SLC30A10

Summary

SLC30A10 (solute carrier family 30 member 10, HGNC:25355) is a protein-coding gene on chromosome 1q41, encoding Calcium/manganese antiporter SLC30A10 (Q6XR72). Calcium:manganese antiporter of the plasma membrane mediating the efflux of intracellular manganese coupled to an active extracellular calcium exchange.

This gene is highly expressed in the liver and is inducible by manganese. Its protein product appears to be critical in maintaining manganese levels, and has higher specificity for manganese than zinc. Loss of function mutations appear to result in a pleomorphic phenotype, including dystonia and adult-onset parkinsonism. Alternatively spliced transcript variants have been observed for this gene.

Source: NCBI Gene 55532 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome (Strong, GenCC)
• GWAS associations: 58
• Clinical variants (ClinVar): 314 total — 6 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 49
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_018713

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25355
Approved symbol	SLC30A10
Name	solute carrier family 30 member 10
Location	1q41
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp547M236, ZnT-10, ZRC1, ZNT8, ZNT10
Ensembl gene	ENSG00000196660
Ensembl biotype	protein_coding
OMIM	611146
Entrez	55532

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000356609, ENST00000366926, ENST00000484079, ENST00000484239, ENST00000696608, ENST00000886494, ENST00000886495, ENST00000886496

RefSeq mRNA: 4 — MANE Select: NM_018713 NM_001376929, NM_001416004, NM_001416005, NM_018713

CCDS: CCDS31026, CCDS91159

Canonical transcript exons

ENST00000366926 — 4 exons

Exon	Start	End
ENSE00001443005	219927801	219928557
ENSE00001919403	219910445	219915948
ENSE00003510577	219918255	219918494
ENSE00003608838	219927028	219927105

Expression profiles

Bgee: expression breadth ubiquitous, 111 present calls, max score 95.17.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1577 / max 188.4865, expressed in 230 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17536	1.1713	180
17535	0.7154	146
17534	0.2710	92

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	95.17	gold quality
right lobe of liver	UBERON:0001114	92.07	gold quality
mucosa of transverse colon	UBERON:0004991	90.75	gold quality
liver	UBERON:0002107	90.25	gold quality
endothelial cell	CL:0000115	88.68	gold quality
duodenum	UBERON:0002114	88.43	gold quality
choroid plexus epithelium	UBERON:0003911	88.35	gold quality
adrenal tissue	UBERON:0018303	81.62	gold quality
pigmented layer of retina	UBERON:0001782	81.52	gold quality
colonic mucosa	UBERON:0000317	80.96	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.47	gold quality
buccal mucosa cell	CL:0002336	79.01	silver quality
mucosa of sigmoid colon	UBERON:0004993	78.27	gold quality
rectum	UBERON:0001052	78.19	gold quality
cortical plate	UBERON:0005343	76.94	gold quality
anterior cingulate cortex	UBERON:0009835	74.21	gold quality
cingulate cortex	UBERON:0003027	74.15	gold quality
ileal mucosa	UBERON:0000331	74.12	gold quality
amygdala	UBERON:0001876	74.12	gold quality
nucleus accumbens	UBERON:0001882	72.99	gold quality
caudate nucleus	UBERON:0001873	72.93	gold quality
ventricular zone	UBERON:0003053	72.51	gold quality
putamen	UBERON:0001874	72.36	gold quality
right frontal lobe	UBERON:0002810	71.06	gold quality
prefrontal cortex	UBERON:0000451	70.97	gold quality
jejunum	UBERON:0002115	70.72	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	70.65	gold quality
hypothalamus	UBERON:0001898	70.38	gold quality
neocortex	UBERON:0001950	69.99	gold quality
temporal lobe	UBERON:0001871	69.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-111727	yes	1711.36
E-MTAB-9388	yes	8.60
E-ANND-3	yes	4.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

50 targeting SLC30A10, 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-190A-3P	100.00	80.35	5520
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-148A-5P	99.30	68.27	1141

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 31)

