SLC41A3

Summary

SLC41A3 (solute carrier family 41 member 3, HGNC:31046) is a protein-coding gene on chromosome 3q21.2-q21.3, encoding Solute carrier family 41 member 3 (Q96GZ6). Na(+)/Mg(2+) ion exchanger that acts as a predominant Mg(2+) efflux system at the mitochondrial inner membrane.

Enables magnesium:sodium antiporter activity. Involved in mitochondrial magnesium ion transmembrane transport. Located in mitochondrial inner membrane and plasma membrane.

Source: NCBI Gene 54946 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 106 total
• MANE Select transcript: NM_017836

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31046
Approved symbol	SLC41A3
Name	solute carrier family 41 member 3
Location	3q21.2-q21.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20473
Ensembl gene	ENSG00000114544
Ensembl biotype	protein_coding
OMIM	610803
Entrez	54946

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 29 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000315891, ENST00000346785, ENST00000360370, ENST00000383598, ENST00000504035, ENST00000504118, ENST00000505996, ENST00000506102, ENST00000507008, ENST00000507280, ENST00000508835, ENST00000509064, ENST00000509452, ENST00000510651, ENST00000512470, ENST00000512557, ENST00000513464, ENST00000513723, ENST00000514023, ENST00000514333, ENST00000514677, ENST00000514891, ENST00000910125, ENST00000910126, ENST00000910127, ENST00000910128, ENST00000910129, ENST00000910130, ENST00000910131, ENST00000947432, ENST00000947433, ENST00000947434, ENST00000947435, ENST00000947436, ENST00000947437, ENST00000947438

RefSeq mRNA: 5 — MANE Select: NM_017836 NM_001008485, NM_001008486, NM_001008487, NM_001164475, NM_017836

CCDS: CCDS33842, CCDS33843, CCDS33844, CCDS43144, CCDS54635

Canonical transcript exons

ENST00000360370 — 11 exons

Exon	Start	End
ENSE00001559606	126084093	126084124
ENSE00002084619	126006357	126007225
ENSE00003462142	126015494	126015573
ENSE00003478742	126008732	126008880
ENSE00003602380	126012615	126012749
ENSE00003642951	126026335	126026479
ENSE00003656958	126022786	126022932
ENSE00003671645	126050943	126051050
ENSE00003680006	126067947	126068246
ENSE00003685678	126033607	126033678
ENSE00003692093	126016731	126016875

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 96.17.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.1359 / max 87.0869, expressed in 1767 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44314	6.7813	1745
44316	1.9078	1085
44315	0.1491	30
44312	0.1348	48
44317	0.1251	70
44309	0.0153	3
44313	0.0152	10
44311	0.0044	2
44310	0.0030	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	96.17	gold quality
cerebellar hemisphere	UBERON:0002245	96.08	gold quality
cerebellar cortex	UBERON:0002129	96.05	gold quality
descending thoracic aorta	UBERON:0002345	95.14	gold quality
cerebellum	UBERON:0002037	95.13	gold quality
left ovary	UBERON:0002119	95.07	gold quality
prefrontal cortex	UBERON:0000451	95.06	gold quality
anterior cingulate cortex	UBERON:0009835	95.06	gold quality
cingulate cortex	UBERON:0003027	95.02	gold quality
right frontal lobe	UBERON:0002810	94.97	gold quality
right ovary	UBERON:0002118	94.80	gold quality
thoracic aorta	UBERON:0001515	94.72	gold quality
ascending aorta	UBERON:0001496	94.70	gold quality
right testis	UBERON:0004534	94.36	gold quality
middle temporal gyrus	UBERON:0002771	94.19	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.19	gold quality
left testis	UBERON:0004533	94.13	gold quality
cortical plate	UBERON:0005343	94.11	gold quality
body of uterus	UBERON:0009853	94.01	gold quality
aorta	UBERON:0000947	93.99	gold quality
right adrenal gland cortex	UBERON:0035827	93.95	gold quality
left adrenal gland	UBERON:0001234	93.89	gold quality
left adrenal gland cortex	UBERON:0035825	93.86	gold quality
right coronary artery	UBERON:0001625	93.68	gold quality
amygdala	UBERON:0001876	93.68	gold quality
adenohypophysis	UBERON:0002196	93.64	gold quality
right adrenal gland	UBERON:0001233	93.62	gold quality
neocortex	UBERON:0001950	93.60	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.60	gold quality
popliteal artery	UBERON:0002250	93.55	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-4850	no	189.77
E-GEOD-99795	no	89.79
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting SLC41A3, 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-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-6760-5P	98.87	66.73	1515
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-6864-5P	98.38	66.59	1079
HSA-MIR-6511B-5P	97.98	65.64	823
HSA-MIR-6811-5P	97.98	64.96	848
HSA-MIR-12127	97.93	66.67	793
HSA-MIR-3920	97.75	69.02	1168
HSA-MIR-4253	97.48	65.11	692
HSA-MIR-6862-5P	97.48	64.84	713
HSA-MIR-509-3-5P	97.21	67.74	1517
HSA-MIR-509-5P	97.21	67.90	1512

Literature-anchored findings (GeneRIF, showing 2)

• Data identify SLC41A3 as the first mammalian mitochondrial Mg(2+) efflux system, which greatly enhances the understanding of intracellular Mg(2+) homeostasis. (PMID:27302215)
• SLC41A3 Exhibits as a Carcinoma Biomarker and Promoter in Liver Hepatocellular Carcinoma. (PMID:34819993)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc41a3	ENSDARG00000061272
mus_musculus	Slc41a3	ENSMUSG00000030089
rattus_norvegicus	Slc41a3	ENSRNOG00000045821
drosophila_melanogaster	CG33181	FBGN0053181
caenorhabditis_elegans	ZK1053.6	WBGENE00014201
caenorhabditis_elegans		WBGENE00019504
caenorhabditis_elegans		WBGENE00022682

Paralogs (2): SLC41A1 (ENSG00000133065), SLC41A2 (ENSG00000136052)

Protein

Protein identifiers

Solute carrier family 41 member 3 — Q96GZ6 (reviewed: Q96GZ6)

All UniProt accessions (11): D6R925, D6R9M9, D6R9S7, D6R9X6, D6RC02, D6RDB0, D6RDM3, D6RF72, D6RHE3, D6RJC0, Q96GZ6

UniProt curated annotations — full annotation on UniProt →

Function. Na(+)/Mg(2+) ion exchanger that acts as a predominant Mg(2+) efflux system at the mitochondrial inner membrane.

Subcellular location. Mitochondrion inner membrane.

Similarity. Belongs to the SLC41A transporter family.

Isoforms (9)

UniProt ID	Names	Canonical?
Q96GZ6-1	1	yes
Q96GZ6-2	2
Q96GZ6-3	3
Q96GZ6-4	4
Q96GZ6-5	5
Q96GZ6-6	6
Q96GZ6-7	7
Q96GZ6-8	8
Q96GZ6-9	9

RefSeq proteins (5): NP_001008485, NP_001008486, NP_001008487, NP_001157947, NP_060306* (*=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 (30 total): transmembrane region 10, splice variant 10, sequence conflict 5, sequence variant 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96GZ6-F1	79.10	0.42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 109 (showing top): GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_MAGNESIUM_ION_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, GOCC_MITOCHONDRIAL_ENVELOPE, chr3q21, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_SODIUM_ION_TRANSPORT, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, GOCC_ORGANELLE_INNER_MEMBRANE, GOMF_METAL_ION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_MONOATOMIC_CATION_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_ACTIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_SECONDARY_ACTIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, DODD_NASOPHARYNGEAL_CARCINOMA_DN

GO Biological Process (8): mitochondrial magnesium ion transmembrane transport (GO:0045016), monoatomic ion transport (GO:0006811), monoatomic cation transport (GO:0006812), magnesium ion transport (GO:0015693), metal ion transport (GO:0030001), sodium ion transmembrane transport (GO:0035725), transmembrane transport (GO:0055085), monoatomic cation transmembrane transport (GO:0098655)

GO Molecular Function (5): magnesium:sodium antiporter activity (GO:0061768), protein binding (GO:0005515), monoatomic cation transmembrane transporter activity (GO:0008324), magnesium ion transmembrane transporter activity (GO:0015095), obsolete inorganic cation transmembrane transporter activity (GO:0022890)

GO Cellular Component (4): mitochondrial inner membrane (GO:0005743), plasma membrane (GO:0005886), mitochondrion (GO:0005739), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
magnesium ion transmembrane transport	2
transport	2
monoatomic cation transport	2
monoatomic cation transmembrane transport	2
monoatomic ion transport	1
metal ion transport	1
sodium ion transport	1
cellular process	1
monoatomic ion 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
metal ion transmembrane transporter activity	1
organelle inner membrane	1
mitochondrial membrane	1
membrane	1
cell periphery	1
cytoplasm	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

540 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC41A3	TRPM6	Q9BX84	791
SLC41A3	MRS2	Q9HD23	695
SLC41A3	CNNM2	Q9H8M5	688
SLC41A3	TRPM7	Q96QT4	679
SLC41A3	SPRYD7	Q5W111	600
SLC41A3	MAGT1	Q9H0U3	597
SLC41A3	MMGT1	Q8N4V1	519
SLC41A3	CNNM3	Q8NE01	515
SLC41A3	CNNM1	Q9NRU3	515
SLC41A3	CLDN16	Q9Y5I7	512
SLC41A3	CNNM4	Q6P4Q7	512
SLC41A3	FXYD2	P54710	504
SLC41A3	NIPAL3	Q6P499	498
SLC41A3	SLC12A3	P55017	492
SLC41A3	CLDN19	Q8N6F1	490

IntAct

53 interactions, top by confidence:

A	B	Type	Score
SLC41A3	REL	psi-mi:“MI:0915”(physical association)	0.560
NHERF4	SLC41A3	psi-mi:“MI:0915”(physical association)	0.560
REL	SLC41A3	psi-mi:“MI:0915”(physical association)	0.560
SLC41A3	NHERF4	psi-mi:“MI:0915”(physical association)	0.560
SLC41A3	SUFU	psi-mi:“MI:0915”(physical association)	0.560
CCL3L1	SLC41A3	psi-mi:“MI:0915”(physical association)	0.560
ARLN	SLC41A3	psi-mi:“MI:0915”(physical association)	0.560
TMBIM6	SLC41A3	psi-mi:“MI:0915”(physical association)	0.560
IGFBP5	SLC41A3	psi-mi:“MI:0915”(physical association)	0.560
SLC41A3	SMCO4	psi-mi:“MI:0915”(physical association)	0.560
PLP1	SLC41A3	psi-mi:“MI:0915”(physical association)	0.560
TSPO2	SLC41A3	psi-mi:“MI:0915”(physical association)	0.560
SLC41A3	BDNF	psi-mi:“MI:0915”(physical association)	0.560
GAPDH	SLC41A3	psi-mi:“MI:0915”(physical association)	0.560
SLC41A3	CCR2	psi-mi:“MI:0915”(physical association)	0.370
SLC41A3	GPR37	psi-mi:“MI:0915”(physical association)	0.370
SLC41A3	NPSR1	psi-mi:“MI:0915”(physical association)	0.370
SLC41A3	SMO	psi-mi:“MI:0915”(physical association)	0.370
MAPK6	SLC41A3	psi-mi:“MI:0915”(physical association)	0.370
SLC41A3	CREB3	psi-mi:“MI:0915”(physical association)	0.370
ZDHHC12	NBAS	psi-mi:“MI:0914”(association)	0.350
ZACN	FAM234B	psi-mi:“MI:0914”(association)	0.350
HTR3A	EXTL3	psi-mi:“MI:0914”(association)	0.350
OR13J1	FZD7	psi-mi:“MI:0914”(association)	0.350

BioGRID (104): SLC41A3 (Two-hybrid), PDZD3 (Two-hybrid), SLC41A3 (Affinity Capture-MS), SLC41A3 (Reconstituted Complex), SLC41A3 (Two-hybrid), SLC41A3 (Affinity Capture-MS), SLC41A3 (Affinity Capture-MS), SLC41A3 (Affinity Capture-MS), SLC41A3 (Affinity Capture-MS), SLC41A3 (Affinity Capture-RNA), SLC41A3 (Proximity Label-MS), SLC41A3 (Two-hybrid), SLC41A3 (Two-hybrid), IGFBP5 (Two-hybrid), PLP1 (Two-hybrid)

ESM2 similar proteins: A0A075B734, A1L272, A2IBY8, A8W649, A9Y006, D4A7H1, E7EXX2, F7B113, O14520, O35454, O54794, O62735, O94956, P34080, P35525, P41181, P47862, P47863, P47864, P51789, P51797, P56402, P56403, P79099, Q06495, Q06496, Q08DE6, Q4R691, Q5PQL3, Q62052, Q866S3, Q8BLV3, Q8BXB6, Q8BZ00, Q8IVB4, Q8K078, Q8MIQ9, Q8R2N1, Q8TCT8, Q921R8

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	7
Benign	14

Top pathogenic / likely-pathogenic (0)

SpliceAI

1705 predictions. Top by Δscore:

Variant	Effect	Δscore
3:126008726:GCTTA:G	donor_gain	1.0000
3:126008727:CTTAC:C	donor_gain	1.0000
3:126008728:TTAC:T	donor_loss	1.0000
3:126008728:TTACC:T	donor_gain	1.0000
3:126008729:TA:T	donor_loss	1.0000
3:126008729:TACCT:T	donor_gain	1.0000
3:126008730:A:AC	donor_gain	1.0000
3:126008730:A:C	donor_gain	1.0000
3:126008730:ACC:A	donor_loss	1.0000
3:126008731:C:CC	donor_gain	1.0000
3:126008731:C:T	donor_gain	1.0000
3:126008731:CCT:C	donor_loss	1.0000
3:126008876:GATTT:G	acceptor_gain	1.0000
3:126008877:ATTT:A	acceptor_gain	1.0000
3:126008878:TTT:T	acceptor_gain	1.0000
3:126008879:TT:T	acceptor_gain	1.0000
3:126008881:C:CC	acceptor_gain	1.0000
3:126008881:CTGAA:C	acceptor_loss	1.0000
3:126008882:T:C	acceptor_loss	1.0000
3:126015488:ACGT:A	donor_loss	1.0000
3:126015491:TA:T	donor_loss	1.0000
3:126015492:A:AT	donor_loss	1.0000
3:126015493:C:CA	donor_loss	1.0000
3:126015493:CCA:C	donor_gain	1.0000
3:126015569:CGAAA:C	acceptor_gain	1.0000
3:126015574:C:CC	acceptor_gain	1.0000
3:126016726:CTCA:C	donor_loss	1.0000
3:126016727:TCAC:T	donor_loss	1.0000
3:126016728:CACC:C	donor_loss	1.0000
3:126016729:A:T	donor_loss	1.0000

AlphaMissense

3122 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:126012713:C:G	R336P	0.997
3:126012715:G:C	S335R	0.995
3:126012715:G:T	S335R	0.995
3:126012717:T:G	S335R	0.995
3:126022850:G:C	S227R	0.994
3:126022850:G:T	S227R	0.994
3:126022852:T:G	S227R	0.994
3:126026372:G:C	S187R	0.990
3:126026372:G:T	S187R	0.990
3:126026374:T:G	S187R	0.990
3:126012704:G:A	T339I	0.989
3:126022842:T:G	D230A	0.989
3:126026369:A:C	S188R	0.989
3:126026369:A:T	S188R	0.989
3:126026371:T:G	S188R	0.989
3:126022808:G:C	S241R	0.988
3:126022808:G:T	S241R	0.988
3:126022810:T:G	S241R	0.988
3:126050953:A:G	L124P	0.988
3:126012698:A:G	L341P	0.987
3:126016765:A:G	W286R	0.987
3:126016765:A:T	W286R	0.987
3:126016733:G:C	S296R	0.986
3:126016733:G:T	S296R	0.986
3:126016735:T:G	S296R	0.986
3:126022842:T:C	D230G	0.985
3:126022879:C:G	D218H	0.984
3:126022842:T:A	D230V	0.983
3:126026473:C:G	A154P	0.983
3:126007180:A:G	W434R	0.982

dbSNP variants (sampled 300 via entrez): RS1000052601 (3:126092324 C>T), RS1000083037 (3:126021324 G>A), RS1000171506 (3:126067531 C>T), RS1000232780 (3:126072042 T>C), RS1000243563 (3:126024184 A>G), RS1000250942 (3:126071695 A>T), RS1000282866 (3:126043913 G>A), RS1000430825 (3:126037614 T>C), RS1000436309 (3:126096466 C>T), RS1000448016 (3:126009252 G>A,T), RS1000483174 (3:126037380 T>C), RS1000522615 (3:126076935 C>T), RS1000532158 (3:126054926 C>T), RS1000533635 (3:126096829 T>G), RS1000641052 (3:126096672 C>T)

Disease associations

OMIM: gene MIM:610803 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST011354_15	Bell’s palsy	3.000000e-06

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
Benzo(a)pyrene	affects methylation	2
Aflatoxin B1	decreases expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
potassium perchlorate	decreases expression	1
sodium arsenite	increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
bisphenol S	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	decreases expression	1
Arsenic Trioxide	decreases expression	1
Arsenic	increases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Dexamethasone	affects cotreatment, increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Valproic Acid	decreases expression	1
Zearalenone	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	increases methylation	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3HI	Abcam HEK293T SLC41A3 KO	Transformed cell line	Female
CVCL_D4P0	HCT116-SLC41A3-KO-c10	Cancer cell line	Male
CVCL_D4P1	HCT116-SLC41A3-KO-c6	Cancer cell line	Male
CVCL_TN68	HAP1 SLC41A3 (-) 1	Cancer cell line	Male
CVCL_TN69	HAP1 SLC41A3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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