SLC30A2

Summary

SLC30A2 (solute carrier family 30 member 2, HGNC:11013) is a protein-coding gene on chromosome 1p36.11, encoding Proton-coupled zinc antiporter SLC30A2 (Q9BRI3). Electroneutral proton-coupled antiporter concentrating zinc ions into a variety of intracellular organelles including endosomes, zymogen granules and mitochondria.

The protein encoded by this gene is a zinc transporter that acts as a homodimer. The encoded protein plays a role in secreting zinc into breast milk. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 7780 — RefSeq curated summary.

At a glance

• Gene–disease (curated): zinc deficiency, transient neonatal (Definitive, ClinGen)
• Clinical variants (ClinVar): 58 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 4
• MANE Select transcript: NM_001004434

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11013
Approved symbol	SLC30A2
Name	solute carrier family 30 member 2
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000158014
Ensembl biotype	protein_coding
OMIM	609617
Entrez	7780

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000374276, ENST00000374278, ENST00000498060, ENST00000902326, ENST00000902327, ENST00000946935, ENST00000946936

RefSeq mRNA: 2 — MANE Select: NM_001004434 NM_001004434, NM_032513

CCDS: CCDS272, CCDS30644

Canonical transcript exons

ENST00000374276 — 8 exons

Exon	Start	End
ENSE00001036548	26039777	26039911
ENSE00001036549	26041700	26041805
ENSE00001819183	26037252	26039305
ENSE00001929827	26045847	26046118
ENSE00003279495	26042549	26042708
ENSE00003325836	26043398	26043551
ENSE00003413049	26044997	26045217
ENSE00003590075	26044298	26044444

Expression profiles

Bgee: expression breadth ubiquitous, 115 present calls, max score 97.11.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3120 / max 136.3927, expressed in 83 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11138	0.2212	60
11137	0.0428	21
11139	0.0342	13
11136	0.0138	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	97.11	silver quality
body of pancreas	UBERON:0001150	95.31	gold quality
epithelial cell of pancreas	CL:0000083	89.13	gold quality
placenta	UBERON:0001987	88.83	gold quality
pancreatic ductal cell	CL:0002079	88.20	silver quality
pancreas	UBERON:0001264	86.92	gold quality
tibialis anterior	UBERON:0001385	82.70	silver quality
adult mammalian kidney	UBERON:0000082	78.58	gold quality
gall bladder	UBERON:0002110	77.59	gold quality
right lobe of thyroid gland	UBERON:0001119	77.07	gold quality
tibia	UBERON:0000979	76.83	gold quality
left lobe of thyroid gland	UBERON:0001120	76.23	gold quality
upper arm skin	UBERON:0004263	75.48	gold quality
kidney	UBERON:0002113	75.45	gold quality
ileal mucosa	UBERON:0000331	75.40	silver quality
left ventricle myocardium	UBERON:0006566	75.02	gold quality
apex of heart	UBERON:0002098	74.99	gold quality
thyroid gland	UBERON:0002046	74.48	gold quality
cardiac muscle of right atrium	UBERON:0003379	74.10	gold quality
amniotic fluid	UBERON:0000173	73.73	silver quality
islet of Langerhans	UBERON:0000006	73.25	gold quality
heart left ventricle	UBERON:0002084	72.60	gold quality
nasal cavity epithelium	UBERON:0005384	72.45	gold quality
cardiac ventricle	UBERON:0002082	72.34	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.85	gold quality
deltoid	UBERON:0001476	71.50	silver quality
decidua	UBERON:0002450	70.23	gold quality
quadriceps femoris	UBERON:0001377	69.94	gold quality
endometrium	UBERON:0001295	69.28	gold quality
myocardium	UBERON:0002349	69.04	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9841	yes	1459.56
E-MTAB-10855	yes	1289.53
E-ANND-3	yes	5.25
E-GEOD-124858	no	6.42

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MTF1, NR3C1, STAT5A

miRNA regulators (miRDB)

44 targeting SLC30A2, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-10A-5P	98.89	69.85	712
HSA-MIR-10B-5P	98.89	69.86	711
HSA-MIR-7113-3P	98.75	65.71	1120
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-6818-3P	98.56	68.23	1307

