635
GO:0042493	Process	Response to drug	IEA
GO:0042734	Component	Presynaptic membrane	IBA	21873635
GO:0043005	Component	Neuron projection	IBA	21873635
GO:0043014	Function	Alpha-tubulin binding	IEA
GO:0045121	Component	Membrane raft	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0048265	Process	Response to pain	IEA
GO:0048487	Function	Beta-tubulin binding	IEA
GO:0051583	Process	Dopamine uptake involved in synaptic transmission	IBA	21873635
GO:0051620	Process	Norepinephrine uptake	ISS
GO:0070050	Process	Neuron cellular homeostasis	TAS	18331289

Other IDs

• MIM: 163970
• HGNC: 11048
• e!Ensembl: ENSG00000103546

Protein

• UniProt ID: P23975
• Protein name: Sodium-dependent noradrenaline transporter (Norepinephrine transporter) (NET) (Solute carrier family 6 member 2)
• Protein function: Mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline), the primary signaling neurotransmitter in the autonomic sympathetic nervous system (PubMed:2008212, PubMed:8125921, PubMed:38750358). Is responsib
• PDB: 8HFE, 8HFF, 8HFG, 8HFI, 8HFL, 8I3V, 8WGR, 8WGX, 8WTU, 8WTV, 8WTW, 8WTX, 8WTY, 8XB2, 8XB3, 8XB4, 8Y8Z, 8Y90, 8Y91, 8Y92, 8Y93, 8Y94, 8Y95, 8YR2, 8Z1L, 8ZOY, 8ZP1, 8ZP2, 8ZPB
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00209	SNF	56 → 580	Sodium:neurotransmitter symporter family	Family

• Sequence:

  MLLARMNPQVQPENNGADTGPEQPLRARKTAELLVVKERNGVQCLLAPRDGDAQPRETWG
  KKIDFLLSVVGFAVDLANVWRFPYLCYKNGGGAFLIPYTLFLIIAGMPLFYMELALGQYN
  REGAATVWKICPFFKGVGYAVILIALYVGFYYNVIIAWSLYYLFSSFTLNLPWTDCGHTW
  NSPNCTDPKLLNGSVLGNHTKYSKYKFTPAAEFYERGVLHLHESSGIHDIGLPQWQLLLC
  LMVVVIVLYFSLWKGVKTSGKVVWITATLPYFVLFVLLVHGVTLPGASNGINAYLHIDFY
  RLKEATVWIDAATQIFFSLGAGFGVLIAFASYNKFDNNCYRDALLTSSINCITSFVSGFA
  IFSILGYMAHEHKVNIEDVATEGAGLVFILYPEAISTLSGSTFWAVVFFVMLLALGLDSS
  MGGMEAVITGLADDFQVLKRHRKLFTFGVTFSTFLLALFCITKGGIYVLTLLDTFAAGTS
  ILFAVLMEAIGVSWFYGVDRFSNDIQQMMGFRPGLYWRLCWKFVSPAFLLFVVVVSIINF
  KPLTYDDYIFPPWANWVGWGIALSSMVLVPIYVIYKFLSTQGSLWERLAYGITPENEHHL
  VAQRDIRQFQLQHWLAI

• Sequence length: 617

Pathways

KEGG:

Synaptic vesicle cycle

Reactome:

Na+/Cl- dependent neurotransmitter transporters
Defective SLC6A2 causes orthostatic intolerance (OI)

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Hypertension	Hypertensive disease	rs13306026, rs13333226	22533655
Mitral valve prolapse	Mitral Valve Prolapse Syndrome	rs768737101	10684912
Neurocirculatory asthenia	Neurocirculatory Asthenia	rs121918126	10684912
Schizophrenia	Schizophrenia	rs74315508, rs74315509, rs13447324, rs1558507406, rs387906932, rs387906933, rs863223354, rs863223355, rs776061422, rs863223349, rs748809996, rs759748655, rs863223353, rs863223350, rs863223356, rs781821239, rs863223348, rs863223346, rs863223347, rs863223351, rs863223352, rs61734270, rs797045205, rs869312829, rs869312830, rs770913157, rs869312832, rs869312831, rs781720548, rs1262969313	12097806, 20543991
Seizure	Complex partial seizures, Generalized seizures, Visual seizure, Tonic - clonic seizures, Single Seizure	rs587784365, rs28939683, rs74315390, rs28939684, rs74315391, rs267607198, rs74315392, rs118192244, rs118192250, rs121917749, rs121917750, rs121917751, rs121917752, rs267606670, rs267607061, rs121912707, rs118192249, rs118192251, rs118192217, rs118192218, rs118192219, rs118192222, rs118192226, rs118192228, rs118192234, rs118192236, rs118192235, rs118192241, rs118192242, rs118192185, rs118192188, rs118192245, rs118192246, rs118192186, rs118192194, rs118192197, rs118192199, rs118192201, rs118192202, rs118192203, rs118192204, rs118192205, rs118192206, rs118192208, rs118192211, rs118192216, rs118192239, rs387906684, rs387906686, rs387906687, rs1596893185, rs387907126, rs387907281, rs397515405, rs587778771, rs730882067, rs730882073, rs397514579, rs397514582, rs587776976, rs398122394, rs121918784, rs121918751, rs121918735, rs398123588, rs587780450, rs61749751, rs587777620, rs727503974, rs730882124, rs794726710, rs794726697, rs794726799, rs794727444, rs794727740, rs796053166, rs794726825, rs796052676, rs796053219, rs796053220, rs796053228, rs796052653, rs759584387, rs796052650, rs796052641, rs796052626, rs796052623, rs796052663, rs796052615, rs796052802, rs797044999, rs797045047, rs797045942, rs797045941, rs118192212, rs797044938, rs777257591, rs864321712, rs879255652, rs886039268, rs886039517, rs886039529, rs199497486, rs886039496, rs886039903, rs886041300, rs769827124, rs886041339, rs886041591, rs587783092, rs1555850151, rs1057516123, rs1057516121, rs1057516115, rs1057516111, rs1057516106, rs1057516105, rs756921902, rs1057516089, rs1057516087, rs1057516080, rs1057516076, rs1060499544, rs1555850512, rs1057517919, rs118192231, rs1057520413, rs1060503101, rs1064796294, rs1064794981, rs1064794632, rs1064797245, rs1131691830, rs1131692231, rs1131691936, rs1554626549, rs1553579225, rs1553531385, rs121918736, rs1554898088, rs1553579282, rs763353895, rs1553463119, rs1554093891, rs77838305, rs1555408401, rs1554627439, rs1554097873, rs1555850403, rs1064794719, rs1315483224, rs1567134495, rs770187706, rs1057518555, rs1576983339, rs1574192005, rs1459374430, rs1586800133, rs1574641522, rs1572096837, rs1572630269, rs1574554892, rs1574556643, rs1574571769, rs1574641605, rs1574697769, rs1574716524, rs1574746733, rs1574746935, rs1574752700, rs1574754680, rs863225030, rs1601545088, rs1600714727, rs1371059392, rs1600767259, rs1339542565, rs1600785769, rs2065899210, rs1600732174, rs1162306056, rs879255709, rs1900111672, rs2066910297, rs1554122080, rs796052941, rs1600789325, rs2082695884, rs1737677036, rs1737495759, rs868389022, rs1737685202, rs1737672350, rs762737130	15911120

Unknown
Disease name	Disease term	dbSNP ID	References
Bipolar disorder	Bipolar Disorder		12097806, 17654409, 7615302
Clonic seizures	Clonic Seizures		15911120
Hypotonic seizures	Epileptic drop attack		15911120
Jacksonian seizure	Jacksonian Seizure		15911120
Mental depression	Mental Depression, Depressive disorder, Unipolar Depression, Recurrent depression, Major Depressive Disorder	rs587778876, rs587778877	23636256, 25650523, 25422957, 23969988, 24655776, 23969988, 24655776, 25422957, 25650523, 23636256, 24655776, 25512257, 25650523, 26061302, 24312678, 23969988, 18081710, 24312678, 24655776, 26061302, 25650523, 25512257
Mood disorder	Mood Disorders		21547899, 11927173, 17654409
Postural orthostatic tachycardia syndrome	Postural orthostatic tachycardia syndrome due to NET deficiency