SLC30A5

Summary

SLC30A5 (solute carrier family 30 member 5, HGNC:19089) is a protein-coding gene on chromosome 5q13.1-q13.2, encoding Proton-coupled zinc antiporter SLC30A5 (Q8TAD4). Together with SLC30A6 forms a functional proton-coupled zinc ion antiporter mediating zinc entry into the lumen of organelles along the secretory pathway.

This gene encodes a member of the SLC30A/ZnT family of zinc transporter proteins. ZnT proteins mediate both cellular zinc efflux and zinc sequestration into membrane-bound organelles. The encoded protein plays a role in the early secretory pathway as a heterodimer with zinc transporter 6, and may also regulate zinc sequestration into secretory granules of pancreatic beta cells. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 19.

Source: NCBI Gene 64924 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cardiomyopathy (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 100 total — 2 likely-pathogenic
• Phenotypes (HPO): 2
• Druggable target: yes
• MANE Select transcript: NM_022902

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19089
Approved symbol	SLC30A5
Name	solute carrier family 30 member 5
Location	5q13.1-q13.2
Locus type	gene with protein product
Status	Approved
Aliases	ZTL1, ZnT-5, FLJ12496, FLJ12756, ZNT5, MGC5499, ZNTL1
Ensembl gene	ENSG00000145740
Ensembl biotype	protein_coding
OMIM	607819
Entrez	64924

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 16 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000380860, ENST00000396591, ENST00000502979, ENST00000504103, ENST00000507354, ENST00000511158, ENST00000512367, ENST00000513937, ENST00000862254, ENST00000862255, ENST00000862256, ENST00000862257, ENST00000862258, ENST00000862259, ENST00000862260, ENST00000862261, ENST00000968696, ENST00000968697, ENST00000968698

RefSeq mRNA: 3 — MANE Select: NM_022902 NM_001251969, NM_022902, NM_024055

CCDS: CCDS34173, CCDS3996, CCDS58955

Canonical transcript exons

ENST00000396591 — 16 exons

Exon	Start	End
ENSE00000972019	69123199	69123425
ENSE00000972020	69128004	69128132
ENSE00001525561	69129447	69131069
ENSE00001625421	69104631	69104716
ENSE00001716130	69103062	69103128
ENSE00001767654	69100807	69100929
ENSE00002074836	69094014	69094338
ENSE00003463121	69121694	69121895
ENSE00003463607	69115237	69115407
ENSE00003469800	69118499	69118628
ENSE00003492423	69116394	69116602
ENSE00003546463	69117239	69117396
ENSE00003549881	69108349	69108436
ENSE00003588017	69113140	69113227
ENSE00003626394	69114420	69114496
ENSE00003694339	69115926	69116214

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 50.0131 / max 443.3760, expressed in 1826 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56831	47.8053	1826
56829	1.8110	1070
56830	0.3968	178

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	99.16	gold quality
stromal cell of endometrium	CL:0002255	95.68	gold quality
tendon of biceps brachii	UBERON:0008188	95.51	gold quality
body of pancreas	UBERON:0001150	94.78	gold quality
pancreas	UBERON:0001264	93.36	gold quality
bronchial epithelial cell	CL:0002328	93.35	gold quality
tendon	UBERON:0000043	93.32	gold quality
calcaneal tendon	UBERON:0003701	93.20	gold quality
endometrium	UBERON:0001295	93.16	gold quality
ventricular zone	UBERON:0003053	92.74	gold quality
islet of Langerhans	UBERON:0000006	92.44	gold quality
caput epididymis	UBERON:0004358	92.24	gold quality
mucosa of sigmoid colon	UBERON:0004993	92.19	gold quality
tibia	UBERON:0000979	92.16	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.12	gold quality
adenohypophysis	UBERON:0002196	92.10	gold quality
left lobe of thyroid gland	UBERON:0001120	91.98	gold quality
rectum	UBERON:0001052	91.89	gold quality
adrenal tissue	UBERON:0018303	91.73	gold quality
thyroid gland	UBERON:0002046	91.68	gold quality
right lobe of thyroid gland	UBERON:0001119	91.62	gold quality
corpus epididymis	UBERON:0004359	91.60	gold quality
palpebral conjunctiva	UBERON:0001812	91.54	gold quality
endocervix	UBERON:0000458	91.50	gold quality
colonic mucosa	UBERON:0000317	91.45	gold quality
gall bladder	UBERON:0002110	91.42	gold quality
right atrium auricular region	UBERON:0006631	91.39	gold quality
minor salivary gland	UBERON:0001830	91.36	gold quality
mucosa of transverse colon	UBERON:0004991	91.32	gold quality
body of uterus	UBERON:0009853	91.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-30	yes	112788.35
E-GEOD-180759	yes	11352.31
E-ANND-3	yes	11.29

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): XBP1

miRNA regulators (miRDB)

44 targeting SLC30A5, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-372-5P	99.41	69.11	2299
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-3692-5P	99.29	67.04	1421

Literature-anchored findings (GeneRIF, showing 10)

• cloning and characterization of ZnT-5 which is expressed in pancreatic beta cells (PMID:11904301)
• A novel zinc-regulated human zinc transporter, hZTL1, is localized to the enterocyte apical membrane (PMID:11937503)
• hZnT-5 is up-regulated in response to cellular zinc depletion in Raji cells. (PMID:17971500)
• Data show that ZNT5 is extensively present in the Abeta-positive plaques in the cortex of human AD brains. (PMID:18639746)
• The cytosolic C-terminal tail of ZnT5 is important for its interaction with ZnT6 as a heterodimer. (PMID:19759014)
• exons 15 to 17 include a signal that results in trafficking of ZnT5 to the Golgi apparatus and that the 3’ end of exon 14 includes a signal that leads to retention in the ER. (PMID:21887337)
• Results identify a unique class of transporters Znt5 and Znt8 and the structural motif required to discriminate between Zn(2+) and Cd(2+) transport. (PMID:22529353)
• Overexpression of ZnT5 is accompanied by activation of PI3K/Akt pathway and inhibiting HG-induced apoptosis. (PMID:23275032)
• There was a significant increase in protein levels of ZnT5 in the prefrontal cortex in Major depression disorder, relative to control subjects. (PMID:27661418)
• Bi-allelic loss of function variants in SLC30A5 as cause of perinatal lethal cardiomyopathy. (PMID:33547425)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc30a5	ENSDARG00000051921
mus_musculus	Slc30a5	ENSMUSG00000021629
rattus_norvegicus	Slc30a5	ENSRNOG00000018746
caenorhabditis_elegans	slc-30A5	WBGENE00013668

Paralogs (8): SLC30A4 (ENSG00000104154), SLC30A3 (ENSG00000115194), SLC30A6 (ENSG00000152683), SLC30A2 (ENSG00000158014), SLC30A7 (ENSG00000162695), SLC30A8 (ENSG00000164756), SLC30A1 (ENSG00000170385), SLC30A10 (ENSG00000196660)

Protein

Protein identifiers

Proton-coupled zinc antiporter SLC30A5 — Q8TAD4 (reviewed: Q8TAD4)

Alternative names: Solute carrier family 30 member 5, Zinc transporter 5, ZnT-like transporter 1

All UniProt accessions (4): D6REM2, H0Y957, H0YAH4, Q8TAD4

UniProt curated annotations — full annotation on UniProt →

Function. Together with SLC30A6 forms a functional proton-coupled zinc ion antiporter mediating zinc entry into the lumen of organelles along the secretory pathway. By contributing to zinc ion homeostasis within the early secretory pathway, regulates the activation and folding of enzymes like alkaline phosphatases and enzymes involved in phosphatidylinositol glycan anchor biosynthesis. Through the transport of zinc into secretory granules of pancreatic beta-cells, plays an important role in the storage and secretion of insulin. Zinc ion:proton antiporter mediating influx and efflux of zinc at the plasma membrane.

Subunit / interactions. Heterodimer with SLC30A6/ZNT6; form a functional zinc ion transmembrane transporter.

Subcellular location. Golgi apparatus. Golgi stack membrane. Cytoplasmic vesicle. COPII-coated vesicle membrane. Secretory vesicle membrane. trans-Golgi network membrane Endoplasmic reticulum membrane. Cell membrane. Apical cell membrane.

Tissue specificity. Ubiquitously expressed. Highly expressed in pancreas, liver and kidney. Expressed abundantly in insulin-containing beta cells, undetectable in other endocrine cell types including glucagon-secreting alpha cells and most acinar cells (at protein level).

Post-translational modifications. Could homodimerize through the formation of dityrosine bonds upon oxidative stress.

Induction. Expression is regulated by zinc. Up-regulated by endoplasmic reticulum stress.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q8TAD4-1	1, ZnT5A	yes
Q8TAD4-2	2, ZnT5B
Q8TAD4-3	3
Q8TAD4-4	4

RefSeq proteins (3): NP_001238898, NP_075053, NP_076960 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002524	Cation_efflux	Family
IPR027469	Cation_efflux_TMD_sf	Homologous_superfamily
IPR045316	Msc2-like	Family
IPR058533	Cation_efflux_TM	Domain

Pfam: PF01545

Catalyzed reactions (Rhea), 1 shown:

• Zn(2+)(in) + 2 H(+)(out) = Zn(2+)(out) + 2 H(+)(in) (RHEA:72627)

UniProt features (57 total): topological domain 17, transmembrane region 16, splice variant 6, sequence conflict 5, binding site 4, mutagenesis site 4, region of interest 3, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TAD4-F1	76.95	0.30

Functional residue map

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

Ligand- & substrate-binding residues (4): 451; 455; 595; 599

Post-translational modifications (1): 1

Mutagenesis-validated functional residues (4):

Position	Phenotype
451	loss of zinc transporter activity.
451	no effect on zinc ion transmembrane transporter activity. no effect on zinc ion import into golgi. loss of specificity f
599	loss of zinc transporter activity. no effect on localization to the trans-golgi network.
599	no effect on zinc transporter activity. no effect on localization to the trans-golgi network.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-264876	Insulin processing
R-HSA-435368	Zinc efflux and compartmentalization by the SLC30 family

MSigDB gene sets: 261 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_10, GOBP_RESPONSE_TO_ZINC_ION, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, PAX4_01, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_GLYCOLIPID_BIOSYNTHETIC_PROCESS, GOCC_SECRETORY_GRANULE, GOBP_TRANSITION_METAL_ION_TRANSPORT, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_RESPONSE_TO_METAL_ION

GO Biological Process (13): GPI anchor biosynthetic process (GO:0006506), cobalt ion transport (GO:0006824), zinc ion transport (GO:0006829), intracellular zinc ion homeostasis (GO:0006882), response to zinc ion (GO:0010043), insulin processing (GO:0030070), zinc ion import into organelle (GO:0062111), zinc ion transmembrane transport (GO:0071577), zinc ion import across plasma membrane (GO:0071578), zinc ion import into Golgi lumen (GO:1904257), monoatomic ion transport (GO:0006811), monoatomic cation transport (GO:0006812), transmembrane transport (GO:0055085)

GO Molecular Function (7): zinc ion transmembrane transporter activity (GO:0005385), antiporter activity (GO:0015297), zinc efflux transmembrane transporter activity (GO:0022883), metal ion binding (GO:0046872), zinc:proton antiporter activity (GO:0140826), protein binding (GO:0005515), monoatomic cation transmembrane transporter activity (GO:0008324)

GO Cellular Component (17): Golgi membrane (GO:0000139), nucleoplasm (GO:0005654), nucleolus (GO:0005730), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), ER to Golgi transport vesicle membrane (GO:0012507), membrane (GO:0016020), apical plasma membrane (GO:0016324), secretory granule (GO:0030141), secretory granule membrane (GO:0030667), cytoplasmic vesicle (GO:0031410), trans-Golgi network membrane (GO:0032588), Golgi cis cisterna membrane (GO:1990674), endoplasmic reticulum (GO:0005783), transport vesicle membrane (GO:0030658), Golgi cisterna membrane (GO:0032580)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Peptide hormone metabolism	1
Zinc transporters	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monoatomic cation transmembrane transport	3
zinc ion transmembrane transport	3
bounding membrane of organelle	3
organelle membrane	3
cytoplasm	3
endomembrane system	3
transition metal ion transport	2
transport	2
zinc ion transmembrane transporter activity	2
nuclear lumen	2
cellular anatomical structure	2
intracellular membrane-bounded organelle	2
cytoplasmic vesicle membrane	2
GPI anchor metabolic process	1
glycolipid biosynthetic process	1
glycerophospholipid biosynthetic process	1
GPI anchored protein biosynthesis	1
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
response to metal ion	1
peptide hormone processing	1
insulin metabolic process	1
zinc ion transport	1
inorganic cation import across plasma membrane	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
secondary active transmembrane transporter activity	1
monoatomic cation efflux transmembrane transporter activity	1
cation binding	1
metal cation:proton antiporter activity	1
binding	1
monoatomic ion transmembrane transporter activity	1
Golgi apparatus	1
intracellular membraneless organelle	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1

Protein interactions and networks

STRING

1376 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC30A5	SLC30A6	Q6NXT4	983
SLC30A5	ALPL	P05186	857
SLC30A5	SLC30A9	Q6PML9	841
SLC30A5	SLC39A7	Q92504	826
SLC30A5	SLC39A1	Q9NY26	797
SLC30A5	SLC39A9	Q9NUM3	794
SLC30A5	SLC39A6	Q13433	789
SLC30A5	SLC39A13	Q96H72	789
SLC30A5	MARVELD2	Q8N4S9	764
SLC30A5	SLC39A5	Q6ZMH5	753
SLC30A5	SLC39A10	Q9ULF5	753
SLC30A5	SLC39A14	Q15043	726
SLC30A5	SLC39A11	Q8N1S5	725
SLC30A5	SLC39A8	Q9C0K1	699
SLC30A5	SLC12A2	P55011	676

IntAct

113 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
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
MAS1	POTEF	psi-mi:“MI:0914”(association)	0.530
SPPL2B	UQCRQ	psi-mi:“MI:0914”(association)	0.530
CD83	BTAF1	psi-mi:“MI:0914”(association)	0.530
FUT3	C1QL1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
DPEP1	ILVBL	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
CSGALNACT2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
CYB5D2	ABLIM1	psi-mi:“MI:0914”(association)	0.530
CHRNA9	CHEK1	psi-mi:“MI:0914”(association)	0.530

BioGRID (379): SLC30A6 (Affinity Capture-Western), SLC30A5 (Affinity Capture-MS), SLC30A5 (Affinity Capture-MS), SLC30A5 (Affinity Capture-MS), SLC30A5 (Affinity Capture-MS), SLC30A5 (Affinity Capture-MS), SLC30A5 (Proximity Label-MS), SLC30A5 (Proximity Label-MS), SLC30A5 (Proximity Label-MS), SLC30A5 (Affinity Capture-MS), SLC30A5 (Affinity Capture-MS), SLC30A5 (Affinity Capture-MS), SLC30A5 (Affinity Capture-MS), SLC30A5 (Affinity Capture-MS), SLC30A5 (Affinity Capture-MS)

ESM2 similar proteins: A2AWR3, A6QL92, A6QPI1, B9FMX4, D3ZWZ9, F4IKF6, O35458, O35633, P58355, Q12791, Q28CE7, Q4LE88, Q4V3B8, Q569T7, Q5M8T2, Q5R4D7, Q5R6J3, Q5R831, Q5R9A7, Q5RD30, Q5ZLF4, Q62976, Q6DCG9, Q6DG36, Q6DIV6, Q6P499, Q6PF45, Q6UWJ1, Q7Z3F1, Q8BGF8, Q8BGN5, Q8BH01, Q8BUV8, Q8CA03, Q8R314, Q8R4H9, Q8RWF4, Q8RWH8, Q8TAD4, Q8WV83

Diamond homologs: A4IFD7, A5PMX1, P20107, P30540, Q03455, Q28CE7, Q52KD7, Q54F34, Q54T06, Q5BJM8, Q5MNV6, Q5ZLF4, Q688R1, Q6DG36, Q6NRI1, Q6P3N9, Q8H329, Q8NEW0, Q8R4H9, Q8TAD4, Q9HGQ3, Q9JKN1, Q9SI03, S7V0D3, O13918, P32798, Q95QW4, Q9ZT63, A7Z1S6, O07084, O45923, P0CE46, P13512, P55237, P75757, P94178, Q2HJ10, Q3UVU3, Q54QU8, Q5I020

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 119 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytosolic calcium ion concentration	7	7.7×	7e-03
G protein-coupled receptor signaling pathway	13	4.4×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	70
Likely benign	2
Benign	5

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
976212	NM_022902.5(SLC30A5):c.832_836del (p.Ile278fs)	Likely pathogenic
988899	NM_022902.5(SLC30A5):c.1981_1982del (p.His661fs)	Likely pathogenic

SpliceAI

2435 predictions. Top by Δscore:

Variant	Effect	Δscore
5:69103125:CCAGG:C	donor_loss	1.0000
5:69103126:CAGGT:C	donor_loss	1.0000
5:69103127:AGGTA:A	donor_loss	1.0000
5:69103128:GG:G	donor_loss	1.0000
5:69103129:G:A	donor_loss	1.0000
5:69103130:T:G	donor_loss	1.0000
5:69104013:T:G	donor_gain	1.0000
5:69104629:A:AG	acceptor_gain	1.0000
5:69104630:G:GG	acceptor_gain	1.0000
5:69113303:GGA:G	donor_gain	1.0000
5:69113305:A:AG	donor_gain	1.0000
5:69115987:T:TA	acceptor_gain	1.0000
5:69116155:A:T	donor_gain	1.0000
5:69116187:GTA:G	donor_gain	1.0000
5:69116190:G:GG	donor_gain	1.0000
5:69116213:GT:G	donor_gain	1.0000
5:69116215:G:GG	donor_gain	1.0000
5:69117224:T:TA	acceptor_gain	1.0000
5:69117363:G:GG	donor_gain	1.0000
5:69118626:ACAGT:A	donor_loss	1.0000
5:69118627:CAGT:C	donor_loss	1.0000
5:69118628:AGTA:A	donor_loss	1.0000
5:69118629:G:A	donor_loss	1.0000
5:69118629:G:GG	donor_gain	1.0000
5:69118630:T:G	donor_loss	1.0000
5:69118631:AA:A	donor_loss	1.0000
5:69121693:GCCA:G	acceptor_gain	1.0000
5:69121891:GAGGG:G	donor_gain	1.0000
5:69121893:GGG:G	donor_gain	1.0000
5:69121893:GGGGT:G	donor_loss	1.0000

AlphaMissense

5038 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:69116193:A:C	S351R	1.000
5:69116195:T:A	S351R	1.000
5:69116195:T:G	S351R	1.000
5:69116601:T:C	L427P	1.000
5:69117291:T:C	L445P	1.000
5:69117300:A:C	D448A	1.000
5:69117300:A:T	D448V	1.000
5:69117303:G:A	G449E	1.000
5:69117308:C:G	H451D	1.000
5:69117312:T:C	M452T	1.000
5:69117313:G:A	M452I	1.000
5:69117313:G:C	M452I	1.000
5:69117313:G:T	M452I	1.000
5:69117320:G:C	D455H	1.000
5:69117321:A:C	D455A	1.000
5:69117321:A:G	D455G	1.000
5:69117321:A:T	D455V	1.000
5:69117322:C:A	D455E	1.000
5:69117322:C:G	D455E	1.000
5:69117341:G:A	G462R	1.000
5:69117341:G:C	G462R	1.000
5:69117345:T:C	L463P	1.000
5:69117351:C:A	A465D	1.000
5:69118535:T:A	N492K	1.000
5:69118535:T:G	N492K	1.000
5:69118546:T:C	L496P	1.000
5:69121723:C:A	N533K	1.000
5:69121723:C:G	N533K	1.000
5:69123210:C:G	H595D	1.000
5:69123222:G:C	D599H	1.000

dbSNP variants (sampled 300 via entrez): RS1000041054 (5:69095678 G>T), RS1000219883 (5:69130093 T>C), RS1000272060 (5:69129846 T>C), RS1000445903 (5:69123112 A>G), RS1000484147 (5:69117429 T>C,G), RS1000514772 (5:69116985 A>G), RS1000552094 (5:69128526 G>C), RS1000604484 (5:69128214 A>T), RS1000745652 (5:69124151 A>C), RS1000794794 (5:69120857 T>C), RS1000822192 (5:69100607 T>A,C), RS1000884169 (5:69102156 C>A), RS1001199382 (5:69124491 C>T), RS1001300137 (5:69123606 G>C), RS1001309611 (5:69109131 A>G)

Disease associations

OMIM: gene MIM:607819 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
cardiomyopathy	Moderate	Autosomal recessive
dilated cardiomyopathy	Limited	Autosomal recessive

Mondo (4): hypertrophic cardiomyopathy (MONDO:0005045), hydrops fetalis (MONDO:0015193), dilated cardiomyopathy (MONDO:0005021), cardiomyopathy (MONDO:0004994)

Orphanet (2): Hydrops fetalis (Orphanet:1041), Rare hypertrophic cardiomyopathy (Orphanet:217569)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0001639	Hypertrophic cardiomyopathy
HP:0001789	Hydrops fetalis

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004649_3	Isovolumetric relaxation time	2.000000e-06
GCST006624_103	Systolic blood pressure	7.000000e-16
GCST009391_1322	Metabolite levels	8.000000e-06
GCST90013406_199	Liver enzyme levels (alkaline phosphatase)	2.000000e-14

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008204	left ventricular diastolic function measurement
EFO:0006335	systolic blood pressure
EFO:0010519	pantothenic acid measurement
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D015160	Hydrops Fetalis	C12.050.703.277.060.480; C15.378.295.480; C15.378.420.826.100.350; C16.300.060.480; C16.320.365.826.100.350; C20.306.480; C23.888.277.395

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067413 (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
6.96	Kd	108.9	nM	CHEMBL5653589
6.95	ED50	112.2	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	2149414: Binding affinity to human SLC30A5 incubated for 45 mins by Kinobead based pull down assay	kd	0.1089	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Zinc	affects cotreatment, decreases expression, increases response to substance, increases transport, increases uptake	6
Valproic Acid	affects expression, decreases expression, increases expression, increases methylation	4
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	affects cotreatment, decreases expression, increases expression	3
zinc chloride	decreases expression, decreases reaction	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
bisphenol F	increases methylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
ochratoxin A	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CD 437	decreases expression	1
2-palmitoylglycerol	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-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
Grape Seed Proanthocyanidins	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Calcitriol	decreases expression	1
Cisplatin	decreases response to substance, increases expression	1
Dactinomycin	decreases expression, decreases reaction	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Mercuric Chloride	affects cotreatment, increases expression	1
Thimerosal	affects cotreatment, increases 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
CHEMBL5652456	Binding	Binding affinity to human SLC30A5 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

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

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

Cellosaurus	Name	Category	Sex
CVCL_B3HD	Abcam HEK293T SLC30A5 KO	Transformed cell line	Female
CVCL_D4LG	HCT116-SLC30A5-KO-c5	Cancer cell line	Male
CVCL_D4LH	HCT116-SLC30A5-KO-c8	Cancer cell line	Male
CVCL_TM92	HAP1 SLC30A5 (-) 1	Cancer cell line	Male
CVCL_XT15	HAP1 SLC30A5 (-) 2	Cancer cell line	Male
CVCL_XT16	HAP1 SLC30A5 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT00348530	PHASE4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	PHASE4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	PHASE4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	PHASE4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	PHASE4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	PHASE4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	PHASE4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	PHASE4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	PHASE4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	PHASE4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	PHASE4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	PHASE4	COMPLETED	123-I mIBG (AdreView) Heart-to-Mediastinal (H/M) Ratio and SPECT Imaging on a Small Field of View-High Efficiency Cardiac SPECT System
NCT02640846	PHASE4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	PHASE4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	PHASE4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	PHASE4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05718128	PHASE4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	PHASE4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT00879060	PHASE4	COMPLETED	Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy
NCT01721967	PHASE4	COMPLETED	Ranolazine for the Treatment of Chest Pain in HCM Patients
NCT02948998	PHASE4	UNKNOWN	Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy
NCT03249272	PHASE4	TERMINATED	Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve
NCT04133532	PHASE4	COMPLETED	Effect of Metoprolol in Post Alcohol Septal Ablation Patients With Hypertrophic Cardiomyopathy
NCT06401343	PHASE4	RECRUITING	Use of SGLT2i in noHCM With HFpEF
NCT07103655	PHASE4	NOT_YET_RECRUITING	The Therapeutic Value of Mavacamten in Hypertrophic Cardiomyopathy With Mid-to-Apical Left Ventricular Obstruction
NCT07600177	PHASE4	RECRUITING	Mavacamten to Aficamten Transition in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation