SLC30A6

Summary

SLC30A6 (solute carrier family 30 member 6, HGNC:19305) is a protein-coding gene on chromosome 2p22.3, encoding Zinc transporter 6 (Q6NXT4). Has probably no intrinsic transporter activity but together with SLC30A5 forms a functional zinc ion:proton antiporter heterodimer, mediating zinc entry into the lumen of organelles along the secretory pathway.

This gene encodes a member of a family of proteins that function as zinc transporters. This protein can regulate subcellular levels of zinc in the Golgi and vesicles. Expression of this gene is altered in the Alzheimer’s disease brain plaques.

Source: NCBI Gene 55676 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 94 total — 9 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_017964

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19305
Approved symbol	SLC30A6
Name	solute carrier family 30 member 6
Location	2p22.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31101, ZNT6
Ensembl gene	ENSG00000152683
Ensembl biotype	protein_coding
OMIM	611148
Entrez	55676

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 13 protein_coding, 3 nonsense_mediated_decay

ENST00000282587, ENST00000357055, ENST00000379343, ENST00000406369, ENST00000435660, ENST00000440718, ENST00000449777, ENST00000454324, ENST00000457724, ENST00000866170, ENST00000866171, ENST00000911305, ENST00000911306, ENST00000911307, ENST00000911308, ENST00000954367

RefSeq mRNA: 8 — MANE Select: NM_017964 NM_001193513, NM_001193514, NM_001193515, NM_001330476, NM_001330477, NM_001330478, NM_001330479, NM_017964

CCDS: CCDS1780, CCDS54341, CCDS54342, CCDS54343, CCDS82434

Canonical transcript exons

ENST00000282587 — 14 exons

Exon	Start	End
ENSE00001070189	32175319	32175361
ENSE00001295357	32197344	32197392
ENSE00001821173	32220213	32224379
ENSE00003467444	32192918	32192953
ENSE00003477506	32204590	32204692
ENSE00003511828	32206886	32206933
ENSE00003524122	32193889	32193983
ENSE00003575367	32171287	32171373
ENSE00003585099	32192336	32192416
ENSE00003588103	32209493	32209561
ENSE00003662243	32165864	32165903
ENSE00003715642	32184273	32184338
ENSE00003717788	32174063	32174147
ENSE00003740144	32197707	32197826

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 92.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.6920 / max 348.0970, expressed in 1796 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19633	16.1719	1788
19634	2.6821	1406
19632	0.8381	585

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	92.19	silver quality
tibialis anterior	UBERON:0001385	91.45	silver quality
ileal mucosa	UBERON:0000331	90.94	gold quality
calcaneal tendon	UBERON:0003701	90.79	gold quality
adrenal tissue	UBERON:0018303	90.34	gold quality
secondary oocyte	CL:0000655	90.01	gold quality
deltoid	UBERON:0001476	89.78	silver quality
kidney epithelium	UBERON:0004819	88.42	silver quality
islet of Langerhans	UBERON:0000006	87.91	gold quality
upper arm skin	UBERON:0004263	87.75	silver quality
myocardium	UBERON:0002349	87.55	silver quality
nasal cavity epithelium	UBERON:0005384	86.26	silver quality
tibia	UBERON:0000979	85.33	gold quality
bone marrow cell	CL:0002092	84.94	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.73	gold quality
stromal cell of endometrium	CL:0002255	84.69	gold quality
muscle tissue	UBERON:0002385	84.46	gold quality
tendon	UBERON:0000043	84.21	gold quality
oocyte	CL:0000023	83.95	gold quality
vastus lateralis	UBERON:0001379	83.84	gold quality
cartilage tissue	UBERON:0002418	83.71	gold quality
skeletal muscle tissue	UBERON:0001134	83.67	gold quality
placenta	UBERON:0001987	83.46	gold quality
epithelial cell of pancreas	CL:0000083	83.29	gold quality
smooth muscle tissue	UBERON:0001135	83.11	gold quality
quadriceps femoris	UBERON:0001377	83.06	silver quality
epithelium of nasopharynx	UBERON:0001951	83.04	gold quality
nasopharynx	UBERON:0001728	83.03	gold quality
palpebral conjunctiva	UBERON:0001812	83.03	gold quality
pancreas	UBERON:0001264	82.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.47
E-MTAB-7249	no	1105.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

124 targeting SLC30A6, 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-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-548AR-3P	99.85	71.26	3889

Literature-anchored findings (GeneRIF, showing 12)

• Our results show that Zn transporter-4 and Zn transporter-6 are significantly (P<0.05) increased in hippocampus/parahippocampal gyrus of early Alzheimer’s disease and Alzheimer’s disease subjects. (PMID:16580781)
• hZnT-6 is up-regulated in response to cellular zinc depletion in Raji & THP-1 cells. (PMID:17971500)
• Data show that ZNT6 is extensively present in the Abeta-positive plaques in the cortex of human AD brains. (PMID:18639746)
• our results suggest that alterations in Zn transport proteins ZnT-1, ZnT-4 and ZnT-6 may contribute to the pathology observed in preclinical Alzheimer’s disease subjects before onset of clinical symptoms (PMID:19371353)
• The cytosolic C-terminal tail of ZnT5 is important for its interaction with ZnT6 as a heterodimer. (PMID:19759014)
• The results of this study showed that signi fi cant positive correlations between ZIP1,ZnT1, and ZnT6 in most brain in patient with Alzheimer’s disease. (PMID:22349685)
• results of this study suggested that ZnT6 protein levels are decreased in the spinal cords of sporadic ALS patients. (PMID:25284286)
• There was a significant increase in protein levels of ZnT6 in the prefrontal cortex in Major depression disorder, relative to control subjects. (PMID:27661418)
• A genetic variant within SLC30A6 has a protective role in the severity of Rheumatoid Arthritis. (PMID:27758124)
• Increased expression of zinc transporter ZIP4, ZIP11, ZnT1, and ZnT6 predicts poor prognosis in pancreatic cancer. (PMID:33631610)
• An Overexpression of SLC30A6 Gene Contributes to Cardiomyocyte Dysfunction via Affecting Mitochondria and Inducing Activations in K-Acetylation and Epigenetic Proteins. (PMID:38091184)
• SENP1 mediates zinc-induced ZnT6 deSUMOylation at Lys-409 involved in the regulation of zinc metabolism in Golgi apparatus. (PMID:39367979)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc30a6	ENSDARG00000077368
mus_musculus	Slc30a6	ENSMUSG00000024069
rattus_norvegicus	Slc30a6	ENSRNOG00000005856
caenorhabditis_elegans		WBGENE00006590

Paralogs (8): SLC30A4 (ENSG00000104154), SLC30A3 (ENSG00000115194), SLC30A5 (ENSG00000145740), SLC30A2 (ENSG00000158014), SLC30A7 (ENSG00000162695), SLC30A8 (ENSG00000164756), SLC30A1 (ENSG00000170385), SLC30A10 (ENSG00000196660)

Protein

Protein identifiers

Zinc transporter 6 — Q6NXT4 (reviewed: Q6NXT4)

Alternative names: Solute carrier family 30 member 6

All UniProt accessions (6): Q6NXT4, B5MCR8, C9JZR9, F8WCU3, F8WD78, F8WEL5

UniProt curated annotations — full annotation on UniProt →

Function. Has probably no intrinsic transporter activity but together with SLC30A5 forms a functional zinc ion:proton antiporter heterodimer, mediating zinc entry into the lumen of organelles along the secretory pathway. As part of that zinc ion:proton antiporter, contributes to zinc ion homeostasis within the early secretory pathway and regulates the activation and folding of enzymes like alkaline phosphatases and enzymes involved in phosphatidylinositol glycan anchor biosynthesis.

Subunit / interactions. Heterodimer with SLC30A5; form a functional zinc ion transmembrane transporter.

Subcellular location. Golgi apparatus. trans-Golgi network membrane.

Tissue specificity. Expressed in brain; especially in cerebellum, hippocampus, parahippocampal gyrus, superior and middle temporal gyrus. Also expressed in B-cells, colon, eye, and lung. Lower expression was present in bone, brain, cervix, ear, heart, kidney, muscle, nerve, pancreas, prostate, skin, stomach, and testis.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q6NXT4-1	1	yes
Q6NXT4-2	2
Q6NXT4-4	4
Q6NXT4-3	3

RefSeq proteins (8): NP_001180442, NP_001180443, NP_001180444, NP_001317405, NP_001317406, NP_001317407, NP_001317408, NP_060434* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002524	Cation_efflux	Family
IPR027469	Cation_efflux_TMD_sf	Homologous_superfamily
IPR052005	CDF_SLC30A	Family
IPR058533	Cation_efflux_TM	Domain

Pfam: PF01545

UniProt features (24 total): topological domain 7, transmembrane region 6, mutagenesis site 4, splice variant 3, sequence conflict 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NXT4-F1	71.44	0.32

Functional residue map

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

Mutagenesis-validated functional residues (4):

Position	Phenotype
66	no effect on heterodimer formation with slc30a5 and no effect on zinc transport; when associated with h-201.
70	no effect on heterodimer formation with slc30a5 and no effect on zinc transport; when associated with a-205.
201	no effect on heterodimer formation with slc30a5 and no effect on zinc transport; when associated with h-66.
205	no effect on heterodimer formation with slc30a5 and no effect on zinc transport; when associated with a-70.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 155 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_TRANSITION_METAL_ION_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MONOATOMIC_CATION_TRANSPORT, GOCC_TRANS_GOLGI_NETWORK, GOMF_PROTON_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, BROWN_MYELOID_CELL_DEVELOPMENT_UP, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_REGULATION_OF_TRANSPORT, GRADE_COLON_AND_RECTAL_CANCER_DN, GOBP_REGULATION_OF_MONOATOMIC_ION_TRANSPORT, MILI_PSEUDOPODIA_CHEMOTAXIS_DN, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_APICAL_PART_OF_CELL

GO Biological Process (7): zinc ion transport (GO:0006829), regulation of zinc ion transport (GO:0071579), zinc ion import into Golgi lumen (GO:1904257), monoatomic ion transport (GO:0006811), monoatomic cation transport (GO:0006812), transmembrane transport (GO:0055085), zinc ion transmembrane transport (GO:0071577)

GO Molecular Function (4): zinc ion transmembrane transporter activity (GO:0005385), antiporter activity (GO:0015297), protein binding (GO:0005515), monoatomic cation transmembrane transporter activity (GO:0008324)

GO Cellular Component (3): Golgi apparatus (GO:0005794), trans-Golgi network membrane (GO:0032588), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
zinc ion transport	2
transport	2
monoatomic cation transmembrane transport	2
transition metal ion transport	1
regulation of metal ion transport	1
zinc ion import into organelle	1
cytosol to Golgi apparatus transport	1
monoatomic ion transport	1
cellular process	1
transition metal ion transmembrane transporter activity	1
zinc ion transmembrane transport	1
secondary active transmembrane transporter activity	1
binding	1
monoatomic ion transmembrane transporter activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
trans-Golgi network	1
organelle membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1410 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC30A6	SLC30A5	Q8TAD4	983
SLC30A6	SLC30A1	Q9Y6M5	956
SLC30A6	SLC30A4	O14863	888
SLC30A6	ALPL	P05186	885
SLC30A6	SLC39A7	Q92504	861
SLC30A6	SLC30A9	Q6PML9	838
SLC30A6	SLC30A10	Q6XR72	786
SLC30A6	SLC39A9	Q9NUM3	777
SLC30A6	SLC39A13	Q96H72	754
SLC30A6	SLC39A1	Q9NY26	754
SLC30A6	SLC39A6	Q13433	753
SLC30A6	SLC39A11	Q8N1S5	753
SLC30A6	SLC39A5	Q6ZMH5	743
SLC30A6	SLC39A10	Q9ULF5	733
SLC30A6	SLC39A12	Q504Y0	715

IntAct

83 interactions, top by confidence:

A	B	Type	Score
SLC30A5	SLC30A6	psi-mi:“MI:0915”(physical association)	0.840
SLC30A6	SLC30A5	psi-mi:“MI:0915”(physical association)	0.840
SLC30A6	SLC30A5	psi-mi:“MI:0403”(colocalization)	0.840
SLC30A5	SLC30A6	psi-mi:“MI:0403”(colocalization)	0.840
SLC30A5	SLC30A6	psi-mi:“MI:0914”(association)	0.840
B3GNT3	PGRMC1	psi-mi:“MI:0914”(association)	0.670
NIPAL1	ESYT2	psi-mi:“MI:0914”(association)	0.640
	UBXN8	psi-mi:“MI:0914”(association)	0.530
KCNA5	TMEM223	psi-mi:“MI:0914”(association)	0.530
CSGALNACT2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
CHRNA9	CHEK1	psi-mi:“MI:0914”(association)	0.530
RIC3	ATP9A	psi-mi:“MI:0914”(association)	0.530
FUT3	C1QL1	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
GORASP2	PGRMC1	psi-mi:“MI:0914”(association)	0.350
RAB1A	SCAMP3	psi-mi:“MI:0914”(association)	0.350
RAB1B	TOMM40	psi-mi:“MI:0914”(association)	0.350
TMED10	PGRMC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (239): SLC30A6 (Affinity Capture-Western), SLC30A6 (Affinity Capture-MS), SLC30A6 (Affinity Capture-MS), SLC30A6 (Affinity Capture-MS), SPECC1L (Affinity Capture-MS), HDGFRP3 (Affinity Capture-MS), ACTB (Affinity Capture-MS), ACTBL2 (Affinity Capture-MS), MYO18A (Affinity Capture-MS), C12orf43 (Affinity Capture-MS), SLC30A6 (Proximity Label-MS), SLC30A6 (Proximity Label-MS), SLC30A6 (Proximity Label-MS), SLC30A6 (Affinity Capture-MS), SLC30A6 (Affinity Capture-MS)

ESM2 similar proteins: A2RV80, A7MBL8, B1H1G2, B8Q0B2, D3ZEH5, Q0IH22, Q0VC54, Q28C34, Q3BCU4, Q3TDN0, Q4R5B4, Q5F361, Q5F3F5, Q5PQZ7, Q5RF53, Q5RH73, Q5U308, Q5XIK2, Q641K1, Q68DH5, Q6IQC7, Q6NRD0, Q6NXT4, Q6P4P2, Q6R5J2, Q7L1W4, Q7ZYD9, Q8BGR2, Q8BJM5, Q8BM85, Q8BPM2, Q8C561, Q8CIF6, Q8JH92, Q8N6S4, Q8NBJ9, Q8NE79, Q8TEA7, Q8VDD9, Q8WWQ0

Diamond homologs: Q0VC54, Q5I0B2, Q5ZIH3, Q6AZN8, Q6GPY1, Q6NXT4, Q6P0D1, Q8BJM5, O13918, O35149, O55174

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 93 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
COPII-mediated vesicle transport	5	12.4×	5e-03
COPI-mediated anterograde transport	6	10.0×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytosolic calcium ion concentration	7	10.0×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	0
Uncertain significance	63
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
219052	Single allele	Pathogenic
219054	Single allele	Pathogenic
219055	Single allele	Pathogenic
219061	Single allele	Pathogenic
219062	Single allele	Pathogenic
219077	Single allele	Pathogenic
219078	Single allele	Pathogenic
219085	Single allele	Pathogenic
979970	GRCh37/hg19 2p22.3(chr2:32269694-32457939)x1	Pathogenic

SpliceAI

2525 predictions. Top by Δscore:

Variant	Effect	Δscore
2:32174061:A:AG	acceptor_gain	1.0000
2:32174062:G:GG	acceptor_gain	1.0000
2:32192916:A:AG	acceptor_gain	1.0000
2:32192917:G:GG	acceptor_gain	1.0000
2:32192917:GTGCA:G	acceptor_gain	1.0000
2:32192954:G:GG	donor_gain	1.0000
2:32197705:A:AG	acceptor_gain	1.0000
2:32197706:G:GA	acceptor_gain	1.0000
2:32197706:GCT:G	acceptor_gain	1.0000
2:32197706:GCTT:G	acceptor_gain	1.0000
2:32197823:TTAA:T	donor_gain	1.0000
2:32204588:A:AG	acceptor_gain	1.0000
2:32204589:G:GG	acceptor_gain	1.0000
2:32204589:GTA:G	acceptor_gain	1.0000
2:32210890:T:A	acceptor_gain	1.0000
2:32168023:G:GT	donor_gain	0.9900
2:32184271:A:AG	acceptor_gain	0.9900
2:32184272:G:GG	acceptor_gain	0.9900
2:32184272:GTTTA:G	acceptor_gain	0.9900
2:32192917:GT:G	acceptor_gain	0.9900
2:32193883:TTTTA:T	acceptor_loss	0.9900
2:32193884:TTTA:T	acceptor_loss	0.9900
2:32193885:TTA:T	acceptor_loss	0.9900
2:32193886:TA:T	acceptor_loss	0.9900
2:32193887:A:AG	acceptor_gain	0.9900
2:32193887:AGG:A	acceptor_gain	0.9900
2:32193888:G:A	acceptor_loss	0.9900
2:32193888:G:GG	acceptor_gain	0.9900
2:32193888:GGG:G	acceptor_gain	0.9900
2:32193979:AGAAG:A	donor_loss	0.9900

AlphaMissense

3000 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:32204663:A:C	S247R	1.000
2:32204665:T:A	S247R	1.000
2:32204665:T:G	S247R	1.000
2:32204688:T:C	L255P	1.000
2:32209508:G:A	G278R	1.000
2:32209508:G:C	G278R	1.000
2:32209509:G:A	G278E	1.000
2:32209512:T:A	V279D	1.000
2:32209515:T:C	L280S	1.000
2:32209538:T:A	W288R	1.000
2:32209538:T:C	W288R	1.000
2:32220216:G:A	G297R	1.000
2:32220216:G:C	G297R	1.000
2:32220217:G:A	G297E	1.000
2:32220229:T:A	V301E	1.000
2:32220238:G:C	R304P	1.000
2:32220246:G:C	A307P	1.000
2:32220262:T:A	V312D	1.000
2:32220265:T:C	L313P	1.000
2:32220313:T:A	V329D	1.000
2:32193905:G:C	G140R	0.999
2:32197355:A:C	S170R	0.999
2:32197357:C:A	S170R	0.999
2:32197357:C:G	S170R	0.999
2:32204606:G:C	D228H	0.999
2:32204607:A:C	D228A	0.999
2:32204607:A:T	D228V	0.999
2:32204672:A:C	S250R	0.999
2:32204674:T:A	S250R	0.999
2:32204674:T:G	S250R	0.999

dbSNP variants (sampled 300 via entrez): RS1000036373 (2:32198939 T>C), RS1000137619 (2:32194699 C>G), RS1000190239 (2:32176621 G>A), RS1000203304 (2:32194151 A>C), RS1000221260 (2:32176328 G>C), RS1000254216 (2:32194417 C>T), RS1000328099 (2:32181451 A>G), RS1000348330 (2:32224154 A>T), RS1000350144 (2:32219299 G>A), RS1000360397 (2:32164046 C>T), RS1000474367 (2:32193348 G>A), RS1000480124 (2:32200001 A>C,G), RS1000536441 (2:32188625 C>T), RS1000589944 (2:32193022 G>A,C,T), RS1000594157 (2:32203208 G>T)

Disease associations

OMIM: gene MIM:611148 | disease phenotypes: MIM:182601, MIM:616050, MIM:616115

GenCC curated gene-disease

Mondo (3): hereditary spastic paraplegia 4 (MONDO:0008438), periodic fever-infantile enterocolitis-autoinflammatory syndrome (MONDO:0014472), familial cold autoinflammatory syndrome 4 (MONDO:0014498)

Orphanet (4): Autosomal dominant spastic paraplegia type 4 (Orphanet:100985), Periodic fever-infantile enterocolitis-autoinflammatory syndrome (Orphanet:436166), Familial cold urticaria (Orphanet:47045), NLRC4-related familial cold autoinflammatory syndrome (Orphanet:576349)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002255_2	Inflammatory biomarkers	3.000000e-19
GCST006103_6	Interleukin-6 levels	4.000000e-06
GCST006661_237	Male-pattern baldness	7.000000e-26
GCST006661_314	Male-pattern baldness	4.000000e-20
GCST009736_3	Interleukin-18 levels	1.000000e-15

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004812	interleukin-1 beta measurement
EFO:0004810	interleukin-6 measurement
EFO:0004581	interleukin 18 measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536865	Spastic paraplegia 4, autosomal dominant (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067359 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.68	Kd	209.3	nM	CHEMBL5653589
6.68	ED50	209.3	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149415: Binding affinity to human SLC30A6 incubated for 45 mins by Kinobead based pull down assay	kd	0.2093	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Acetaminophen	increases expression, decreases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Zinc	affects cotreatment, increases expression, increases transport	2
Cyclosporine	decreases expression, increases expression	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
bisphenol A	decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
ochratoxin A	affects cotreatment, decreases expression	1
ferrous chloride	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	affects cotreatment, decreases expression, increases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	increases expression	1
jinfukang	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Vehicle Emissions	increases abundance, increases expression	1
Calcitriol	decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Lead	affects expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Nickel	increases expression	1
Ozone	increases oxidation, increases abundance, affects cotreatment	1
Testosterone	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652457	Binding	Binding affinity to human SLC30A6 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D4LI	HCT116-SLC30A6-KO-c1	Cancer cell line	Male
CVCL_D4LJ	HCT116-SLC30A6-KO-c2	Cancer cell line	Male
CVCL_TM93	HAP1 SLC30A6 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03204773	Not specified	COMPLETED	Studying Non-motor Symptoms in HSP
NCT04712812	Not specified	RECRUITING	Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia
NCT06553976	Not specified	RECRUITING	Spastic Paraplegia - Centers of Excellence Research Network