SLC41A2

Summary

SLC41A2 (solute carrier family 41 member 2, HGNC:31045) is a protein-coding gene on chromosome 12q23.3, encoding Solute carrier family 41 member 2 (Q96JW4). Acts as a plasma-membrane magnesium transporter.

Predicted to enable magnesium ion transmembrane transporter activity. Involved in magnesium ion transport. Located in plasma membrane.

Source: NCBI Gene 84102 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 97 total
• MANE Select transcript: NM_001352171

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31045
Approved symbol	SLC41A2
Name	solute carrier family 41 member 2
Location	12q23.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434K0427
Ensembl gene	ENSG00000136052
Ensembl biotype	protein_coding
OMIM	610802
Entrez	84102

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 18 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000258538, ENST00000411411, ENST00000415674, ENST00000417469, ENST00000424946, ENST00000432951, ENST00000433540, ENST00000437220, ENST00000449866, ENST00000549713, ENST00000906846, ENST00000906847, ENST00000906848, ENST00000906849, ENST00000906850, ENST00000906851, ENST00000906852, ENST00000906853, ENST00000963050

RefSeq mRNA: 11 — MANE Select: NM_001352171 NM_001352169, NM_001352170, NM_001352171, NM_001352172, NM_001387125, NM_001387126, NM_001387127, NM_001387128, NM_001387129, NM_001387130, NM_032148

CCDS: CCDS9100

Canonical transcript exons

ENST00000258538 — 11 exons

Exon	Start	End
ENSE00000922975	104845843	104845974
ENSE00000922976	104861291	104861370
ENSE00000922978	104886293	104886439
ENSE00000922980	104895274	104895345
ENSE00000922981	104909655	104909762
ENSE00000937858	104866432	104866579
ENSE00000937859	104844472	104844620
ENSE00001255321	104927973	104928694
ENSE00001650772	104801801	104805337
ENSE00003790761	104889033	104889177
ENSE00003916167	104958088	104958290

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 95.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.0878 / max 147.2639, expressed in 1371 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133019	6.8426	1253
133020	1.2452	649

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	95.00	gold quality
jejunal mucosa	UBERON:0000399	94.73	gold quality
secondary oocyte	CL:0000655	93.20	gold quality
ileal mucosa	UBERON:0000331	92.94	gold quality
duodenum	UBERON:0002114	92.56	gold quality
epithelial cell of pancreas	CL:0000083	92.45	gold quality
colonic epithelium	UBERON:0000397	92.45	gold quality
liver	UBERON:0002107	92.38	gold quality
right lobe of liver	UBERON:0001114	91.60	gold quality
islet of Langerhans	UBERON:0000006	90.32	gold quality
adrenal tissue	UBERON:0018303	90.22	gold quality
parotid gland	UBERON:0001831	88.41	gold quality
corpus epididymis	UBERON:0004359	88.20	gold quality
cartilage tissue	UBERON:0002418	88.00	gold quality
descending thoracic aorta	UBERON:0002345	87.90	gold quality
germinal epithelium of ovary	UBERON:0001304	87.61	gold quality
rectum	UBERON:0001052	86.68	gold quality
pancreas	UBERON:0001264	86.67	gold quality
stomach	UBERON:0000945	86.59	gold quality
sperm	CL:0000019	86.54	gold quality
colonic mucosa	UBERON:0000317	86.29	gold quality
body of stomach	UBERON:0001161	86.26	gold quality
mucosa of transverse colon	UBERON:0004991	85.73	gold quality
thoracic aorta	UBERON:0001515	85.71	gold quality
ascending aorta	UBERON:0001496	85.52	gold quality
gall bladder	UBERON:0002110	85.49	gold quality
tendon	UBERON:0000043	85.19	gold quality
mucosa of sigmoid colon	UBERON:0004993	85.12	gold quality
body of pancreas	UBERON:0001150	84.74	gold quality
seminal vesicle	UBERON:0000998	83.83	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.39
E-MTAB-8498	yes	9.15
E-MTAB-2983	no	479.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

96 targeting SLC41A2, 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-8485	100.00	77.57	4731
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-545-3P	99.95	70.74	2783

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc41a2b	ENSDARG00000073881
danio_rerio	slc41a2a	ENSDARG00000075803
mus_musculus	Slc41a2	ENSMUSG00000034591
rattus_norvegicus	Slc41a2	ENSRNOG00000008713
drosophila_melanogaster	CG33181	FBGN0053181
caenorhabditis_elegans	ZK1053.6	WBGENE00014201
caenorhabditis_elegans		WBGENE00019504
caenorhabditis_elegans		WBGENE00022682

Paralogs (2): SLC41A3 (ENSG00000114544), SLC41A1 (ENSG00000133065)

Protein

Protein identifiers

Solute carrier family 41 member 2 — Q96JW4 (reviewed: Q96JW4)

All UniProt accessions (9): C9J2P6, C9JA64, C9JCR2, C9JDQ2, Q96JW4, C9JIL4, C9JKF2, C9JYJ7, H7BZT9

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a plasma-membrane magnesium transporter. Can also mediate the transport of other divalent metal cations in an order of Ba(2+) > Ni(2+) > Co(2+) > Fe(2+) > Mn(2+).

Subcellular location. Cell membrane.

Similarity. Belongs to the SLC41A transporter family.

RefSeq proteins (11): NP_001339098, NP_001339099, NP_001339100, NP_001339101, NP_001374054, NP_001374055, NP_001374056, NP_001374057, NP_001374058, NP_001374059, NP_115524 (=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), 5 shown:

• Fe(2+)(in) = Fe(2+)(out) (RHEA:28486)
• Co(2+)(in) = Co(2+)(out) (RHEA:28578)
• Mn(2+)(in) = Mn(2+)(out) (RHEA:28699)
• Mg(2+)(in) = Mg(2+)(out) (RHEA:29827)
• Ni(2+)(in) = Ni(2+)(out) (RHEA:29831)

UniProt features (27 total): topological domain 12, transmembrane region 11, modified residue 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96JW4-F1	72.69	0.39

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 136, 137

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: 184 (showing top): GOBP_TRANSITION_METAL_ION_TRANSPORT, GOBP_MAGNESIUM_ION_TRANSPORT, GOBP_IRON_ION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, AAACCAC_MIR140, TCF11_01, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, GOBP_TRANSMEMBRANE_TRANSPORT, PITX2_Q2, HOWLIN_CITED1_TARGETS_2_DN, MASSARWEH_TAMOXIFEN_RESISTANCE_UP, GOMF_METAL_ION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_MONOATOMIC_CATION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, chr12q23

GO Biological Process (11): cobalt ion transport (GO:0006824), iron ion transport (GO:0006826), manganese ion transport (GO:0006828), nickel cation transport (GO:0015675), magnesium ion transport (GO:0015693), monoatomic ion transport (GO:0006811), monoatomic cation transport (GO:0006812), metal ion transport (GO:0030001), transmembrane transport (GO:0055085), monoatomic cation transmembrane transport (GO:0098655), magnesium ion transmembrane transport (GO:1903830)

GO Molecular Function (4): magnesium ion transmembrane transporter activity (GO:0015095), protein binding (GO:0005515), monoatomic cation transmembrane transporter activity (GO:0008324), obsolete inorganic cation transmembrane transporter activity (GO:0022890)

GO Cellular Component (2): plasma membrane (GO:0005886), 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
transition metal ion transport	4
monoatomic cation transmembrane transport	3
transport	2
monoatomic cation transport	2
metal ion transport	1
monoatomic ion transport	1
cellular process	1
monoatomic ion transmembrane transport	1
magnesium ion transport	1
metal ion transmembrane transporter activity	1
magnesium ion transmembrane transport	1
binding	1
monoatomic ion transmembrane transporter activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

612 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC41A2	TRPM6	Q9BX84	755
SLC41A2	TRPM7	Q96QT4	737
SLC41A2	MRS2	Q9HD23	692
SLC41A2	CNNM2	Q9H8M5	671
SLC41A2	MAGT1	Q9H0U3	616
SLC41A2	CNNM1	Q9NRU3	598
SLC41A2	NIPAL3	Q6P499	507
SLC41A2	CNNM3	Q8NE01	498
SLC41A2	NIPA1	Q7RTP0	495
SLC41A2	CNNM4	Q6P4Q7	477
SLC41A2	SLC35H1	Q9NQQ7	474
SLC41A2	NIPAL1	Q6NVV3	467
SLC41A2	CLDN16	Q9Y5I7	461
SLC41A2	NIPA2	Q8N8Q9	460
SLC41A2	SLC38A6	Q8IZM9	458

IntAct

101 interactions, top by confidence:

A	B	Type	Score
SLC41A2	KASH5	psi-mi:“MI:0915”(physical association)	0.720
KASH5	SLC41A2	psi-mi:“MI:0915”(physical association)	0.720
SLC41A2	HHLA2	psi-mi:“MI:0915”(physical association)	0.560
SLC41A2	AMIGO1	psi-mi:“MI:0915”(physical association)	0.560
SLC41A2	SLC6A15	psi-mi:“MI:0915”(physical association)	0.560
SLC41A2	SHISAL1	psi-mi:“MI:0915”(physical association)	0.560
SLC41A2	GPR42	psi-mi:“MI:0915”(physical association)	0.560
SLC41A2	LYVE1	psi-mi:“MI:0915”(physical association)	0.560
SSMEM1	SLC41A2	psi-mi:“MI:0915”(physical association)	0.560
SLC41A2	MFF	psi-mi:“MI:0915”(physical association)	0.560
FATE1	SLC41A2	psi-mi:“MI:0915”(physical association)	0.560
LDLRAD1	SLC41A2	psi-mi:“MI:0915”(physical association)	0.560
IGFBP5	SLC41A2	psi-mi:“MI:0915”(physical association)	0.560
FUT3	SLC41A2	psi-mi:“MI:0915”(physical association)	0.560
CLN5	SLC41A2	psi-mi:“MI:0915”(physical association)	0.560
PVR	SLC41A2	psi-mi:“MI:0915”(physical association)	0.560
ERVFRD-1	SLC41A2	psi-mi:“MI:0915”(physical association)	0.560
SHISAL1	SLC41A2	psi-mi:“MI:0915”(physical association)	0.560
LEUTX	SLC41A2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (43): CCDC155 (Two-hybrid), SLC41A2 (Two-hybrid), SLC41A2 (Two-hybrid), SLC41A2 (Synthetic Lethality), SLC41A2 (Affinity Capture-RNA), SLC41A2 (Two-hybrid), SLC41A2 (Two-hybrid), SLC41A2 (Two-hybrid), SLC41A2 (Two-hybrid), SLC41A2 (Two-hybrid), SLC41A2 (Two-hybrid), SLC41A2 (Two-hybrid), SLC41A2 (Two-hybrid), SLC41A2 (Two-hybrid), KIAA1644 (Two-hybrid)

ESM2 similar proteins: A0A2K1ZPK4, A0A2K2AIF4, A0A2K2BF92, B9GNS0, B9H7I1, E7EXX2, O22881, O54902, O77741, P41251, P49279, P49280, P49281, P49282, P49283, P51027, P56436, P70553, Q0D7E4, Q21433, Q21434, Q27946, Q27981, Q4R335, Q5QN13, Q5ZHX6, Q6DFC0, Q6DIV6, Q6PF45, Q6YWQ4, Q6ZG85, Q7XIV8, Q869V1, Q8BGY9, Q8BYR8, Q8H3P9, Q8H4H5, Q8UWF0, Q8VDT1, Q8VXB5

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	1
Benign	24

Top pathogenic / likely-pathogenic (0)

SpliceAI

1760 predictions. Top by Δscore:

Variant	Effect	Δscore
12:104861366:CAATG:C	acceptor_gain	1.0000
12:104861369:TG:T	acceptor_gain	1.0000
12:104909653:A:AC	donor_gain	1.0000
12:104909654:C:CC	donor_gain	1.0000
12:104909654:CTG:C	donor_gain	1.0000
12:104909654:CTGCA:C	donor_gain	1.0000
12:104927970:CA:C	donor_loss	1.0000
12:104927971:A:AT	donor_loss	1.0000
12:104844530:C:CT	donor_gain	0.9900
12:104844618:CTC:C	acceptor_gain	0.9900
12:104845837:ACAT:A	donor_loss	0.9900
12:104845838:CATA:C	donor_loss	0.9900
12:104845840:TA:T	donor_loss	0.9900
12:104845841:ACC:A	donor_loss	0.9900
12:104845842:C:CG	donor_loss	0.9900
12:104845971:ATACC:A	acceptor_loss	0.9900
12:104845972:TAC:T	acceptor_gain	0.9900
12:104845972:TACC:T	acceptor_loss	0.9900
12:104845973:ACCTG:A	acceptor_loss	0.9900
12:104845974:CCTGA:C	acceptor_loss	0.9900
12:104845975:C:A	acceptor_loss	0.9900
12:104845976:T:A	acceptor_loss	0.9900
12:104861285:TCTTA:T	donor_loss	0.9900
12:104861286:CT:C	donor_loss	0.9900
12:104861287:TTA:T	donor_loss	0.9900
12:104861288:TACC:T	donor_loss	0.9900
12:104861289:A:AC	donor_gain	0.9900
12:104861289:A:C	donor_loss	0.9900
12:104861290:C:CC	donor_gain	0.9900
12:104861367:AATG:A	acceptor_gain	0.9900

AlphaMissense

3754 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:104805225:C:T	G550E	1.000
12:104805226:C:A	G550W	1.000
12:104805226:C:G	G550R	1.000
12:104805226:C:T	G550R	1.000
12:104805234:T:G	D547A	1.000
12:104805249:A:G	L542P	1.000
12:104845929:G:A	T434I	1.000
12:104845938:C:A	R431M	1.000
12:104845940:G:C	S430R	1.000
12:104845940:G:T	S430R	1.000
12:104845942:T:G	S430R	1.000
12:104845961:A:C	N423K	1.000
12:104845961:A:T	N423K	1.000
12:104861353:A:G	L398P	1.000
12:104866447:G:T	A387D	1.000
12:104866466:A:G	W381R	1.000
12:104866466:A:T	W381R	1.000
12:104886348:G:C	D324E	1.000
12:104886348:G:T	D324E	1.000
12:104886349:T:A	D324V	1.000
12:104886349:T:C	D324G	1.000
12:104886349:T:G	D324A	1.000
12:104886350:C:G	D324H	1.000
12:104886352:C:A	G323V	1.000
12:104886352:C:T	G323D	1.000
12:104886353:C:A	G323C	1.000
12:104886353:C:G	G323R	1.000
12:104886357:A:C	S321R	1.000
12:104886357:A:T	S321R	1.000
12:104886359:T:G	S321R	1.000

dbSNP variants (sampled 300 via entrez): RS1000005611 (12:104928784 AAC>A), RS1000013041 (12:104831738 T>C), RS1000015644 (12:104835252 T>C), RS1000067864 (12:104834950 T>G), RS1000082940 (12:104842494 T>A), RS1000093863 (12:104889737 G>A,C), RS1000157100 (12:104956553 C>A), RS1000157860 (12:104921987 T>A), RS1000163075 (12:104805707 A>C), RS1000168948 (12:104864846 C>G), RS1000248494 (12:104958265 T>C), RS1000280241 (12:104951544 A>G), RS1000319081 (12:104903907 A>G), RS1000323053 (12:104816025 G>C), RS1000364234 (12:104949810 C>T)

Disease associations

OMIM: gene MIM:610802 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST010923_11	Beta blocker survival benefit in heart failure with reduced ejection fraction (time to all cause mortality x beta blocker interaction)	8.000000e-06
GCST011998_10	Glucocorticoid receptor gene expression in B-cell precursor acute lymphoblastic leukaemia	9.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004352	mortality
EFO:0007766	response to beta blocker

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

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases methylation	6
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
potassium chromate(VI)	affects cotreatment, decreases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
bisphenol A	increases expression	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression	1
entinostat	increases expression	1
dimethylarsinous acid	increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
3,4,5,4’-tetramethoxystilbene	affects expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	increases expression, affects cotreatment	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Lead	affects 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_D4NY	HCT116-SLC41A2-KO-c4	Cancer cell line	Male
CVCL_D4NZ	HCT116-SLC41A2-KO-c6	Cancer cell line	Male
CVCL_TN67	HAP1 SLC41A2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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