SLC25A3

Summary

SLC25A3 (solute carrier family 25 member 3, HGNC:10989) is a protein-coding gene on chromosome 12q23.1, encoding Solute carrier family 25 member 3 (Q00325). Inorganic ion transporter that transports phosphate or copper ions across the mitochondrial inner membrane into the matrix compartment. It is a selective cancer dependency (DepMap: 72.2% of cell lines).

The protein encoded by this gene catalyzes the transport of phosphate into the mitochondrial matrix, either by proton cotransport or in exchange for hydroxyl ions. The protein contains three related segments arranged in tandem which are related to those found in other characterized members of the mitochondrial carrier family. Both the N-terminal and C-terminal regions of this protein protrude toward the cytosol. Multiple alternatively spliced transcript variants have been isolated.

Source: NCBI Gene 5250 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cardiomyopathy-hypotonia-lactic acidosis syndrome (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 238 total — 8 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 14
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 72.2% of screened cell lines
• MANE Select transcript: NM_002635

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10989
Approved symbol	SLC25A3
Name	solute carrier family 25 member 3
Location	12q23.1
Locus type	gene with protein product
Status	Approved
Aliases	PiC, PTP
Ensembl gene	ENSG00000075415
Ensembl biotype	protein_coding
OMIM	600370
Entrez	5250

Gene structure

Transcript identifiers

Ensembl transcripts: 40 — 34 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay

ENST00000188376, ENST00000228318, ENST00000401722, ENST00000546766, ENST00000547444, ENST00000547534, ENST00000547869, ENST00000547908, ENST00000548480, ENST00000548847, ENST00000549338, ENST00000550695, ENST00000551123, ENST00000551265, ENST00000551917, ENST00000552981, ENST00000875100, ENST00000875101, ENST00000875102, ENST00000875103, ENST00000918869, ENST00000918870, ENST00000918871, ENST00000918872, ENST00000918873, ENST00000918874, ENST00000918875, ENST00000918876, ENST00000918877, ENST00000918878, ENST00000918879, ENST00000918880, ENST00000944337, ENST00000944338, ENST00000944339, ENST00000944340, ENST00000944341, ENST00000944342, ENST00000944343, ENST00000944344

RefSeq mRNA: 3 — MANE Select: NM_002635 NM_002635, NM_005888, NM_213611

CCDS: CCDS9065, CCDS9066

Canonical transcript exons

ENST00000552981 — 8 exons

Exon	Start	End
ENSE00000753648	98595727	98595848
ENSE00001354489	98593975	98594135
ENSE00003513235	98601171	98601281
ENSE00003531208	98597856	98598035
ENSE00003596970	98601368	98606367
ENSE00003600795	98599955	98600127
ENSE00003692700	98598522	98598703
ENSE00003903306	98593686	98593740

Expression profiles

Bgee: expression breadth ubiquitous, 306 present calls, max score 99.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 479.9556 / max 1791.2157, expressed in 1829 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127552	478.4815	1829
127554	1.4741	808

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	99.91	gold quality
apex of heart	UBERON:0002098	99.85	gold quality
myocardium	UBERON:0002349	99.84	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.84	gold quality
heart right ventricle	UBERON:0002080	99.83	gold quality
cardiac ventricle	UBERON:0002082	99.83	gold quality
heart left ventricle	UBERON:0002084	99.83	gold quality
tibialis anterior	UBERON:0001385	99.76	gold quality
ileal mucosa	UBERON:0000331	99.72	gold quality
heart	UBERON:0000948	99.72	gold quality
right adrenal gland	UBERON:0001233	99.72	gold quality
right adrenal gland cortex	UBERON:0035827	99.71	gold quality
deltoid	UBERON:0001476	99.70	gold quality
cardiac atrium	UBERON:0002081	99.70	gold quality
left adrenal gland	UBERON:0001234	99.69	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	99.69	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.69	gold quality
esophagus squamous epithelium	UBERON:0006920	99.69	gold quality
colonic mucosa	UBERON:0000317	99.68	gold quality
jejunal mucosa	UBERON:0000399	99.68	gold quality
adrenal cortex	UBERON:0001235	99.68	gold quality
vastus lateralis	UBERON:0001379	99.68	gold quality
biceps brachii	UBERON:0001507	99.68	gold quality
right atrium auricular region	UBERON:0006631	99.68	gold quality
left adrenal gland cortex	UBERON:0035825	99.68	gold quality
gastrocnemius	UBERON:0001388	99.67	gold quality
metanephros cortex	UBERON:0010533	99.67	gold quality
muscle of leg	UBERON:0001383	99.66	gold quality
mucosa of transverse colon	UBERON:0004991	99.66	gold quality
epithelium of esophagus	UBERON:0001976	99.65	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	41.22
E-HCAD-13	yes	26.53
E-CURD-46	yes	21.33
E-GEOD-135922	yes	19.75
E-CURD-112	yes	19.62
E-CURD-122	yes	18.73
E-MTAB-10042	yes	17.14
E-MTAB-9689	no	830.68
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYC

miRNA regulators (miRDB)

39 targeting SLC25A3, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-10B-3P	99.04	66.98	988
HSA-MIR-155-3P	99.03	67.99	924
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-4709-3P	98.88	68.04	1594
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-629-5P	98.78	68.72	1032

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 72.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 9)

• An analysis of the promoter region of the human mitochondrial phosphate transporter, including its activation and inhibition domains, is reported. (PMID:15984930)
• SLC25A3 protein deficiency is associated with lactic acidosis, hypertrophic cardiomyopathy, and muscular hypotonia (PMID:17273968)
• This protein has been found differentially expressed in the Wernicke’s Area from patients with schizophrenia. (PMID:19405953)
• Compares and contrasts all the known human SLC25A* genes and includes functional information. (PMID:23266187)
• these results indicate that PiC depletion may need to be profound (>85%) to substantially affect maximal oxphos and that pathogenesis associated with PiC depletion or loss of function may be independent of phosphate limitation when ATP requirements are not high. (PMID:27780865)
• SLC25A3 is a mitochondrial copper transporter. (PMID:29237729)
• Getting out what you put in: Copper in mitochondria and its impacts on human disease. (PMID:32979421)
• SLC25A3 negatively regulates NLRP3 inflammasome activation by restricting the function of NLRP3. (PMID:38552738)
• METTL14-mediated methylation of SLC25A3 mitigates mitochondrial damage in osteoblasts, leading to the improvement of osteoporosis. (PMID:38897394)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc25a3b	ENSDARG00000025566
danio_rerio	slc25a3a	ENSDARG00000027424
mus_musculus	Slc25a3	ENSMUSG00000061904
rattus_norvegicus	Slc25a3	ENSRNOG00000091320
drosophila_melanogaster	Mpcp2	FBGN0026409
drosophila_melanogaster	Mpcp1	FBGN0034497

Paralogs (49): SLC25A13 (ENSG00000004864), SLC25A5 (ENSG00000005022), SLC25A39 (ENSG00000013306), SLC25A40 (ENSG00000075303), 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), SLC25A4 (ENSG00000151729), 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

Solute carrier family 25 member 3 — Q00325 (reviewed: Q00325)

Alternative names: Phosphate carrier protein, mitochondrial, Phosphate transport protein

All UniProt accessions (8): Q00325, A0A024RBE8, A0A024RBH9, F8VVM2, F8VWQ0, F8VWR4, F8VY00, F8VYH5

UniProt curated annotations — full annotation on UniProt →

Function. Inorganic ion transporter that transports phosphate or copper ions across the mitochondrial inner membrane into the matrix compartment. Mediates proton-coupled symport of phosphate ions necessary for mitochondrial oxidative phosphorylation of ADP to ATP. Transports copper ions probably in the form of anionic copper(I) complexes to maintain mitochondrial matrix copper pool and to supply copper for cytochrome C oxidase complex assembly. May also play a role in regulation of the mitochondrial permeability transition pore (mPTP).

Subunit / interactions. Interacts with PPIF; the interaction is impaired by CsA. (Microbial infection) Interacts with human cytomegalovirus protein UL13; this interaction promotes copper accumulation in the mitochondria.

Subcellular location. Mitochondrion inner membrane.

Disease relevance. Mitochondrial phosphate carrier deficiency (MPCD) [MIM:610773] An autosomal recessive disorder of oxidative phosphorylation. Patients have lactic acidosis, hypertrophic cardiomyopathy and muscular hypotonia and die within the first year of life. The disease is caused by variants affecting the gene represented in this entry.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q00325-1	A, SLC25A3-A	yes
Q00325-2	B, SLC25A3-B

RefSeq proteins (3): NP_002626, NP_005879, NP_998776 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018108	MCP_transmembrane	Repeat
IPR023395	MCP_dom_sf	Homologous_superfamily
IPR044677	SLC25A3/Pic2/Mir1-like	Family