Literature-anchored findings (GeneRIF, showing 20)

• a mutation in SLC30A2 (ZnT-2) may have a role in transient neonatal zinc deficiency (PMID:17065149)
• ZnT2 can facilitate vesicular zinc accumulation independently of AP-3 function, and validate the M1 fibroblastoid line as a human cell culture system amenable to the study of vesicular zinc regulation. (PMID:17349999)
• hZnT-2 was not detectable in leukocytes. (PMID:17971500)
• The localization and function of each ZnT2 isoform, was examined. (PMID:19496757)
• Pancreatic release of zinc by acinar cells is through the secretory process and apical membrane and involves transporter ZnT2 (PMID:21462106)
• Results indicated that -697G>T and 1031A>G polymorphisms in the SLC30A2 gene may be associated with low-milk-zinc in Chinese breastfeeding women. (PMID:22364884)
• inactivating ZnT-2 mutations are an underlying basis of TNZD and provide the first evidence for the dominant inheritance of heterozygous ZnT-2 mutations via negative dominance due to homodimer formation. (PMID:22733820)
• PRL-R attenuation post-transcriptionally increased ZnT2 abundance and redistributed intracellular Zn pools into lysosomes and mitochondria. (PMID:24333596)
• Human ZnT2 expression is regulated by MTF-1. (PMID:25618524)
• Our study indicates that SLC30A2 variants are common in this population, dysregulate Zn management and can lead to breast cell dysfunction. (PMID:26293594)
• findings establish that some heterozygous loss of function ZnT2 mutations disrupt zinc binding and zinc permeation, thereby suggesting a haploinsufficiency state for the unaffected WT ZnT2 allele in Transient Neonatal Zinc Deficiency (PMID:27137936)
• many SLC30A2/ZnT2 mutations cause or potentially cause transient neonatal zinc deficiency, as shown in three cases of Japanese infants (PMID:27304099)
• Article highlights the importance of early diagnosis of SLC30A2/ZnT2 variants in order to supplement zinc-deficient infants in real-time, thus preventing TNZD morbidity and enhancing newborn health. [Review] (PMID:28665435)
• ZNT2 was localized on the cell surface of both human and mouse beta-cells, suggesting a role of ZNT2 in direct export of zinc out of the beta-cell (PMID:29372370)
• This study confirms that ZnT2 is important for normal breast function in women during lactation, and suggests that women who harbor defective variants in ZnT2 may be at-risk for poor lactation performance. (PMID:29476070)
• High proportion of alleles was found in the general population due to loss of function mutations in the zinc transporter ZnT2, which result in impaired zinc secretion into breast milk consequently causing transient neonatal zinc deficiency in exclusively breastfed infants. (PMID:30450693)
• Milk-derived miRNA profiles elucidate molecular pathways that underlie breast dysfunction in women with common genetic variants in SLC30A2. (PMID:31481661)
• A novel homozygous mutation p.E88K in maternal SLC30A2 gene as a cause of transient neonatal zinc deficiency. (PMID:32278324)
• Thr288Ser mutation in SLC30A2/ZnT2 impairs critical functions of mammary epithelial cells, resulting in milk volume and altering lysosome function and cell energetics. (PMID:32320289)
• Loss-of-function SLC30A2 mutants are associated with gut dysbiosis and alterations in intestinal gene expression in preterm infants. (PMID:34965180)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc30a2	ENSDARG00000021305
mus_musculus	Slc30a2	ENSMUSG00000028836
rattus_norvegicus	Slc30a2	ENSRNOG00000054142

Paralogs (8): SLC30A4 (ENSG00000104154), SLC30A3 (ENSG00000115194), SLC30A5 (ENSG00000145740), SLC30A6 (ENSG00000152683), SLC30A7 (ENSG00000162695), SLC30A8 (ENSG00000164756), SLC30A1 (ENSG00000170385), SLC30A10 (ENSG00000196660)

Protein

Protein identifiers

Proton-coupled zinc antiporter SLC30A2 — Q9BRI3 (reviewed: Q9BRI3)