• identified the full-length sequences of SLC30A10, extending the SLC30 family to ten members; used an expressed sequence tag (EST) data mining strategy to determine the pattern of ZnT genes expression in tissues (PMID:15154973)
• SLC30A10 mutations cause a treatable recessive disease with pleomorphic phenotype, and provide compelling evidence that SLC30A10 plays a pivotal role in manganese transport. (PMID:22341971)
• This work has confirmed that SLC30A10 functions as a Mn transporter in humans that, when defective, causes Mn accumulation in liver and brain. (PMID:22341972)
• The study demonstrates down-regulation by Zn of ZnT10 mRNA levels in cultured intestinal and neuroblastoma cell lines and demonstrate reduced transcription from the ZnT10 promoter at an elevated extracellular Zn concentration. (PMID:22706290)
• This review will address Mn transport proteins, the newly discovered SLC30A10 mutations and their implications to Parkinsonism and Mn regulation. (PMID:23357421)
• a case of inherited manganism caused by SLC30A10 mutation is presented (PMID:23369405)
• ZnT10 is significantly decreased in the frontal cortex in Alzheimer’s disease. (PMID:23741496)
• These results suggest that both the up-regulation of ZIP14 and the down-regulation of ZnT10 by IL-6 might have enhanced the accumulation of manganese in SH-SY5Y cells. (PMID:24576911)
• SLC30A10 is a cell surface-localized manganese efflux transporter that reduces manganese levels and protects against manganese toxicity. (PMID:25319704)
• We describe early disease manifestations (including videos) in 5 previously unreported Indian children, carrying novel homozygous SLC30A10 mutation (PMID:25778823)
• allele was also associated with increased sway velocity (15%, P = .033; adjusted for age and sex) and reduced SLC30A10 expression (PMID:26628504)
• results indicate that residues in the transmembrane and C-terminal domains together confer optimal manganese transport capability to SLC30A10 and suggest that the mechanism of ion coordination in the transmembrane domain of SLC30A10 may be substantially different from that in YiiP/other SLC30 proteins. (PMID:27307044)
• Structural homology analysis provide evidence that L349P mutation severe structural changes of ZnT-10 in its CTD domain resulting in abnormal reduced function. (PMID:27550551)
• SLC30A10 has a protective role in 1-methyl-4-phenylpyridinium-induced toxicity via PERK-ATF4 pathway. (PMID:28688763)
• xpressing either wild-type or mutant forms of SLC30A10 was sufficient to inhibit the effect of ATP2C1 in response to Mn challenge in both zebrafish embryos and HeLa cells. These findings suggest that either activating ATP2C1 or restoring the Mn-induced trafficking of ATP2C1 can reduce Mn accumulation, providing a possible target for treating HMDPC. (PMID:28692648)
• Study shows that individuals harboring loss-of-function mutations in SLC30A10 or SLC39A14 develop inherited forms of Mn-induced neurotoxicity. (PMID:28789954)
• The study indicates that common single nucleotide polymorphisms in manganese transporters (SLC30A10 and SLC39A8) influence manganese homeostasis in early development. (PMID:28917719)
• Mutational analysis of SLC30A10 gene revealed 6 novel homozygous mutations .Treatment using 2,3 dimercaptosuccinic acid as a manganese chelating agent showed satisfactory results with improvement of biochemical markers, hepatic manifestations and relative amelioration of the neurological symptoms (PMID:29193034)
• In the course of differentiation, the most pronounced changes in the expression levels were observed for the mRNAs that encode SLC30A10 and SLC23A3 transporters. Their increase correlated with an increase in the apical membrane area, indicating that SLC30A10 and SLC23A3 mRNA levels assessed by qRT-PCR may be employed as cell differentiation biomarkers in Caco-2 models. (PMID:30113032)
• identified suborganelle Golgi nanovesicles as the main compartment of Mn accumulation in SLC30A10 mutants (PMID:30272946)
• Zinc transporter 10 (ZnT10)-dependent extrusion of cellular Mn(2+) is driven by an active Ca(2+)-coupled exchange. (PMID:30755481)
• A case of dystonia with polycythemia and hypermanganesemia caused by SLC30A10 mutation: a treatable inborn error of manganese metabolism. (PMID:31288771)
• Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis. (PMID:32247823)
• The Functions of ZIP8, ZIP14, and ZnT10 in the Regulation of Systemic Manganese Homeostasis. (PMID:32392784)
• Long noncoding RNA SLC30A10 promotes colorectal tumor proliferation and migration via miR-21c/APC axis. (PMID:32633358)
• Characterization of in vitro models of SLC30A10 deficiency. (PMID:33713241)
• GWAS of serum ALT and AST reveals an association of SLC30A10 Thr95Ile with hypermanganesemia symptoms. (PMID:34315874)
• Manganese transport in mammals by zinc transporter family proteins, ZNT and ZIP. (PMID:34924116)
• A rare genetic variant in the manganese transporter SLC30A10 and elevated liver enzymes in the general population. (PMID:35397106)
• Manganese efflux transporter SLC30A10 missense polymorphism T95I associated with liver injury retains manganese efflux activity. (PMID:36414535)
• Cell-free SLC30A10 messenger ribonucleic acid (mRNA) expression and their association with vitamin-D level among non-small cell lung cancer (NSCLC) patients. (PMID:38384053)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc30a10	ENSDARG00000103983
mus_musculus	Slc30a10	ENSMUSG00000026614
rattus_norvegicus	Slc30a10	ENSRNOG00000002397
drosophila_melanogaster	ZnT35C	FBGN0028516
drosophila_melanogaster	ZnT63C	FBGN0035432
drosophila_melanogaster	ZnT33D	FBGN0051860

Paralogs (8): SLC30A4 (ENSG00000104154), SLC30A3 (ENSG00000115194), SLC30A5 (ENSG00000145740), SLC30A6 (ENSG00000152683), SLC30A2 (ENSG00000158014), SLC30A7 (ENSG00000162695), SLC30A8 (ENSG00000164756), SLC30A1 (ENSG00000170385)

Protein

Protein identifiers

Calcium/manganese antiporter SLC30A10 — Q6XR72 (reviewed: Q6XR72)

Alternative names: Solute carrier family 30 member 10, Zinc transporter 10

All UniProt accessions (2): Q6XR72, A0A8Q3WLF3

UniProt curated annotations — full annotation on UniProt →

Function. Calcium:manganese antiporter of the plasma membrane mediating the efflux of intracellular manganese coupled to an active extracellular calcium exchange. Required for intracellular manganese homeostasis, an essential cation for the function of several enzymes, including some crucially important for the metabolism of neurotransmitters and other neuronal metabolic pathways. Manganese can also be cytotoxic and induce oxidative stress, mitochondrial dysfunction and apoptosis. Could also have an intracellular zinc ion transporter activity, directly regulating intracellular zinc ion homeostasis and more indirectly various signaling pathway and biological processes.

Subunit / interactions. Forms homodimers. Forms heterodimers and high-molecular weight oligomers with SLC30A3, SLC30A2 and SLC30A4; heterodimerization is mediated by covalent-bound tyrosine residues, occurs probably in a tissue-specific manner and could mediate the intracellular zinc transport activity into early endosomes and recycling endosomes.

Subcellular location. Cell membrane. Golgi apparatus membrane. Recycling endosome membrane. Early endosome membrane.

Tissue specificity. Specifically expressed in fetal liver and fetal brain. Expressed in adult tissues with relative levels small intestine > liver > testes > brain > ovary > colon > cervix > prostate > placenta. Expressed in liver and neurons of the nervous system (at protein level).

Disease relevance. Hypermanganesemia with dystonia 1 (HMNDYT1) [MIM:613280] A metabolic autosomal recessive disorder characterized by dystonia, parkinsonism, extrapyramidal signs, severe hypermanganesemia, polycythemia, and chronic hepatic disease, including steatosis and cirrhosis. The disease is caused by variants affecting the gene represented in this entry.

Induction. Down-regulated by zinc. Down-regulated by angiotensin-2. Up-regulated by manganese.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6XR72-4	1	yes
Q6XR72-2	2
Q6XR72-3	3

RefSeq proteins (4): NP_001363858, NP_001402933, NP_001402934, NP_061183* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002524	Cation_efflux	Family
IPR027469	Cation_efflux_TMD_sf	Homologous_superfamily
IPR027470	Cation_efflux_CTD	Domain
IPR058533	Cation_efflux_TM	Domain

Pfam: PF01545, PF16916

Catalyzed reactions (Rhea), 2 shown:

• Zn(2+)(in) = Zn(2+)(out) (RHEA:29351)
• Mn(2+)(out) + Ca(2+)(in) = Mn(2+)(in) + Ca(2+)(out) (RHEA:73059)

UniProt features (43 total): mutagenesis site 18, topological domain 7, transmembrane region 6, sequence variant 5, splice variant 3, region of interest 2, chain 1, site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9KVX	ELECTRON MICROSCOPY	2.79
9KVZ	ELECTRON MICROSCOPY	2.94
9KVY	ELECTRON MICROSCOPY	3.34

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6XR72-F1	67.63	0.26

Functional residue map

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

Catalytic / active sites (1): 43 (important for coupling of manganese to calcium transport)

Mutagenesis-validated functional residues (18):

Position	Phenotype
4	decreased interaction with slc30a3. no effect on self-association. decreased zinc ion transmembrane transporter activity
25	no effect on localization to the plasma membrane. loss of calcium:manganese antiporter activity.
40	no effect on localization to the plasma membrane. loss of calcium:manganese antiporter activity.
43	no effect on localization to the plasma membrane. changed calcium:manganese antiporter activity. enhanced coupling betwe
43	loss of calcium:manganese antiporter activity.
43	no effect on localization to the plasma membrane. loss of calcium:manganese antiporter activity. loss of calcium:mangane
43	loss of calcium:manganese antiporter activity. uncoupling between manganese and calcium exchange.
47	no effect on localization to the plasma membrane. no effect on calcium:manganese antiporter activity.
47	loss of calcium:manganese antiporter activity.
52	loss of calcium:manganese antiporter activity and increased zinc ion transmembrane transporter activity; when associated
127	no effect on localization to the plasma membrane. no effect on localization to the plasma membrane and decreased calcium
196	loss of localization to the plasma membrane.
242	loss of calcium:manganese antiporter activity and increased zinc ion transmembrane transporter activity; when associated
244	no effect on localization to the plasma membrane. no effect on localization to the plasma membrane and decreased calcium
244	loss of calcium:manganese antiporter activity.
248	no effect on localization to the plasma membrane. loss of manganese ion export across plasma membrane.
333	decreased calcium:manganese antiporter activity.
350	decreased calcium:manganese antiporter activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-425410	Metal ion SLC transporters

MSigDB gene sets: 252 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BENPORATH_ES_WITH_H3K27ME3, GOBP_RESPONSE_TO_ZINC_ION, MYOGENIN_Q6, GOCC_VACUOLAR_MEMBRANE, GOBP_TRANSITION_METAL_ION_TRANSPORT, GOBP_RESPONSE_TO_ANGIOTENSIN, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_RESPONSE_TO_METAL_ION, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, GOBP_ERBB_SIGNALING_PATHWAY, GOBP_DETOXIFICATION

GO Biological Process (15): manganese ion transport (GO:0006828), intracellular zinc ion homeostasis (GO:0006882), epidermal growth factor receptor signaling pathway (GO:0007173), detoxification of zinc ion (GO:0010312), intracellular manganese ion homeostasis (GO:0030026), zinc ion import into organelle (GO:0062111), positive regulation of ERK1 and ERK2 cascade (GO:0070374), zinc ion transmembrane transport (GO:0071577), manganese ion export across plasma membrane (GO:0140048), cellular response to angiotensin (GO:1904385), monoatomic ion transport (GO:0006811), monoatomic cation transport (GO:0006812), zinc ion transport (GO:0006829), manganese ion homeostasis (GO:0055071), transmembrane transport (GO:0055085)

GO Molecular Function (6): manganese ion transmembrane transporter activity (GO:0005384), zinc ion transmembrane transporter activity (GO:0005385), calcium:manganese antiporter activity (GO:0140983), protein binding (GO:0005515), monoatomic cation transmembrane transporter activity (GO:0008324), antiporter activity (GO:0015297)

GO Cellular Component (9): Golgi membrane (GO:0000139), early endosome (GO:0005769), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), membrane (GO:0016020), early endosome membrane (GO:0031901), recycling endosome (GO:0055037), recycling endosome membrane (GO:0055038), endosome (GO:0005768)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
SLC-mediated transmembrane transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transition metal ion transport	2
intracellular monoatomic cation homeostasis	2
inorganic ion homeostasis	2
zinc ion transmembrane transport	2
monoatomic cation transmembrane transport	2
manganese ion transmembrane transport	2
transport	2
transition metal ion transmembrane transporter activity	2
endosome	2
endomembrane system	2
endosome membrane	2
ERBB signaling pathway	1
detoxification of inorganic compound	1
stress response to zinc ion	1
manganese ion homeostasis	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
zinc ion transport	1
export across plasma membrane	1
cellular response to peptide hormone stimulus	1
response to angiotensin	1
monoatomic ion transport	1
monoatomic cation homeostasis	1
cellular process	1
manganese ion transmembrane transporter activity	1
calcium:monoatomic cation antiporter activity	1
binding	1
monoatomic ion transmembrane transporter activity	1
secondary active transmembrane transporter activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasm	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cellular anatomical structure	1
early endosome	1
recycling endosome	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

1273 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC30A10	PTPRN	Q16849	932
SLC30A10	GAD2	Q05329	877
SLC30A10	INS	P01308	854
SLC30A10	SLC39A14	Q15043	800
SLC30A10	SLC30A6	Q6NXT4	786
SLC30A10	INSM2	Q96T92	773
SLC30A10	SLC30A9	Q6PML9	763
SLC30A10	SLC39A8	Q9C0K1	758
SLC30A10	SLC39A7	Q92504	731
SLC30A10	SLC39A1	Q9NY26	706
SLC30A10	SLC39A13	Q96H72	677
SLC30A10	SLC39A5	Q6ZMH5	673
SLC30A10	SLC39A10	Q9ULF5	670
SLC30A10	SLC39A11	Q8N1S5	661
SLC30A10	SLC39A6	Q13433	660

IntAct

15 interactions, top by confidence:

A	B	Type	Score
SLC30A2	SLC30A10	psi-mi:“MI:0914”(association)	0.650
SLC30A10	SLC30A2	psi-mi:“MI:0403”(colocalization)	0.650
SLC30A10	SLC30A2	psi-mi:“MI:0915”(physical association)	0.650
SLC30A10	SLC30A3	psi-mi:“MI:0915”(physical association)	0.520
SLC30A4	SLC30A10	psi-mi:“MI:0914”(association)	0.500
SLC30A4	SLC30A10	psi-mi:“MI:0915”(physical association)	0.500
SLC30A10	SLC30A10	psi-mi:“MI:0915”(physical association)	0.400
SLC2A2	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC30A10	GOLIM4	psi-mi:“MI:0914”(association)	0.350
TFRC	SLC30A4	psi-mi:“MI:0403”(colocalization)	0.270
TFRC	SLC30A10	psi-mi:“MI:0403”(colocalization)	0.270

BioGRID (183): TFRC (Co-fractionation), SYP (Co-fractionation), SLC30A10 (Affinity Capture-Western), SLC30A10 (Affinity Capture-Western), SLC30A10 (Affinity Capture-Western), SLC30A10 (Affinity Capture-Western), SLC30A3 (Affinity Capture-Western), SLC30A10 (Affinity Capture-MS), ABCE1 (Affinity Capture-MS), ACAT1 (Affinity Capture-MS), ADCY9 (Affinity Capture-MS), ADPGK (Affinity Capture-MS), AKAP12 (Affinity Capture-MS), ARMCX2 (Affinity Capture-MS), ARMCX3 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2KQY6, A4IFD7, A5D7L5, A5PMX1, O13918, O14863, O35149, O45923, O55174, P0CE46, P20107, P32798, P97441, Q08E25, Q15043, Q28CE7, Q2HJ10, Q3UVU3, Q4R6K2, Q52KD7, Q5BJM8, Q5FVQ0, Q5I020, Q5MNV6, Q5R617, Q5RAB7, Q5XHB4, Q5ZLF4, Q60738, Q62720, Q62941, Q6DBM8, Q6DG36, Q6NRI1, Q6P3N9, Q6QIX3, Q6XR72, Q75N73, Q8BGG0, Q8H329

Diamond homologs: A5PMX1, O13918, P20107, P30540, P32798, Q3UVU3, Q4R6K2, Q54F34, Q5MNV6, Q60738, Q62720, Q6AZN8, Q6DG36, Q6P0D1, Q6XR72, Q9Y6M5, P9WGF4, P9WGF5, Q03455, Q08970, Q28CE7, Q5BJM8, Q5I020, Q5XHB4, Q5ZLF4, Q6ICY4, Q8H329, Q8NEW0, Q9BRI3, Q9JKN1, A4IFD7, A7Z1S6, O07084, O14863, O35149, O45923, O55174, P0CE46, P13512, P55237

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	4
Uncertain significance	149
Likely benign	98
Benign	32

Top pathogenic / likely-pathogenic (10)

Variant ID	HGVS	Classification
30885	NM_018713.3(SLC30A10):c.314_322del (p.Ala105_Pro107del)	Pathogenic
30886	NM_018713.3(SLC30A10):c.266T>C (p.Leu89Pro)	Pathogenic
30887	NM_018713.3(SLC30A10):c.585del (p.Thr196fs)	Pathogenic
30888	NM_018713.3(SLC30A10):c.507del (p.Pro170fs)	Pathogenic
30889	NM_018713.3(SLC30A10):c.1235del (p.Gln412fs)	Pathogenic
4736552	NM_018713.3(SLC30A10):c.222C>G (p.Tyr74Ter)	Pathogenic
2682640	NM_018713.3(SLC30A10):c.392T>G (p.Leu131Arg)	Likely pathogenic
3362498	NM_018713.3(SLC30A10):c.134dup (p.Ser46fs)	Likely pathogenic
38410	NM_018713.3(SLC30A10):c.922C>T (p.Gln308Ter)	Likely pathogenic
3895514	NM_018713.3(SLC30A10):c.511C>T (p.Gln171Ter)	Likely pathogenic

SpliceAI

542 predictions. Top by Δscore:

Variant	Effect	Δscore
1:219915944:ACTCA:A	acceptor_gain	1.0000
1:219915945:CTCA:C	acceptor_gain	1.0000
1:219915945:CTCAC:C	acceptor_gain	1.0000
1:219915946:TCA:T	acceptor_gain	1.0000
1:219915946:TCACT:T	acceptor_gain	1.0000
1:219915947:CA:C	acceptor_gain	1.0000
1:219915947:CAC:C	acceptor_gain	1.0000
1:219915948:ACT:A	acceptor_loss	1.0000
1:219915949:C:CC	acceptor_gain	1.0000
1:219915949:CTAT:C	acceptor_loss	1.0000
1:219915955:C:CT	acceptor_gain	1.0000
1:219918253:A:AC	donor_gain	1.0000
1:219918253:ACT:A	donor_gain	1.0000
1:219918254:C:CC	donor_gain	1.0000
1:219918254:CT:C	donor_gain	1.0000
1:219918254:CTC:C	donor_gain	1.0000
1:219918254:CTCAG:C	donor_gain	1.0000
1:219918258:G:C	donor_gain	1.0000
1:219927022:TCCTA:T	donor_loss	1.0000
1:219927023:CCTAC:C	donor_loss	1.0000
1:219927024:CTAC:C	donor_loss	1.0000
1:219927025:TA:T	donor_loss	1.0000
1:219927026:A:T	donor_loss	1.0000
1:219927027:CCT:C	donor_gain	1.0000
1:219927840:T:TA	donor_gain	1.0000
1:219915956:A:T	acceptor_gain	0.9900
1:219918251:TTACT:T	donor_loss	0.9900
1:219918252:TA:T	donor_loss	0.9900
1:219918254:C:A	donor_loss	0.9900
1:219918254:CTCA:C	donor_gain	0.9900

AlphaMissense

3153 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:219918470:T:G	D248A	0.997
1:219928340:G:A	S34F	0.997
1:219915867:G:T	A347D	0.996
1:219918367:G:C	S282R	0.996
1:219918367:G:T	S282R	0.996
1:219918369:T:G	S282R	0.996
1:219918469:A:C	D248E	0.996
1:219918469:A:T	D248E	0.996
1:219918470:T:A	D248V	0.996
1:219918470:T:C	D248G	0.996
1:219928143:C:G	A100P	0.996
1:219928321:G:C	D40E	0.996
1:219928321:G:T	D40E	0.996
1:219918468:C:G	A249P	0.995
1:219928060:G:C	N127K	0.995
1:219928060:G:T	N127K	0.995
1:219928083:C:G	G120R	0.995
1:219928319:G:A	S41F	0.995
1:219928322:T:G	D40A	0.995
1:219928341:A:G	S34P	0.995
1:219915861:A:G	L349P	0.994
1:219918458:G:A	S252F	0.994
1:219918471:C:G	D248H	0.994
1:219928082:C:T	G120D	0.994
1:219928169:G:T	A91E	0.994
1:219928319:G:T	S41Y	0.994
1:219928322:T:C	D40G	0.994
1:219928331:A:G	L37P	0.994
1:219928355:C:T	G29D	0.994
1:219915868:C:G	A347P	0.993

dbSNP variants (sampled 300 via entrez): RS1000025595 (1:219921785 T>C), RS1000112886 (1:219958617 CAAG>C), RS1000117284 (1:219939742 C>T), RS1000137271 (1:219942078 T>C), RS1000173096 (1:219951168 C>T), RS1000270558 (1:219959017 A>G), RS1000272654 (1:219952630 T>C), RS1000410003 (1:219953832 G>A), RS1000448962 (1:219946999 C>T), RS1000489477 (1:219940029 C>T), RS1000528225 (1:219928893 G>C), RS1000555340 (1:219945283 G>A,T), RS1000563301 (1:219947246 C>A,T), RS1000712371 (1:219933570 T>C), RS1000770298 (1:219952422 C>A,T)

Disease associations

OMIM: gene MIM:611146 | disease phenotypes: MIM:613280

GenCC curated gene-disease

Disease	Classification	Inheritance
cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome	Strong	Autosomal recessive

Mondo (1): cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome (MONDO:0013208)

Orphanet (1): Cirrhosis-dystonia-polycythemia-hypermanganesemia syndrome (Orphanet:309854)

HPO phenotypes

49 total (30 of 49 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000338	Hypomimic face
HP:0000952	Jaundice
HP:0001260	Dysarthria
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001300	Parkinsonism
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001392	Abnormality of the liver
HP:0001394	Cirrhosis
HP:0001409	Portal hypertension
HP:0001410	Decreased liver function
HP:0001413	Micronodular cirrhosis
HP:0001639	Hypertrophic cardiomyopathy
HP:0001744	Splenomegaly
HP:0001901	Polycythemia
HP:0001928	Abnormality of coagulation
HP:0002040	Esophageal varix
HP:0002063	Rigidity
HP:0002067	Bradykinesia
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002075	Dysdiadochokinesis
HP:0002078	Truncal ataxia
HP:0002154	Hyperglycinemia
HP:0002172	Postural instability
HP:0002240	Hepatomegaly
HP:0002313	Spastic paraparesis
HP:0002345	Action tremor

GWAS associations

58 associations (top):

Study	Trait	p-value
GCST002063_9	Sexual dimorphism in anthropometric traits	7.000000e-16
GCST003929_2	Urinary electrolytes (magnesium/calcium ratio)	3.000000e-09
GCST003999_5	Nose size	2.000000e-10
GCST004619_70	Reticulocyte fraction of red cells	5.000000e-16
GCST004622_142	Reticulocyte count	2.000000e-13
GCST005348_129	Total body bone mineral density	3.000000e-09
GCST005956_83	Waist-to-hip ratio adjusted for BMI	1.000000e-19
GCST005957_15	Waist-to-hip ratio adjusted for BMI (age <50)	5.000000e-14
GCST005958_1	Waist-to-hip ratio adjusted for BMI (age >50)	1.000000e-23
GCST005962_1	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	4.000000e-33
GCST006629_78	Pulse pressure	4.000000e-23
GCST007093_34	Osteoarthritis	1.000000e-06
GCST007692_90	Chronic obstructive pulmonary disease	4.000000e-11
GCST010002_379	Refractive error	1.000000e-40
GCST010173_81	Triglyceride levels	2.000000e-13
GCST010241_224	Apolipoprotein A1 levels	2.000000e-09
GCST010242_302	HDL cholesterol levels	1.000000e-14
GCST010244_257	Triglyceride levels	2.000000e-21
GCST010418_1	Liver fibrosis and steatohepatitis severity (MRI cT1 measure)	3.000000e-08
GCST010988_270	Adult body size	1.000000e-08
GCST012490_196	Femur bone mineral density x serum urate levels interaction	9.000000e-10
GCST90002385_107	High light scatter reticulocyte count	1.000000e-27
GCST90002386_227	High light scatter reticulocyte percentage of red cells	1.000000e-32
GCST90002387_243	Immature fraction of reticulocytes	3.000000e-29
GCST90002404_447	Red cell distribution width	1.000000e-12
GCST90002405_101	Reticulocyte count	3.000000e-17
GCST90002406_122	Reticulocyte fraction of red cells	2.000000e-21
GCST90011898_32	Alanine aminotransferase levels	1.000000e-11
GCST90013662_1	Extrahepatic cholangiocarcinoma	1.000000e-08
GCST90013663_100	Alanine aminotransferase levels	2.000000e-24

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0004343	waist-hip ratio
EFO:0005951	sexual dimorphism
EFO:0007903	magnesium:calcium ratio
EFO:0007986	reticulocyte count
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0005763	pulse pressure measurement
EFO:0004530	triglyceride measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0006845	liver disease biomarker
EFO:0010821	liver fat measurement
EFO:0004531	urate measurement
EFO:0009188	Red cell distribution width
EFO:0004736	aspartate aminotransferase measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C548016	Hypermanganesemia with Dystonia Polycythemia and Cirrhosis (supp.)

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 — SLC30 zinc transporter family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	6
Manganese	affects transport, decreases abundance, increases secretion, decreases reaction, increases abundance (+2 more)	5
Aflatoxin B1	affects expression, decreases expression, decreases methylation	5
trichostatin A	affects cotreatment, increases expression	3
Cyclosporine	decreases expression	3
Vorinostat	affects cotreatment, increases expression	2
Edetic Acid	decreases reaction, increases abundance, increases expression	2
Estradiol	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
aristolochic acid I	increases expression	1
pirinixic acid	increases activity, increases expression, affects binding	1
bisphenol A	affects expression	1
sodium arsenite	decreases expression	1
2,2-dithiobis(4,6-dichlorophenol)	affects response to substance	1
ciglitazone	affects binding, increases expression	1
GW 501516	affects binding, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
3-iodothyronamine	affects uptake	1
Grape Seed Proanthocyanidins	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Azathioprine	decreases expression	1
Cadmium	increases response to substance, affects expression	1
Calcitriol	affects binding, increases reaction, increases activity, increases expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Quercetin	decreases expression	1
Rifampin	decreases expression	1

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4T6	HuH7-SLC30A10-KO-c18	Cancer cell line	Male
CVCL_D4T7	HuH7-SLC30A10-KO-c5	Cancer cell line	Male
CVCL_TM87	HAP1 SLC30A10 (-) 1	Cancer cell line	Male
CVCL_TM88	HAP1 SLC30A10 (-) 2	Cancer cell line	Male
CVCL_TM89	HAP1 SLC30A10 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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