Pfam: PF00153

Catalyzed reactions (Rhea), 1 shown:

• phosphate(in) + H(+)(in) = phosphate(out) + H(+)(out) (RHEA:29939)

UniProt features (24 total): topological domain 7, transmembrane region 6, modified residue 4, repeat 3, transit peptide 1, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q00325-F1	80.14	0.35

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 (4): 99, 112, 196, 209

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 315 (showing top): BORCZUK_MALIGNANT_MESOTHELIOMA_UP, HONMA_DOCETAXEL_RESISTANCE, GGTGTGT_MIR329, GRUETZMANN_PANCREATIC_CANCER_DN, GCM_NPM1, MORF_UBE2I, MORF_HDAC1, MORF_UBE2N, MORF_RAD21, HSIAO_HOUSEKEEPING_GENES, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, LANG_MYB_FAMILY_TARGETS, GOBP_INORGANIC_ANION_TRANSPORT, TGACCTY_ERR1_Q2, GOBP_MONOATOMIC_CATION_TRANSPORT

GO Biological Process (3): phosphate ion transmembrane transport (GO:0035435), mitochondrial phosphate ion transmembrane transport (GO:1990547), proton transmembrane transport (GO:1902600)

GO Molecular Function (5): phosphate transmembrane transporter activity (GO:0005315), phosphate:proton symporter activity (GO:0015317), protein-containing complex binding (GO:0044877), protein binding (GO:0005515), symporter activity (GO:0015293)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), plasma membrane (GO:0005886), membrane (GO:0016020), extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
secondary active transmembrane transporter activity	2
binding	2
phosphate ion transport	1
transmembrane transport	1
phosphate ion transmembrane transport	1
monoatomic cation transmembrane transport	1
phosphate transmembrane transporter activity	1
solute:proton symporter activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
membrane	1
cell periphery	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

3104 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC25A3	RING1	Q06587	984
SLC25A3	CBX1	P23197	983
SLC25A3	BMI1	P35226	970
SLC25A3	R4GMX3	R4GMX3	970
SLC25A3	PCGF2	P35227	907
SLC25A3	CBX2	Q14781	876
SLC25A3	ACER3	Q9NUN7	852
SLC25A3	RNF2	Q99496	824
SLC25A3	MTCH1	Q9NZJ7	824
SLC25A3	MTCH2	Q9Y6C9	813
SLC25A3	SLC25A5	P05141	693
SLC25A3	ATP5F1B	P06576	671
SLC25A3	SLC25A4	P12235	653
SLC25A3	ATP5F1C	P36542	646
SLC25A3	SLC25A6	P12236	601

IntAct

258 interactions, top by confidence:

A	B	Type	Score
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
GAPDH	S100A8	psi-mi:“MI:0914”(association)	0.650
SH3KBP1	USP27X	psi-mi:“MI:0914”(association)	0.640
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
RAF1	CALU	psi-mi:“MI:0914”(association)	0.640
GRB2	ARHGEF35	psi-mi:“MI:0914”(association)	0.530
PRKCZ	IPO5	psi-mi:“MI:0914”(association)	0.530
MAP2K2	BAG2	psi-mi:“MI:0914”(association)	0.530
	XPO1	psi-mi:“MI:0914”(association)	0.530
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
KIF1C	KIF1B	psi-mi:“MI:2364”(proximity)	0.480
TUBA1A	TUBAL3	psi-mi:“MI:0914”(association)	0.420
FLT4	ILVBL	psi-mi:“MI:0914”(association)	0.420
AATK	NDUFA4	psi-mi:“MI:0914”(association)	0.420
MET	NDUFA4	psi-mi:“MI:0914”(association)	0.420
SLC25A3	TOP1	psi-mi:“MI:0915”(physical association)	0.400
SLC25A3	MBD1	psi-mi:“MI:0915”(physical association)	0.370
OTUB1		psi-mi:“MI:0914”(association)	0.350
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
NFKB1	NFKB1	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350

BioGRID (482): SLC25A3 (Affinity Capture-MS), SLC25A3 (Affinity Capture-MS), SLC25A3 (Affinity Capture-RNA), SLC25A3 (Affinity Capture-RNA), SLC25A3 (Affinity Capture-MS), SLC25A3 (Affinity Capture-MS), SLC25A3 (Affinity Capture-RNA), ACADM (Co-fractionation), AFG3L2 (Co-fractionation), ALDH3A2 (Co-fractionation), ATAD3A (Co-fractionation), ATP5F1 (Co-fractionation), CANX (Co-fractionation), CCT3 (Co-fractionation), CCT4 (Co-fractionation)

ESM2 similar proteins: G2QNH0, G3XP90, G3Y1Q5, G3YAF3, G3YC86, G3YD89, O04619, O13844, O22342, O49447, O97470, P02723, P04709, P04710, P0C582, P12857, P16036, P18238, P18239, P23641, P25083, P27080, P27081, P31167, P31691, P31692, P34519, P40614, P40941, P49382, P90992, Q00325, Q09188, Q26365, Q27238, Q2YDD9, Q3V132, Q41629, Q41630, Q4R8M0

Diamond homologs: A0PC02, A2ADF7, A6RF73, B0G143, F1RFX9, G3XP90, G3Y1Q5, G3YFS7, G5EE96, K3VFR5, O77792, O81845, O89035, O95258, O97562, O97649, P04575, P05141, P0C582, P10861, P12234, P14271, P16036, P22292, P25874, P32332, P38702, P38921, P51881, P55851, P55916, P56499, P56500, P56501, P70406, P90992, P97700, Q000K2, Q00325, Q01888

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 210 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
PI3K/AKT Signaling in Cancer	5	11.9×	6e-03
Constitutive Signaling by Aberrant PI3K in Cancer	9	7.4×	7e-04
FCGR3A-mediated phagocytosis	6	7.2×	1e-02
Regulation of actin dynamics for phagocytic cup formation	6	7.1×	1e-02
Intracellular signaling by second messengers	12	7.1×	6e-05
PIP3 activates AKT signaling	16	6.9×	1e-06
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	11	6.9×	2e-04
VEGFA-VEGFR2 Pathway	7	6.3×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	6	14.0×	3e-03
insulin-like growth factor receptor signaling pathway	5	13.7×	6e-03
cellular response to nerve growth factor stimulus	5	12.9×	6e-03
extrinsic apoptotic signaling pathway via death domain receptors	5	11.1×	8e-03
tumor necrosis factor-mediated signaling pathway	6	10.9×	6e-03
obsolete positive regulation of NF-kappaB transcription factor activity	7	8.0×	6e-03
cell surface receptor protein tyrosine kinase signaling pathway	8	7.7×	5e-03
protein phosphorylation	11	4.1×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	4
Uncertain significance	85
Likely benign	103
Benign	19

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
2718297	NM_002635.4(SLC25A3):c.621_622del (p.Tyr207_Lys208delinsTer)	Pathogenic
3244390	NC_000012.11:g.(?98993713)(98993925_?)del	Pathogenic
3244391	NC_000012.11:g.(?98987757)(98989355_?)del	Pathogenic
3661894	NM_002635.4(SLC25A3):c.5_14del (p.Phe2fs)	Pathogenic
4764988	NM_002635.4(SLC25A3):c.562C>T (p.Arg188Ter)	Pathogenic
9149	NM_005888.4(SLC25A3):c.215G>A (p.Gly72Glu)	Pathogenic
977463	NM_002635.4(SLC25A3):c.883_895delinsCAGATAC (p.Gly295_Ser299delinsGlnIlePro)	Pathogenic
977465	NM_002635.4(SLC25A3):c.596T>G (p.Leu199Trp)	Pathogenic
1495713	NM_002635.4(SLC25A3):c.642-2A>G	Likely pathogenic
2825261	NM_005888.4(SLC25A3):c.158-1G>C	Likely pathogenic
2837960	NM_002635.4(SLC25A3):c.280-1G>C	Likely pathogenic
4724978	NM_005888.4(SLC25A3):c.158-1_164del	Likely pathogenic

SpliceAI

1153 predictions. Top by Δscore:

Variant	Effect	Δscore
12:98593711:G:GT	donor_gain	1.0000
12:98593737:GGGA:G	donor_gain	1.0000
12:98593738:GGAG:G	donor_gain	1.0000
12:98593741:G:GG	donor_gain	1.0000
12:98593884:G:GT	donor_gain	1.0000
12:98595423:A:AG	acceptor_gain	1.0000
12:98595725:A:AG	acceptor_gain	1.0000
12:98595726:G:GG	acceptor_gain	1.0000
12:98595726:GA:G	acceptor_gain	1.0000
12:98597399:G:GT	donor_gain	1.0000
12:98597848:A:AG	acceptor_gain	1.0000
12:98597849:A:G	acceptor_gain	1.0000
12:98597852:A:AG	acceptor_gain	1.0000
12:98597852:AAAG:A	acceptor_gain	1.0000
12:98597853:A:G	acceptor_gain	1.0000
12:98597854:A:AC	acceptor_loss	1.0000
12:98597854:AGGT:A	acceptor_gain	1.0000
12:98597855:G:A	acceptor_loss	1.0000
12:98597855:GGT:G	acceptor_gain	1.0000
12:98597855:GGTG:G	acceptor_gain	1.0000
12:98598032:AGAGG:A	donor_loss	1.0000
12:98598034:AGGT:A	donor_loss	1.0000
12:98598036:GTAT:G	donor_loss	1.0000
12:98598037:T:G	donor_loss	1.0000
12:98598512:T:A	acceptor_gain	1.0000
12:98598513:G:A	acceptor_gain	1.0000
12:98598517:TTTAG:T	acceptor_loss	1.0000
12:98598518:TTA:T	acceptor_loss	1.0000
12:98598519:TA:T	acceptor_loss	1.0000
12:98598520:A:AG	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000456480 (12:98593708 A>C,G), RS1000505517 (12:98606342 A>C), RS1000558747 (12:98597845 T>G), RS1000797927 (12:98603704 G>A,T), RS1000909522 (12:98606639 G>C), RS1001056905 (12:98600915 T>A,G), RS1001300247 (12:98599344 C>T), RS1001368549 (12:98593387 G>A,C,T), RS1001431866 (12:98594481 C>A,T), RS1001470353 (12:98606407 A>G), RS1001641381 (12:98605153 C>T), RS1001727213 (12:98594885 T>G), RS1002233133 (12:98599205 G>A), RS1002455377 (12:98604645 T>A,C), RS1002972318 (12:98597832 T>G)

Disease associations

OMIM: gene MIM:600370 | disease phenotypes: MIM:610773

GenCC curated gene-disease

Disease	Classification	Inheritance
cardiomyopathy-hypotonia-lactic acidosis syndrome	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
mitochondrial disease	Moderate	AR

Mondo (1): cardiomyopathy-hypotonia-lactic acidosis syndrome (MONDO:0012557)

Orphanet (1): Cardiomyopathy-hypotonia-lactic acidosis syndrome (Orphanet:91130)

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000961	Cyanosis
HP:0001252	Hypotonia
HP:0001508	Failure to thrive
HP:0001639	Hypertrophic cardiomyopathy
HP:0001942	Metabolic acidosis
HP:0002093	Respiratory insufficiency
HP:0002098	Respiratory distress
HP:0002151	Increased circulating lactate concentration
HP:0003128	Lactic acidosis
HP:0003198	Myopathy
HP:0009805	Low-output congestive heart failure
HP:0012087	Abnormal mitochondrial shape
HP:0012103	Abnormality of the mitochondrion

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563665	Mitochondrial Phosphate Carrier Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295795 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Mitochondrial phosphate transporters

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.09	Kd	8084	nM	CHEMBL5653589
5.09	ED50	8084	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 5 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149409: Binding affinity to human SLC25A3 incubated for 45 mins by Kinobead based pull down assay	kd	8.0844	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, increases methylation, decreases reaction, increases abundance	5
methacrylaldehyde	affects cotreatment, increases expression, decreases expression, increases abundance	2
Acrolein	affects cotreatment, increases expression, decreases expression, increases abundance	2
Ozone	increases expression, decreases expression, increases abundance, affects cotreatment	2
Cyclosporine	decreases expression, increases methylation	2
bisphenol F	increases expression	1
ginger extract	decreases reaction, increases abundance, increases expression	1
biochanin A	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
arsenite	affects binding, decreases reaction, increases reaction	1
ochratoxin A	increases expression	1
cupric oxide	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CD 437	decreases expression	1
corosolic acid	decreases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
bisphenol B	increases expression	1
bisphenol AF	increases expression	1
Glyphosate	decreases expression	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Atrazine	increases expression	1
Benzene	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	increases abundance, increases expression	1
Cuprizone	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Furaldehyde	increases expression, affects cotreatment, affects localization	1
Haloperidol	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4270842	Binding	Binding affinity to phosphate carrier protein in human Hela cells lysates assessed as protein enrichment by measuring normalized heavy/light ratio at by nano-LC-ESIMS/MS analysis	Determination of Gymnemic Acid I as a Protein Biosynthesis Inhibitor Using Chemical Proteomics. — J Nat Prod

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TM30	HAP1 SLC25A3 (-) 1	Cancer cell line	Male
CVCL_TM31	HAP1 SLC25A3 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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