SLC39A8 (solute carrier family 39 member 8)

Gene

• Entrez ID: 64116
• Gene name: Solute carrier family 39 member 8
• Gene symbol: SLC39A8
• Synonyms: BIGM103, CDG2N, LZT-Hs6, PP3105, ZIP8
• Chromosome: 4
• Chromosome location: 4q24
• Summary: This gene encodes a member of the SLC39 family of solute-carrier genes, which show structural characteristics of zinc transporters. The encoded protein is glycosylated and found in the plasma membrane and mitochondria, and functions in the cellular import

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs373562040	C>A,T	Pathogenic	Coding sequence variant, genic upstream transcript variant, 5 prime UTR variant, missense variant
rs778210210	C>G	Pathogenic	Coding sequence variant, genic upstream transcript variant, 5 prime UTR variant, missense variant
rs779241085	C>A	Conflicting-interpretations-of-pathogenicity, pathogenic	Coding sequence variant, missense variant
rs864309659	A>T	Uncertain-significance, pathogenic	Genic downstream transcript variant, coding sequence variant, missense variant
rs864309660	C>G	Pathogenic	Genic downstream transcript variant, coding sequence variant, missense variant
rs1057521727	G>T	Likely-pathogenic	Genic downstream transcript variant, coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT024337	hsa-miR-215-5p	Microarray	19074876
MIRT026917	hsa-miR-192-5p	Microarray	19074876
MIRT043292	hsa-miR-331-3p	CLASH	23622248
MIRT038538	hsa-miR-30c-1-3p	CLASH	23622248
MIRT052741	hsa-miR-1260b	CLASH	23622248
MIRT054483	hsa-miR-488-3p	Luciferase reporter assay, Immunoblotting, qRT-PCR	23688035
MIRT1363693	hsa-miR-1299	CLIP-seq
MIRT1363694	hsa-miR-1305	CLIP-seq
MIRT1363695	hsa-miR-139-5p	CLIP-seq
MIRT1363696	hsa-miR-378	CLIP-seq
MIRT1363697	hsa-miR-378b	CLIP-seq
MIRT1363698	hsa-miR-378c	CLIP-seq
MIRT1363699	hsa-miR-378d	CLIP-seq
MIRT1363700	hsa-miR-378e	CLIP-seq
MIRT1363701	hsa-miR-378f	CLIP-seq
MIRT1363702	hsa-miR-378h	CLIP-seq
MIRT1363703	hsa-miR-378i	CLIP-seq
MIRT1363704	hsa-miR-422a	CLIP-seq
MIRT1363705	hsa-miR-4535	CLIP-seq
MIRT1363706	hsa-miR-4638-3p	CLIP-seq
MIRT1363707	hsa-miR-4761-5p	CLIP-seq
MIRT1363708	hsa-miR-4782-5p	CLIP-seq
MIRT1363709	hsa-miR-488	CLIP-seq
MIRT1363710	hsa-miR-492	CLIP-seq
MIRT1363711	hsa-miR-498	CLIP-seq
MIRT1363712	hsa-miR-516b	CLIP-seq
MIRT1363713	hsa-miR-582-5p	CLIP-seq
MIRT1363714	hsa-miR-640	CLIP-seq
MIRT1363715	hsa-miR-1276	CLIP-seq
MIRT1363716	hsa-miR-1976	CLIP-seq
MIRT1363717	hsa-miR-299-3p	CLIP-seq
MIRT1363718	hsa-miR-370	CLIP-seq
MIRT1363719	hsa-miR-4274	CLIP-seq
MIRT1363720	hsa-miR-4519	CLIP-seq
MIRT1363721	hsa-miR-4648	CLIP-seq
MIRT1363722	hsa-miR-4654	CLIP-seq
MIRT1363723	hsa-miR-4661-5p	CLIP-seq
MIRT1363724	hsa-miR-4769-5p	CLIP-seq
MIRT1363725	hsa-miR-1200	CLIP-seq
MIRT1363726	hsa-miR-3117-5p	CLIP-seq
MIRT1363727	hsa-miR-380	CLIP-seq
MIRT1363728	hsa-miR-4289	CLIP-seq
MIRT1363729	hsa-miR-4324	CLIP-seq
MIRT1363730	hsa-miR-4330	CLIP-seq
MIRT1363731	hsa-miR-4494	CLIP-seq
MIRT1363732	hsa-miR-4499	CLIP-seq
MIRT1363733	hsa-miR-4513	CLIP-seq
MIRT1363734	hsa-miR-4645-5p	CLIP-seq
MIRT1363735	hsa-miR-4673	CLIP-seq
MIRT1363736	hsa-miR-499a-5p	CLIP-seq
MIRT1363737	hsa-miR-544b	CLIP-seq
MIRT2107869	hsa-miR-127-5p	CLIP-seq
MIRT2107870	hsa-miR-3065-5p	CLIP-seq
MIRT1363726	hsa-miR-3117-5p	CLIP-seq
MIRT2107871	hsa-miR-570	CLIP-seq
MIRT2331683	hsa-miR-3120-3p	CLIP-seq
MIRT2331684	hsa-miR-3171	CLIP-seq
MIRT1363719	hsa-miR-4274	CLIP-seq
MIRT2394784	hsa-miR-3591-3p	CLIP-seq
MIRT2394785	hsa-miR-4477a	CLIP-seq
MIRT2107869	hsa-miR-127-5p	CLIP-seq
MIRT2107870	hsa-miR-3065-5p	CLIP-seq
MIRT1363726	hsa-miR-3117-5p	CLIP-seq
MIRT2107871	hsa-miR-570	CLIP-seq
MIRT1363713	hsa-miR-582-5p	CLIP-seq
MIRT2691211	hsa-miR-1294	CLIP-seq
MIRT2691212	hsa-miR-3184	CLIP-seq
MIRT2691213	hsa-miR-342-5p	CLIP-seq
MIRT2691214	hsa-miR-423-5p	CLIP-seq
MIRT2691215	hsa-miR-4316	CLIP-seq
MIRT2691216	hsa-miR-452	CLIP-seq
MIRT2691217	hsa-miR-4664-5p	CLIP-seq
MIRT2691218	hsa-miR-4676-3p	CLIP-seq
MIRT2691219	hsa-miR-4694-5p	CLIP-seq
MIRT2691220	hsa-miR-4727-5p	CLIP-seq
MIRT2691221	hsa-miR-4769-3p	CLIP-seq
MIRT2691222	hsa-miR-4803	CLIP-seq
MIRT2691223	hsa-miR-634	CLIP-seq
MIRT2691224	hsa-miR-758	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
SP1	Activation	18556457

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005381	Function	Iron ion transmembrane transporter activity	IDA	22898811
GO:0005384	Function	Manganese ion transmembrane transporter activity	IMP	28481222, 29453449, 31699897
GO:0005385	Function	Zinc ion transmembrane transporter activity	IBA	21873635
GO:0005385	Function	Zinc ion transmembrane transporter activity	IDA	19401385
GO:0005385	Function	Zinc ion transmembrane transporter activity	IMP	29337306
GO:0005765	Component	Lysosomal membrane	IDA	18390834, 19401385
GO:0005886	Component	Plasma membrane	IDA	18390834
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	IBA	21873635
GO:0006351	Process	Transcription, DNA-templated	IEA
GO:0006355	Process	Regulation of transcription, DNA-templated	IMP	29337306
GO:0006487	Process	Protein N-linked glycosylation	ISS
GO:0006525	Process	Arginine metabolic process	ISS
GO:0006824	Process	Cobalt ion transport	ISS
GO:0006829	Process	Zinc ion transport	IMP	12504855
GO:0006876	Process	Cellular cadmium ion homeostasis	IMP	27466201
GO:0006882	Process	Cellular zinc ion homeostasis	IBA	21873635
GO:0006882	Process	Cellular zinc ion homeostasis	IDA	19401385
GO:0015086	Function	Cadmium ion transmembrane transporter activity	IMP	27466201
GO:0015087	Function	Cobalt ion transmembrane transporter activity	ISS
GO:0015106	Function	Bicarbonate transmembrane transporter activity	ISS
GO:0015296	Function	Anion:cation symporter activity	ISS
GO:0015698	Process	Inorganic anion transport	IEA
GO:0015701	Process	Bicarbonate transport	ISS
GO:0016323	Component	Basolateral plasma membrane	IDA	31699897
GO:0016324	Component	Apical plasma membrane	IDA	31699897
GO:0030026	Process	Cellular manganese ion homeostasis	ISS
GO:0030198	Process	Extracellular matrix organization	IMP	29337306
GO:0031090	Component	Organelle membrane	IDA	12504855
GO:0042391	Process	Regulation of membrane potential	IMP	18390834
GO:0061757	Process	Leukocyte adhesion to arterial endothelial cell	ISS
GO:0070574	Process	Cadmium ion transmembrane transport	IMP	27466201
GO:0071421	Process	Manganese ion transmembrane transport	IMP	28481222, 29453449, 31699897
GO:0071577	Process	Zinc ion transmembrane transport	IDA	19401385
GO:0071577	Process	Zinc ion transmembrane transport	IMP	18390834
GO:0071578	Process	Zinc ion import across plasma membrane	IBA	21873635
GO:0071578	Process	Zinc ion import across plasma membrane	IMP	29337306
GO:0097079	Function	Selenite:proton symporter activity	IDA	27166256
GO:0097080	Process	Plasma membrane selenite transport	IDA	27166256
GO:0098711	Process	Iron ion import across plasma membrane	IDA	22898811
GO:0140412	Function	Zinc:bicarbonate symporter activity	IEA
GO:1990079	Process	Cartilage homeostasis	ISS
GO:1990540	Process	Mitochondrial manganese ion transmembrane transport	IMP	29453449

Other IDs

• MIM: 608732
• HGNC: 20862
• e!Ensembl: ENSG00000138821

Protein

• UniProt ID: Q9C0K1
• Protein name: Metal cation symporter ZIP8 (BCG-induced integral membrane protein in monocyte clone 103 protein) (LIV-1 subfamily of ZIP zinc transporter 6) (LZT-Hs6) (Solute carrier family 39 member 8) (Zrt- and Irt-like protein 8) (ZIP-8)
• Protein function: Electroneutral divalent metal cation:bicarbonate symporter of the plasma membrane mediating the cellular uptake of zinc and manganese, two divalent metal cations important for development, tissue homeostasis and immunity (PubMed:12504855, PubMed
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02535	Zip	126 → 451	ZIP Zinc transporter	Family

• Sequence:

  MAPGRAVAGLLLLAAAGLGGVAEGPGLAFSEDVLSVFGANLSLSAAQLQHLLEQMGAASR
  VGVPEPGQLHFNQCLTAEEIFSLHGFSNATQITSSKFSVICPAVLQQLNFHPCEDRPKHK
  TRPSHSEVWGYGFLSVTIINLASLLGLILTPLIKKSYFPKILTFFVGLAIGTLFSNAIFQ
  LIPEAFGFDPKVDSYVEKAVAVFGGFYLLFFFERMLKMLLKTYGQNGHTHFGNDNFGPQE
  KTHQPKALPAINGVTCYANPAVTEANGHIHFDNVSVVSLQDGKKEPSSCTCLKGPKLSEI
  GTIAWMITLCDALHNFIDGLAIGASCTLSLLQGLSTSIAILCEEFPHELGDFVILLNAGM
  STRQALLFNFLSACSCYVGLAFGILVGNNFAPNIIFALAGGMFLYISLADMFPEMNDMLR
  EKVTGRKTDFTFFMIQNAGMLTGFTAILLITLYAGEIELE

• Sequence length: 460

Pathways

KEGG:

Ferroptosis
Alzheimer disease
Parkinson disease

Reactome:

Zinc influx into cells by the SLC39 gene family

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Arthritis	Degenerative polyarthritis	rs1594890601, rs1594882933, rs184370809, rs776489319, rs1594883470	30664745
Atrial fibrillation	Atrial Fibrillation	rs120074192, rs121908590, rs121908593, rs121434558, rs587776851, rs387906612, rs387906613, rs387906614, rs387906615, rs199472687, rs199472705, rs199473324, rs587777336, rs587777339, rs587777557, rs587777558, rs587777559, rs587777560, rs886037778, rs769405762, rs770372675	27790247
Congenital disorder of glycosylation	CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IIn, SLC39A8-CDG	rs121434387, rs1264383808, rs766244312, rs1555497568, rs1555496968, rs267606740, rs1568296260, rs1562937199, rs28939378, rs121908583, rs1568757730, rs28936415, rs587776874, rs387906831, rs151173406, rs387907202, rs387907203, rs397515327, rs398124348, rs374928784, rs398124401, rs587777114, rs587777115, rs587777116, rs752922461, rs794727073, rs797044712, rs765191836, rs376663459, rs778210210, rs864309659, rs869025583, rs751325113, rs369160589, rs1085307116, rs1085307117, rs746019074, rs1135401817, rs773281248, rs1555575860, rs753780084, rs1553121545, rs764831063, rs1185483085, rs867045420, rs1554464495, rs1460811017, rs1297536872, rs1555388034, rs1334593208, rs1555493029, rs1555497604, rs1031719032, rs768656482, rs937887233, rs1272097668, rs1569508922, rs1048764460, rs373260156, rs1569547876, rs1563018529, rs777937112, rs1231928102, rs1584977236, rs1582461023, rs1422285851, rs139624629, rs1597225261, rs763516132, rs200605408, rs1596252105, rs1596252196, rs121908340, rs1596256204, rs553396382, rs1180515976, rs1299775990, rs1596261161, rs1596261208, rs1428414601, rs1596261268, rs16835020, rs1270276368, rs373355236, rs1582477100, rs747606976, rs2049726544, rs781115721, rs1926621737, rs1444255127, rs1663960324, rs1665467473, rs1431963909, rs1663959543, rs376870425	26637978, 26637979, 27604308, 29903433
Craniosynostosis	Craniosynostosis	rs104893895, rs587777006, rs587777007, rs587777008, rs587777010, rs281865153, rs281865154, rs864321680, rs864321681, rs1057517670, rs1085307122, rs1064794325, rs1884302, rs1555750816, rs1599823350
Developmental delay	Global developmental delay, Profound global developmental delay	rs28941770, rs199469464, rs281865469, rs143747297, rs398123009, rs587777428, rs786205133, rs606231459, rs797044854, rs797045027, rs864309504, rs878853160, rs886039902, rs886042046, rs886041291, rs886041382, rs1057518991, rs1057518699, rs753254213, rs748294403, rs762552974, rs1135401795, rs1553121073, rs1553122926, rs1364690005, rs1554086554, rs1554210415, rs1554168326, rs1554776342, rs1553873247, rs1567860112, rs779009256, rs1557447255, rs1564568350, rs780011005, rs1597464953, rs1200336864, rs1569513017, rs1587459606, rs1570332505, rs748888652, rs1575155995, rs2087029320, rs1589669105, rs1601769604, rs1184981709, rs749201074
Diabetes	Diabetes	rs80356611	27790247
Diabetes mellitus	Diabetes Mellitus	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, 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, rs1553638903, rs1553638909, rs948820149, rs371977235, rs1553784995, 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	27790247
Hypertension	Hypertensive disease	rs13306026, rs13333226	21909115
Nystagmus	Nystagmus	rs137852207, rs137852208, rs1928435502, rs137852209, rs137852210, rs1929191668, rs137852211, rs137852212, rs2124209414, rs387906720, rs387906721, rs1602791884, rs786205896
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	29483656, 26198764

Unknown
Disease name	Disease term	dbSNP ID	References
Astigmatism	Astigmatism
Cerebellar atrophy	Cerebellar atrophy
Cerebral cortical atrophy	Cerebral cortical atrophy
Coronary heart disease	Coronary heart disease	rs9289231, rs281864746	27790247
Dwarfism	Dwarfism
Eczema	Eczema		30595370
Elbow flexion contracture	Flexion contracture - elbow
Heart failure	Heart failure	rs121918074, rs142027794, rs148791216, rs72648927, rs71578935, rs142416150, rs199830512, rs755445214, rs150102469, rs779568205, rs907992794, rs1202130741	27790247
Hyperopia	Hyperopia
Malignant neoplasm	Malignant Neoplasms		27790247
Osteopenia	Osteopenia
Strabismus	Strabismus
Stroke	Cerebrovascular accident		27790247
Sudden episodic apnea	Sudden episodic apnea
Syndactyly of the toes	Cutaneous syndactyly of toes