SLC25A2

Summary

SLC25A2 (solute carrier family 25 member 2, HGNC:22921) is a protein-coding gene on chromosome 5q31.3, encoding Mitochondrial ornithine transporter 2 (Q9BXI2). Mitochondrial transporter of the positively charged amino acids ornithine, lysine and arginine, and the neutral amino acid citrulline.

This intronless gene encodes a protein that localizes to the mitochondrial inner membrane and likely functions as a transporter of small molecules such as ornithine. This gene is located between the protocadherin beta and gamma gene clusters on chromosome 5.

Source: NCBI Gene 83884 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_031947

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22921
Approved symbol	SLC25A2
Name	solute carrier family 25 member 2
Location	5q31.3
Locus type	gene with protein product
Status	Approved
Aliases	ORNT2
Ensembl gene	ENSG00000120329
Ensembl biotype	protein_coding
OMIM	608157
Entrez	83884

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000239451

RefSeq mRNA: 1 — MANE Select: NM_031947 NM_031947

CCDS: CCDS4258

Canonical transcript exons

ENST00000239451 — 1 exons

Exon	Start	End
ENSE00000814265	141302635	141304049

Expression profiles

Bgee: expression breadth broad, 44 present calls, max score 79.22.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0053 / max 4.9619, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63839	0.0053	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.22	gold quality
sperm	CL:0000019	76.22	silver quality
tibialis anterior	UBERON:0001385	72.69	silver quality
pancreatic ductal cell	CL:0002079	69.55	silver quality
left testis	UBERON:0004533	68.97	gold quality
right testis	UBERON:0004534	67.83	gold quality
buccal mucosa cell	CL:0002336	67.78	gold quality
testis	UBERON:0000473	67.54	gold quality
epithelial cell of pancreas	CL:0000083	64.34	gold quality
ileal mucosa	UBERON:0000331	64.17	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	60.11	gold quality
adult organism	UBERON:0007023	55.68	silver quality
bone marrow cell	CL:0002092	55.42	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
calcaneal tendon	UBERON:0003701	53.09	silver quality
myocardium	UBERON:0002349	50.25	gold quality
stromal cell of endometrium	CL:0002255	50.14	silver quality
lower esophagus mucosa	UBERON:0035834	48.58	gold quality
tendon	UBERON:0000043	48.15	silver quality
quadriceps femoris	UBERON:0001377	47.99	gold quality
adrenal tissue	UBERON:0018303	47.40	silver quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
vastus lateralis	UBERON:0001379	45.40	gold quality
bone marrow	UBERON:0002371	44.15	gold quality
layer of synovial tissue	UBERON:0007616	43.55	gold quality
skin of hip	UBERON:0001554	43.47	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting SLC25A2, 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-8485	100.00	77.57	4731
HSA-MIR-548AT-5P	99.96	70.83	2666
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-6755-5P	99.95	65.59	464
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-3171	99.49	69.06	776
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-3124-3P	98.87	68.95	2123
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-6838-3P	98.40	65.88	559
HSA-MIR-6732-3P	98.17	67.52	802
HSA-MIR-3132	97.96	67.91	711
HSA-MIR-146B-3P	97.83	65.29	782
HSA-MIR-197-5P	97.23	68.10	596
HSA-MIR-2909	96.36	67.30	562
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-6775-3P	95.76	65.91	982
HSA-MIR-127-3P	93.92	66.42	36

Literature-anchored findings (GeneRIF, showing 4)

• expression, reconstitution, functional characterization, and tissue distribution of two human isoforms ORC1 and ORC2 (PMID:12807890)
• Here we identify a new intronless gene, ORNT2, located on chromosome 5. (PMID:12948741)
• characterized mutations of the proposed substrate binding site in ORC1 and ORC2; demonstrated that the residue at position 179 in the 2 soforms is largely responsible for the difference in their substrate specificity;concluded that Arg-179 is a key residue in the opening of the carrier to the matrix side (PMID:22262851)
• Compares and contrasts all the known human SLC25A* genes and includes functional information. (PMID:23266187)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Slc25a2	ENSMUSG00000050304
rattus_norvegicus	Taf7	ENSRNOG00000020024

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), 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

Mitochondrial ornithine transporter 2 — Q9BXI2 (reviewed: Q9BXI2)

Alternative names: Solute carrier family 25 member 2

All UniProt accessions (1): Q9BXI2

UniProt curated annotations — full annotation on UniProt →

Function. Mitochondrial transporter of the positively charged amino acids ornithine, lysine and arginine, and the neutral amino acid citrulline. In addition, transports the basic amino acids histidine, homoarginine, and asymmetric dimethylarginine (aDMA), but not symmetric DMA, and the D-forms of lysine, arginine, ornithine and histidine. Functions by both counter-exchange and uniport mechanisms.

Subcellular location. Mitochondrion membrane. Mitochondrion inner membrane.

Tissue specificity. Expressed in liver, testis, spleen, lung, pancreas, and small intestine and expressed poorly in other tissues.

Activity regulation. Inhibited by pyridoxal 5’-phosphate, N-ethylmaleimide, spermine and spermidine.

Miscellaneous. In mice, SLC25A2/ORNT2 is a pseudogene.

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

RefSeq proteins (1): NP_114153* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018108	MCP_transmembrane	Repeat
IPR023395	MCP_dom_sf	Homologous_superfamily
IPR050567	Mitochondrial_Carrier	Family

Pfam: PF00153

Catalyzed reactions (Rhea), 12 shown:

• L-arginine(in) = L-arginine(out) (RHEA:32143)
• L-citrulline(in) + L-ornithine(out) + H(+)(in) = L-citrulline(out) + L-ornithine(in) + H(+)(out) (RHEA:70787)
• L-ornithine(out) + L-lysine(in) = L-ornithine(in) + L-lysine(out) (RHEA:70799)
• L-histidine(in) + L-ornithine(out) + H(+)(in) = L-histidine(out) + L-ornithine(in) + H(+)(out) (RHEA:70815)
• L-homoarginine(in) + L-ornithine(out) = L-homoarginine(out) + L-ornithine(in) (RHEA:70819)
• L-lysine(in) = L-lysine(out) (RHEA:70935)
• L-ornithine(in) = L-ornithine(out) (RHEA:71199)
• N(omega),N(omega)-dimethyl-L-arginine(in) + L-arginine(out) = N(omega),N(omega)-dimethyl-L-arginine(out) + L-arginine(in) (RHEA:72811)
• N(omega),N(omega)-dimethyl-L-arginine(in) + L-lysine(out) = N(omega),N(omega)-dimethyl-L-arginine(out) + L-lysine(in) (RHEA:72815)
• N(omega),N(omega)-dimethyl-L-arginine(in) + L-ornithine(out) = N(omega),N(omega)-dimethyl-L-arginine(out) + L-ornithine(in) (RHEA:72819)
• D-ornithine(in) + L-ornithine(out) = D-ornithine(out) + L-ornithine(in) (RHEA:73471)
• D-arginine(in) + L-ornithine(out) = D-arginine(out) + L-ornithine(in) (RHEA:73475)

UniProt features (18 total): transmembrane region 6, mutagenesis site 5, sequence variant 3, repeat 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXI2-F1	88.42	0.52

Functional residue map

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

Mutagenesis-validated functional residues (5):

Position	Phenotype
74	does not significantly change the substrate specificity.
179	does not significantly change the substrate specificity.
179	ornithine homo-exchange is enhanced 18-fold. vmax value 33-fold higher than wild-type.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-70635	Urea cycle

MSigDB gene sets: 72 (showing top): GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_AMINO_ACID_TRANSMEMBRANE_TRANSPORT, GOBP_MITOCHONDRIAL_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_MITOCHONDRIAL_TRANSMEMBRANE_TRANSPORT, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_AMIDE_BIOSYNTHETIC_PROCESS, GOBP_AMINO_ACID_TRANSPORT, GOBP_BASIC_AMINO_ACID_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, GOCC_MITOCHONDRIAL_ENVELOPE, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_ORGANIC_CATION_TRANSPORT, GOBP_TRANSMEMBRANE_TRANSPORT, chr5q31

GO Biological Process (6): urea cycle (GO:0000050), ornithine metabolic process (GO:0006591), L-ornithine transmembrane transport (GO:1903352), L-lysine transmembrane transport (GO:1903401), L-arginine transmembrane transport (GO:1903826), mitochondrial L-ornithine transmembrane transport (GO:1990575)

GO Molecular Function (5): L-ornithine transmembrane transporter activity (GO:0000064), L-lysine transmembrane transporter activity (GO:0015189), antiporter activity (GO:0015297), L-arginine transmembrane transporter activity (GO:0061459), protein binding (GO:0005515)

GO Cellular Component (4): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020), mitochondrial membrane (GO:0031966)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
L-alpha-amino acid transmembrane transport	3
L-amino acid transmembrane transporter activity	3
L-ornithine transmembrane transport	2
basic amino acid transmembrane transporter activity	2
biosynthetic process	1
urea metabolic process	1
non-proteinogenic amino acid metabolic process	1
ornithine transport	1
L-lysine transport	1
basic amino acid transmembrane transport	1
mitochondrial transmembrane transport	1
L-lysine transmembrane transport	1
secondary active transmembrane transporter activity	1
L-arginine transmembrane transport	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
cellular anatomical structure	1
mitochondrion	1
mitochondrial envelope	1
organelle membrane	1

Protein interactions and networks

STRING

414 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC25A2	MTCH1	Q9NZJ7	641
SLC25A2	MTCH2	Q9Y6C9	565
SLC25A2	OAT	P04181	546
SLC25A2	TMEM210	A6NLX4	494
SLC25A2	SMIM9	A6NGZ8	474
SLC25A2	SLC25A53	Q5H9E4	451
SLC25A2	SLC25A10	Q9UBX3	405
SLC25A2	PRAMEF18	Q5VWM3	398
SLC25A2	TAF7	Q15545	377
SLC25A2	KIAA1143	Q96AT1	374
SLC25A2	AGXT2	Q9BYV1	356
SLC25A2	SLC25A51	Q9H1U9	342
SLC25A2	NRN1L	Q496H8	336
SLC25A2	CBY2	Q8NA61	336
SLC25A2	SLC25A52	Q3SY17	327

IntAct

10 interactions, top by confidence:

A	B	Type	Score
RHBDD2	SLC25A2	psi-mi:“MI:0915”(physical association)	0.560
rep	SLC25A2	psi-mi:“MI:0915”(physical association)	0.490
SLC25A2	HERC3	psi-mi:“MI:0914”(association)	0.350
	DENND11	psi-mi:“MI:0914”(association)	0.350
M	DENND11	psi-mi:“MI:0914”(association)	0.350
SLC25A2	PGAM2	psi-mi:“MI:0914”(association)	0.350
SLC25A2	RHBDD2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): ACTBL2 (Affinity Capture-MS), HERC3 (Affinity Capture-MS), SLC25A2 (Two-hybrid), SLC25A2 (Affinity Capture-MS), SLC25A2 (Affinity Capture-MS), PGAM2 (Affinity Capture-MS), ANKRD40 (Affinity Capture-MS), SLC25A2 (Two-hybrid), SLC25A2 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A0G2K309, A0A1D6N272, A3KPP4, G3XP90, G3YD89, O13844, P04575, P04633, P12234, P12242, P16036, P33303, Q08DK7, Q0VCH6, Q1LZB3, Q27257, Q29RM1, Q3KQZ1, Q3TZX3, Q505J6, Q58DS3, Q5HZE0, Q5IS35, Q5NVC1, Q5R7W2, Q5SWT3, Q6AYL0, Q6DFK2, Q6P036, Q6P316, Q7K566, Q8BGP6, Q8BL03, Q8BZ09, Q8N8R3, Q8TBP6, Q8VEM8, Q93XM7, Q99JD3, Q9BSK2

Diamond homologs: A0A0G2K309, F4HW79, O04200, O22261, O43772, O94502, P10566, P32331, P38087, P39953, P40556, P97521, Q06143, Q08DK7, Q12289, Q12375, Q27257, Q3ZBJ8, Q54BM3, Q54FE6, Q54W11, Q5HZE0, Q5XGI1, Q68F18, Q6BPW0, Q6GLJ0, Q6GQ22, Q76P23, Q84UC7, Q8BL03, Q8BW66, Q8CFJ7, Q8HXY2, Q8N413, Q8N8R3, Q8RXZ9, Q93XM7, Q9BXI2, Q9CA93, Q9UTD6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

201 predictions. Top by Δscore:

