SLC25A23

Summary

SLC25A23 (solute carrier family 25 member 23, HGNC:19375) is a protein-coding gene on chromosome 19p13.3, encoding Mitochondrial adenyl nucleotide antiporter SLC25A23 (Q9BV35). Electroneutral antiporter that mediates the transport of adenine nucleotides through the inner mitochondrial membrane.

Enables ADP:phosphate antiporter activity and ATP:phosphate antiporter activity. Involved in mitochondrial transmembrane transport; positive regulation of mitochondrial calcium ion concentration; and regulation of cellular hyperosmotic salinity response. Located in mitochondrion.

Source: NCBI Gene 79085 — RefSeq curated summary.

At a glance

• Gene–disease (curated): lissencephaly spectrum disorders (Strong, ClinGen) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 1,334 total — 14 pathogenic, 12 likely-pathogenic
• MANE Select transcript: NM_024103

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19375
Approved symbol	SLC25A23
Name	solute carrier family 25 member 23
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ30339, MGC2615, APC2
Ensembl gene	ENSG00000125648
Ensembl biotype	protein_coding
OMIM	608746
Entrez	79085

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000264088, ENST00000301454, ENST00000334510, ENST00000593600, ENST00000595267, ENST00000595810, ENST00000597039, ENST00000597307, ENST00000598704, ENST00000598908, ENST00000600682, ENST00000601322, ENST00000601760, ENST00000948191

RefSeq mRNA: 1 — MANE Select: NM_024103 NM_024103

CCDS: CCDS32882

Canonical transcript exons

ENST00000301454 — 10 exons

Exon	Start	End
ENSE00001316028	6440064	6442159
ENSE00001606463	6454559	6454717
ENSE00001612652	6453981	6454088
ENSE00001714127	6452312	6452479
ENSE00001716060	6454323	6454475
ENSE00003508671	6458198	6458324
ENSE00003645674	6457503	6457590
ENSE00003655810	6444151	6444301
ENSE00003788872	6456420	6456531
ENSE00003847603	6459473	6459792

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 99.07.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.3756 / max 1011.7339, expressed in 1762 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178645	32.8053	1758
178640	0.8781	503
178643	0.6084	303
178646	0.5251	285
178639	0.2115	71
178641	0.1730	53
178644	0.0903	33
178642	0.0838	27

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	99.07	gold quality
caudate nucleus	UBERON:0001873	98.97	gold quality
buccal mucosa cell	CL:0002336	98.84	gold quality
right frontal lobe	UBERON:0002810	98.77	gold quality
anterior cingulate cortex	UBERON:0009835	98.72	gold quality
cingulate cortex	UBERON:0003027	98.58	gold quality
amygdala	UBERON:0001876	98.33	gold quality
putamen	UBERON:0001874	98.24	gold quality
prefrontal cortex	UBERON:0000451	98.06	gold quality
lower esophagus	UBERON:0013473	97.47	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.47	gold quality
temporal lobe	UBERON:0001871	97.38	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.22	gold quality
Ammon’s horn	UBERON:0001954	97.11	gold quality
frontal cortex	UBERON:0001870	96.96	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.92	gold quality
lateral globus pallidus	UBERON:0002476	96.91	gold quality
neocortex	UBERON:0001950	96.85	gold quality
telencephalon	UBERON:0001893	96.84	gold quality
cerebellar hemisphere	UBERON:0002245	96.81	gold quality
cerebellar cortex	UBERON:0002129	96.78	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.76	gold quality
entorhinal cortex	UBERON:0002728	96.65	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.57	gold quality
lower esophagus mucosa	UBERON:0035834	96.47	gold quality
postcentral gyrus	UBERON:0002581	96.46	gold quality
parietal lobe	UBERON:0001872	96.44	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.37	gold quality
cerebral cortex	UBERON:0000956	96.32	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.28	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	16.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

162 targeting SLC25A23, 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-4713-3P	100.00	65.92	505
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-520F-3P	99.82	71.32	1216

Literature-anchored findings (GeneRIF, showing 7)

