SLC24A2

Summary

SLC24A2 (solute carrier family 24 member 2, HGNC:10976) is a protein-coding gene on chromosome 9p22.1, encoding Sodium/potassium/calcium exchanger 2 (Q9UI40). Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) in exchange for 4 Na(+).

This gene encodes a member of the calcium/cation antiporter superfamily of transport proteins. The encoded protein belongs to the SLC24 branch of exchangers, which can mediate the extrusion of one Ca2+ ion and one K+ ion in exchange for four Na+ ions. This family member is a retinal cone/brain exchanger that can mediate a light-induced decrease in free Ca2+ concentration. This protein may also play a neuroprotective role during ischemic brain injury. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 25769 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 122 total
• Druggable target: yes
• MANE Select transcript: NM_020344

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10976
Approved symbol	SLC24A2
Name	solute carrier family 24 member 2
Location	9p22.1
Locus type	gene with protein product
Status	Approved
Aliases	NCKX2
Ensembl gene	ENSG00000155886
Ensembl biotype	protein_coding
OMIM	609838
Entrez	25769

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000286344, ENST00000341998, ENST00000903165, ENST00000903166, ENST00000903167, ENST00000903168, ENST00000903169, ENST00000903170, ENST00000903171, ENST00000911594

RefSeq mRNA: 4 — MANE Select: NM_020344 NM_001193288, NM_001375850, NM_001375851, NM_020344

CCDS: CCDS55297, CCDS6493

Canonical transcript exons

ENST00000341998 — 11 exons

Exon	Start	End
ENSE00001023258	19520894	19521060
ENSE00001023259	19573351	19573469
ENSE00001023261	19576924	19577022
ENSE00001023263	19550137	19550268
ENSE00001141315	19507455	19516402
ENSE00001186838	19528049	19528138
ENSE00001186852	19597229	19597279
ENSE00001186856	19619584	19619692
ENSE00001186864	19622261	19622299
ENSE00001376810	19785937	19787019
ENSE00003938411	19788885	19789037

Expression profiles

Bgee: expression breadth ubiquitous, 110 present calls, max score 99.40.

FANTOM5 (CAGE): breadth broad, TPM avg 8.2987 / max 608.3186, expressed in 203 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100177	6.6616	188
100178	1.0511	115
100179	0.3182	86
205443	0.1136	67
100169	0.0708	28
100168	0.0648	18
100167	0.0185	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.40	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.16	gold quality
postcentral gyrus	UBERON:0002581	99.15	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.15	gold quality
parietal lobe	UBERON:0001872	98.96	gold quality
pons	UBERON:0000988	98.78	gold quality
middle temporal gyrus	UBERON:0002771	98.03	gold quality
inferior vagus X ganglion	UBERON:0005363	97.60	gold quality
primary visual cortex	UBERON:0002436	97.09	gold quality
entorhinal cortex	UBERON:0002728	97.00	gold quality
subthalamic nucleus	UBERON:0001906	96.94	gold quality
lateral globus pallidus	UBERON:0002476	96.65	gold quality
superior frontal gyrus	UBERON:0002661	96.65	gold quality
corpus callosum	UBERON:0002336	96.63	gold quality
occipital lobe	UBERON:0002021	96.39	gold quality
superior vestibular nucleus	UBERON:0007227	96.33	gold quality
cerebellar vermis	UBERON:0004720	96.03	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.90	gold quality
ventral tegmental area	UBERON:0002691	94.82	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.02	gold quality
substantia nigra pars compacta	UBERON:0001965	92.84	gold quality
prefrontal cortex	UBERON:0000451	90.89	gold quality
globus pallidus	UBERON:0001875	90.58	gold quality
Ammon’s horn	UBERON:0001954	89.47	gold quality
frontal cortex	UBERON:0001870	89.32	gold quality
medial globus pallidus	UBERON:0002477	89.01	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.57	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.45	gold quality
cerebral cortex	UBERON:0000956	88.43	gold quality
spinal cord	UBERON:0002240	88.41	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-75140	yes	1754.00
E-HCAD-35	yes	122.55
E-HCAD-25	yes	62.11
E-MTAB-7316	yes	30.85
E-GEOD-84465	yes	11.70
E-ANND-3	yes	6.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

444 targeting SLC24A2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408

Literature-anchored findings (GeneRIF, showing 15)

• The oligomeric state of this protein is studied. (PMID:12502543)
• This is the first systematic NCKX mutagenesis study in which 96 residues are mutated in the human cone NCKX2 cDNA, and functional consequences of these mutations are measured. (PMID:12525183)
• results appear to rule out a critical importance of an intramolecular disulfide linkage in NCKX2 protein synthesis and folding as had been reported before (PMID:15196038)
• Glu(188) and Asp(548) are the central residues of a single cation binding pocket that can accommodate both K(+) and Ca(2+). Furthermore, a single set of residues lines a transport pathway for both K(+) and Ca(2+). (PMID:15583008)
• Charge-removing replacement of Asp(575) by either asparagine or cysteine rendered the mutant NCKX2 proteins independent of K(+), whereas the charge-conservative substitution of Asp(575) to glutamate resulted in a nonfunctional mutant NCKX2 protein (PMID:15611132)
• Several residues in helix H2 of NCKX2 are in the proximity of residues in helices H8 and to aspartate575 in H9; the residues found here are conserved in NCKX1-5 isoforms. (PMID:15909993)
• PKC-mediated activation of NCKX2 is sensitive to mutation of multiple PKC consensus sites via a mechanism that may involve several phosphorylation events (PMID:17038313)
• A regulatory kinetic state of calcium (Ca2+) transport via NCKX2 Na+/Ca2+-K+ exchangers may play a prominent role in regulation of Ca2+ extrusion in cellular environments such as neuronal synapses that experience frequent and dynamic Ca2+ fluxes. (PMID:17164249)
• non-synonymous single nucleotide polymorphism in SLC24A5 alters a residue that is important for NCKX5 and NCKX2 activity (PMID:18166528)
• identified 31 residues that, when substituted, result in shifts in Na(+) affinity, either toward higher or lower K(m) values when compared with wild type NCKX2 (K(m) for Na(+) 58 mm) (PMID:20231282)
• Functional and structural properties of the NCKX2 Na(+)-Ca (2+)/K (+) exchanger: a comparison with the NCX1 Na (+)/Ca (2+) exchanger. (PMID:23224872)
• a new mutation in SLC24A2 gene was identified to decrease the stability of SLC24A2 (PMID:28413183)
• residues in the two regions with the highest degree of homology between the different NCKX isoforms (alpha-1 and alpha-2 repeats) were examined to determine which residues are important for Ca(2+) coordination. (PMID:30173760)
• A Genome-Wide Scan on Individual Typology Angle Found Variants at SLC24A2 Associated with Skin Color Variation in Chinese Populations. (PMID:34570997)
• Multiomics Integrated Analysis Identifies SLC24A2 as a Potential Link between Type 2 Diabetes and Cancer. (PMID:35601016)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc24a2	ENSDARG00000042988
danio_rerio	SLC24A2	ENSDARG00000063158
mus_musculus	Slc24a2	ENSMUSG00000037996
rattus_norvegicus	Slc24a2	ENSRNOG00000008169
drosophila_melanogaster	Nckx30C	FBGN0028704
caenorhabditis_elegans	ncx-4	WBGENE00003569
caenorhabditis_elegans		WBGENE00003570

Paralogs (4): SLC24A1 (ENSG00000074621), SLC24A4 (ENSG00000140090), SLC24A3 (ENSG00000185052), SLC24A5 (ENSG00000188467)

Protein

Protein identifiers

Sodium/potassium/calcium exchanger 2 — Q9UI40 (reviewed: Q9UI40)

Alternative names: Na(+)/K(+)/Ca(2+)-exchange protein 2, Retinal cone Na-Ca+K exchanger, Solute carrier family 24 member 2

All UniProt accessions (1): Q9UI40

UniProt curated annotations — full annotation on UniProt →

Function. Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) in exchange for 4 Na(+). Required for learming and memory by regulating neuronal Ca(2+), which is essential for the development of synaptic plasticity.

Subcellular location. Cell membrane.

Similarity. Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC24A subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UI40-1	1	yes
Q9UI40-2	2

RefSeq proteins (4): NP_001180217, NP_001362779, NP_001362780, NP_065077* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004481	K/Na/Ca-exchanger	Family
IPR004837	NaCa_Exmemb	Domain
IPR044880	NCX_ion-bd_dom_sf	Homologous_superfamily

Pfam: PF01699

Catalyzed reactions (Rhea), 1 shown:

• Ca(2+)(out) + K(+)(out) + 4 Na(+)(in) = Ca(2+)(in) + K(+)(in) + 4 Na(+)(out) (RHEA:69967)

UniProt features (36 total): topological domain 12, transmembrane region 11, region of interest 3, repeat 2, compositionally biased region 2, modified residue 2, chain 1, glycosylation site 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UI40-F1	67.75	0.28

Functional residue map

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

Post-translational modifications (2): 336, 340

Glycosylation sites (1): 111

Mutagenesis-validated functional residues (1):

Position	Phenotype
111	loss of n-glycosylation.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-425561	Sodium/Calcium exchangers
R-HSA-382551	Transport of small molecules
R-HSA-425393
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 260 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_MEMORY, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_SODIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, AAGCCAT_MIR135A_MIR135B, GOBP_PHOTOTRANSDUCTION, CHX10_01, PID_CONE_PATHWAY, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_REGULATION_OF_SYNAPTIC_PLASTICITY, GOBP_LONG_TERM_SYNAPTIC_DEPRESSION, GOBP_CALCIUM_ION_IMPORT

GO Biological Process (21): monoatomic ion transport (GO:0006811), intracellular calcium ion homeostasis (GO:0006874), phototransduction (GO:0007602), learning (GO:0007612), memory (GO:0007613), monoatomic ion transmembrane transport (GO:0034220), sodium ion transmembrane transport (GO:0035725), cone photoresponse recovery (GO:0036368), establishment of localization in cell (GO:0051649), long-term synaptic potentiation (GO:0060291), long-term synaptic depression (GO:0060292), neuron cellular homeostasis (GO:0070050), calcium ion import (GO:0070509), calcium ion transmembrane transport (GO:0070588), cellular response to high light intensity (GO:0071486), potassium ion transmembrane transport (GO:0071805), calcium ion import across plasma membrane (GO:0098703), potassium ion transport (GO:0006813), sodium ion transport (GO:0006814), calcium ion transport (GO:0006816), transmembrane transport (GO:0055085)

GO Molecular Function (4): calcium channel activity (GO:0005262), calcium, potassium:sodium antiporter activity (GO:0008273), symporter activity (GO:0015293), antiporter activity (GO:0015297)

GO Cellular Component (5): photoreceptor inner segment (GO:0001917), plasma membrane (GO:0005886), presynapse (GO:0098793), postsynapse (GO:0098794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Metal ion SLC transporters	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
monoatomic cation transmembrane transport	3
metal ion transport	3
learning or memory	2
regulation of synaptic plasticity	2
calcium ion transport	2
secondary active transmembrane transporter activity	2
synapse	2
transport	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
signal transduction	1
detection of light stimulus	1
monoatomic ion transport	1
transmembrane transport	1
sodium ion transport	1
response to light stimulus	1
establishment of localization	1
cellular localization	1
positive regulation of synaptic transmission	1
negative regulation of synaptic transmission	1
cellular homeostasis	1
response to high light intensity	1
cellular response to light intensity	1
potassium ion transport	1
calcium ion import	1
calcium ion transmembrane import into cytosol	1
inorganic cation import across plasma membrane	1
calcium ion import into cytosol	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
calcium:sodium antiporter activity	1
solute:potassium antiporter activity	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1775 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC24A2	SAG	P10523	537
SLC24A2	GUCA1A	P43080	520
SLC24A2	GUCA1B	Q9UMX6	508
SLC24A2	CNGB1	Q14028	493
SLC24A2	GUCA1C	O95843	478
SLC24A2	RCVRN	P35243	459
SLC24A2	RHO	P08100	459
SLC24A2	PDE6C	P51160	456
SLC24A2	CCDC196	A0A1B0GTZ2	450
SLC24A2	OPN1SW	P03999	429
SLC24A2	RNF220	Q5VTB9	418
SLC24A2	PDE6H	Q13956	409
SLC24A2	CNGB3	Q9NQW8	402
SLC24A2	NAGLU	P54802	387
SLC24A2	NPY2R	P49146	384

