SLC39A14

Summary

SLC39A14 (solute carrier family 39 member 14, HGNC:20858) is a protein-coding gene on chromosome 8p21.3, encoding Metal cation symporter ZIP14 (Q15043). Electroneutral transporter of the plasma membrane mediating the cellular uptake of the divalent metal cations zinc, manganese and iron that are important for tissue homeostasis, metabolism, development and immunity.

This gene encodes a member of the the SLC39A family of divalent metal transporters that mediates the cellular uptake of manganese, zinc, iron, and cadmium. The encoded protein contains eight transmembrane domains, a histidine-rich motif, and a metalloprotease motif, and is expressed on the plasma membrane and the endocytic vesicle membrane. It is an important transporter of nontransferrin-bound iron and a critical regulator of manganese homeostasis. Naturally occurring mutations in this gene are associated with neurodegeneration with brain iron accumulation and early-onset parkinsonism-dystonia with hypermanganesemia.

Source: NCBI Gene 23516 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hypermanganesemia with dystonia 2 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 285 total — 9 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 72
• Druggable target: yes
• MANE Select transcript: NM_001128431

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20858
Approved symbol	SLC39A14
Name	solute carrier family 39 member 14
Location	8p21.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0062, NET34, ZIP14, ZIP-14
Ensembl gene	ENSG00000104635
Ensembl biotype	protein_coding
OMIM	608736
Entrez	23516

Gene structure

Transcript identifiers

Ensembl transcripts: 84 — 83 protein_coding, 1 retained_intron

ENST00000240095, ENST00000289952, ENST00000359741, ENST00000381237, ENST00000517370, ENST00000517552, ENST00000518348, ENST00000519960, ENST00000520644, ENST00000520832, ENST00000522881, ENST00000524285, ENST00000851569, ENST00000851570, ENST00000851571, ENST00000851572, ENST00000851573, ENST00000851574, ENST00000851575, ENST00000851576, ENST00000851577, ENST00000851578, ENST00000851579, ENST00000851580, ENST00000851581, ENST00000851582, ENST00000851583, ENST00000851584, ENST00000851585, ENST00000851586, ENST00000851587, ENST00000851588, ENST00000851589, ENST00000851590, ENST00000851591, ENST00000851592, ENST00000851593, ENST00000851594, ENST00000851595, ENST00000851596, ENST00000851597, ENST00000851598, ENST00000851599, ENST00000851600, ENST00000851601, ENST00000851602, ENST00000851603, ENST00000851604, ENST00000851605, ENST00000851606, ENST00000851607, ENST00000851608, ENST00000851609, ENST00000851610, ENST00000851611, ENST00000851612, ENST00000851613, ENST00000851614, ENST00000851615, ENST00000851616, ENST00000851617, ENST00000851618, ENST00000851619, ENST00000930815, ENST00000930819, ENST00000930820, ENST00000930821, ENST00000930822, ENST00000930823, ENST00000941284, ENST00000941285, ENST00000941286, ENST00000941287, ENST00000941288, ENST00000941289, ENST00000941290, ENST00000941291, ENST00000941292, ENST00000941293, ENST00000941294, ENST00000941295, ENST00000941296, ENST00000941297, ENST00000941298

RefSeq mRNA: 10 — MANE Select: NM_001128431 NM_001128431, NM_001135153, NM_001135154, NM_001351655, NM_001351656, NM_001351657, NM_001351658, NM_001351659, NM_001351660, NM_015359

CCDS: CCDS47822, CCDS47823, CCDS6030

Canonical transcript exons

ENST00000381237 — 9 exons

Exon	Start	End
ENSE00000683828	22408310	22408496
ENSE00000683833	22412037	22412206
ENSE00000818422	22414780	22414902
ENSE00001041907	22417651	22417835
ENSE00001159960	22415769	22415957
ENSE00001487903	22419552	22422736
ENSE00001487906	22367278	22367408
ENSE00003463584	22416073	22416280
ENSE00003795542	22404696	22404980

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.4995 / max 716.6121, expressed in 1714 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87752	22.9311	1697
87753	1.5580	1080
87755	0.7746	463
87754	0.6493	403
87759	0.3828	208
87760	0.3561	139
87758	0.2753	148
87763	0.2433	96
87762	0.1639	76
87761	0.0954	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	99.45	gold quality
body of pancreas	UBERON:0001150	98.98	gold quality
liver	UBERON:0002107	98.96	gold quality
right lobe of liver	UBERON:0001114	98.91	gold quality
tibia	UBERON:0000979	98.84	gold quality
jejunal mucosa	UBERON:0000399	98.78	gold quality
duodenum	UBERON:0002114	98.63	gold quality
pancreas	UBERON:0001264	98.50	gold quality
pericardium	UBERON:0002407	98.30	gold quality
oocyte	CL:0000023	98.26	gold quality
islet of Langerhans	UBERON:0000006	98.13	gold quality
ileal mucosa	UBERON:0000331	97.54	gold quality
heart right ventricle	UBERON:0002080	97.36	gold quality
secondary oocyte	CL:0000655	97.24	gold quality
type B pancreatic cell	CL:0000169	97.13	gold quality
choroid plexus epithelium	UBERON:0003911	96.93	gold quality
vena cava	UBERON:0004087	96.29	gold quality
synovial joint	UBERON:0002217	96.23	gold quality
periodontal ligament	UBERON:0008266	95.97	gold quality
left adrenal gland	UBERON:0001234	95.90	gold quality
decidua	UBERON:0002450	95.83	gold quality
colonic mucosa	UBERON:0000317	95.79	gold quality
right adrenal gland cortex	UBERON:0035827	95.75	gold quality
thyroid gland	UBERON:0002046	95.73	gold quality
left lobe of thyroid gland	UBERON:0001120	95.72	gold quality
right adrenal gland	UBERON:0001233	95.72	gold quality
body of stomach	UBERON:0001161	95.70	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.60	gold quality
layer of synovial tissue	UBERON:0007616	95.48	gold quality
left adrenal gland cortex	UBERON:0035825	95.47	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	109.26
E-CURD-7	no	1193.51
E-MTAB-6142	no	110.46
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

172 targeting SLC39A14, 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-4682	100.00	68.89	1258
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-4775	99.98	75.00	6394
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-551B-5P	99.96	71.28	3493
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1468-3P	99.96	72.74	3797

Literature-anchored findings (GeneRIF, showing 34)

• ZIP14 (SLC39A14)was shown to function as a zinc influx transporter in a temperature-dependant manner. (PMID:15642354)
• Zip14 expression is up-regulated through IL-6 (PMID:15863613)
• HFE decreases the stability of Zip14 and therefore reduces the iron loading in HepG2 cells (PMID:18524764)
• These results suggest that endosomal ZIP14 participates in the cellular assimilation of iron from transferrin, thus identifying a potentially new role for ZIP14 in iron metabolism. (PMID:20682781)
• Alternative splicing of SLC39A14 was identified in colorectal tumors and found to be regulated by the Wnt pathway. (PMID:20938052)
• ZIP14 downregulation is likely involved in the depletion of zinc in the hepatoma cells in Hepatocellular cancer (PMID:21373779)
• The transporter ZIP14 is up-regulated along the entire gastrointestinal tract by proinflammatory conditions. (PMID:21462106)
• Data suggest that Zip-14 mRNA level in enterocytes increases with iron or zinc depletion; Zip-14 transcript level in enterocytes decreases with zinc supplementation. (PMID:22137264)
• the SLC39A14-exon4B transcript variant is a colorectal cancer biomarker with high sensitivity and organ-confined specificity. (PMID:22173985)
• Observations indicate that ZIP14 and ZIP8 are both broad-scope metal-ion transporters that can mediate the cellular uptake of nutritionally important metals as well as the toxic heavy metal cadmium. (PMID:22318508)
• Zip14 expression induced by lipopolysaccharides in macrophages attenuates inflammatory response (PMID:23052185)
• Data show the role of ZIP14 in the hepatocyte is multi-functional since zinc and iron trafficking are altered in the Zip14(-/-) mice and their phenotype shows defects in glucose homeostasis. (PMID:23110240)
• Polymorphisms in SLC39A14 and SLC39A8 seemed to affect blood cadmium concentrations, for SLC39A14 this effect may occur via differential gene expression. (PMID:24514587)
• 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)
• Asparagine-linked (N-linked) glycosylation of ZIP14, particularly the glycosylation at N102, was required for efficient membrane extraction of ZIP14 and therefore is necessary for its iron sensitivity. (PMID:24927598)
• Integrative analysis of four RNA-Seq datasets and differential expression revealed for the first time, splicing alterations of SLC39A14 and NR1I3 in hepatocellular carcinoma. (PMID:26711644)
• Missense mutations solute carrier family 39 (zinc transporter), member 14 (SLC39A14) impair manganese uptake. (PMID:27231142)
• Zip14 activity is needed for adaptation to endoplasmic reticulum stress in liver. (PMID:28673968)
• Study shows that individuals harboring loss-of-function mutations in SLC30A10 or SLC39A14 develop inherited forms of Mn-induced neurotoxicity. (PMID:28789954)
• These results suggest that the wild type p53 plays a role in regulating ZIP14, but not DMT1 in HepG2 cells. (PMID:29292794)
• Increased free Zn(2+) correlates with induction of sarco(endo)plasmic reticulum stress via altered expression levels of Zn(2+) -transporters, Zip8, Zip14, and ZnT8, in heart failure. (PMID:29333637)
• SLC39A14 mutation is associated with dystonia. (PMID:29685658)
• Expression of zinc transporters ZIP4, ZIP14 and ZnT9 in hepatic carcinogenesis-An immunohistochemical study (PMID:29895370)
• Both ZIP8 and ZIP14 have roles in manganese metabolism of alveolar epithelial cells. (PMID:31261654)
• solute carriers ZIP8 and ZIP14 regulate manganese accumulation in brain microvascular endothelial cells and control brain manganese levels (PMID:31699897)
• The Functions of ZIP8, ZIP14, and ZnT10 in the Regulation of Systemic Manganese Homeostasis. (PMID:32392784)
• Circular RNA circ_001842 plays an oncogenic role in renal cell carcinoma by disrupting microRNA-502-5p-mediated inhibition of SLC39A14. (PMID:32729666)
• Human placental cell line HTR-8/SVneo accumulates cadmium by divalent metal transporters DMT1 and ZIP14. (PMID:33146651)
• Knockdown of Circ_SLC39A8 protects against the progression of osteoarthritis by regulating miR-591/IRAK3 axis. (PMID:33658057)
• HIF-1alpha Dependent Upregulation of ZIP8, ZIP14, and TRPA1 Modify Intracellular Zn(2+) Accumulation in Inflammatory Synoviocytes. (PMID:34198528)
• Manganese transport in mammals by zinc transporter family proteins, ZNT and ZIP. (PMID:34924116)
• Calcium and the Ca-ATPase SPCA1 modulate plasma membrane abundance of ZIP8 and ZIP14 to regulate Mn(II) uptake in brain microvascular endothelial cells. (PMID:35787370)
• Circ_000829 Plays an Anticancer Role in Renal Cell Carcinoma by Suppressing SRSF1-Mediated Alternative Splicing of SLC39A14. (PMID:36062189)
• Hereditary Disorders of Manganese Metabolism: Pathophysiology of Childhood-Onset Dystonia-Parkinsonism in SLC39A14 Mutation Carriers and Genetic Animal Models. (PMID:36361624)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc39a14	ENSDARG00000102387
mus_musculus	Slc39a14	ENSMUSG00000022094
rattus_norvegicus	Slc39a14	ENSRNOG00000009832

Paralogs (6): SLC39A8 (ENSG00000138821), SLC39A5 (ENSG00000139540), SLC39A6 (ENSG00000141424), SLC39A4 (ENSG00000147804), SLC39A12 (ENSG00000148482), SLC39A10 (ENSG00000196950)

Protein

Protein identifiers

Metal cation symporter ZIP14 — Q15043 (reviewed: Q15043)

Alternative names: LIV-1 subfamily of ZIP zinc transporter 4, Solute carrier family 39 member 14, Zrt- and Irt-like protein 14

All UniProt accessions (9): A0A0S2Z534, E5RFF5, E5RFT1, E5RFZ8, E5RGA7, E5RIP4, E5RJ40, E5RJG5, Q15043

UniProt curated annotations — full annotation on UniProt →

Function. Electroneutral transporter of the plasma membrane mediating the cellular uptake of the divalent metal cations zinc, manganese and iron that are important for tissue homeostasis, metabolism, development and immunity. Functions as an energy-dependent symporter, transporting through the membranes an electroneutral complex composed of a divalent metal cation and two bicarbonate anions. Beside these endogenous cellular substrates, can also import cadmium a non-essential metal which is cytotoxic and carcinogenic. Controls the cellular uptake by the intestinal epithelium of systemic zinc, which is in turn required to maintain tight junctions and the intestinal permeability. Modifies the activity of zinc-dependent phosphodiesterases, thereby indirectly regulating G protein-coupled receptor signaling pathways important for gluconeogenesis and chondrocyte differentiation. Regulates insulin receptor signaling, glucose uptake, glycogen synthesis and gluconeogenesis in hepatocytes through the zinc-dependent intracellular catabolism of insulin. Through zinc cellular uptake also plays a role in the adaptation of cells to endoplasmic reticulum stress. Major manganese transporter of the basolateral membrane of intestinal epithelial cells, it plays a central role in manganese systemic homeostasis through intestinal manganese uptake. Also involved in manganese extracellular uptake by cells of the blood-brain barrier. May also play a role in manganese and zinc homeostasis participating in their elimination from the blood through the hepatobiliary excretion. Also functions in the extracellular uptake of free iron. May also function intracellularly and mediate the transport from endosomes to cytosol of iron endocytosed by transferrin. Plays a role in innate immunity by regulating the expression of cytokines by activated macrophages.

Subunit / interactions. Homotrimer.

Subcellular location. Cell membrane. Apical cell membrane. Basolateral cell membrane. Early endosome membrane. Late endosome membrane. Lysosome membrane.

Tissue specificity. Ubiquitously expressed, with higher expression in liver, pancreas, fetal liver, thyroid gland, left and right ventricle, right atrium and fetal heart. Weakly expressed in spleen, thymus, and peripheral blood leukocytes. Expressed in liver and in brain by large neurons in the globus pallidus, the insular cortex and the dentate nucleus and to a lower extent in the putamen and the caudate nucleus (at protein level). Expressed in osteoblasts and giant osteoclast-like cells, but not in osteocytes found osteoblastoma and giant cell tumors (at protein level). Expressed by microvascular capillary endothelial cells that constitute the blood-brain barrier (at protein level). Expressed by macrophages. Widely expressed but not detected in brain, heart, skeletal muscle, placenta and fetal skin.

Post-translational modifications. Ubiquitinated. Ubiquitination occurs upon iron depletion. The ubiquitinated form undergoes proteasomal degradation. N-glycosylated. N-glycosylation at Asn-102 is required for iron-regulated extraction of the transporter from membranes and subsequent proteasomal degradation.

Disease relevance. Hypermanganesemia with dystonia 2 (HMNDYT2) [MIM:617013] A metabolic autosomal recessive disorder characterized by increased blood manganese levels, neurodegeneration, and rapidly progressive parkinsonism and dystonia. Affected individuals present with loss of developmental milestones, progressive dystonia and bulbar dysfunction in infancy or early childhood. Towards the end of the first decade, they manifest severe generalized pharmacoresistant dystonia, spasticity, limb contractures and scoliosis, and loss of independent ambulation. Cognition may be impaired, but is better preserved than motor function. The disease is caused by variants affecting the gene represented in this entry. Hyperostosis cranialis interna (HCIN) [MIM:144755] An autosomal dominant bone disorder characterized by endosteal hyperostosis and osteosclerosis of the calvaria and the skull base. The progressive bone overgrowth causes entrapment and dysfunction of cranial nerves I, II, V, VII, and VIII, its first symptoms often presenting during the second decade of life. The disease is caused by variants affecting the gene represented in this entry. Conditional knockin mice overexpressing Arg-438 variant, which is the mouse equivalent of human variant Leu-441, in osteoblasts have a severe skeletal phenotype marked by a drastic increase in cortical thickness due to an enhanced endosteal bone formation, resembling the underlying pathology in HCI patients.

Induction. Up-regulated by iron (at protein level). Down-regulation upon iron depletion occurs through proteasomal degradation of the intracellular pool. Up-regulated by tunicamycin, a drug inducing endoplasmic reticulum stress (at protein level). Up-regulated by lipopolysaccharide/LPS.

Similarity. Belongs to the ZIP transporter (TC 2.A.5) family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q15043-1	1, ZIP14B	yes
Q15043-2	3
Q15043-3	2, ZIP14A

RefSeq proteins (10): NP_001121903, NP_001128625, NP_001128626, NP_001338584, NP_001338585, NP_001338586, NP_001338587, NP_001338588, NP_001338589, NP_056174 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003689	ZIP	Family
IPR050799	ZIP_Transporter	Family

Pfam: PF02535

Catalyzed reactions (Rhea), 4 shown:

• Zn(2+)(out) + 2 hydrogencarbonate(out) = Zn(2+)(in) + 2 hydrogencarbonate(in) (RHEA:62252)
• Cd(2+)(out) + 2 hydrogencarbonate(out) = Cd(2+)(in) + 2 hydrogencarbonate(in) (RHEA:62256)
• Mn(2+)(out) + 2 hydrogencarbonate(out) = Mn(2+)(in) + 2 hydrogencarbonate(in) (RHEA:62260)
• Fe(2+)(out) + 2 hydrogencarbonate(out) = Fe(2+)(in) + 2 hydrogencarbonate(in) (RHEA:62368)

UniProt features (33 total): topological domain 7, transmembrane region 6, sequence variant 5, glycosylation site 3, mutagenesis site 3, sequence conflict 3, short sequence motif 2, splice variant 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15043-F1	73.65	0.29

Functional residue map

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

Glycosylation sites (3): 77, 87, 102

Mutagenesis-validated functional residues (3):

Position	Phenotype
77	decreased n-glycosylation.
87	decreased n-glycosylation.
102	decreased n-glycosylation.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-442380	Zinc influx into cells by the SLC39 gene family
R-HSA-382551	Transport of small molecules
R-HSA-425366
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-425410	Metal ion SLC transporters
R-HSA-435354	Zinc transporters

MSigDB gene sets: 507 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_CARTILAGE_DEVELOPMENT, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, KAAB_FAILED_HEART_ATRIUM_DN, BASSO_B_LYMPHOCYTE_NETWORK, GOCC_VACUOLAR_MEMBRANE, GOBP_TRANSITION_METAL_ION_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_INTRACELLULAR_IRON_ION_HOMEOSTASIS, GOBP_REGULATION_OF_HORMONE_LEVELS, HNF1_Q6, GGGTGGRR_PAX4_03, GOBP_IRON_ION_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (25): chondrocyte differentiation (GO:0002062), gluconeogenesis (GO:0006094), intracellular zinc ion homeostasis (GO:0006882), insulin receptor signaling pathway (GO:0008286), regulation of hormone levels (GO:0010817), intracellular monoatomic cation homeostasis (GO:0030003), cellular response to insulin stimulus (GO:0032869), iron import into cell (GO:0033212), iron ion transmembrane transport (GO:0034755), positive regulation of G protein-coupled receptor signaling pathway (GO:0045745), manganese ion homeostasis (GO:0055071), cellular response to glucose stimulus (GO:0071333), manganese ion transmembrane transport (GO:0071421), zinc ion transmembrane transport (GO:0071577), zinc ion import across plasma membrane (GO:0071578), obsolete inorganic cation transmembrane transport (GO:0098662), import across plasma membrane (GO:0098739), monoatomic ion transport (GO:0006811), iron ion transport (GO:0006826), zinc ion transport (GO:0006829), bicarbonate transport (GO:0015701), metal ion transport (GO:0030001), transmembrane transport (GO:0055085), cadmium ion transmembrane transport (GO:0070574), monoatomic anion transmembrane transport (GO:0098656)

GO Molecular Function (9): iron ion transmembrane transporter activity (GO:0005381), manganese ion transmembrane transporter activity (GO:0005384), zinc ion transmembrane transporter activity (GO:0005385), cadmium ion transmembrane transporter activity (GO:0015086), ferrous iron transmembrane transporter activity (GO:0015093), monoatomic anion:monoatomic cation symporter activity (GO:0015296), monoatomic cation:bicarbonate symporter activity (GO:0140410), protein binding (GO:0005515), metal ion transmembrane transporter activity (GO:0046873)

GO Cellular Component (9): lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), early endosome membrane (GO:0031901), late endosome membrane (GO:0031902), lysosome (GO:0005764), endosome (GO:0005768)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Zinc transporters	1
Transport of small molecules	1
SLC-mediated transmembrane transport	1
Metal ion SLC transporters	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transition metal ion transmembrane transporter activity	4
monoatomic cation transmembrane transport	3
inorganic ion homeostasis	2
monoatomic cation homeostasis	2
iron ion transport	2
zinc ion transmembrane transport	2
transition metal ion transport	2
solute:monoatomic cation symporter activity	2
plasma membrane region	2
endosome membrane	2
cell differentiation	1
cartilage development	1
glucose metabolic process	1
hexose biosynthetic process	1
intracellular monoatomic cation homeostasis	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
regulation of biological quality	1
intracellular monoatomic ion homeostasis	1
response to insulin	1
cellular response to peptide hormone stimulus	1
intracellular iron ion homeostasis	1
establishment of localization in cell	1
G protein-coupled receptor signaling pathway	1
regulation of G protein-coupled receptor signaling pathway	1
positive regulation of signal transduction	1
intracellular glucose homeostasis	1
response to glucose	1
cellular response to hexose stimulus	1
manganese ion transport	1
zinc ion transport	1
inorganic cation import across plasma membrane	1
transmembrane transport	1
import into cell	1
transport	1
iron ion transmembrane transport	1
manganese ion transmembrane transport	1
cadmium ion transmembrane transport	1
iron ion transmembrane transporter activity	1
monoatomic anion transmembrane transporter activity	1

Protein interactions and networks

STRING

1042 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC39A14	SLC11A2	P49281	932
SLC39A14	SLC30A10	Q6XR72	800
SLC39A14	SLC39A1	Q9NY26	794
SLC39A14	SLC40A1	Q9NP59	786
SLC39A14	TFRC	P02786	780
SLC39A14	SLC39A9	Q9NUM3	772
SLC39A14	H3BSS0	H3BSS0	758
SLC39A14	HAMP	P81172	757
SLC39A14	SLC30A1	Q9Y6M5	755
SLC39A14	SLC30A7	Q8NEW0	754
SLC39A14	SLC39A11	Q8N1S5	746
SLC39A14	SLC30A4	O14863	732
SLC39A14	SLC30A5	Q8TAD4	726
SLC39A14	SLC30A2	Q9BRI3	716
SLC39A14	SLC30A6	Q6NXT4	701

IntAct

54 interactions, top by confidence:

A	B	Type	Score
TSPAN15	ADAM10	psi-mi:“MI:0914”(association)	0.840
TSPAN5	ADAM10	psi-mi:“MI:0914”(association)	0.800
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
VAPB	FAM83G	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CD81	C2orf72	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
SLC39A14	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
ADAM10	TSPAN9	psi-mi:“MI:0914”(association)	0.350
P2RY6	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC15A3		psi-mi:“MI:0914”(association)	0.350
UNC93B1		psi-mi:“MI:0914”(association)	0.350
rep	GPR89A	psi-mi:“MI:0914”(association)	0.350
M	TM9SF1	psi-mi:“MI:0914”(association)	0.350
SLC15A4	ESYT2	psi-mi:“MI:0914”(association)	0.350
CNR2	ILVBL	psi-mi:“MI:0914”(association)	0.350
POMK	ESYT2	psi-mi:“MI:0914”(association)	0.350
COMTD1	TARS3	psi-mi:“MI:0914”(association)	0.350
MFSD4A	UBXN8	psi-mi:“MI:0914”(association)	0.350
SPPL2B	HAS3	psi-mi:“MI:0914”(association)	0.350
ADGRE5	SCAMP3	psi-mi:“MI:0914”(association)	0.350
P2RY2	SCAMP3	psi-mi:“MI:0914”(association)	0.350
AGPAT3	WBP4	psi-mi:“MI:0914”(association)	0.350
STING1	NPC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (371): SLC39A14 (Proximity Label-MS), SLC39A14 (Proximity Label-MS), SLC39A14 (Affinity Capture-MS), SLC39A14 (Affinity Capture-MS), SLC39A14 (Proximity Label-MS), SLC39A14 (Proximity Label-MS), SLC39A14 (Proximity Label-MS), SLC39A14 (Proximity Label-MS), SLC39A14 (Proximity Label-MS), SLC39A14 (Proximity Label-MS), SLC39A14 (Proximity Label-MS), SLC39A14 (Proximity Label-MS), SLC39A14 (Affinity Capture-MS), SLC39A14 (Affinity Capture-MS), SLC39A14 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2KQY6, A0A6I8PMZ8, A0JPN2, A4IGY6, A5D7L5, A7T1N0, B3DHU2, O43868, O75899, O88871, O94402, P04919, P0DX17, P23562, P26432, P26433, P48764, P55205, Q08E40, Q0DHJ5, Q0DWA9, Q0VCH8, Q15043, Q28C60, Q4VAE3, Q504Y0, Q5FVQ0, Q5FWH7, Q5RAB7, Q5Z413, Q6DCK1, Q6L8F3, Q6PI78, Q75N73, Q78IQ7, Q80T41, Q8K596, Q8VIH3, Q8W469, Q91W10

Diamond homologs: A0A0G2KQY6, A0A6I8PMZ8, A4IGY6, A5D7H1, A5D7L5, A8WMY3, A8X482, L5KLU7, P0DX17, Q06916, Q15043, Q1KZG0, Q29175, Q2M1K6, Q31125, Q504Y0, Q5FVQ0, Q5FWH7, Q5R6I6, Q5RAB7, Q5RFD5, Q5TJF6, Q6L8F3, Q6MGB4, Q6P5F6, Q6PEH9, Q75N73, Q78IQ7, Q8AW42, Q8BZH0, Q91W10, Q92504, Q96H72, Q9C0K1, Q9M647, Q9PUB8, Q9ULF5, Q9UT11, Q9V3A4, Q9XTQ7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 62 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
Innate Immune System	7	4.5×	3e-03
Neutrophil degranulation	7	4.0×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	4
Uncertain significance	95
Likely benign	113
Benign	40

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1334419	NM_001128431.4(SLC39A14):c.1336C>T (p.Pro446Ser)	Pathogenic
2091463	NM_001128431.4(SLC39A14):c.178C>T (p.Gln60Ter)	Pathogenic
242924	NM_001128431.4(SLC39A14):c.292T>G (p.Phe98Val)	Pathogenic
242925	NM_001128431.4(SLC39A14):c.313G>T (p.Glu105Ter)	Pathogenic
242926	NM_015359.6(SLC39A14):c.477_478del (p.Ser160fs)	Pathogenic
242927	NM_001128431.4(SLC39A14):c.1147G>A (p.Gly383Arg)	Pathogenic
242928	NM_001128431.4(SLC39A14):c.1407C>G (p.Asn469Lys)	Pathogenic
3775321	NM_015359.6(SLC39A14):c.520dup (p.Val174fs)	Pathogenic
523143	NM_001128431.4(SLC39A14):c.1322T>G (p.Leu441Arg)	Pathogenic
2506025	NM_001128431.4(SLC39A14):c.628-2A>G	Likely pathogenic
4086055	NM_001128431.4(SLC39A14):c.152A>G (p.Tyr51Cys)	Likely pathogenic
446707	NM_001128431.4(SLC39A14):c.751-9C>G	Likely pathogenic
4686585	NM_001128431.4(SLC39A14):c.971G>A (p.Trp324Ter)	Likely pathogenic

SpliceAI

2197 predictions. Top by Δscore:

Variant	Effect	Δscore
8:22404691:CACA:C	acceptor_loss	1.0000
8:22404694:A:AG	acceptor_gain	1.0000
8:22404694:A:C	acceptor_loss	1.0000
8:22404695:G:GC	acceptor_loss	1.0000
8:22404695:G:GG	acceptor_gain	1.0000
8:22404695:GGTTT:G	acceptor_gain	1.0000
8:22404978:ACGGT:A	donor_loss	1.0000
8:22404979:CGGTA:C	donor_loss	1.0000
8:22404981:G:C	donor_loss	1.0000
8:22404981:G:GG	donor_gain	1.0000
8:22404982:T:A	donor_loss	1.0000
8:22408305:TTCA:T	acceptor_loss	1.0000
8:22408308:A:AG	acceptor_gain	1.0000
8:22408308:AGT:A	acceptor_gain	1.0000
8:22408309:G:GG	acceptor_gain	1.0000
8:22408309:GT:G	acceptor_gain	1.0000
8:22408309:GTG:G	acceptor_gain	1.0000
8:22408309:GTGC:G	acceptor_gain	1.0000
8:22408309:GTGCT:G	acceptor_gain	1.0000
8:22408454:GAGAA:G	donor_gain	1.0000
8:22412078:T:TA	acceptor_gain	1.0000
8:22412088:T:A	acceptor_gain	1.0000
8:22412089:G:A	acceptor_gain	1.0000
8:22412096:AGCGT:A	acceptor_gain	1.0000
8:22412097:GCGTG:G	acceptor_gain	1.0000
8:22412204:G:GT	donor_gain	1.0000
8:22414769:T:A	acceptor_gain	1.0000
8:22414770:G:A	acceptor_gain	1.0000
8:22415765:CCAGC:C	acceptor_loss	1.0000
8:22415767:A:AG	acceptor_gain	1.0000

AlphaMissense

3243 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:22412196:T:C	L206P	1.000
8:22416177:T:A	N348K	1.000
8:22416177:T:G	N348K	1.000
8:22416185:A:T	D351V	1.000
8:22416186:T:A	D351E	1.000
8:22416186:T:G	D351E	1.000
8:22416187:G:C	G352R	1.000
8:22416188:G:A	G352D	1.000
8:22416188:G:T	G352V	1.000
8:22416191:T:C	L353P	1.000
8:22416229:G:C	G366R	1.000
8:22417666:T:C	L388P	1.000
8:22417737:G:C	G412R	1.000
8:22417803:G:A	G434R	1.000
8:22417803:G:C	G434R	1.000
8:22417804:G:A	G434E	1.000
8:22417809:T:C	F436L	1.000
8:22417811:C:A	F436L	1.000
8:22417811:C:G	F436L	1.000
8:22419643:G:A	G475E	1.000
8:22412090:G:A	G171R	0.999
8:22412090:G:C	G171R	0.999
8:22412157:T:C	L193P	0.999
8:22412165:G:A	G196R	0.999
8:22412165:G:C	G196R	0.999
8:22412166:G:A	G196E	0.999
8:22412172:T:C	L198P	0.999
8:22412196:T:A	L206H	0.999
8:22416143:C:A	A337D	0.999
8:22416160:A:C	S343R	0.999

dbSNP variants (sampled 300 via entrez): RS1000001325 (8:22380876 C>T), RS1000045005 (8:22368971 G>A), RS1000068799 (8:22380554 G>A), RS1000106370 (8:22401384 G>T), RS1000120736 (8:22368567 C>T), RS1000126791 (8:22421996 G>A,C), RS1000192459 (8:22401815 C>T), RS1000201609 (8:22423320 TTTGTTG>T,TTTG,TTTGTTGTTG,TTTGTTGTTGTTG), RS1000303719 (8:22385287 G>A), RS1000319043 (8:22396702 G>A), RS1000364230 (8:22433166 T>A), RS1000415187 (8:22422301 A>G), RS1000415834 (8:22396226 G>A), RS1000454582 (8:22407143 A>G), RS1000487426 (8:22376006 A>T)

Disease associations

OMIM: gene MIM:608736 | disease phenotypes: MIM:144755, MIM:617013

GenCC curated gene-disease

Disease	Classification	Inheritance
hypermanganesemia with dystonia 2	Strong	Autosomal recessive
hyperostosis cranialis interna	Limited	Autosomal dominant

Mondo (3): hyperostosis cranialis interna (MONDO:0007765), hypermanganesemia with dystonia 2 (MONDO:0014864), congenital heart disease (MONDO:0005453)

Orphanet (2): Hyperostosis cranialis interna (Orphanet:443098), Dystonia-parkinsonism-hypermanganesemia syndrome (Orphanet:521406)

HPO phenotypes

72 total (30 of 72 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000256	Macrocephaly
HP:0000265	Mastoiditis
HP:0000338	Hypomimic face
HP:0000360	Tinnitus
HP:0000407	Sensorineural hearing impairment
HP:0000458	Anosmia
HP:0000520	Proptosis
HP:0000648	Optic atrophy
HP:0000737	Irritability
HP:0000975	Hyperhidrosis
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001300	Parkinsonism
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001344	Absent speech
HP:0001347	Hyperreflexia
HP:0001348	Brisk reflexes
HP:0001751	Abnormal vestibular function
HP:0001771	Achilles tendon contracture
HP:0002059	Cerebral atrophy
HP:0002067	Bradykinesia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002701_20	Verbal declarative memory	2.000000e-06
GCST002701_21	Verbal declarative memory	2.000000e-06
GCST005208_2	B-type natriuretic peptide to N-terminal pro B-type natriuretic peptide ratio	2.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004874	memory performance
EFO:0006805	word list delayed recall measurement
EFO:0006806	paragraph delayed recall measurement
EFO:0008469	B-type natriuretic peptide to N-terminal pro B-type natriuretic peptide ratio

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
C564168	Hyperostosis Cranialis Interna (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066476 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs17060812	Efficacy	3	nortriptyline	Depression

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17060812	SLC39A14	3	2.75	1	nortriptyline

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — SLC39 family of metal ion transporters

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.47	Kd	3.372	nM	CHEMBL3752910
8.47	ED50	3.372	nM	CHEMBL3752910
5.52	Kd	3031	nM	CHEMBL5653589
5.52	ED50	3031	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149424: Binding affinity to human SLC39A14 incubated for 45 mins by Kinobead based pull down assay	kd	0.0034	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149424: Binding affinity to human SLC39A14 incubated for 45 mins by Kinobead based pull down assay	kd	3.0311	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	7
Cadmium	affects transport, affects uptake, decreases reaction, increases abundance, increases palmitoylation (+3 more)	6
Cadmium Chloride	affects reaction, decreases reaction, increases abundance, increases palmitoylation, decreases expression (+1 more)	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
Estradiol	affects cotreatment, increases expression	3
Manganese	affects cotreatment, increases abundance, increases expression, affects uptake, increases import (+1 more)	3
methylmercuric chloride	decreases expression, increases expression	2
bisphenol A	decreases expression, decreases methylation	2
epigallocatechin gallate	decreases reaction, increases expression	2
entinostat	increases expression, affects cotreatment	2
Nickel	increases expression	2
Dronabinol	decreases expression	2
Tunicamycin	increases expression	2
Cyclosporine	decreases expression, increases expression	2
Aflatoxin B1	decreases methylation	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
ochratoxin A	affects cotreatment, decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
coumarin	increases phosphorylation	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	affects cotreatment, 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
CHEMBL5652466	Binding	Binding affinity to human SLC39A14 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

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

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

Cellosaurus	Name	Category	Sex
CVCL_B3HH	Abcam HEK293T SLC39A14 KO	Transformed cell line	Female
CVCL_D4NG	HCT116-SLC39A14-KO-c8	Cancer cell line	Male
CVCL_D4NH	HCT116-SLC39A14-KO-c9	Cancer cell line	Male
CVCL_TN54	HAP1 SLC39A14 (-) 1	Cancer cell line	Male
CVCL_TN55	HAP1 SLC39A14 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE