SLC25A4

Summary

SLC25A4 (solute carrier family 25 member 4, HGNC:10990) is a protein-coding gene on chromosome 4q35.1, encoding ADP/ATP translocase 1 (P12235). ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell.

This gene is a member of the mitochondrial carrier subfamily of solute carrier protein genes. The product of this gene functions as a gated pore that translocates ADP from the cytoplasm into the mitochondrial matrix and ATP from the mitochondrial matrix into the cytoplasm. The protein forms a homodimer embedded in the inner mitochondria membrane. Mutations in this gene have been shown to result in autosomal dominant progressive external opthalmoplegia and familial hypertrophic cardiomyopathy.

Source: NCBI Gene 291 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial DNA depletion syndrome 12B (cardiomyopathic type), autosomal recessive (Definitive, ClinGen) — +7 more curated relationships
• Clinical variants (ClinVar): 303 total — 13 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 122
• Druggable target: yes
• MANE Select transcript: NM_001151

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10990
Approved symbol	SLC25A4
Name	solute carrier family 25 member 4
Location	4q35.1
Locus type	gene with protein product
Status	Approved
Aliases	T1, AAC1
Ensembl gene	ENSG00000151729
Ensembl biotype	protein_coding
OMIM	103220
Entrez	291

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 nonsense_mediated_decay

ENST00000281456, ENST00000491736, ENST00000889779, ENST00000889780, ENST00000889781, ENST00000928668, ENST00000948441, ENST00000948442, ENST00000948443, ENST00000948444

RefSeq mRNA: 1 — MANE Select: NM_001151 NM_001151

CCDS: CCDS34114

Canonical transcript exons

ENST00000281456 — 4 exons

Exon	Start	End
ENSE00001001423	185143266	185143483
ENSE00001683990	185145759	185145899
ENSE00003702771	185146814	185150382
ENSE00003709956	185144764	185145250

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 44.4611 / max 2785.0257, expressed in 1715 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50873	44.4611	1715

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	99.88	gold quality
heart right ventricle	UBERON:0002080	99.85	gold quality
apex of heart	UBERON:0002098	99.79	gold quality
cardiac ventricle	UBERON:0002082	99.77	gold quality
heart left ventricle	UBERON:0002084	99.77	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.77	gold quality
body of tongue	UBERON:0011876	99.75	gold quality
triceps brachii	UBERON:0001509	99.74	gold quality
myocardium	UBERON:0002349	99.72	gold quality
vastus lateralis	UBERON:0001379	99.70	gold quality
diaphragm	UBERON:0001103	99.69	gold quality
cardiac atrium	UBERON:0002081	99.69	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	99.68	gold quality
right atrium auricular region	UBERON:0006631	99.68	gold quality
quadriceps femoris	UBERON:0001377	99.66	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.63	gold quality
hindlimb stylopod muscle	UBERON:0004252	99.58	gold quality
biceps brachii	UBERON:0001507	99.57	gold quality
skeletal muscle tissue	UBERON:0001134	99.55	gold quality
gastrocnemius	UBERON:0001388	99.55	gold quality
gluteal muscle	UBERON:0002000	99.43	gold quality
deltoid	UBERON:0001476	99.38	gold quality
vena cava	UBERON:0004087	99.38	gold quality
heart	UBERON:0000948	99.29	gold quality
muscle organ	UBERON:0001630	99.18	gold quality
skeletal muscle organ	UBERON:0014892	99.18	gold quality
muscle of leg	UBERON:0001383	99.01	gold quality
tibialis anterior	UBERON:0001385	99.00	gold quality
muscle tissue	UBERON:0002385	98.88	gold quality
pons	UBERON:0000988	98.76	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	29.29
E-MTAB-8142	yes	17.08
E-GEOD-135922	yes	13.07
E-HCAD-10	yes	12.68
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, MECP2, MYC, TFCP2, YY1

miRNA regulators (miRDB)

120 targeting SLC25A4, 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-3163	100.00	77.23	8605
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-590-3P	99.96	74.34	6478
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728

Literature-anchored findings (GeneRIF, showing 40)