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SLC22A6	CLGN	psi-mi:“MI:0914”(association)	0.350
SLC24A2	SEC22B	psi-mi:“MI:0914”(association)	0.350

BioGRID (20): SLC24A2 (Affinity Capture-Western), SLC24A2 (Affinity Capture-MS), SLC24A2 (Affinity Capture-MS), AFG3L2 (Affinity Capture-MS), CKAP5 (Affinity Capture-MS), EEF1A2 (Affinity Capture-MS), EEF1D (Affinity Capture-MS), EEF1G (Affinity Capture-MS), AGPAT6 (Affinity Capture-MS), LRRC59 (Affinity Capture-MS), PA2G4 (Affinity Capture-MS), PEX11B (Affinity Capture-MS), PRPF8 (Affinity Capture-MS), PUF60 (Affinity Capture-MS), RNPS1 (Affinity Capture-MS)

ESM2 similar proteins: A1L3P4, A4IHB9, D3ZJ86, D4A7H1, F7B113, O00341, O16452, O54701, P19634, P23791, P26431, P26432, P26434, P31596, P35449, P43004, P43006, P48761, P48762, P48763, P48764, P50482, Q01345, Q28036, Q3ZAS0, Q4R335, Q56XP4, Q61165, Q68KI4, Q6AI14, Q6DFC0, Q84WG1, Q8BLV3, Q8BUE1, Q8BUN9, Q8BYR8, Q8BZ00, Q8IVB4, Q8JZR4, Q8RWU6

Diamond homologs: B8K1V7, O22252, O54701, P23685, P32418, P48765, P48766, P48767, P48768, P57103, P70414, P70549, Q01728, Q2R041, Q6H641, Q8BUN9, Q8CGQ8, Q8K596, Q8NFF2, Q99PD7, Q9EPQ0, Q9HC58, Q9UI40, Q9UPR5, Q9VDG5, Q9VN12, S4R2P9, O60721, O46383, Q28139, Q91WD8, Q9IAL7, Q9IAL8, Q9QZM6, Q9U6A0, P45394, P87122, Q0ZAI3, Q49SH1, Q57556

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
SRC_kinase_family	“up-regulates quantity”	SLC24A2	phosphorylation
AP2M1	“down-regulates quantity”	SLC24A2	binding
SLC24A2	“down-regulates quantity”	calcium(2+)	relocalization
SLC24A2	“down-regulates quantity”	potassium(1+)	relocalization
SLC24A2	“up-regulates quantity”	sodium(1+)	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	98
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2490 predictions. Top by Δscore:

Variant	Effect	Δscore
9:19550135:A:AC	donor_gain	1.0000
9:19550136:C:CC	donor_gain	1.0000
9:19550136:CAGG:C	donor_gain	1.0000
9:19576917:CACT:C	donor_loss	1.0000
9:19576918:ACTC:A	donor_loss	1.0000
9:19576919:CTCA:C	donor_loss	1.0000
9:19576922:A:AC	donor_gain	1.0000
9:19576922:AC:A	donor_gain	1.0000
9:19576923:C:CC	donor_gain	1.0000
9:19576923:C:CT	donor_loss	1.0000
9:19576923:CC:C	donor_gain	1.0000
9:19576923:CCCA:C	donor_gain	1.0000
9:19577021:CC:C	acceptor_gain	1.0000
9:19577022:CC:C	acceptor_gain	1.0000
9:19619578:GTTTA:G	donor_loss	1.0000
9:19619579:TTTA:T	donor_loss	1.0000
9:19619580:TTACC:T	donor_loss	1.0000
9:19619581:TA:T	donor_loss	1.0000
9:19619689:TAGC:T	acceptor_gain	1.0000
9:19619693:C:CA	acceptor_loss	1.0000
9:19619693:C:CC	acceptor_gain	1.0000
9:19783360:T:TA	donor_gain	1.0000
9:19520892:AC:A	donor_gain	0.9900
9:19520893:CC:C	donor_gain	0.9900
9:19520893:CCCTA:C	donor_gain	0.9900
9:19528139:C:CC	acceptor_gain	0.9900
9:19550129:TTAC:T	donor_loss	0.9900
9:19550130:TACT:T	donor_loss	0.9900
9:19550131:ACT:A	donor_loss	0.9900
9:19550132:CT:C	donor_loss	0.9900