Alternative names: Solute carrier family 30 member 2, Zinc transporter 2

All UniProt accessions (1): Q9BRI3

UniProt curated annotations — full annotation on UniProt →

Function. Electroneutral proton-coupled antiporter concentrating zinc ions into a variety of intracellular organelles including endosomes, zymogen granules and mitochondria. Thereby, plays a crucial role in cellular zinc homeostasis to confer upon cells protection against its potential cytotoxicity. Regulates the zinc concentration of milk, through the transport of zinc ions into secretory vesicles of mammary cells. By concentrating zinc ions into lysosomes participates to lysosomal-mediated cell death during early mammary gland involution. Electroneutral proton-coupled antiporter mediating the efflux of zinc ions through the plasma membrane.

Subunit / interactions. Homodimer. Interacts (via lysosomal targeting motif) with AP3D1; in AP-3-mediated transport to lysosomes. Interacts with TMEM163.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle membrane. Zymogen granule membrane. Endosome membrane. Lysosome membrane. Mitochondrion inner membrane Cell membrane.

Post-translational modifications. Phosphorylated at Ser-296. Phosphorylation at Ser-296 prevents localization to lysosomes. Dephosphorylation of Ser-296 which triggers localization to lysosomes, accumulation of zinc into lysosomes and lysosomal-mediated cell death is induced by TNF.

Disease relevance. Zinc deficiency, transient neonatal (TNZD) [MIM:608118] A disorder occurring in breast-fed infants as a consequence of low milk zinc concentration in their nursing mothers, which cannot be corrected by maternal zinc supplementation. A large amount of zinc, an essential trace mineral, is required for normal growth particularly in infants, and breast milk normally contains adequate zinc to meet the requirement for infants up to 4 to 6 months of age. Zinc deficiency can lead to dermatitis, alopecia, decreased growth, and impaired immune function. The disorder shows autosomal dominant inheritance with incomplete penetrance. The disease is caused by variants affecting the gene represented in this entry.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BRI3-2	1, Long isoform	yes
Q9BRI3-1	2, Short isoform

RefSeq proteins (2): NP_001004434, NP_115902 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002524	Cation_efflux	Family
IPR027469	Cation_efflux_TMD_sf	Homologous_superfamily
IPR027470	Cation_efflux_CTD	Domain
IPR036837	Cation_efflux_CTD_sf	Homologous_superfamily
IPR050681	CDF/SLC30A	Family
IPR058533	Cation_efflux_TM	Domain

Pfam: PF01545, PF16916

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (31 total): binding site 8, topological domain 6, transmembrane region 5, mutagenesis site 5, short sequence motif 2, sequence variant 2, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BRI3-F1	77.86	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 (8): 53 (in chain a); 106; 110; 223; 227; 304 (in chain b); 321 (in chain b); 355 (in chain b)

Post-translational modifications (1): 296

Mutagenesis-validated functional residues (5):

Position	Phenotype
51–54	loss of localization to mitochondrial inner membrane. loss of function in zinc ion import into mitochondrion.
134–140	increased homodimerization activity.
294	loss of interaction with ap3d1. loss of localization to lysosome.
296	decreased phosphorylation. increased localization to lysosome.
296	loss of localization to lysosome.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 117 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_RESPONSE_TO_ZINC_ION, GOBP_LYSOSOMAL_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_TRANSITION_METAL_ION_TRANSPORT, GOBP_VACUOLAR_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_RESPONSE_TO_METAL_ION, GOCC_MITOCHONDRIAL_ENVELOPE, GOMF_PROTON_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_ZYMOGEN_GRANULE, GOCC_SECRETORY_VESICLE

GO Biological Process (13): intracellular zinc ion homeostasis (GO:0006882), response to zinc ion (GO:0010043), zinc ion import into organelle (GO:0062111), zinc ion transmembrane transport (GO:0071577), zinc export across plasma membrane (GO:0140882), zinc ion import into secretory vesicle (GO:0140914), zinc ion import into zymogen granule (GO:0140915), zinc ion import into lysosome (GO:0140916), zinc ion import into mitochondrion (GO:0140917), monoatomic ion transport (GO:0006811), monoatomic cation transport (GO:0006812), zinc ion transport (GO:0006829), transmembrane transport (GO:0055085)

GO Molecular Function (7): zinc ion transmembrane transporter activity (GO:0005385), identical protein binding (GO:0042802), metal ion binding (GO:0046872), zinc:proton antiporter activity (GO:0140826), protein binding (GO:0005515), monoatomic cation transmembrane transporter activity (GO:0008324), antiporter activity (GO:0015297)

GO Cellular Component (14): cytoplasm (GO:0005737), mitochondrial inner membrane (GO:0005743), lysosomal membrane (GO:0005765), late endosome (GO:0005770), plasma membrane (GO:0005886), endosome membrane (GO:0010008), transport vesicle membrane (GO:0030658), zymogen granule membrane (GO:0042589), secretory vesicle (GO:0099503), mitochondrion (GO:0005739), lysosome (GO:0005764), endosome (GO:0005768), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Zinc transporters	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
zinc ion transmembrane transport	3
intercellular transport	3
zinc ion import into organelle	3
monoatomic cation transmembrane transport	2
transport	2
cellular anatomical structure	2
endosome	2
cytoplasmic vesicle membrane	2
bounding membrane of organelle	2
cytoplasmic vesicle	2
cytoplasm	2
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
response to metal ion	1
zinc ion transport	1
export across plasma membrane	1
zinc ion import into secretory vesicle	1
lysosomal transport	1
vacuolar transmembrane transport	1
monoatomic ion transport	1
transition metal ion transport	1
cellular process	1
transition metal ion transmembrane transporter activity	1
protein binding	1
cation binding	1
zinc ion transmembrane transporter activity	1
metal cation:proton antiporter activity	1
binding	1
monoatomic ion transmembrane transporter activity	1
secondary active transmembrane transporter activity	1
intracellular anatomical structure	1
organelle inner membrane	1
mitochondrial membrane	1
lysosome	1
lytic vacuole membrane	1
membrane	1
cell periphery	1
transport vesicle	1
secretory granule membrane	1
zymogen granule	1

Protein interactions and networks

STRING

880 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC30A2	SLC30A9	Q6PML9	808
SLC30A2	SLC39A13	Q96H72	795
SLC30A2	SLC39A4	Q6P5W5	742
SLC30A2	SLC39A7	Q92504	738
SLC30A2	SLC39A5	Q6ZMH5	737
SLC30A2	SLC39A12	Q504Y0	735
SLC30A2	SLC39A10	Q9ULF5	733
SLC30A2	SLC39A1	Q9NY26	732
SLC30A2	SLC39A14	Q15043	716
SLC30A2	SLC39A6	Q13433	715
SLC30A2	SLC39A8	Q9C0K1	684
SLC30A2	SLC39A11	Q8N1S5	679
SLC30A2	SLC39A9	Q9NUM3	652
SLC30A2	H3BSS0	H3BSS0	620
SLC30A2	SLC30A6	Q6NXT4	561

IntAct

284 interactions, top by confidence:

A	B	Type	Score
KASH5	SLC30A2	psi-mi:“MI:0915”(physical association)	0.810
SLC30A2	KASH5	psi-mi:“MI:0915”(physical association)	0.810
SLC30A2	CCL4	psi-mi:“MI:0915”(physical association)	0.780
SLC30A2	PVR	psi-mi:“MI:0915”(physical association)	0.780
SLC30A2	TNFRSF12A	psi-mi:“MI:0915”(physical association)	0.780
PVR	SLC30A2	psi-mi:“MI:0915”(physical association)	0.780
TNFRSF12A	SLC30A2	psi-mi:“MI:0915”(physical association)	0.780
CCL4	SLC30A2	psi-mi:“MI:0915”(physical association)	0.780
SLC30A2	ADAM33	psi-mi:“MI:0915”(physical association)	0.720
ADAM33	SLC30A2	psi-mi:“MI:0915”(physical association)	0.720
SLC30A3	SLC30A2	psi-mi:“MI:0403”(colocalization)	0.670
SLC30A3	SLC30A2	psi-mi:“MI:0915”(physical association)	0.670
SLC30A2	SLC30A3	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (146): SLC30A2 (Two-hybrid), SLC30A2 (Two-hybrid), CCL4L2 (Two-hybrid), TNFRSF12A (Two-hybrid), ADAM33 (Two-hybrid), CCDC155 (Two-hybrid), SLC30A2 (Two-hybrid), SLC30A2 (Two-hybrid), CCDC155 (Two-hybrid), CREB3 (Two-hybrid), SLC30A2 (Two-hybrid), SLC30A2 (Two-hybrid), SLC30A2 (Two-hybrid), CTSD (Co-fractionation), SLC30A3 (Affinity Capture-Western)

ESM2 similar proteins: A0A0G2KQY6, A0A3Q7ZPG5, A4IFD7, A4IIC5, A5PMX1, A8WMY3, O13918, O14863, O35149, O45923, O55174, O59758, O80632, P0CE46, P20107, P32798, P40544, P97441, Q28CE7, Q2HJ10, Q3KR82, Q52KD7, Q5BJM8, Q5I020, Q5MNV6, Q5NA18, Q5XHB4, Q5ZIU9, Q62941, Q6DBM8, Q6DG36, Q6NRI1, Q6NTL1, Q6P3N9, Q6QIX3, Q8BFU1, Q8BGG0, Q8H329, Q8IWU4, Q8LE59

Diamond homologs: O14863, O35149, O45923, O55174, P0CE46, P13512, P30540, P75757, P94178, P97441, Q08E25, Q2HJ10, Q54QU8, Q54T06, Q5I020, Q5R617, Q5XHB4, Q62941, Q6DBM8, Q6P0D1, Q6QIX3, Q83SA2, Q8BGG0, Q8IWU4, Q8X400, Q99726, Q9BRI3, Q9LXS1, Q9M271, Q9TTF3, Q9ZT63, A7Z1S6, O07084, Q66D85, Q688R1, Q6D7E5, Q8Z8B6, Q8ZGY6, Q8ZQT3, S7V0D3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 72 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
zinc ion transmembrane transport	5	59.5×	7e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	45
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
3340912	NM_001004434.3(SLC30A2):c.652C>T (p.Arg218Ter)	Pathogenic
3602182	NM_001004434.3(SLC30A2):c.663del (p.Phe221fs)	Pathogenic
39552	NM_001004434.3(SLC30A2):c.161A>G (p.His54Arg)	Pathogenic
39553	NM_001004434.3(SLC30A2):c.259G>A (p.Gly87Arg)	Pathogenic
1806288	NM_001004434.3(SLC30A2):c.528del (p.Thr177fs)	Likely pathogenic

SpliceAI

1432 predictions. Top by Δscore:

Variant	Effect	Δscore
1:26039301:CTGAG:C	acceptor_gain	1.0000
1:26039302:TGAGC:T	acceptor_loss	1.0000
1:26039306:C:CC	acceptor_gain	1.0000
1:26039314:C:CT	acceptor_gain	1.0000
1:26039314:C:T	acceptor_gain	1.0000
1:26039315:G:T	acceptor_gain	1.0000
1:26039770:CACT:C	donor_loss	1.0000
1:26039771:ACTC:A	donor_loss	1.0000
1:26039772:CTCA:C	donor_loss	1.0000
1:26039773:TCA:T	donor_loss	1.0000
1:26039774:CACC:C	donor_loss	1.0000
1:26039775:A:AC	donor_gain	1.0000
1:26039776:C:A	donor_loss	1.0000
1:26039776:C:CC	donor_gain	1.0000
1:26039911:CCT:C	acceptor_loss	1.0000
1:26039912:C:CA	acceptor_loss	1.0000
1:26041694:GGTTA:G	donor_loss	1.0000
1:26041695:GTTA:G	donor_loss	1.0000
1:26041696:TTAC:T	donor_loss	1.0000
1:26041697:TA:T	donor_loss	1.0000
1:26041702:T:A	donor_gain	1.0000
1:26041802:CTGG:C	acceptor_gain	1.0000
1:26041803:TGG:T	acceptor_gain	1.0000
1:26041804:GG:G	acceptor_gain	1.0000
1:26041804:GGCT:G	acceptor_loss	1.0000
1:26041805:GC:G	acceptor_loss	1.0000
1:26041806:C:CC	acceptor_gain	1.0000
1:26041806:CTG:C	acceptor_loss	1.0000
1:26041807:T:A	acceptor_loss	1.0000
1:26041809:C:CT	acceptor_gain	1.0000

AlphaMissense

2428 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:26041764:G:C	F209L	0.993
1:26041764:G:T	F209L	0.993
1:26041766:A:G	F209L	0.993
1:26041778:A:G	C205R	0.993
1:26042588:G:C	S182R	0.993
1:26042588:G:T	S182R	0.993
1:26042590:T:G	S182R	0.993
1:26043516:A:G	W103R	0.993
1:26043516:A:T	W103R	0.993
1:26042600:G:C	D178E	0.992
1:26042600:G:T	D178E	0.992
1:26039881:A:T	V241D	0.991
1:26043476:C:G	R116P	0.991
1:26039791:A:T	V271D	0.990
1:26039823:C:A	W260C	0.990
1:26039823:C:G	W260C	0.990
1:26042601:T:G	D178A	0.989
1:26043403:G:C	N140K	0.989
1:26043403:G:T	N140K	0.989
1:26039797:A:G	L269P	0.988
1:26042601:T:C	D178G	0.988
1:26043420:A:G	C135R	0.988
1:26039825:A:G	W260R	0.987
1:26039825:A:T	W260R	0.987
1:26039270:C:G	A288P	0.986
1:26039869:A:G	L245P	0.986
1:26042602:C:G	D178H	0.986
1:26041786:T:C	D202G	0.985
1:26043425:G:C	S133W	0.985
1:26042604:C:T	G177D	0.984

dbSNP variants (sampled 300 via entrez): RS1000312421 (1:26043679 T>A,C), RS1000343592 (1:26043389 C>G), RS1000436014 (1:26040807 C>T), RS1000721139 (1:26038917 A>C,G), RS1000763544 (1:26038612 G>A,C), RS1000782651 (1:26040559 T>C), RS1000827790 (1:26037316 C>T), RS1001254778 (1:26038869 C>T), RS1001309316 (1:26042230 G>A), RS1002578274 (1:26042350 A>G), RS1002803298 (1:26037624 TGG>T), RS1003788180 (1:26041108 A>G), RS1004250123 (1:26041004 G>A), RS1004317212 (1:26038004 A>G), RS1004545646 (1:26045581 T>C)

Disease associations

OMIM: gene MIM:609617 | disease phenotypes: MIM:608118

GenCC curated gene-disease

Disease	Classification	Inheritance
zinc deficiency, transient neonatal	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
zinc deficiency, transient neonatal	Definitive	AD

Mondo (2): zinc deficiency, transient neonatal (MONDO:0011973), prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000964	Eczematoid dermatitis
HP:0001596	Alopecia
HP:0031831	Decreased serum zinc

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C564286	Zinc Deficiency, Neonatal, due to Low Breast Milk Zinc (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

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

Chemical	Actions (top 5)	PubMed papers
Zinc	decreases secretion, increases abundance, increases export, increases secretion, increases transport (+1 more)	5
Cadmium	increases abundance, increases expression	4
Cadmium Chloride	increases reaction, increases abundance, increases expression, decreases reaction, affects reaction (+1 more)	4
Valproic Acid	affects cotreatment, increases expression, increases methylation	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
methylmercuric chloride	increases expression	1
terbufos	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
zinc chloride	increases expression, affects binding, decreases reaction, increases reaction, affects reaction	1
entinostat	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
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Estradiol	affects cotreatment, increases expression	1
Colforsin	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Paraquat	decreases expression	1
Parathion	increases methylation	1
Progesterone	affects cotreatment, increases expression	1
Silver	increases expression	1
Triclosan	decreases expression	1
Ziram	increases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer