SLC41A1

Summary

SLC41A1 (solute carrier family 41 member 1, HGNC:19429) is a protein-coding gene on chromosome 1q32.1, encoding Solute carrier family 41 member 1 (Q8IVJ1). Na(+)/Mg(2+) ion exchanger that acts as a predominant Mg(2+) efflux system at the plasma membrane.

Enables magnesium:sodium antiporter activity. Involved in cellular response to magnesium ion; intracellular magnesium ion homeostasis; and magnesium ion transmembrane transport. Located in basolateral plasma membrane. Part of protein-containing complex. Implicated in nephronophthisis.

Source: NCBI Gene 254428 — RefSeq curated summary.

At a glance

• Gene–disease (curated): kidney disorder (Limited, ClinGen) — +1 more curated relationship
• GWAS associations: 20
• Clinical variants (ClinVar): 157 total — 1 pathogenic
• Phenotypes (HPO): 14
• MANE Select transcript: NM_173854

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19429
Approved symbol	SLC41A1
Name	solute carrier family 41 member 1
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	MgtE
Ensembl gene	ENSG00000133065
Ensembl biotype	protein_coding
OMIM	610801
Entrez	254428

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 16 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000367137, ENST00000468057, ENST00000484000, ENST00000484228, ENST00000911124, ENST00000911125, ENST00000911126, ENST00000911127, ENST00000911128, ENST00000911129, ENST00000911130, ENST00000937879, ENST00000948594, ENST00000948595, ENST00000948596, ENST00000948597, ENST00000948598, ENST00000948599, ENST00000948600

RefSeq mRNA: 1 — MANE Select: NM_173854 NM_173854

CCDS: CCDS30988

Canonical transcript exons

ENST00000367137 — 11 exons

Exon	Start	End
ENSE00001443612	205810070	205811087
ENSE00001443613	205812808	205813198
ENSE00001842444	205789095	205791718
ENSE00003491121	205795344	205795478
ENSE00003506770	205796924	205797003
ENSE00003584356	205798957	205799101
ENSE00003601286	205799759	205799830
ENSE00003626426	205797904	205798051
ENSE00003638050	205800953	205801060
ENSE00003642537	205798669	205798815
ENSE00003688191	205794870	205795018

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 99.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.3701 / max 379.4949, expressed in 1713 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17038	4.4498	1185
17040	3.6535	1503
17039	2.2633	1216
17041	1.2786	738
17036	0.6261	377
17037	0.0814	31
201902	0.0174	11

Top tissues by expression

255 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	99.57	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.41	gold quality
myocardium	UBERON:0002349	98.43	gold quality
apex of heart	UBERON:0002098	98.19	gold quality
cardiac ventricle	UBERON:0002082	98.02	gold quality
heart left ventricle	UBERON:0002084	98.02	gold quality
cardiac atrium	UBERON:0002081	97.47	gold quality
heart right ventricle	UBERON:0002080	97.46	gold quality
right atrium auricular region	UBERON:0006631	97.35	gold quality
heart	UBERON:0000948	96.56	gold quality
tibialis anterior	UBERON:0001385	96.08	silver quality
body of tongue	UBERON:0011876	95.86	gold quality
body of pancreas	UBERON:0001150	95.13	gold quality
vena cava	UBERON:0004087	95.13	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.65	gold quality
deltoid	UBERON:0001476	94.53	gold quality
skeletal muscle tissue	UBERON:0001134	93.81	gold quality
biceps brachii	UBERON:0001507	93.64	gold quality
muscle tissue	UBERON:0002385	93.18	gold quality
quadriceps femoris	UBERON:0001377	93.06	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.00	gold quality
pancreas	UBERON:0001264	92.78	gold quality
left lobe of thyroid gland	UBERON:0001120	92.58	gold quality
gastrocnemius	UBERON:0001388	92.56	gold quality
tongue	UBERON:0001723	92.55	gold quality
muscle of leg	UBERON:0001383	92.48	gold quality
vastus lateralis	UBERON:0001379	92.46	gold quality
thyroid gland	UBERON:0002046	92.31	gold quality
cartilage tissue	UBERON:0002418	92.26	gold quality
descending thoracic aorta	UBERON:0002345	91.89	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-13	no	2.91
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

150 targeting SLC41A1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-3671	99.90	73.04	3897

Literature-anchored findings (GeneRIF, showing 16)

• Data report the identification and structural characterization of solute carrier family 41 member 1 (SLC41A1), a eukaryotic protein with homology to the bacterial MgtE family of potential Mg(2+) transporters. (PMID:12810078)
• The SLC41A1 transcript is present in many tissues, notably renal epithelial cells, and is upregulated in some tissues with magnesium deficiency. (PMID:15713785)
• SLC41A1 is a novel mammalian Mg2+ carrier (PMID:18367447)
• Results indicate that SLC41A1 proteins are a central component of Mg(2+) transport systems, and that their Mg(2+) transport function is regulated primarily through an endosomal recycling mechanism involving the SLC41A1 N-terminal cytoplasmic domain. (PMID:21696366)
• Direct DNA sequencing of the SLC41A1 and RAB7L1 genes within the PARK16 locus in 205 Chinese Parkinson’s disease patients shows no significant difference with controls. (PMID:21812739)
• The human SLC41A1 gene encodes for the Na+/Mg(2)+ exchanger, the predominant Mg(2)+ efflux system. (PMID:22031603)
• In normal human kidney tissue, endogenous SLC41A1 specifically localized to renal tubules situated at the corticomedullary boundary, consistent with the region of cystogenesis observed in nephronophthisis. (PMID:23661805)
• Binding partners of SLC41A1, were identified. (PMID:23823179)
• SLC41A1 is significantly overexpressed in nearly 55% of preeclamptic placentas (PMID:23844728)
• Alanine350Valine substitution in Na/Mg(2) exchanger SLC41A1, potentially associated with Parkinson’s disease, is a gain-of-function mutation. (PMID:23976986)
• This study has shown loss of Mg(2+) efflux function consequent to SLC41A1 R244H variant and SLC41A1 coding variants seem to be rare in Taiwanese Parkinson disease. (PMID:24661466)
• Authors performed direct DNA sequencing of the SLC41A1 gene in 100 early-onset PD cases. (PMID:26308152)
• Na+-dependent Mg2+ efflux conducted by Na+/Mg2+ exchanger SLC41A1 is regulated by insulin. (PMID:26355001)
• The association of rs11240569 polymorphism in SLC41A1 gene with reduced risk of Parkinson’s Disease was replicated in our population. (PMID:27612022)
• Knockdown of SLC41A1 magnesium transporter promotes mineralization and attenuates magnesium inhibition during osteogenesis of mesenchymal stromal cells. (PMID:28222767)
• Alzheimer’s Disease-Associated SNP rs708727 in SLC41A1 May Increase Risk for Parkinson’s Disease: Report from Enlarged Slovak Study. (PMID:35163527)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc41a1	ENSDARG00000070214
mus_musculus	Slc41a1	ENSMUSG00000013275
rattus_norvegicus	Slc41a1	ENSRNOG00000042320
drosophila_melanogaster	CG33181	FBGN0053181
caenorhabditis_elegans	ZK1053.6	WBGENE00014201
caenorhabditis_elegans		WBGENE00019504
caenorhabditis_elegans		WBGENE00022682

Paralogs (2): SLC41A3 (ENSG00000114544), SLC41A2 (ENSG00000136052)

Protein

Protein identifiers

Solute carrier family 41 member 1 — Q8IVJ1 (reviewed: Q8IVJ1)

All UniProt accessions (2): B2RMP2, Q8IVJ1

UniProt curated annotations — full annotation on UniProt →

Function. Na(+)/Mg(2+) ion exchanger that acts as a predominant Mg(2+) efflux system at the plasma membrane. Transporter activity is driven by the inwardly directed electrochemical gradient for Na(+) ions, thus directly depends on the extracellular Na(+) ion concentration set by Na(+)/K(+) pump. Generates circadian cellular Mg(2+) fluxes that feed back to regulate clock-controlled gene expression and metabolism and facilitate higher energetic demands during the day. Has a role in regulating the activity of ATP-dependent enzymes, including those operating in Krebs cycle and the electron transport chain.

Subcellular location. Cell membrane. Basolateral cell membrane.

Tissue specificity. Highest expression levels in heart and testis, slightly less in skeletal muscles, prostate, adrenal gland and thyroid, and weakest in the hematopoietic tissues bones marrow, lymph node, thymus and spleen. In the kidney, it is expressed in the distal convoluted tubules, macula densa, and thick ascending limb tubular segments of the nephrons.

Post-translational modifications. Phosphorylated.

Disease relevance. Nephronophthisis-like nephropathy 2 (NPHPL2) [MIM:619468] A disorder with features of nephronophthisis, a cystic kidney disease leading to end-stage renal failure. Nephronophthisis is histologically characterized by modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts. Typical clinical manifestation are chronic renal failure, anemia, polyuria, polydipsia, isosthenuria, and growth retardation. Associations with extrarenal symptoms are frequent. NPHPL2 is an autosomal recessive form characterized by onset of progressive renal insufficiency in the first decades of life. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. The exchange activity is regulated by phosphorylation in a cyclic AMP signaling-dependent way. Temperature-sensitive, reduction or elevation of the temperature significantly decreases or increases its activity respectively.

Similarity. Belongs to the SLC41A transporter family.

RefSeq proteins (1): NP_776253* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006667	SLC41_membr_dom	Domain
IPR036739	SLC41_membr_dom_sf	Homologous_superfamily
IPR045349	SLC41A1-3	Family

Pfam: PF01769

Catalyzed reactions (Rhea), 1 shown:

• Mg(2+)(in) + 2 Na(+)(out) = Mg(2+)(out) + 2 Na(+)(in) (RHEA:66616)

UniProt features (27 total): transmembrane region 10, sequence conflict 10, region of interest 2, compositionally biased region 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IVJ1-F1	78.41	0.43

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-425410	Metal ion SLC transporters
R-HSA-382551	Transport of small molecules
R-HSA-425366
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 235 (showing top): WWTAAGGC_UNKNOWN, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, TGACCTY_ERR1_Q2, GOBP_MAGNESIUM_ION_TRANSPORT, GGGTGGRR_PAX4_03, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_RESPONSE_TO_METAL_ION, GOBP_RESPONSE_TO_MAGNESIUM_ION, GATA3_01, BACH2_01, GATA1_04, MAF_Q6, GOBP_MONOATOMIC_ION_HOMEOSTASIS, DOUGLAS_BMI1_TARGETS_UP, RGAGGAARY_PU1_Q6

GO Biological Process (8): intracellular magnesium ion homeostasis (GO:0010961), magnesium ion transport (GO:0015693), metal ion transport (GO:0030001), cellular response to magnesium ion (GO:0071286), magnesium ion transmembrane transport (GO:1903830), monoatomic ion transport (GO:0006811), monoatomic cation transport (GO:0006812), sodium ion transmembrane transport (GO:0035725)

GO Molecular Function (6): magnesium ion transmembrane transporter activity (GO:0015095), transmembrane transporter activity (GO:0022857), obsolete inorganic cation transmembrane transporter activity (GO:0022890), magnesium:sodium antiporter activity (GO:0061768), protein binding (GO:0005515), monoatomic cation transmembrane transporter activity (GO:0008324)

GO Cellular Component (4): plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), protein-containing complex (GO:0032991), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
SLC-mediated transmembrane transport	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monoatomic cation transmembrane transport	3
magnesium ion homeostasis	1
intracellular monoatomic cation homeostasis	1
metal ion transport	1
monoatomic cation transport	1
response to magnesium ion	1
cellular response to metal ion	1
magnesium ion transport	1
transport	1
monoatomic ion transport	1
sodium ion transport	1
metal ion transmembrane transporter activity	1
magnesium ion transmembrane transport	1
transporter activity	1
transmembrane transport	1
sodium ion transmembrane transporter activity	1
magnesium ion transmembrane transporter activity	1
metal cation:monoatomic cation antiporter activity	1
binding	1
monoatomic ion transmembrane transporter activity	1
membrane	1
cell periphery	1
basal plasma membrane	1
plasma membrane region	1
cellular_component	1
cellular anatomical structure	1

Protein interactions and networks

STRING

834 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC41A1	RAB29	O14966	924
SLC41A1	PM20D1	Q6GTS8	923
SLC41A1	NUCKS1	Q9H1E3	917
SLC41A1	TRPM6	Q9BX84	799
SLC41A1	SLC45A3	Q96JT2	790
SLC41A1	CNNM2	Q9H8M5	789
SLC41A1	TRPM7	Q96QT4	781
SLC41A1	MAGT1	Q9H0U3	764
SLC41A1	MRS2	Q9HD23	761
SLC41A1	CNNM4	Q6P4Q7	694
SLC41A1	CNNM1	Q9NRU3	676
SLC41A1	CNNM3	Q8NE01	672
SLC41A1	CLDN16	Q9Y5I7	663
SLC41A1	NIPAL3	Q6P499	655
SLC41A1	LRRK2	Q5S007	626

IntAct

110 interactions, top by confidence:

A	B	Type	Score
SLC41A1	SCAMP2	psi-mi:“MI:0915”(physical association)	0.560
SLC41A1	GPR61	psi-mi:“MI:0915”(physical association)	0.560
SLC41A1	GPR42	psi-mi:“MI:0915”(physical association)	0.560
SLC41A1	CD79A	psi-mi:“MI:0915”(physical association)	0.560
SLC41A1	GJA5	psi-mi:“MI:0915”(physical association)	0.560
SCAMP2	SLC41A1	psi-mi:“MI:0915”(physical association)	0.560
SLC41A1	SSMEM1	psi-mi:“MI:0915”(physical association)	0.560
AMIGO1	SLC41A1	psi-mi:“MI:0915”(physical association)	0.560
SLC41A1	KASH5	psi-mi:“MI:0915”(physical association)	0.560
	SLC41A1	psi-mi:“MI:0915”(physical association)	0.560
CLN5	SLC41A1	psi-mi:“MI:0915”(physical association)	0.560
SLC41A1	TMEM237	psi-mi:“MI:0915”(physical association)	0.560
OPRM1	SLC41A1	psi-mi:“MI:0915”(physical association)	0.560
SLC41A1	TAAR9	psi-mi:“MI:0915”(physical association)	0.560
SLC41A1	SLC13A4	psi-mi:“MI:0915”(physical association)	0.560
SLC41A1	SYNDIG1	psi-mi:“MI:0915”(physical association)	0.560
AVPR2	SLC41A1	psi-mi:“MI:0915”(physical association)	0.560
AQP6	SLC41A1	psi-mi:“MI:0915”(physical association)	0.560
SLC10A1	SLC41A1	psi-mi:“MI:0915”(physical association)	0.560
TRHR	SLC41A1	psi-mi:“MI:0915”(physical association)	0.560
GJA5	SLC41A1	psi-mi:“MI:0915”(physical association)	0.560
SLC41A1	LHFPL5	psi-mi:“MI:0915”(physical association)	0.560
FFAR3	SLC41A1	psi-mi:“MI:0915”(physical association)	0.560
GPR42	SLC41A1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (89): SLC41A1 (Affinity Capture-MS), SLC41A1 (Affinity Capture-MS), SLC41A1 (Affinity Capture-MS), SLC41A1 (Affinity Capture-MS), SLC41A1 (Two-hybrid), SLC41A1 (Two-hybrid), SLC41A1 (Two-hybrid), SLC41A1 (Two-hybrid), SLC41A1 (Two-hybrid), SLC41A1 (Two-hybrid), SLC41A1 (Two-hybrid), SLC41A1 (Two-hybrid), SLC41A1 (Two-hybrid), SLC41A1 (Two-hybrid), SLC41A1 (Two-hybrid)

ESM2 similar proteins: A0A2K2AIF4, A0A2K2BF92, A0A6P3HVI0, A1L272, A2SWM2, B8AF63, B9H7I1, B9N9Y7, E2RFJ3, E7EXX2, O02228, O54902, O77741, O80605, P41251, P49279, P49280, P49281, P49282, P51027, P56436, P57057, P70553, Q0D7E4, Q27946, Q27981, Q5M7K3, Q5R6B8, Q5R839, Q653V6, Q6DIV6, Q6PF45, Q6YK44, Q86UD5, Q8AVC3, Q8BJA2, Q8CH36, Q8H4H5, Q8IVJ1, Q8L4X4

Diamond homologs: E7EXX2, Q3SWT5, Q4R335, Q5R839, Q5ZHX6, Q6DFC0, Q8BJA2, Q8BYR8, Q8IVJ1, Q921R8, Q96GZ6, Q96JW4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 44 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
G protein-coupled receptor signaling pathway	10	9.1×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

157 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	89
Likely benign	43
Benign	11

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1192530	NM_173854.6(SLC41A1):c.698G>T (p.Gly233Val)	Pathogenic

SpliceAI

1634 predictions. Top by Δscore:

Variant	Effect	Δscore
1:205794940:CAG:C	donor_gain	1.0000
1:205797002:CA:C	acceptor_gain	1.0000
1:205797004:C:CC	acceptor_gain	1.0000
1:205797898:GCCTA:G	donor_loss	1.0000
1:205797899:CCTAC:C	donor_loss	1.0000
1:205797900:CTACC:C	donor_loss	1.0000
1:205797901:TACC:T	donor_loss	1.0000
1:205797903:C:CA	donor_loss	1.0000
1:205797903:CCTG:C	donor_gain	1.0000
1:205797956:C:A	donor_gain	1.0000
1:205798008:C:CT	acceptor_gain	1.0000
1:205798653:A:AC	donor_gain	1.0000
1:205798654:C:CC	donor_gain	1.0000
1:205798654:CT:C	donor_gain	1.0000
1:205798664:CTCA:C	donor_loss	1.0000
1:205798666:CA:C	donor_loss	1.0000
1:205798667:A:AC	donor_gain	1.0000
1:205798667:ACT:A	donor_gain	1.0000
1:205798668:C:CT	donor_gain	1.0000
1:205798668:CT:C	donor_gain	1.0000
1:205798668:CTC:C	donor_gain	1.0000
1:205798668:CTCA:C	donor_gain	1.0000
1:205798668:CTCAG:C	donor_gain	1.0000
1:205798671:A:AC	donor_gain	1.0000
1:205798671:AGTT:A	donor_gain	1.0000
1:205798671:AGTTC:A	donor_gain	1.0000
1:205798672:G:C	donor_gain	1.0000
1:205798691:G:C	donor_gain	1.0000
1:205798811:CATAC:C	acceptor_gain	1.0000
1:205798812:ATAC:A	acceptor_gain	1.0000

AlphaMissense

3329 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:205791619:C:A	G486W	1.000
1:205791652:C:G	D475H	1.000
1:205795442:C:G	R370P	1.000
1:205795444:G:C	S369R	1.000
1:205795444:G:T	S369R	1.000
1:205795446:T:G	S369R	1.000
1:205795463:A:G	L363P	1.000
1:205795465:A:C	N362K	1.000
1:205795465:A:T	N362K	1.000
1:205795469:C:T	G361D	1.000
1:205795470:C:G	G361R	1.000
1:205796995:C:T	G334D	1.000
1:205796996:C:G	G334R	1.000
1:205797906:G:C	S330R	1.000
1:205797906:G:T	S330R	1.000
1:205797908:T:G	S330R	1.000
1:205797938:A:G	W320R	1.000
1:205797938:A:T	W320R	1.000
1:205798724:G:C	D263E	1.000
1:205798724:G:T	D263E	1.000
1:205798725:T:A	D263V	1.000
1:205798725:T:C	D263G	1.000
1:205798725:T:G	D263A	1.000
1:205798726:C:G	D263H	1.000
1:205798728:C:A	G262V	1.000
1:205798728:C:T	G262D	1.000
1:205798729:C:A	G262C	1.000
1:205798729:C:G	G262R	1.000
1:205798733:G:C	S260R	1.000
1:205798733:G:T	S260R	1.000

dbSNP variants (sampled 300 via entrez): RS1000380156 (1:205811763 A>G), RS1000432259 (1:205811374 G>A), RS1000715233 (1:205813213 C>A,G,T), RS1000894599 (1:205807138 C>T), RS1000898862 (1:205807815 CCTGA>C), RS1001315904 (1:205793712 C>G), RS1001376451 (1:205793842 C>T), RS1001419287 (1:205801731 G>C), RS1001481034 (1:205813424 G>A,C), RS1001505154 (1:205812203 C>T), RS1001681496 (1:205806406 A>G), RS1001832595 (1:205813336 C>A,T), RS1001870347 (1:205801437 C>T), RS1002062621 (1:205807481 A>G), RS1002064515 (1:205812555 C>A)

Disease associations

OMIM: gene MIM:610801 | disease phenotypes: MIM:619468

GenCC curated gene-disease

Disease	Classification	Inheritance
kidney disorder	Limited	Autosomal recessive
nephronophthisis-like nephropathy 2	Limited	Unknown

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
kidney disorder	Limited	AR

Mondo (2): nephronophthisis-like nephropathy 2 (MONDO:0859175), kidney disorder (MONDO:0005240)

Orphanet (0):

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000103	Polyuria
HP:0001954	Recurrent fever
HP:0001959	Polydipsia
HP:0002110	Bronchiectasis
HP:0002113	Pulmonary infiltrates
HP:0002205	Recurrent respiratory infections
HP:0003259	Elevated circulating creatinine concentration
HP:0003593	Infantile onset
HP:0003774	Stage 5 chronic kidney disease
HP:0012735	Cough
HP:0032417	Periglomerular fibrosis
HP:0032622	Tubular luminal dilatation

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST000530_4	Parkinson’s disease	2.000000e-12
GCST001126_10	Parkinson’s disease	1.000000e-07
GCST001796_1	Prostate-specific antigen levels	2.000000e-19
GCST002606_1	Prostate cancer	4.000000e-08
GCST002703_2	Prostate-specific antigen levels	4.000000e-15
GCST004625_43	Monocyte count	1.000000e-10
GCST004902_40	Parkinson’s disease	1.000000e-23
GCST006408_17	Allergic sensitization	9.000000e-07
GCST006414_111	Atrial fibrillation	2.000000e-08
GCST010697_7	Cortical surface area (min-P)	8.000000e-11
GCST010698_41	Subcortical volume (min-P)	8.000000e-12
GCST010699_29	Brain morphology (min-P)	3.000000e-09
GCST010700_18	Cortical thickness (MOSTest)	5.000000e-12
GCST010701_13	Cortical surface area (MOSTest)	3.000000e-08
GCST010702_124	Subcortical volume (MOSTest)	3.000000e-09
GCST010703_107	Brain morphology (MOSTest)	2.000000e-20
GCST010796_1104	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010989_190	Body size at age 10	3.000000e-13
GCST90002393_175	Monocyte count	7.000000e-17
GCST90002400_538	Plateletcrit	1.000000e-11

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0005091	monocyte count
EFO:0005298	allergic sensitization measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0004327	electrocardiography
EFO:0009819	comparative body size at age 10, self-reported
EFO:0007985	platelet crit

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC41 family of divalent cation transporters

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
beta-methylcholine	affects expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Calcitriol	increases expression, affects cotreatment	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Lead	affects expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Quercetin	decreases expression	1
Dihydrotestosterone	increases expression	1
Testosterone	affects cotreatment, increases expression	1
Thiram	increases expression	1
Tretinoin	decreases expression	1
Triclosan	decreases expression	1
Valproic Acid	affects expression	1
Aflatoxin B1	increases methylation	1
Lactic Acid	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D4NW	HCT116-SLC41A1-KO-c5	Cancer cell line	Male
CVCL_D4NX	HCT116-SLC41A1-KO-c7	Cancer cell line	Male
CVCL_TN66	HAP1 SLC41A1 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00067990	PHASE4	COMPLETED	Angiotensin II Blockade for Chronic Allograft Nephropathy
NCT00117078	PHASE4	COMPLETED	Aranesp® Monthly Preference Study - 2
NCT00117130	PHASE4	COMPLETED	Study to Evaluate Effectiveness of Aranesp®
NCT00132431	PHASE4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00140985	PHASE4	COMPLETED	Antiproteinuric Efficacy of Losartan Potassium in Patients With Non-Diabetic Proteinuric Renal Diseases (0954-213)
NCT00246129	PHASE4	COMPLETED	CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation
NCT00275535	PHASE4	COMPLETED	The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients
NCT00282217	PHASE4	COMPLETED	Study Evaluating Sirolimus in the Treatment of Kidney Transplant
NCT00289614	PHASE4	COMPLETED	Patients With Renal Impairment and Diabetes Undergoing Computed Tomography (CT)
NCT00290069	PHASE4	UNKNOWN	Renal Function Optimization With Mycophenolate Mofetil (MMF) Immunosuppressor Regimes (ALHAMBRA)
NCT00338468	PHASE4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00368901	PHASE4	COMPLETED	STAAR-2 Clinical Study
NCT00369733	PHASE4	COMPLETED	STAAR-3 Clinical Study
NCT00369772	PHASE4	COMPLETED	STAAR-1 Clinical Study
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00443508	PHASE4	UNKNOWN	Reduction or Discontinuation of CNI’s With Conversion to Everolimus-Based Immunosuppresion
NCT00452478	PHASE4	TERMINATED	Conversion From Standard Phosphate Binder Therapy to Fosrenol® (Lanthanum Carbonate) in Chronic Kidney Disease Stage 5
NCT00492518	PHASE4	COMPLETED	Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy
NCT00505102	PHASE4	UNKNOWN	Safe Renal Function In Long Term Heart Transplanted Patients
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00688480	PHASE4	COMPLETED	Do Xanthine Oxidase Inhibitors Reduce Both Left Ventricular Hypertrophy and Endothelial Dysfunction in Cardiovascular Patients With Renal Dysfunction?
NCT00863707	PHASE4	COMPLETED	A Study of the Safety and Tolerance of Regadenoson in Subjects With Renal Impairment
NCT01101698	PHASE4	UNKNOWN	Vitamin K2 and Vessel Calcification in Chronic Kidney Disease Patients
NCT01150201	PHASE4	COMPLETED	Aliskiren Combined With Losartan in Proteinuric, Non-diabetic Chronic Kidney Disease
NCT01155141	PHASE4	COMPLETED	Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
NCT01228279	PHASE4	COMPLETED	Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis
NCT01334333	PHASE4	COMPLETED	Comparison of Medication Adherence Between Once and Twice Daily Tacrolimus in Stable Renal Transplant Recipients
NCT01437943	PHASE4	TERMINATED	Effect of Short Term Aliskiren Treatment in Kidney Transplant Patients
NCT01545479	PHASE4	COMPLETED	Increased Renal Oxygenation and Angiotensin Converting Enzyme Inhibition
NCT01614431	PHASE4	COMPLETED	N Acetyl Cysteine for Cystinosis Patients
NCT01631149	PHASE4	COMPLETED	Effect of Deep BLock on Intraoperative Surgical Conditions
NCT01722513	PHASE4	UNKNOWN	Efficacy and Safety of Alprostadil Prevent Contrast Induced Nephropathy
NCT01985360	PHASE4	COMPLETED	ISCHEMIA-Chronic Kidney Disease Trial
NCT02311010	PHASE4	UNKNOWN	Practical Use of Advagraf de Novo After Kidney Transplantation According to Recipient Genetic Polymorphism
NCT02413073	PHASE4	COMPLETED	Whole Body Vibration in Kidney Disease
NCT02444013	PHASE4	UNKNOWN	Folic Acid for Prevention of Contrast Induced Nephropathy
NCT02663713	PHASE4	COMPLETED	A Randomized, Pharmacodynamic Comparison of Low Dose Ticagrelor to Clopidogrel in Patients With Prior Myocardial Infarction
NCT02707809	PHASE4	COMPLETED	Effects of Dexmedetomidine on Microcirculation of Kidney Transplant Recipient
NCT02761577	PHASE4	COMPLETED	A Prospective Study on Incidence and Prevention of Contrast-induced Nephropathy in Croatia
NCT03029351	PHASE4	TERMINATED	GLP-1 Receptor Agonist Therapy and Albuminuria in Patients With Type 2 Diabetes