AlphaMissense

4373 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:19516198:G:C	S647R	1.000
9:19516198:G:T	S647R	1.000
9:19516200:T:G	S647R	1.000
9:19516210:G:C	F643L	1.000
9:19516210:G:T	F643L	1.000
9:19516212:A:G	F643L	1.000
9:19516241:C:T	G633D	1.000
9:19516242:C:G	G633R	1.000
9:19516261:C:A	W626C	1.000
9:19516261:C:G	W626C	1.000
9:19516263:A:G	W626R	1.000
9:19516263:A:T	W626R	1.000
9:19516298:A:G	L614P	1.000
9:19516310:A:G	L610P	1.000
9:19516310:A:T	L610H	1.000
9:19516313:A:G	L609P	1.000
9:19516326:A:G	C605R	1.000
9:19516331:A:G	L603P	1.000
9:19516346:A:T	V598D	1.000
9:19516389:A:G	W584R	1.000
9:19516389:A:T	W584R	1.000
9:19516397:G:C	P581R	1.000
9:19516397:G:T	P581Q	1.000
9:19516400:A:G	L580P	1.000
9:19516400:A:T	L580H	1.000
9:19520894:C:T	G579E	1.000
9:19520895:C:G	G579R	1.000
9:19520895:C:T	G579R	1.000
9:19520905:G:C	D575E	1.000
9:19520905:G:T	D575E	1.000

dbSNP variants (sampled 300 via entrez): RS1000002585 (9:19946936 A>G), RS1000005744 (9:19697299 G>C), RS1000005781 (9:19544758 C>G), RS1000006635 (9:19661858 A>C,G), RS1000007894 (9:19528629 G>A), RS1000008340 (9:20088803 T>C), RS1000008733 (9:20212696 C>A,T), RS1000011873 (9:19841405 G>C), RS1000019262 (9:19864429 A>G), RS1000025694 (9:20151802 T>A), RS1000030877 (9:20095494 T>C), RS1000031181 (9:20182195 T>G), RS1000033149 (9:20271491 A>G), RS1000035208 (9:19656742 C>G), RS1000036861 (9:19916607 C>A,T)

Disease associations

OMIM: gene MIM:609838 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): primary ovarian failure (MONDO:0005387)

Orphanet (1): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000477_56	Cognitive performance	4.000000e-06
GCST001945_4	Body mass index in asthmatics	7.000000e-06
GCST003831_35	Asthma	5.000000e-06
GCST006061_86	Atrial fibrillation	9.000000e-09
GCST007324_30	Adventurousness	3.000000e-08
GCST007325_213	General risk tolerance (MTAG)	3.000000e-08
GCST009391_1910	Metabolite levels	8.000000e-06
GCST010002_317	Refractive error	1.000000e-13
GCST011983_14	Fasting glucose	1.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test
EFO:0004340	body mass index
EFO:0008579	risk-taking behaviour
EFO:0010463	asymmetric dimethylarginine measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5209635 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — SLC24 family of sodium/potassium/calcium exchangers

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation, affects methylation	3
sodium arsenite	increases expression	2
bisphenol A	affects cotreatment, decreases methylation	1
ferrous chloride	decreases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	affects cotreatment, decreases methylation, increases methylation	1
incobotulinumtoxinA	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Calcitriol	decreases expression	1
Folic Acid	decreases expression	1
Aflatoxin B1	decreases methylation	1
Okadaic Acid	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5209620	Functional	Substrate uptake by the Sodium/Potassium/Calcium Exchanger 2 (NCKX2, SLC24A2) as assessed by Screen Questtrade mark Fluo-8 NW calcium assay kit in HEK-293 JumpIN-SLC24A2 cells (PubChem AID: 1794815)	Fluo-8 based assay for SLC24A2 using HEK293 SLC24A2 JumpIn OE cells

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists