SLC11A1 (solute carrier family 11 member 1)

Gene

• Entrez ID: 6556
• Gene name: Solute carrier family 11 member 1
• Gene symbol: SLC11A1
• Synonyms: LSH, NRAMP, NRAMP1
• Chromosome: 2
• Chromosome location: 2q35
• Summary: This gene is a member of the solute carrier family 11 (proton-coupled divalent metal ion transporters) family and encodes a multi-pass membrane protein. The protein functions as a divalent transition metal (iron and manganese) transporter involved in iron metabolism and host resistance to certain pathogens. Mutations in this gene have been associated with susceptibility to infectious diseases such as tuberculosis and leprosy, and inflammatory diseases such as rheumatoid arthritis and Crohn disease. Alternatively spliced variants that encode different protein isoforms have been described but the full-length nature of only one has been determined. [provided by RefSeq, Jul 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs17235409	G>A,C	Risk-factor	Coding sequence variant, missense variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT491487	hsa-miR-6778-5p	PAR-CLIP	23592263
MIRT491488	hsa-miR-6853-5p	PAR-CLIP	23592263
MIRT491489	hsa-miR-1233-5p	PAR-CLIP	23592263
MIRT491490	hsa-miR-1199-3p	PAR-CLIP	23592263
MIRT491491	hsa-miR-1908-3p	PAR-CLIP	23592263
MIRT621333	hsa-miR-4446-5p	HITS-CLIP	23824327
MIRT621334	hsa-miR-182-5p	HITS-CLIP	23824327
MIRT621335	hsa-miR-5006-3p	HITS-CLIP	23824327
MIRT621336	hsa-miR-4755-5p	HITS-CLIP	23824327
MIRT621337	hsa-miR-196a-3p	HITS-CLIP	23824327
MIRT621338	hsa-miR-6133	HITS-CLIP	23824327
MIRT621339	hsa-miR-6130	HITS-CLIP	23824327
MIRT621340	hsa-miR-6129	HITS-CLIP	23824327
MIRT621341	hsa-miR-6127	HITS-CLIP	23824327
MIRT621342	hsa-miR-4510	HITS-CLIP	23824327
MIRT621343	hsa-miR-4419a	HITS-CLIP	23824327
MIRT621344	hsa-miR-339-5p	HITS-CLIP	23824327
MIRT621345	hsa-miR-6760-5p	HITS-CLIP	23824327
MIRT621346	hsa-miR-6873-5p	HITS-CLIP	23824327

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001818	Process	Negative regulation of cytokine production	ISS
GO:0001819	Process	Positive regulation of cytokine production	ISS
GO:0002309	Process	T cell proliferation involved in immune response	ISS
GO:0002606	Process	Positive regulation of dendritic cell antigen processing and presentation	ISS
GO:0002827	Process	Positive regulation of T-helper 1 type immune response	ISS
GO:0005381	Function	Iron ion transmembrane transporter activity	IBA	21873635
GO:0005384	Function	Manganese ion transmembrane transporter activity	IBA	21873635
GO:0005384	Function	Manganese ion transmembrane transporter activity	ISS
GO:0005764	Component	Lysosome	ISS
GO:0005770	Component	Late endosome	ISS
GO:0005886	Component	Plasma membrane	IBA	21873635
GO:0005886	Component	Plasma membrane	IMP	17932044
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	NAS	8537108
GO:0006826	Process	Iron ion transport	IMP	16510578
GO:0006828	Process	Manganese ion transport	ISS
GO:0006876	Process	Cellular cadmium ion homeostasis	IBA	21873635
GO:0006876	Process	Cellular cadmium ion homeostasis	IGI	17932044
GO:0006879	Process	Cellular iron ion homeostasis	IBA	21873635
GO:0006879	Process	Cellular iron ion homeostasis	IMP	16510578
GO:0006909	Process	Phagocytosis	ISS
GO:0006954	Process	Inflammatory response	ISS
GO:0007035	Process	Vacuolar acidification	ISS
GO:0009617	Process	Response to bacterium	IDA	7717395
GO:0010628	Process	Positive regulation of gene expression	ISS
GO:0015086	Function	Cadmium ion transmembrane transporter activity	IBA	21873635
GO:0015707	Process	Nitrite transport	ISS
GO:0019730	Process	Antimicrobial humoral response	TAS
GO:0030670	Component	Phagocytic vesicle membrane	IBA	21873635
GO:0030670	Component	Phagocytic vesicle membrane	IDA	12070036
GO:0031902	Component	Late endosome membrane	TAS
GO:0032147	Process	Activation of protein kinase activity	ISS
GO:0032496	Process	Response to lipopolysaccharide	IBA	21873635
GO:0032496	Process	Response to lipopolysaccharide	ISS
GO:0032729	Process	Positive regulation of interferon-gamma production	ISS
GO:0034341	Process	Response to interferon-gamma	ISS
GO:0034755	Process	Iron ion transmembrane transport	IEA
GO:0042060	Process	Wound healing	ISS
GO:0042116	Process	Macrophage activation	ISS
GO:0042742	Process	Defense response to bacterium	ISS
GO:0042803	Function	Protein homodimerization activity	IDA	8537108
GO:0042832	Process	Defense response to protozoan	ISS
GO:0043312	Process	Neutrophil degranulation	TAS
GO:0045342	Process	MHC class II biosynthetic process	ISS
GO:0045454	Process	Cell redox homeostasis	TAS
GO:0045730	Process	Respiratory burst	ISS
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	ISS
GO:0046915	Function	Transition metal ion transmembrane transporter activity	IGI	17932044
GO:0048002	Process	Antigen processing and presentation of peptide antigen	ISS
GO:0048255	Process	MRNA stabilization	ISS
GO:0050766	Process	Positive regulation of phagocytosis	ISS
GO:0050829	Process	Defense response to Gram-negative bacterium	ISS
GO:0051139	Function	Metal ion:proton antiporter activity	IBA	21873635
GO:0051139	Function	Metal ion:proton antiporter activity	IGI	17932044
GO:0051139	Function	Metal ion:proton antiporter activity	TAS
GO:0055072	Process	Iron ion homeostasis	ISS
GO:0060586	Process	Multicellular organismal iron ion homeostasis	ISS
GO:0070574	Process	Cadmium ion transmembrane transport	IGI	17932044
GO:0070821	Component	Tertiary granule membrane	IDA	12070036
GO:0070821	Component	Tertiary granule membrane	TAS
GO:0070839	Process	Metal ion export	ISS	17932044
GO:0071421	Process	Manganese ion transmembrane transport	IEA
GO:0101003	Component	Ficolin-1-rich granule membrane	TAS
GO:1902023	Process	L-arginine transport	IEA

Other IDs

• MIM: 600266
• HGNC: 10907
• e!Ensembl: ENSG00000018280

Protein

• UniProt ID: P49279
• Protein name: Natural resistance-associated macrophage protein 1 (NRAMP 1) (Solute carrier family 11 member 1)
• Protein function: Divalent transition metal (iron and manganese) transporter involved in iron metabolism and host resistance to certain pathogens. Macrophage-specific membrane transport function. Controls natural resistance to infection with intracellular parasites. Pathogen resistance involves sequestration of Fe(2+) and Mn(2+), cofactors of both prokaryotic and eukaryotic catalases and superoxide dismutases, not only to protect the macrophage against its own generation of reactive oxygen species, but to deny the cations to the pathogen for synthesis of its protective enzymes.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01566	Nramp	78 → 463	Natural resistance-associated macrophage protein	Family

• Sequence:

  MTGDKGPQRLSGSSYGSISSPTSPTSPGPQQAPPRETYLSEKIPIPDTKPGTFSLRKLWA
  FTGPGFLMSIAFLDPGNIESDLQAGAVAGFKLLWVLLWATVLGLLCQRLAARLGVVTGKD
  LGEVCHLYYPKVPRTVLWLTIELAIVGSDMQEVIGTAIAFNLLSAGRIPLWGGVLITIVD
  TFFFLFLDNYGLRKLEAFFGLLITIMALTFGYEYVVARPEQGALLRGLFLPSCPGCGHPE
  LLQAVGIVGAIIMPHNIYLHSALVKSREIDRARRADIREANMYFLIEATIALSVSFIINL
  FVMAVFGQAFYQKTNQAAFNICANSSLHDYAKIFPMNNATVAVDIYQGGVILGCLFGPAA
  LYIWAIGLLAAGQSSTMTGTYAGQFVMEGFLRLRWSRFARVLLTRSCAILPTVLVAVFRD
  LRDLSGLNDLLNVLQSLLLPFAVLPILTFTSMPTLMQEFANGLLNKVVTSSIMVLVCAIN
  LYFVVSYLPSLPHPAYFGLAALLAAAYLGLSTYLVWTCCLAHGATFLAHSSHHHFLYGLL
  EEDQKGETSG

• Sequence length: 550

Pathways

KEGG:

Lysosome

Reactome:

ROS and RNS production in phagocytes
Metal ion SLC transporters
Neutrophil degranulation
Ion influx/efflux at host-pathogen interface

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Diabetes mellitus	Diabetes Mellitus, Insulin-Dependent, Diabetes Mellitus, Ketosis-Prone, Diabetes Mellitus, Sudden-Onset	rs587776515, rs61730328, rs606231121, rs606231122, rs79020217, rs77625743, rs78378398, rs606231123, rs4402960, rs1362648752, rs3745368, rs3792267, rs3842570, rs5030952, rs2975760, rs119489103, rs7903146, rs12255372, rs11196205, rs104893649, rs80356624, rs80356616, rs80356625, rs80356611, rs104894237, rs80356613, rs137852740, rs137852786, rs387906407, rs151344623, rs28938469, rs28936371, rs137852672, rs80356637, rs80356642, rs80356653, rs137852673, rs137852674, rs80356634, rs80356651, rs193929360, rs137853334, rs137853335, rs137853336, rs-1, rs1600731198, rs137853338, rs121964882, rs121964883, rs387906511, rs121964884, rs121964885, rs2147483647, rs387906512, rs121964887, rs121964888, rs121964889, rs121964890, rs121964891, rs28934878, rs74315383, rs121964893, rs886037620, rs886037621, rs80356663, rs121434593, rs121913150, rs587776825, rs137853236, rs2135842335, rs137853237, rs137853238, rs2135818776, rs1566092470, rs1463923467, rs137853243, rs137853244, rs2135839114, rs137853245, rs2135847417, rs121918407, rs104894005, rs104894006, rs80356655, rs104894008, rs104894009, rs104894010, rs104894011, rs80356654, rs104894016, rs193929376, rs193929374, rs193929375, rs193929373, rs80356666, rs80356669, rs80356664, rs193929366, rs1048095, rs193929355, rs193929356, rs1259467443, rs104893642, rs387906777, rs387906779, rs141804752, rs182349376, rs184917682, rs193922396, rs193922400, rs193922401, rs137852676, rs193922407, rs193922638, rs193922257, rs193922258, rs193922259, rs193922260, rs193922261, rs193922262, rs193922263, rs193922264, rs193922265, rs193922268, rs193921338, rs193922269, rs193922272, rs193922273, rs193922275, rs193922278, rs193922279, rs193922280, rs193922281, rs193922282, rs193922283, rs193922284, rs193922286, rs193922287, rs193922289, rs193922291, rs193922295, rs193922297, rs193922300, rs193922302, rs193922303, rs193922308, rs193922313, rs193922314, rs144723656, rs193922315, rs193922316, rs193922317, rs148311934, rs193922319, rs193922320, rs193922326, rs193922329, rs193922330, rs193922331, rs193922335, rs193922336, rs193922338, rs193922340, rs193922341, rs193922471, rs193922475, rs193922476, rs193922479, rs193922355, rs193922356, rs193922576, rs193922578, rs193922582, rs193922588, rs193922592, rs193922594, rs193922596, rs386134267, rs193922598, rs193922599, rs193922600, rs193922604, rs193922605, rs397514580, rs397515519, rs267601516, rs587780343, rs587780345, rs587780346, rs587780347, rs587780357, rs148954387, rs61736969, rs587783673, rs587783672, rs587783669, rs786204676, rs794727236, rs151344624, rs794727775, rs794727839, rs199946797, rs869320673, rs796065047, rs759072800, rs797045595, rs797045209, rs797045207, rs797045213, rs797045623, rs863225280, rs149703259, rs864321656, rs139964066, rs777870079, rs878853246, rs769268803, rs886039380, rs886041392, rs886041391, rs886042610, rs143064649, rs1057516192, rs746480424, rs1057516281, rs576684889, rs754728827, rs1057520291, rs1057520779, rs893256143, rs1057520504, rs1057524790, rs1057524902, rs1057524904, rs1057524905, rs764232985, rs1064793998, rs1064794268, rs769086289, rs369429452, rs1085307913, rs1131691416, rs765432081, rs1131692182, rs748749585, rs1554335441, rs762263694, rs1312678560, rs767565869, rs1375656631, rs1554335391, rs1360415315, rs1554335616, rs1554335752, rs1554909277, rs769518471, rs757171524, rs768951263, rs762703502, rs1555212248, rs1555212359, rs1555813319, rs1555816654, rs371977235, rs76474829, rs200998587, rs1415041911, rs1554334894, rs1260178539, rs1554335421, rs1555211904, rs779184183, rs1554335564, rs200670692, rs1400535021, rs1554334872, rs1555212749, rs1553876668, rs1553878211, rs954727530, rs1554924035, rs372307320, rs925231098, rs1554913069, rs1554933565, rs766431403, rs746714109, rs751279984, rs770664202, rs1008906426, rs758844607, rs1554924540, rs1566092307, rs753998395, rs1565885935, rs1167124132, rs1376796469, rs556436603, rs1562715657, rs1486280029, rs1564869850, rs755259997, rs769569410, rs1172328722, rs1286294151, rs1375557127, rs1568731279, rs1562715426, rs556581174, rs1564865302, rs1565886545, rs776793516, rs1568724014, rs1392795567, rs781260712, rs1562719705, rs1382448285, rs1564977373, rs750586210, rs1598842892, rs1583592247, rs780612692, rs1593060859, rs1476637197, rs751279776, rs1593060890, rs1191912908, rs1167675604, rs1583601110, rs1593058932, rs778611627, rs753296261	16597321
Rheumatoid arthritis	Rheumatoid Arthritis	rs3766379, rs3792876, rs2071592, rs3087456, rs587776843, rs1566328963	16597321
Sarcoidosis	Sarcoidosis	rs2076530, rs-1	16597321
Inflammatory bowel disease	Inflammatory Bowel Diseases	rs137853579, rs137853580, rs121909601, rs149491038, rs368287711, rs387907326, rs587777338, rs758439420, rs1329427406, rs1264862631, rs1192830343, rs1373354533, rs1419560997, rs1591263883, rs-1, rs1989014468	16597321
Leprosy	Leprosy	rs121917864, rs2239704	16597321
Multiple sclerosis	Multiple Sclerosis, Multiple Sclerosis, Acute Fulminating	rs104895219, rs-1, rs483353022, rs483353023, rs483353028, rs483353029, rs483353024, rs483353030, rs3207617, rs483353031, rs483353032, rs483353033, rs483353034, rs483353035, rs483353036, rs483353039, rs483353038, rs61731956, rs568165874, rs767480544	16597321
Dermatitis	Dermatitis, Atopic	rs61816761, rs150597413, rs138726443, rs201356558, rs149484917, rs372754256, rs747301529, rs567795279, rs745915174	16597321
Arthritis	Juvenile arthritis	rs1594890601, rs1594882933, rs184370809, rs776489319, rs1594883470	16597321

Unknown
Disease name	Disease term	dbSNP ID	References
Crohn disease	Crohn Disease, Regional enteritis	rs2066847, rs2066844, rs886052047, rs5743265, rs111608429, rs104895438	16059695
Autoimmune diabetes	Diabetes, Autoimmune		16597321
Buruli ulcer	Buruli Ulcer
Crohn`s disease of large bowel	Crohn`s disease of large bowel		16059695
Crohn`s disease of the ileum	Crohn`s disease of the ileum		16059695
Brittle diabetes mellitus	Brittle diabetes		16597321
Eczema	Eczema, Infantile		16597321
Ileocolitis	IIeocolitis		16059695
Juvenile arthritis	Juvenile psoriatic arthritis		16597321
Kidney failure	Kidney Failure, Acute		20623750
Seronegative polyarthritis	Polyarthritis, Juvenile, Rheumatoid Factor Negative		16597321
Polyarthritis, rheumatoid factor positive	Polyarthritis, Juvenile, Rheumatoid Factor Positive		16597321
Acute kidney insufficiency	Acute Kidney Insufficiency		20623750
Still disease	Juvenile-Onset Still Disease		16597321
Ulcerative colitis	Ulcerative Colitis		16059695