• SCaMC-3 is a member of a novel human subfamily of mitochondrial carriers with calcium-binding domains (PMID:15054102)
• identification of three isoforms of the mitochondrial ATP-Mg/Pi carrier APC1, APC2 and APC3; they are most likely responsible for the net uptake or efflux of adenine nucleotides into or from the mitochondria (PMID:15123600)
• Northern blot analysis reveals the presence of the transcript in brain, heart, skeletal muscle, liver and small intestine. The SLC25A23 gene undergoes alternative splicing suggesting a modular nature of the encoded product. (PMID:15716113)
• Compares and contrasts all the known human SLC25A* genes and includes functional information. (PMID:23266187)
• SLC25A23 augments mitochondrial Ca(2) uptake, interacts with MCU, and induces oxidative stress-mediated cell death. (PMID:24430870)
• Our results showed EZH2 to be highly overexpressed in astrocytic tumors with a significant positive correlation with grade.we identified SLC25A23 as important target of H3K27me3 modification, which was downregulated in GBM and its low expression was associated with poor prognosis in glioblastomas (GBMs). (PMID:27993893)
• direct measurements of Mg(2+), Mn(2+), Fe(2+), Zn(2+) and Cu(2+) showed that they are cotransported with ATP by both hAPCs and AtAPCs. It is likely that in vivo APCs transport free ATP and ATP-Mg complex to different degrees, and probably trace amounts of other Metals(2+) in complex with ATP. (PMID:28695448)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc25a23a	ENSDARG00000005690
danio_rerio	slc25a23b	ENSDARG00000024708
mus_musculus	Slc25a23	ENSMUSG00000046329
rattus_norvegicus	Slc25a23	ENSRNOG00000047781

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), 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

Mitochondrial adenyl nucleotide antiporter SLC25A23 — Q9BV35 (reviewed: Q9BV35)

Alternative names: Mitochondrial ATP-Mg/Pi carrier protein 2, Short calcium-binding mitochondrial carrier protein 3, Solute carrier family 25 member 23

All UniProt accessions (8): Q9BV35, M0QZJ5, M0QZP9, M0QZT4, M0R1W8, M0R1X8, M0R2F3, M0R2I4

UniProt curated annotations — full annotation on UniProt →

Function. Electroneutral antiporter that mediates the transport of adenine nucleotides through the inner mitochondrial membrane. Originally identified as an ATP-magnesium/inorganic phosphate antiporter, it also acts as a broad specificity adenyl nucleotide antiporter. By regulating the mitochondrial matrix adenine nucleotide pool could adapt to changing cellular energetic demands and indirectly regulate adenine nucleotide-dependent metabolic pathways. Also acts as a regulator of mitochondrial calcium uptake and can probably transport trace amounts of other divalent metal cations in complex with ATP. In vitro, a low activity is also observed with guanyl and pyrimidine nucleotides.

Subunit / interactions. Interacts with MCU. Interacts with MICU1.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Expressed at low levels in most tissues examined, with highest expression in brain, skeletal muscle and pancreas.

Activity regulation. Activated by an increase in cytosolic calcium levels that induce a conformational change of the N-terminal regulatory domain, uncapping the channel and allowing transport. Inhibited by bathophenanthroline, mersalyl, p-hydroxymercuribenzoate, bromcresol purple, tannic acid, pyridoxal 5’-phosphate and p-hydroxymercuribenzoate.

Domain organisation. The regulatory N-terminal domain/NTD, binds calcium in the mitochondrial intermembrane space and regulates the antiporter activity of the transmembrane domain/TMD. In absence of calcium, the apo form of the N-terminal domain is intrinsically disordered and binds to the transmembrane domain, inhibiting the transporter activity. Binding of calcium leads to a major conformational change and abolishes the interaction with the transmembrane domain and the inhibition of the transporter activity. The C-terminal mitochondrial carrier domain/transmembrane domain/TMD bears the transmembrane transporter activity. Linker region/H9 could directly block the transport of substrates across the transporter.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q9BV35-1	1, SCaMC-3a	yes
Q9BV35-2	2, SCaMC-3b
Q9BV35-3	3, SCaMC-3c
Q9BV35-4	4, SCaMC-3d

RefSeq proteins (1): NP_077008* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR002067	MCP	Family
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018108	MCP_transmembrane	Repeat
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR023395	MCP_dom_sf	Homologous_superfamily

Pfam: PF00153, PF13499

Catalyzed reactions (Rhea), 12 shown:

• Mg(2+)(out) + phosphate(in) + ATP(out) = Mg(2+)(in) + phosphate(out) + ATP(in) (RHEA:65840)
• ADP(out) + phosphate(in) + H(+)(out) = ADP(in) + phosphate(out) + H(+)(in) (RHEA:65844)
• AMP(out) + phosphate(in) = AMP(in) + phosphate(out) (RHEA:70259)
• phosphate(in) + ATP(out) + 2 H(+)(out) = phosphate(out) + ATP(in) + 2 H(+)(in) (RHEA:72035)
• dADP(in) + ADP(out) = dADP(out) + ADP(in) (RHEA:72855)
• Mg(2+)(in) + ADP(out) + ATP(in) + H(+)(out) = Mg(2+)(out) + ADP(in) + ATP(out) + H(+)(in) (RHEA:73659)
• ADP(out) + diphosphate(in) = ADP(in) + diphosphate(out) (RHEA:73671)
• dAMP(in) + ADP(out) + H(+)(out) = dAMP(out) + ADP(in) + H(+)(in) (RHEA:73675)
• 3’-AMP(in) + ADP(out) + H(+)(out) = 3’-AMP(out) + ADP(in) + H(+)(in) (RHEA:73679)
• dAMP(out) + phosphate(in) = dAMP(in) + phosphate(out) (RHEA:73687)
• 3’-AMP(out) + phosphate(in) = 3’-AMP(in) + phosphate(out) (RHEA:73691)
• dADP(out) + phosphate(in) + H(+)(out) = dADP(in) + phosphate(out) + H(+)(in) (RHEA:73695)

UniProt features (42 total): binding site 10, topological domain 7, transmembrane region 6, region of interest 4, mutagenesis site 4, domain 3, repeat 3, splice variant 3, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BV35-F1	78.93	0.27

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 (10): 22; 24; 26; 28; 33; 90; 92; 94; 96; 101

Mutagenesis-validated functional residues (4):

Position	Phenotype
22	abolishes the ability to regulate mitochondrial calcium uptake; when associated with k-33; a-90 and k-101.
33	abolishes the ability to regulate mitochondrial calcium uptake; when associated with a-22; a-90 and k-101.
90	abolishes the ability to regulate mitochondrial calcium uptake; when associated with a-22; k-33 and k-101.
101	abolishes the ability to regulate mitochondrial calcium uptake; when associated with a-22; k-33 and a-90.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 723 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GCM_MAP4K4, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, PEREZ_TP63_TARGETS, GOBP_ACTIVATION_OF_GTPASE_ACTIVITY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_HYPEROSMOTIC_RESPONSE, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_NUCLEOTIDE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_RESPONSE_TO_METAL_ION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_MITOCHONDRIAL_CALCIUM_ION_HOMEOSTASIS, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A5

GO Biological Process (14): regulation of oxidative phosphorylation (GO:0002082), renal system process (GO:0003014), mitochondrial calcium ion transmembrane transport (GO:0006851), ADP transport (GO:0015866), ATP transport (GO:0015867), calcium import into the mitochondrion (GO:0036444), obsolete regulation of sequestering of calcium ion (GO:0051282), adenine nucleotide transport (GO:0051503), positive regulation of mitochondrial calcium ion concentration (GO:0051561), cellular response to calcium ion (GO:0071277), regulation of cellular hyperosmotic salinity response (GO:1900069), mitochondrial ATP transmembrane transport (GO:1990544), regulation of cellular respiration (GO:0043457), transmembrane transport (GO:0055085)

GO Molecular Function (8): adenine nucleotide transmembrane transporter activity (GO:0000295), ATP transmembrane transporter activity (GO:0005347), calcium ion binding (GO:0005509), ATP:phosphate antiporter activity (GO:0140987), ADP:phosphate antiporter activity (GO:0140988), protein binding (GO:0005515), antiporter activity (GO:0015297), metal ion binding (GO:0046872)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
adenine nucleotide transport	3
purine ribonucleotide transport	2
ATP transport	2
organophosphate:phosphate antiporter activity	2
oxidative phosphorylation	1
regulation of aerobic respiration	1
system process	1
calcium ion transmembrane transport	1
mitochondrial calcium ion transmembrane transport	1
intercellular transport	1
purine nucleotide transport	1
mitochondrial calcium ion homeostasis	1
response to calcium ion	1
cellular response to metal ion	1
cellular hyperosmotic salinity response	1
regulation of cellular response to osmotic stress	1
regulation of response to salt stress	1
purine-containing compound transmembrane transport	1
nucleotide transmembrane transport	1
regulation of generation of precursor metabolites and energy	1
cellular respiration	1
transport	1
cellular process	1
purine nucleotide transmembrane transporter activity	1
adenine nucleotide transmembrane transporter activity	1
purine ribonucleotide transmembrane transporter activity	1
metal ion binding	1
ATP transmembrane transporter activity	1
ADP transmembrane transporter activity	1
binding	1
secondary active transmembrane transporter activity	1
cation binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1274 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC25A23	MICU1	Q9BPX6	985
SLC25A23	MCUR1	Q96AQ8	959
SLC25A23	MICU2	Q8IYU8	911
SLC25A23	MCUB	Q9NWR8	833
SLC25A23	MCU	Q8NE86	742
SLC25A23	MICU3	Q86XE3	729
SLC25A23	MTCH1	Q9NZJ7	669
SLC25A23	MTCH2	Q9Y6C9	597
SLC25A23	SMDT1	Q9H4I9	594
SLC25A23	CALML6	Q8TD86	567
SLC25A23	CALML4	Q96GE6	567
SLC25A23	TXNRD3	Q86VQ6	507
SLC25A23	LIN7C	Q9NUP9	496
SLC25A23	TIMM8B	Q9Y5J9	491
SLC25A23	LETM1	O95202	480

IntAct

46 interactions, top by confidence:

A	B	Type	Score
APPBP2	SLC25A23	psi-mi:“MI:0915”(physical association)	0.560
SLC25A23	APPBP2	psi-mi:“MI:0915”(physical association)	0.560
TMEM108	TCAF2	psi-mi:“MI:0914”(association)	0.530
VSIG4	TCAF2	psi-mi:“MI:0914”(association)	0.530
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC2A12	METTL15	psi-mi:“MI:0914”(association)	0.530
LRP1	NME4	psi-mi:“MI:0914”(association)	0.530
PDCD1	RTL8C	psi-mi:“MI:0914”(association)	0.530
SYP	APBB1	psi-mi:“MI:0914”(association)	0.530
MID1IP1	SLC25A23	psi-mi:“MI:0915”(physical association)	0.400
MLH1	SLC25A23	psi-mi:“MI:0915”(physical association)	0.370
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
PDCD1	TMEM223	psi-mi:“MI:0914”(association)	0.350
NRG1	HS6ST1	psi-mi:“MI:0914”(association)	0.350
SLC5A8	GPR89A	psi-mi:“MI:0914”(association)	0.350
SYP	APBB1	psi-mi:“MI:0914”(association)	0.350
CD79B	GOLIM4	psi-mi:“MI:0914”(association)	0.350
AIFM1	NR2F2	psi-mi:“MI:0914”(association)	0.350
SLC22A6	GK	psi-mi:“MI:0914”(association)	0.350
SLC25A25	METAP2	psi-mi:“MI:0914”(association)	0.350
NMES1	NDUFS8	psi-mi:“MI:0914”(association)	0.350
OSTM1	ILVBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (63): SLC25A23 (Two-hybrid), SLC25A23 (Affinity Capture-MS), SLC25A23 (Affinity Capture-MS), SLC25A23 (Affinity Capture-MS), SLC25A23 (Affinity Capture-MS), SLC25A23 (Affinity Capture-MS), SLC25A23 (Affinity Capture-MS), SLC25A23 (Affinity Capture-MS), SLC25A23 (Affinity Capture-MS), SLC25A23 (Affinity Capture-MS), SLC25A23 (Affinity Capture-MS), SLC25A23 (Affinity Capture-MS), SLC25A23 (Affinity Capture-MS), SLC25A23 (Affinity Capture-MS), SLC25A23 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D6N272, A1DI57, A2R5A0, A4RF23, A6RF73, A6SL61, A7ER02, B4F8I5, B4FIJ0, B8ZHC9, F4HW79, G3XP90, G3YC86, G3YD89, K7VYZ9, O13844, P0C546, P0CAT2, P16260, P16261, P38152, Q01888, Q05AQ3, Q08CI8, Q0CEN9, Q0P483, Q0UUH1, Q12251, Q1E7P0, Q2HFL6, Q2UCW8, Q4X022, Q58DS3, Q5AVW1, Q5IS35, Q5PQ27, Q6AYL0, Q6GQS1, Q6P036, Q7S2H8

Diamond homologs: A0A1D6N272, A1DI57, A2ASZ8, A2CEQ0, A2R5A0, A3LVX1, A4RF23, A5DIS9, A5DX39, A6RF73, A6SL61, A7ER02, A7TIQ0, B4FIJ0, F4JU70, O04619, O94370, O95847, P29518, P49382, Q05AQ3, Q0CEN9, Q0P483, Q0UUH1, Q1E7P0, Q29RM1, Q2HFL6, Q2UCW8, Q3ZBJ8, Q4X022, Q54VS7, Q552L9, Q55E45, Q59Q36, Q5AVW1, Q5IS35, Q5NVC1, Q5PQ27, Q5XH95, Q5XHA0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1334 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	12
Uncertain significance	791
Likely benign	413
Benign	54

Top pathogenic / likely-pathogenic (26)

Variant ID	HGVS	Classification
1339351	NM_005883.3(APC2):c.6620C>T (p.Pro2207Leu)	Pathogenic
1807799	GRCh37/hg19 19p13.3(chr19:1205244-1479188)x1	Pathogenic
2020496	NM_005883.3(APC2):c.1741del (p.Leu581fs)	Pathogenic
267259	NM_005883.3(APC2):c.5199dup (p.Lys1734fs)	Pathogenic
2972900	NM_005883.3(APC2):c.1694_1695del (p.Thr565fs)	Pathogenic
3242688	NC_000019.9:g.(?1461942)(1462196_?)del	Pathogenic
3689072	NM_005883.3(APC2):c.1176_1189del (p.Asp392fs)	Pathogenic
4085202	NM_005883.3(APC2):c.1000_1016dup (p.Ala340fs)	Pathogenic
4689442	NM_005883.3(APC2):c.650_656dup (p.Glu220fs)	Pathogenic
4717144	NM_005883.3(APC2):c.1395C>A (p.Tyr465Ter)	Pathogenic
694620	NM_005883.3(APC2):c.1081C>T (p.Gln361Ter)	Pathogenic
694621	NM_005883.3(APC2):c.6645del (p.Ala2217fs)	Pathogenic
694622	NM_005883.3(APC2):c.737C>A (p.Ser246Ter)	Pathogenic
694623	NM_005883.3(APC2):c.2840_2846del (p.Leu947fs)	Pathogenic
2434404	NM_005883.3(APC2):c.6638_6640delinsCT (p.Glu2213fs)	Likely pathogenic
2444065	NM_005883.3(APC2):c.3397C>T (p.Arg1133Ter)	Likely pathogenic
2444253	NM_005883.3(APC2):c.759dup (p.Glu254fs)	Likely pathogenic
3057693	NM_005883.3(APC2):c.1638+1G>C	Likely pathogenic
3255193	NM_005883.3(APC2):c.409del (p.Glu137fs)	Likely pathogenic
3337434	NM_005883.3(APC2):c.2153_2168del (p.Leu718fs)	Likely pathogenic
3347780	NM_005883.3(APC2):c.2916_2923del (p.Cys974fs)	Likely pathogenic
3377276	NM_005883.3(APC2):c.2931del (p.Glu977fs)	Likely pathogenic
3377277	NM_005883.3(APC2):c.6184_6193del (p.Pro2062fs)	Likely pathogenic
3393101	NM_005883.3(APC2):c.797dup (p.Gln267fs)	Likely pathogenic
4796569	NM_005883.3(APC2):c.935dup (p.Cys313fs)	Likely pathogenic
916556	NM_005883.3(APC2):c.665T>C (p.Ile222Thr)	Likely pathogenic

SpliceAI

4221 predictions. Top by Δscore:

Variant	Effect	Δscore
19:1450331:G:GG	donor_gain	1.0000
19:1452980:CCAGA:C	acceptor_loss	1.0000
19:1452982:A:AG	acceptor_gain	1.0000
19:1452983:G:GC	acceptor_loss	1.0000
19:1452983:G:GG	acceptor_gain	1.0000
19:1452983:GAC:G	acceptor_gain	1.0000
19:1452983:GACGC:G	acceptor_gain	1.0000
19:1453083:GAGC:G	donor_gain	1.0000
19:1453140:AAGGT:A	donor_loss	1.0000
19:1453141:AGG:A	donor_loss	1.0000
19:1453142:GGTGG:G	donor_loss	1.0000
19:1453236:C:A	acceptor_gain	1.0000
19:1453242:T:TA	acceptor_gain	1.0000
19:1453242:TGCA:T	acceptor_loss	1.0000
19:1453243:GCA:G	acceptor_loss	1.0000
19:1453244:CA:C	acceptor_loss	1.0000
19:1453245:A:AG	acceptor_gain	1.0000
19:1453245:A:C	acceptor_loss	1.0000
19:1453245:AG:A	acceptor_gain	1.0000
19:1453245:AGGAG:A	acceptor_gain	1.0000
19:1453246:G:GA	acceptor_gain	1.0000
19:1453246:G:T	acceptor_loss	1.0000
19:1453246:GG:G	acceptor_gain	1.0000
19:1453246:GGA:G	acceptor_gain	1.0000
19:1453246:GGAGG:G	acceptor_gain	1.0000
19:1453333:GAAGG:G	donor_gain	1.0000
19:1453335:AGGG:A	donor_loss	1.0000
19:1453336:GG:G	donor_gain	1.0000
19:1453336:GGGT:G	donor_loss	1.0000
19:1453337:GG:G	donor_gain	1.0000

AlphaMissense

3031 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:6442032:G:C	S450R	0.999
19:6442032:G:T	S450R	0.999
19:6442034:T:G	S450R	0.999
19:6442059:G:C	N441K	0.999
19:6442059:G:T	N441K	0.999
19:6442072:C:T	G437E	0.999
19:6442073:C:A	G437W	0.999
19:6442073:C:G	G437R	0.999
19:6442073:C:T	G437R	0.999
19:6444191:A:C	S394R	0.999
19:6444191:A:T	S394R	0.999
19:6444193:T:G	S394R	0.999
19:6444204:C:T	G390D	0.999
19:6444212:G:C	S387R	0.999
19:6444212:G:T	S387R	0.999
19:6444214:T:G	S387R	0.999
19:6444216:G:A	S386F	0.999
19:6452325:A:G	L353P	0.999
19:6452374:C:G	G337R	0.999
19:6452471:C:A	K304N	0.999
19:6452471:C:G	K304N	0.999
19:6454018:G:T	A289D	0.999
19:6454338:G:C	F260L	0.999
19:6454338:G:T	F260L	0.999
19:6454340:A:G	F260L	0.999
19:6454360:G:T	A253D	0.999
19:6454365:C:A	K251N	0.999
19:6454365:C:G	K251N	0.999
19:6454374:A:C	N248K	0.999
19:6454374:A:T	N248K	0.999

dbSNP variants (sampled 300 via entrez): RS1000054490 (19:6442357 G>A), RS1000185656 (19:6457185 C>A,T), RS1000292697 (19:6447662 G>A,C,T), RS1000444622 (19:6436756 C>T), RS1000616978 (19:6446482 C>A), RS1000641123 (19:6457373 G>A,C), RS1000699920 (19:6436442 G>T), RS1000734151 (19:6452774 G>A), RS1000790478 (19:6452326 G>A), RS1000894805 (19:6446271 G>A,C), RS1000932963 (19:6435966 A>G), RS1000941781 (19:6457312 C>A), RS1000951036 (19:6452408 G>A), RS1001060812 (19:6440949 C>A,T), RS1001183302 (19:6456284 T>A,C,G)

Disease associations

OMIM: gene MIM:608746 | disease phenotypes: MIM:617169, MIM:618677, MIM:614039, MIM:189960

GenCC curated gene-disease

Disease	Classification	Inheritance
cortical dysplasia, complex, with other brain malformations 10	Strong	Autosomal recessive
Sotos syndrome	Supportive	Autosomal dominant
intellectual developmental disorder, autosomal recessive 74	Limited	Unknown

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
lissencephaly spectrum disorders	Strong	AR

Mondo (6): intellectual developmental disorder, autosomal recessive 74 (MONDO:0014951), cortical dysplasia, complex, with other brain malformations 10 (MONDO:0032866), breast ductal adenocarcinoma (MONDO:0005590), complex cortical dysplasia with other brain malformations 1 (MONDO:0013541), esophageal atresia/tracheoesophageal fistula (MONDO:0008586), Sotos syndrome (MONDO:0019349)

Orphanet (2): Cortical dysgenesis with pontocerebellar hypoplasia due to TUBB3 mutation (Orphanet:300570), Esophageal atresia (Orphanet:1199)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008153_26	Lean body mass	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004995	lean body mass

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D058495	Sotos Syndrome	C16.131.077.889; C16.131.260.905; C16.320.180.905
C531835	Esophageal atresia with or without tracheoesophageal fistula (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Mitochondrial nucleotide transporter subfamily

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	2
Valproic Acid	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	decreases expression, affects cotreatment	2
GSK-J4	decreases expression	1
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
lead acetate	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cupric chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases expression	1
Cocaine	decreases expression	1
Copper	affects binding, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Heroin	decreases expression	1
Doxorubicin	decreases expression	1
Fluorouracil	affects expression	1

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_B3H6	Abcam HEK293T SLC25A23 KO	Transformed cell line	Female
CVCL_D4CU	HCT116-SLC25A23-KO-c2	Cancer cell line	Male
CVCL_D4CV	HCT116-SLC25A23-KO-c9	Cancer cell line	Male
CVCL_TM24	HAP1 SLC25A23 (-) 1	Cancer cell line	Male
CVCL_XT01	HAP1 SLC25A23 (-) 2	Cancer cell line	Male
CVCL_XT02	HAP1 SLC25A23 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT03792360	PHASE1	WITHDRAWN	Adipose Derived SVF for Aero-digestive & Enterocutaneous Fistulae
NCT04993235	Not specified	UNKNOWN	Body Perception and Representation in Overgrowth Syndromes, Behavioral Assessment and Neuropsychological Development
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery
NCT02033772	Not specified	COMPLETED	Prospective Data Collection of Patients < 6 Months of Age Undergoing Thoracoscopic Surgery
NCT02364843	Not specified	TERMINATED	A Physiological Study to Determine the Enteral Threonine Requirements in Infants Aged 1 to 6 Months
NCT03455881	Not specified	UNKNOWN	Phenotypic and Genetic Assessment of Tracheal and Esophageal Birth Defects in Patients
NCT03730454	Not specified	ACTIVE_NOT_RECRUITING	Transanastomotic Tube for Proximal Esophageal Atresia With Distal Tracheoesophageal Fistula Repair