Variant	Effect	Δscore
5:141303215:TCCAC:T	donor_gain	0.5700
5:141303216:CCACC:C	donor_gain	0.5700
5:141303037:T:TC	acceptor_gain	0.5400
5:141303556:G:C	donor_gain	0.5200
5:141303219:C:CT	donor_gain	0.5100
5:141303302:A:T	acceptor_gain	0.5100
5:141303301:C:CT	acceptor_gain	0.5000
5:141303586:T:A	donor_gain	0.4900
5:141303215:TC:T	donor_gain	0.4800
5:141303216:CC:C	donor_gain	0.4800
5:141303126:G:A	donor_gain	0.4600
5:141303025:C:T	acceptor_gain	0.4500
5:141303298:C:CT	acceptor_gain	0.4500
5:141302992:T:TA	donor_gain	0.4400
5:141303252:T:C	donor_gain	0.4400
5:141303555:A:AC	donor_gain	0.4400
5:141303041:T:TG	acceptor_gain	0.4300
5:141303064:C:CT	acceptor_gain	0.4300
5:141303083:T:TA	donor_gain	0.4200
5:141303434:C:A	donor_gain	0.4200
5:141303646:AGG:A	donor_gain	0.4200
5:141303105:A:AC	donor_gain	0.4100
5:141303106:A:C	donor_gain	0.4100
5:141303005:G:C	acceptor_gain	0.3900
5:141303025:C:CT	acceptor_gain	0.3900
5:141303097:CAACA:C	donor_gain	0.3900
5:141302890:CTCTG:C	donor_gain	0.3800
5:141303042:C:G	acceptor_gain	0.3800
5:141303327:T:TA	donor_gain	0.3800
5:141303122:T:TA	donor_gain	0.3700

AlphaMissense

1955 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:141303620:G:C	F82L	0.992
5:141303620:G:T	F82L	0.992
5:141303622:A:G	F82L	0.992
5:141303165:T:A	K234I	0.991
5:141303164:T:A	K234N	0.989
5:141303164:T:G	K234N	0.989
5:141303473:C:A	K131N	0.988
5:141303473:C:G	K131N	0.988
5:141303621:A:G	F82S	0.988
5:141303823:C:G	A15P	0.988
5:141303221:A:C	S215R	0.987
5:141303221:A:T	S215R	0.987
5:141303223:T:G	S215R	0.987
5:141303811:C:A	G19W	0.987
5:141303302:A:C	F188L	0.986
5:141303302:A:T	F188L	0.986
5:141303304:A:G	F188L	0.986
5:141303670:C:G	G66R	0.986
5:141303764:T:A	K34N	0.986
5:141303764:T:G	K34N	0.986
5:141303752:C:A	Q38H	0.985
5:141303752:C:G	Q38H	0.985
5:141303063:C:T	G268E	0.984
5:141303351:C:T	G172E	0.984
5:141303621:A:C	F82C	0.984
5:141303716:G:C	C50W	0.984
5:141303465:A:G	L134P	0.983
5:141303802:C:G	A22P	0.983
5:141303810:C:T	G19E	0.983
5:141303528:C:T	G113E	0.982

dbSNP variants (sampled 300 via entrez): RS1000010951 (5:141305500 G>A), RS1000146309 (5:141305199 A>G), RS1001139383 (5:141305085 G>A), RS1006348404 (5:141305859 C>G,T), RS10075302 (5:141303391 C>A,T), RS1007565070 (5:141305553 A>G), RS1010751824 (5:141302404 A>C,G), RS1014481860 (5:141304886 A>T), RS1015582701 (5:141304376 G>A), RS1015972758 (5:141302871 A>G), RS1019238492 (5:141304088 T>C), RS1020214121 (5:141304901 T>C), RS1020498431 (5:141305186 C>A,T), RS1022238690 (5:141302180 G>A,C), RS1026340925 (5:141305595 T>A,C)

Disease associations

OMIM: gene MIM:608157 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST001762_330	Obesity-related traits	7.000000e-06
GCST010002_39	Refractive error	2.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004620	vitamin B12 measurement

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 amino acid transporter subfamily

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
mivebresib	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
testosterone undecanoate	affects cotreatment, increases expression	1
kojic acid	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	increases expression, affects cotreatment	1
(+)-JQ1 compound	increases expression	1
Arbutin	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Levonorgestrel	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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