• A114P missense mutation in the human Ant1 protein was found to be associated with autosomal dominant progressive external ophthalmoplegia (PMID:12140186)
• ANC1 is able to restore growth on a nonfermentable carbon source of a yeast mutant strain, and its N-terminal region proves important for its biogenesis and transport activity in yeast mitochondria. (PMID:12450408)
• Autosomal dominant external ophthalmoplegia and bipolar affective disorder associated with a mutation in the ANT1 gene. (PMID:12565915)
• Inhibition of the PT-pore (ANT-1) via up-regulation of cyclophilin D plays a role in tumorigenesis. (PMID:14729611)
• adenine nucleotide translocase 1-induced apoptosis requires nuclear factor B recruitment into mitochondria (PMID:15231833)
• Increased ANT1 expression and mitochondrial dysfunction may thus be initial events in facioscapulohumeral muscular dystrophy pathogenesis (PMID:15551024)
• report a novel heterozygous C to A transversion at nucleotide 269 in the ANT1 gene in a German family with Progressive External Ophthalmoplegia , predicted to convert a highly conserved alanine at codon 90 to aspartic acid. (PMID:15792871)
• After the training period, intracellular energetic units had a higher control of mitochondrial respiration by creatine linked to a more efficient functional coupling adenine nucleotide translocase-mitochondrial creatine kinase. (PMID:16020522)
• The altered isoform expression in DCM hearts entails changes in the kinetic properties of total ANT protein restricting ANT function and contributing to disturbed energy metabolism in DCM. (PMID:16107323)
• Dominant missense mutations were found in the gene encoding the heart and skeletal muscle-specific isoform of the adenine nucleotide translocator (ANT1) in families with autosomal dominant progressive external opthalmoplegia and in a sporadic patient (PMID:16155110)
• Results revealed that ANT1 and ANT3 (adenine nucleotide translocase 1-3) over-expressing HeLa cells increased their atRA sensitivity. (PMID:16556444)
• these data provide evidence for the involvement of ANT-1 and ANT-3 in the induction of the mitochondrial permeability transition pore and indicate the relevance of this phenomenon in ER-mitochondria Ca2+ transfer. (PMID:16887100)
• ANT1 and PolgammaA, which cause additive, deleterious effects on mtDNA maintenance and integrity,complex encephalomyopathy. (PMID:18504126)
• Data show that ANT1 has a role in determining familial progressive external ophthalmoplegia. (PMID:18575922)
• differently from normal myoblasts, the 4qA/B marker interacted directly with the promoters of the FRG1 and ANT1 genes in Facio-Scapulo-Humeral Dystrophy cells (PMID:18852887)
• the presence of the functionally inert catalytic domain alone was sufficient to cause the MT1-MMP to interact with ANT2, thus indicating that there is a non-proteolytic mode of these interactions (PMID:19232058)
• Association of the T(-365)C POLG1, G(-25)A ANT1 and G(-605)T PEO1 gene polymorphisms with diabetic polyneuropathy in patients with type 1 diabetes mellitus (PMID:19425506)
• There was no significant difference in slc25a4 mRNA expression between the AML patients with complete remission and those without remission. (PMID:19840444)
• PGC-1alpha regulates reactive oxygen species generation and apoptosis in endothelial cells by increasing fatty acid oxidation and enhancing ATP/ADP translocase activity. (PMID:19965780)
• Tyrosine phosphorylation by Src within the cavity of the adenine nucleotide translocase 1 regulates ADP/ATP exchange in mitochondria. (PMID:20007455)
• The heterologous expression of ANT1 on endothelial cell membrane enhances the tissue-type plasminogen activator binding ability of endothelial cells and enhances their fibrinolytic properties. (PMID:20160640)
• Data show that MeCP2 cooperates with YY1 in repressing the ANT1 gene encoding a mitochondrial adenine nucleotide translocase. (PMID:20504995)
• The reduction of ANT1 density below a physiological baseline impairs fundamental functions of this protein in ADF cells, leading them to undertake a cell death process. (PMID:20528917)
• The catalytic properties, gene expression and protein levels of certain proteins involved in mitochondrial ATP synthesis, such as F1F0-ATPase, ANT and AK, in human skin fibroblasts with trisomic karyotype, compared them with euploid fibroblasts. (PMID:20698827)
• The respiratory-dependent assembly of ANT1 differentially regulates Bax and Ca2+ mediated cytochrome c release. (PMID:21196320)
• mutant human ANT1 causes dominant mitochondrial defects characterized by decreased ADP-ATP exchange function and abnormal translocator reversal potential (PMID:21586654)
• This report expands the clinical spectrum of ANT1-related human diseases, and emphasises the crucial role of the mitochondrial ADP/ATP carriers in muscle function and pathophysiology of human myopathies. (PMID:22187496)
• Expression of ANT1 were lower in inclusion body myositis samples versus both polymyositis and controls (PMID:22350218)
• Compares and contrasts all the known human SLC25A* genes and includes functional information. (PMID:23266187)
• A 13-generation Mennonite pedigree with autosomal recessive myopathy and cardiomyopathy due to an SLC25A4 frameshift null mutation (c.523delC, p.Q175RfsX38), which codes for the heart-muscle isoform of the adenine nucleotide translocator-1, was studied. (PMID:23401503)
• elevated ANT1 expression supports EV infection and is associated with EV persistence, a condition with adverse prognosis. (PMID:24485628)
• Mitochondrial DNA (mtDNA) content plays an important role in energy production and sustaining normal physiological function. (PMID:24524965)
• Data suggest acetylation of ANT1 at lysines 10/23/92 has dramatic physiological effects on ADP-ATP exchange; extent of acetylation of lysine 23 decreases following physical activity; this change is highly dependent on insulin sensitivity/resistance. (PMID:24884163)
• Identification of ZNF555 as a putative transcriptional factor that impacts ANT1 promoter activity in facioscapulohumeral dystrophy myoblasts. (PMID:26184877)
• ANT1 confers sensitivity of the mitochondrial permeability transition pore to the electrochemical gradient. (PMID:27221760)
• A directed proteomic approach discovered the novel interaction of BKCa with Tom22, a component of the mitochondrion outer membrane import system, and the adenine nucleotide translocator (ANT). (PMID:27592226)
• identification by whole-exome sequencing of seven probands harboring dominant, de novo SLC25A4 mutations; all affected individuals presented at birth, were ventilator dependent and, where tested, revealed severe combined mitochondrial respiratory chain deficiencies associated with a marked loss of mitochondrial DNA copy number in skeletal muscle (PMID:27693233)
• NF-kappaB signalling may repress ANT1 gene transcription and impair mitochondrial functions. (PMID:28317877)
• Patients with SLC25A4 (ANT1) gene mutations present a common phenotype with exercise intolerance, hyperlactatemia, and hypertrophic cardiomyopathy. (PMID:28823815)
• Yeast aac2 R96H and aac2 R252G mutations are equivalent to R80H and R235G human ANT1 pathological mutations. mtDNA instability induced by aac2R96H and aac2R252G is rescued by N-acetylcysteine. (PMID:28947214)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc25a4	ENSDARG00000027355
mus_musculus	Slc25a4	ENSMUSG00000031633
rattus_norvegicus	Slc25a4	ENSRNOG00000010830

Paralogs (49): SLC25A13 (ENSG00000004864), SLC25A5 (ENSG00000005022), SLC25A39 (ENSG00000013306), SLC25A40 (ENSG00000075303), SLC25A3 (ENSG00000075415), SLC25A43 (ENSG00000077713), SLC25A24 (ENSG00000085491), SLC25A1 (ENSG00000100075), SLC25A17 (ENSG00000100372), SLC25A14 (ENSG00000102078), SLC25A15 (ENSG00000102743), SLC25A11 (ENSG00000108528), UCP1 (ENSG00000109424), SLC25A36 (ENSG00000114120), SLC25A12 (ENSG00000115840), SLC25A2 (ENSG00000120329), SLC25A51 (ENSG00000122696), SLC25A16 (ENSG00000122912), SLC25A35 (ENSG00000125434), SLC25A19 (ENSG00000125454), SLC25A23 (ENSG00000125648), SLC25A47 (ENSG00000140107), SLC25A52 (ENSG00000141437), SLC25A38 (ENSG00000144659), SLC25A26 (ENSG00000144741), SLC25A48 (ENSG00000145832), SLC25A37 (ENSG00000147454), SLC25A25 (ENSG00000148339), SLC25A31 (ENSG00000151475), SLC25A27 (ENSG00000153291), SLC25A28 (ENSG00000155287), SLC25A44 (ENSG00000160785), SLC25A45 (ENSG00000162241), SLC25A34 (ENSG00000162461), SLC25A32 (ENSG00000164933), SLC25A6 (ENSG00000169100), SLC25A33 (ENSG00000171612), SLC25A30 (ENSG00000174032), UCP3 (ENSG00000175564), UCP2 (ENSG00000175567)

Protein

Protein identifiers

ADP/ATP translocase 1 — P12235 (reviewed: P12235)

Alternative names: ADP,ATP carrier protein 1, ADP,ATP carrier protein, heart/skeletal muscle isoform T1, Adenine nucleotide translocator 1, Solute carrier family 25 member 4

All UniProt accessions (3): P12235, A0A0S2Z3H3, V9GYG0

UniProt curated annotations — full annotation on UniProt →

Function. ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell. Cycles between the cytoplasmic-open state (c-state) and the matrix-open state (m-state): operates by the alternating access mechanism with a single substrate-binding site intermittently exposed to either the cytosolic (c-state) or matrix (m-state) side of the inner mitochondrial membrane. Substrate exchange across the membrane occurs consecutively with one substrate being transported first, then dissociating from the substrate binding site before the second substrate binds for transport in the opposite direction. In addition to its ADP:ATP antiporter activity, also involved in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity. Plays a role in mitochondrial uncoupling by acting as a proton transporter: proton transport uncouples the proton flows via the electron transport chain and ATP synthase to reduce the efficiency of ATP production and cause mitochondrial thermogenesis. Proton transporter activity is inhibited by ADP:ATP antiporter activity, suggesting that SLC25A4/ANT1 acts as a master regulator of mitochondrial energy output by maintaining a delicate balance between ATP production (ADP:ATP antiporter activity) and thermogenesis (proton transporter activity). Proton transporter activity requires free fatty acids as cofactor, but does not transport it. Also plays a key role in mPTP opening, a non-specific pore that enables free passage of the mitochondrial membranes to solutes of up to 1.5 kDa, and which contributes to cell death. It is however unclear if SLC25A4/ANT1 constitutes a pore-forming component of mPTP or regulates it. Acts as a regulator of mitophagy independently of ADP:ATP antiporter activity: promotes mitophagy via interaction with TIMM44, leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1.

Subunit / interactions. Monomer. Found in a complex with ARL2, ARL2BP and SLC25A4/ANT1. Interacts with ARL2BP. Interacts with ARHGAP11B, thereby inhibiting the mitochondrial permeability transition pore (mPTP). Interacts with TIMM44; leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1. (Microbial infection) Interacts with HIV-1 Vpr.

Subcellular location. Mitochondrion inner membrane. Membrane.

Tissue specificity. Expressed in erythrocytes (at protein level).

Post-translational modifications. Under cell death induction, transglutaminated by TGM2. Transglutamination leads to formation of covalent cross-links between a glutamine and the epsilon-amino group of a lysine residue, forming polymers.

Disease relevance. Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 2 (PEOA2) [MIM:609283] A disorder characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged-red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism. The disease is caused by variants affecting the gene represented in this entry. Mitochondrial DNA depletion syndrome 12B, cardiomyopathic type (MTDPS12B) [MIM:615418] An autosomal recessive mitochondrial disorder characterized by childhood onset of slowly progressive hypertrophic cardiomyopathy and generalized skeletal myopathy resulting in exercise intolerance and, in some patients, muscle weakness and atrophy. Skeletal muscle biopsy shows ragged red fibers, mtDNA depletion, and accumulation of abnormal mitochondria. The disease is caused by variants affecting the gene represented in this entry. Mitochondrial DNA depletion syndrome 12A, cardiomyopathic type (MTDPS12A) [MIM:617184] An autosomal dominant mitochondrial disorder characterized by severe hypotonia due to mitochondrial dysfunction apparent at birth. Affected infants have respiratory insufficiency requiring mechanical ventilation and have poor or no motor development. Many die in infancy, and those that survive have profound hypotonia with significant muscle weakness and inability to walk independently. Some patients develop hypertrophic cardiomyopathy. Muscle samples show mtDNA depletion and severe combined mitochondrial respiratory chain deficiencies. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA) PubMed:23173940. The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR). Proton transporter activity is inhibited by ADP:ATP antiporter activity.

Domain organisation. The transmembrane helices are not perpendicular to the plane of the membrane, but cross the membrane at an angle. Odd-numbered transmembrane helices exhibit a sharp kink, due to the presence of a conserved proline residue.

Similarity. Belongs to the mitochondrial carrier (TC 2.A.29) family.

RefSeq proteins (1): NP_001142* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002067	MCP	Family
IPR002113	ADT_euk_type	Family
IPR018108	MCP_transmembrane	Repeat
IPR023395	MCP_dom_sf	Homologous_superfamily

Pfam: PF00153

Catalyzed reactions (Rhea), 2 shown:

• H(+)(in) = H(+)(out) (RHEA:34979)
• ADP(in) + ATP(out) = ADP(out) + ATP(in) (RHEA:34999)

UniProt features (43 total): sequence variant 10, topological domain 7, modified residue 7, transmembrane region 6, repeat 3, binding site 3, sequence conflict 3, initiator methionine 1, chain 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P12235-F1	92.07	0.71

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 (3): 80; 92; 235

Post-translational modifications (7): 2, 7, 52, 147, 160, 245, 272

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import
R-HSA-166187	Mitochondrial Uncoupling
R-HSA-180897	Vpr-mediated induction of apoptosis by mitochondrial outer membrane permeabilization
R-HSA-83936	Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism
R-HSA-162906	HIV Infection
R-HSA-162909	Host Interactions of HIV factors
R-HSA-1643685	Disease
R-HSA-176033	Interactions of Vpr with host cellular proteins
R-HSA-382551	Transport of small molecules
R-HSA-425397	Transport of vitamins, nucleosides, and related molecules
R-HSA-425407	SLC-mediated transmembrane transport
R-HSA-5663205	Infectious disease
R-HSA-9609507	Protein localization
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 548 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_INTERACTIONS_OF_VPR_WITH_HOST_CELLULAR_PROTEINS, BASSO_B_LYMPHOCYTE_NETWORK, XU_GH1_AUTOCRINE_TARGETS_UP, ATACCTC_MIR202, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, TGACCTY_ERR1_Q2, MEF2_02, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_MITOCHONDRIAL_TRANSPORT, GOBP_NUCLEOTIDE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_MACROAUTOPHAGY, SRF_Q5_01, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT

GO Biological Process (14): generation of precursor metabolites and energy (GO:0006091), apoptotic mitochondrial changes (GO:0008637), ADP transport (GO:0015866), regulation of mitochondrial membrane permeability (GO:0046902), negative regulation of necroptotic process (GO:0060546), mitochondrial ADP transmembrane transport (GO:0140021), negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway (GO:1901029), positive regulation of mitophagy (GO:1901526), mitochondrial ATP transmembrane transport (GO:1990544), adaptive thermogenesis (GO:1990845), obsolete mitochondrial genome maintenance (GO:0000002), adenine transport (GO:0015853), transmembrane transport (GO:0055085), proton transmembrane transport (GO:1902600)

GO Molecular Function (6): ATP:ADP antiporter activity (GO:0005471), proton transmembrane transporter activity (GO:0015078), adenine transmembrane transporter activity (GO:0015207), oxidative phosphorylation uncoupler activity (GO:0017077), protein binding (GO:0005515), antiporter activity (GO:0015297)

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial permeability transition pore complex (GO:0005757), plasma membrane (GO:0005886), membrane (GO:0016020), mitochondrial membrane (GO:0031966)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Protein localization	1
Aerobic respiration and respiratory electron transport	1
Interactions of Vpr with host cellular proteins	1
Transport of vitamins, nucleosides, and related molecules	1
Metabolism	1
Viral Infection Pathways	1
HIV Infection	1
Host Interactions of HIV factors	1
SLC-mediated transmembrane transport	1
Transport of small molecules	1
Disease	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
purine-containing compound transmembrane transport	2
nucleotide transmembrane transport	2
proton transmembrane transport	2
mitochondrial envelope	2
metabolic process	1
apoptotic process	1
mitochondrion organization	1
purine ribonucleotide transport	1
adenine nucleotide transport	1
regulation of membrane permeability	1
regulation of necroptotic process	1
negative regulation of programmed necrotic cell death	1
necroptotic process	1
ADP transport	1
negative regulation of organelle organization	1
negative regulation of mitochondrial membrane permeability	1
mitochondrial outer membrane permeabilization	1
regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway	1
negative regulation of apoptotic signaling pathway	1
mitophagy	1
positive regulation of macroautophagy	1
regulation of mitophagy	1
positive regulation of autophagy of mitochondrion	1
ATP transport	1
temperature homeostasis	1
purine nucleobase transport	1
transport	1
cellular process	1
monoatomic cation transmembrane transport	1
ATP transmembrane transporter activity	1
ADP transmembrane transporter activity	1
antiporter activity	1
monoatomic cation transmembrane transporter activity	1
purine nucleobase transmembrane transporter activity	1
adenine transport	1
transmembrane transporter activity	1
binding	1
secondary active transmembrane transporter activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2619 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC25A4	PPIF	P30405	977
SLC25A4	POLG	P54098	942
SLC25A4	TP53	P04637	924
SLC25A4	TWNK	Q96RR1	921
SLC25A4	POLG2	Q9UHN1	911
SLC25A4	RRM2B	Q7LG56	838
SLC25A4	NKAIN2	Q5VXU1	720
SLC25A4	VDAC1	P21796	705
SLC25A4	MYL3	P08590	667
SLC25A4	VDAC3	Q9Y277	660
SLC25A4	SLC25A3	Q00325	653
SLC25A4	SENP6	Q9GZR1	649
SLC25A4	DGUOK	P78532	647
SLC25A4	PRKAG2	Q9UGJ0	635
SLC25A4	MYBPC3	Q14896	593

IntAct

168 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
NME3	NME4	psi-mi:“MI:0914”(association)	0.640
SLC25A4	SLC25A6	psi-mi:“MI:0915”(physical association)	0.560
SLC25A4	LRRK2	psi-mi:“MI:0915”(physical association)	0.560
NEURL4	APBB1	psi-mi:“MI:0914”(association)	0.530
PRKCZ	IPO5	psi-mi:“MI:0914”(association)	0.530
HLA-DPA1	TYW5	psi-mi:“MI:0914”(association)	0.530
ISLR	BCKDK	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
TNFSF8	LGALS8	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530
NPTN	TNPO2	psi-mi:“MI:0914”(association)	0.530
AAR2	SNRNP200	psi-mi:“MI:0914”(association)	0.530
SLC25A6	HRAS	psi-mi:“MI:0914”(association)	0.530
NEK4	SLC25A4	psi-mi:“MI:0914”(association)	0.510
AR	FOXH1	psi-mi:“MI:0915”(physical association)	0.510
BCL2L13	SLC25A4	psi-mi:“MI:0407”(direct interaction)	0.440
NR4A1	SLC25A4	psi-mi:“MI:0915”(physical association)	0.400
GPR107	SLC25A4	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
CFAP97	CSNK2A1	psi-mi:“MI:0914”(association)	0.350
PCNT	IMP4	psi-mi:“MI:0914”(association)	0.350
NFKB1	NFKB1	psi-mi:“MI:0914”(association)	0.350

BioGRID (298): SLC25A4 (Affinity Capture-RNA), SLC25A4 (Affinity Capture-RNA), SLC25A4 (Affinity Capture-MS), SLC25A4 (Affinity Capture-MS), ATP6V0D1 (Co-fractionation), SLC25A24 (Co-fractionation), SLC25A4 (Co-fractionation), TUBB4B (Co-fractionation), SLC25A4 (Affinity Capture-MS), SLC25A4 (Affinity Capture-MS), SLC25A4 (Affinity Capture-MS), SLC25A4 (Affinity Capture-MS), SLC25A4 (Affinity Capture-MS), FAF2 (Affinity Capture-Western), SLC25A4 (Affinity Capture-Western)

ESM2 similar proteins: A6QR09, F1R4U0, F1RFX9, O43772, O46373, O77792, O95258, O97562, O97649, P02722, P05141, P12235, P12236, P22292, P32007, P32089, P48962, P51881, P53007, P55851, P70406, P79110, P97700, Q000K2, Q02978, Q05962, Q08DK4, Q09073, Q3SZI5, Q5PQM9, Q5R5A1, Q5R5A8, Q5SVS4, Q5U680, Q5XGI1, Q6GQ22, Q6QRN9, Q70HW3, Q8HXE3, Q8HXY2

Diamond homologs: A0A1D6N272, A1DI57, A2A3V2, A2ASZ8, A2CEQ0, A5PJZ1, B0G159, B4F8I5, B4FIJ0, B8ZHC9, F1LX07, F4HW79, F4JU70, K7VYZ9, O04619, O18757, O65023, O75746, O81845, O94502, O97649, P04710, P05141, P0C546, P0CI40, P12235, P12857, P16260, P16261, P25083, P29518, P31167, P31691, P40941, P48962, P55916, Q01888, Q05AQ3, Q0II44, Q0P483

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TSPO2	“up-regulates activity”	SLC25A4	binding
PTPN11	“down-regulates activity”	SLC25A4	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 213 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
FCERI mediated MAPK activation	6	15.1×	2e-03
Generation of second messenger molecules	5	12.5×	9e-03
Downstream TCR signaling	8	7.4×	4e-03
Interferon gamma signaling	8	7.3×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
peptide antigen assembly with MHC class II protein complex	5	28.5×	9e-04
positive regulation of T cell activation	6	14.4×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	8
Uncertain significance	157
Likely benign	81
Benign	32

Top pathogenic / likely-pathogenic (21)

Variant ID	HGVS	Classification
1451765	NM_001151.4(SLC25A4):c.263dup (p.Asn88fs)	Pathogenic
18245	NM_001151.4(SLC25A4):c.340G>C (p.Ala114Pro)	Pathogenic
18246	NM_001151.4(SLC25A4):c.865G>A (p.Val289Met)	Pathogenic
18247	NM_001151.4(SLC25A4):c.293T>C (p.Leu98Pro)	Pathogenic
2019911	NM_001151.4(SLC25A4):c.131_134dup (p.Ser46fs)	Pathogenic
2098505	NM_001151.4(SLC25A4):c.107dup (p.Gln37fs)	Pathogenic
2113960	NM_001151.4(SLC25A4):c.253C>T (p.Gln85Ter)	Pathogenic
215174	NM_001151.4(SLC25A4):c.523del (p.Gln175fs)	Pathogenic
253037	NM_001151.4(SLC25A4):c.239G>A (p.Arg80His)	Pathogenic
253038	NM_001151.4(SLC25A4):c.703C>G (p.Arg235Gly)	Pathogenic
268149	NM_001151.4(SLC25A4):c.116_137del (p.Gln39fs)	Pathogenic
268150	NM_001151.4(SLC25A4):c.707G>C (p.Arg236Pro)	Pathogenic
66011	NM_001151.4(SLC25A4):c.111+1G>A	Pathogenic
18248	NM_001151.4(SLC25A4):c.311A>G (p.Asp104Gly)	Likely pathogenic
215172	NM_001151.4(SLC25A4):c.832G>A (p.Val278Met)	Likely pathogenic
3572858	NM_001151.4(SLC25A4):c.46_47del (p.Gly16fs)	Likely pathogenic
3767159	NM_001151.4(SLC25A4):c.423G>C (p.Leu141Phe)	Likely pathogenic
3778708	NM_001151.4(SLC25A4):c.599-11_621del	Likely pathogenic
452160	NM_001151.4(SLC25A4):c.98A>C (p.Lys33Thr)	Likely pathogenic
635018	NM_001151.4(SLC25A4):c.238C>G (p.Arg80Gly)	Likely pathogenic
994105	NM_001151.4(SLC25A4):c.256_263del (p.Ala86fs)	Likely pathogenic

SpliceAI

859 predictions. Top by Δscore:

Variant	Effect	Δscore
4:185143481:CAGGT:C	donor_loss	1.0000
4:185145896:GGGG:G	donor_gain	1.0000
4:185145897:G:GT	donor_gain	1.0000
4:185145897:GGG:G	donor_gain	1.0000
4:185145898:GG:G	donor_gain	1.0000
4:185145898:GGG:G	donor_gain	1.0000
4:185145899:GG:G	donor_gain	1.0000
4:185143480:GCAG:G	donor_gain	0.9900
4:185143484:G:GG	donor_gain	0.9900
4:185145249:GG:G	donor_gain	0.9900
4:185145250:GG:G	donor_gain	0.9900
4:185145757:AGG:A	acceptor_gain	0.9900
4:185145758:GGG:G	acceptor_gain	0.9900
4:185145900:G:GG	donor_gain	0.9900
4:185146812:A:AG	acceptor_gain	0.9900
4:185146813:G:GG	acceptor_gain	0.9900
4:185145757:A:AG	acceptor_gain	0.9800
4:185145757:AG:A	acceptor_gain	0.9800
4:185145758:G:GG	acceptor_gain	0.9800
4:185145758:GG:G	acceptor_gain	0.9800
4:185145897:GGGGT:G	donor_loss	0.9800
4:185145898:GGGT:G	donor_loss	0.9800
4:185145901:T:A	donor_loss	0.9800
4:185146812:AGCC:A	acceptor_gain	0.9800
4:185146813:GCCG:G	acceptor_gain	0.9800
4:185145754:CACA:C	acceptor_loss	0.9700
4:185145757:A:AT	acceptor_loss	0.9700
4:185145758:GGGAT:G	acceptor_gain	0.9700
4:185146813:GCC:G	acceptor_gain	0.9700
4:185146900:TCCA:T	donor_gain	0.9700

AlphaMissense

1968 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:185143418:G:C	G16R	1.000
4:185143464:G:T	R31M	1.000
4:185143473:T:C	L34P	1.000
4:185144822:G:A	C57Y	1.000
4:185144823:T:G	C57W	1.000
4:185144869:G:C	G73R	1.000
4:185144870:G:A	G73D	1.000
4:185144870:G:T	G73V	1.000
4:185144874:C:A	N74K	1.000
4:185144874:C:G	N74K	1.000
4:185144918:T:C	F89S	1.000
4:185145011:G:A	G120D	1.000
4:185145014:G:A	G121E	1.000
4:185145020:C:A	A123D	1.000
4:185145022:G:A	G124R	1.000
4:185145022:G:C	G124R	1.000
4:185145022:G:T	G124W	1.000
4:185145023:G:A	G124E	1.000
4:185145055:G:C	D135H	1.000
4:185145065:G:T	R138M	1.000
4:185145112:T:C	F154L	1.000
4:185145114:C:A	F154L	1.000
4:185145114:C:G	F154L	1.000
4:185145132:T:G	C160W	1.000
4:185145178:G:C	G176R	1.000
4:185145215:G:C	R188T	1.000
4:185145215:G:T	R188I	1.000
4:185145226:T:C	F192L	1.000
4:185145227:T:C	F192S	1.000
4:185145227:T:G	F192C	1.000

dbSNP variants (sampled 300 via entrez): RS1000660709 (4:185147106 C>A,G), RS1001043282 (4:185148328 G>A), RS1001161277 (4:185141927 T>C,G), RS1001270955 (4:185145448 G>A), RS1001275923 (4:185142120 T>A), RS1001491883 (4:185148169 T>C), RS1001728355 (4:185145107 G>A,C,T), RS10024068 (4:185142187 G>A,T), RS1002489462 (4:185149748 G>A), RS1002582984 (4:185149743 C>A), RS1003102856 (4:185149167 C>T), RS1003109201 (4:185147046 T>C,G), RS1003572853 (4:185146562 G>A), RS1003618782 (4:185143308 C>G,T), RS1003669844 (4:185143234 G>A)

Disease associations

OMIM: gene MIM:103220 | disease phenotypes: MIM:617184, MIM:609283, MIM:615418, MIM:160700, MIM:192600

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial DNA depletion syndrome 12B (cardiomyopathic type), autosomal recessive	Definitive	Autosomal recessive
mitochondrial disease	Definitive	Autosomal recessive
progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2	Strong	Autosomal dominant
mitochondrial DNA depletion syndrome 12A (cardiomyopathic type), autosomal dominant	Strong	Autosomal dominant
Fontaine progeroid syndrome	Strong	Autosomal dominant
Sengers syndrome	Supportive	Autosomal recessive
autosomal dominant progressive external ophthalmoplegia	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
Leigh syndrome	Limited	AD
mitochondrial DNA depletion syndrome 12B (cardiomyopathic type), autosomal recessive	Definitive	AR

Mondo (12): mitochondrial DNA depletion syndrome 12A (cardiomyopathic type), autosomal dominant (MONDO:0014959), progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 2 (MONDO:0012238), mitochondrial DNA depletion syndrome 12B (cardiomyopathic type), autosomal recessive (MONDO:0014175), myopia (MONDO:0001384), hypertrophic cardiomyopathy (MONDO:0005045), inborn mitochondrial myopathy (MONDO:0009637), mitochondrial disease (MONDO:0044970), familial hypertrophic cardiomyopathy (MONDO:0024573), restrictive cardiomyopathy (MONDO:0005201), Sengers syndrome (MONDO:0008922), autosomal dominant progressive external ophthalmoplegia (MONDO:0008003), Fontaine progeroid syndrome (MONDO:0012853)

Orphanet (7): Congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome (Orphanet:1369), Mitochondrial myopathy (Orphanet:206966), Rare hypertrophic cardiomyopathy (Orphanet:217569), Mitochondrial disease (Orphanet:68380), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Restrictive cardiomyopathy (Orphanet:217632), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155)

HPO phenotypes

122 total (30 of 122 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000017	Nocturia
HP:0000338	Hypomimic face
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000496	Abnormality of eye movement
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000512	Abnormal electroretinogram
HP:0000518	Cataract
HP:0000544	External ophthalmoplegia
HP:0000545	Myopia
HP:0000590	Progressive external ophthalmoplegia
HP:0000597	Ophthalmoparesis
HP:0000602	Ophthalmoplegia
HP:0000639	Nystagmus
HP:0000716	Depression
HP:0000739	Anxiety
HP:0000819	Diabetes mellitus
HP:0000821	Hypothyroidism
HP:0000836	Hyperthyroidism
HP:0000853	Goiter
HP:0000939	Osteoporosis
HP:0000969	Edema
HP:0001131	Corneal dystrophy
HP:0001250	Seizure
HP:0001251	Ataxia

GWAS associations

0 associations (top):

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D002313	Cardiomyopathy, Restrictive	C14.280.238.160
D017240	Mitochondrial Myopathies	C05.651.460; C10.668.491.500; C18.452.660.560
D009216	Myopia	C11.744.636
C538280	Cataract and cardiomyopathy (supp.)
C563575	Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions, Autosomal Dominant, 1 (supp.)
C563750	Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions, Autosomal Dominant, 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1879 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Mitochondrial nucleotide transporter subfamily

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.79	Kd	1635	nM	CHEMBL3752910
5.76	ED50	1739	nM	CHEMBL3752910

PubChem BioAssay actives

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

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149410: Binding affinity to human SLC25A4 incubated for 45 mins by Kinobead based pull down assay	kd	1.6354	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation, decreases expression, increases expression, affects cotreatment	5
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	5
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Arsenic	increases expression, affects cotreatment, increases abundance	2
Cadmium	increases expression, increases response to substance	2
Calcitriol	increases expression, affects cotreatment	2
Doxorubicin	affects expression, increases expression	2
Okadaic Acid	affects expression, increases expression	2
dehydroabietylamine	affects activity	1
sodium arsenate	increases abundance, increases expression	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	increases expression	1
closantel	decreases activity	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	increases expression	1
CGP 52608	affects binding, increases reaction	1
CD 437	decreases activity	1
deguelin	decreases expression	1
bisphenol B	increases expression	1
pyrachlostrobin	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
(+)-JQ1 compound	increases expression	1
bisphenol AF	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652452	Binding	Binding affinity to human SLC25A4 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

9 cell lines: 7 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C7DK	Abcam A-549 SLC25A4 KO	Cancer cell line	Male
CVCL_C7EB	Abcam HCT 116 SLC25A4 KO	Cancer cell line	Male
CVCL_D4K7	HCT116-SLC25A4-KO-c10	Cancer cell line	Male
CVCL_D4K8	HCT116-SLC25A4-KO-c8	Cancer cell line	Male
CVCL_D8AE	Ubigene A-549 SLC25A4 KO	Cancer cell line	Male
CVCL_D9RS	Ubigene HEK293 SLC25A4 KO	Transformed cell line	Female
CVCL_IN36	GM25268	Transformed cell line	Female
CVCL_TM44	HAP1 SLC25A4 (-) 1	Cancer cell line	Male
CVCL_TM45	HAP1 SLC25A4 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03351998	PHASE4	COMPLETED	Impact of Statin Therapy on Muscle Mitochondrial Function and Aerobic Capacity
NCT00347204	PHASE4	COMPLETED	Comparison of Acular LS Versus Nevanac for Pain Control in Eyes Undergoing PRK
NCT00349843	PHASE4	COMPLETED	Investigation of Multi-Purpose Solution-Based Corneal Staining and Ocular Comfort
NCT00349882	PHASE4	COMPLETED	Effects of Contact Lens Care Regimens on the Corneal Epithelium
NCT00350246	PHASE4	COMPLETED	Long-term Effects of Laser Refractive Surgery
NCT00404105	PHASE4	COMPLETED	A Comparison of PRK and LASIK for Correction of Myopia
NCT00455455	PHASE4	COMPLETED	Corneal and Conjunctival Sensitivity and Staining Study
NCT00541177	PHASE4	UNKNOWN	Study of Myopia Prevention in Children With Low Concentration of Atropine
NCT00627302	PHASE4	COMPLETED	Efficacy of PEG-400 and Systane Artificial Tears (Alcon) on Quality of Vision
NCT00640341	PHASE4	COMPLETED	Comparative Performance of PureVision, Acuvue Oasys and O2Optix
NCT00770094	PHASE4	UNKNOWN	Multi Laser Platform Comparison Study for LASIK
NCT00821236	PHASE4	COMPLETED	Contralateral Comparison of Three Excimer Laser Systems in Performing LASIK
NCT00889941	PHASE4	COMPLETED	Effect of Preoperative Pupil Size on Quality of Vision After Wavefront-Guided LASIK
NCT00937105	PHASE4	COMPLETED	Daily Wear Corneal Infiltrative Event Study
NCT01173198	PHASE4	COMPLETED	An Evaluation of Outcomes Following Wavefront Optimized or Wavefront Guided Lasik Procedure in Low to Moderate Myopic Patients
NCT01250925	PHASE4	COMPLETED	Effect of Contact Lens Wear on Immune Cell Density and Morphology of the Ocular Surface
NCT01387360	PHASE4	COMPLETED	Presbyopic Supracor Treatment for Near Myopic/Hyperopic Pseudophakic Eyes
NCT01454843	PHASE4	COMPLETED	LASIK Using the Alcon Allegretto Wavefront-Guided Excimer Laser vs AMO Visx Wavefront-Guided Excimer Laser
NCT01693939	PHASE4	COMPLETED	Evaluation of the Post-LASIK Flap Thickness of the FS200 Femtosecond Laser Flap
NCT01706237	PHASE4	WITHDRAWN	Visual Outcomes And Contrast Sensitivity After Myopic Wavefront-Optimized Lasik With Nexisvision Shield Or Bandage Contact Lens
NCT01746589	PHASE4	COMPLETED	Visual Outcomes and Contrast Sensitivity After Myopic LASIK
NCT01977807	PHASE4	UNKNOWN	A Prospective Safety and Effectiveness Study of the 500 Hz Technolas Perfect Vision Excimer Laser in Asian Eyes Using LASIK
NCT02071576	PHASE4	UNKNOWN	A Prospective Safety and Effectiveness Study of the 500 Hz Technolas Perfect Vision Excimer Laser Using LASIK
NCT02112968	PHASE4	UNKNOWN	A Prospective Safety and Effectiveness Study of a New High Repetition Rate Excimer Laser Using LASIK for the Correction of Ammetropia and Presbyopia
NCT02186184	PHASE4	COMPLETED	Effect of Orthokeratology Versus Spectacles on Myopia Progression in Chinese Children: A Crossover Trial
NCT02544529	PHASE4	WITHDRAWN	Echothiophate Iodide for the Prevention of Progression of Myopia
NCT03001401	PHASE4	UNKNOWN	Comparison of Next Generation Laser Techniques of Myopia Correction: iDesign vs. SMILE
NCT03158142	PHASE4	COMPLETED	The Influence of Atropine on Choroidal Thickness
NCT03544827	PHASE4	COMPLETED	The Effects of Low Dose Atropine on Choroidal Thickness
NCT03881670	PHASE4	COMPLETED	On-Eye Optical Quality of Lotrafilcon B Lenses Over 12 Hours
NCT03949101	PHASE4	UNKNOWN	Atropine for Children and Adolescent Myopia Progression Study
NCT04208750	PHASE4	COMPLETED	Clinical Investigation of the Vision-R800 Device.
NCT04283331	PHASE4	UNKNOWN	Anesthetic Impregnated Bandage Soft Contact Lens (BSCL) in Pain Management After Photorefractive Keratectomy (PRK)
NCT05357326	PHASE4	UNKNOWN	Myopia Intervention in Children and Adolescents and Establishment of a Precise Intervention Model
NCT05448989	PHASE4	UNKNOWN	Efficacy and Safety of 1% Atropine 5+3 Regimen in Children and Adolescents Controlling Myopia
NCT05449015	PHASE4	UNKNOWN	Study on the Effect of Two Ways of Cycloplegia on Biological Parameters of Ciliary Muscle
NCT05733741	PHASE4	COMPLETED	Preservative-free Topical Anesthetics for Post-PRK Pain
NCT05803863	PHASE4	UNKNOWN	Efficacy Comparison of 2 Low-dose Atropine Eye Drops in Vietnamese Children Myopia Management
NCT06431841	PHASE4	ACTIVE_NOT_RECRUITING	Atropine and Spectacle Combination Treatment (ASPECT): 12-month Results of a Randomized Clinical Trial for Myopia Control
NCT06450132	PHASE4	ACTIVE_NOT_RECRUITING	Changes in Eye Shape With Myopia Management Interventions