SLC25A21

Summary

SLC25A21 (solute carrier family 25 member 21, HGNC:14411) is a protein-coding gene on chromosome 14q13.3, encoding Mitochondrial 2-oxodicarboxylate carrier (Q9BQT8). Transports dicarboxylates across the inner membranes of mitochondria by a counter-exchange mechanism.

SLC25A21 is a homolog of the S. cerevisiae ODC proteins, mitochondrial carriers that transport C5-C7 oxodicarboxylates across inner mitochondrial membranes. One of the species transported by ODC is 2-oxoadipate, a common intermediate in the catabolism of lysine, tryptophan, and hydroxylysine in mammals. Within mitochondria, 2-oxoadipate is converted into acetyl-CoA.

Source: NCBI Gene 89874 — RefSeq curated summary.

At a glance

• Gene–disease (curated): mitochondrial DNA depletion syndrome 18 (Moderate, GenCC)
• GWAS associations: 12
• Clinical variants (ClinVar): 173 total — 1 pathogenic
• Phenotypes (HPO): 94
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_030631

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14411
Approved symbol	SLC25A21
Name	solute carrier family 25 member 21
Location	14q13.3
Locus type	gene with protein product
Status	Approved
Aliases	ODC1, ODC
Ensembl gene	ENSG00000183032
Ensembl biotype	protein_coding
OMIM	607571
Entrez	89874

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000331299, ENST00000546428, ENST00000555449, ENST00000556444, ENST00000557611

RefSeq mRNA: 2 — MANE Select: NM_030631 NM_001171170, NM_030631

CCDS: CCDS55913, CCDS9663

Canonical transcript exons

ENST00000331299 — 10 exons

Exon	Start	End
ENSE00001293571	37172281	37172606
ENSE00001295305	36813918	36814001
ENSE00001298961	36683828	36683880
ENSE00001313447	36684744	36684925
ENSE00001315058	36677921	36680719
ENSE00001323290	36711318	36711482
ENSE00003487103	36725570	36725677
ENSE00003539208	36874956	36875004
ENSE00003637847	36734507	36734573
ENSE00003674713	36729507	36729566

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 87.51.

FANTOM5 (CAGE): breadth broad, TPM avg 2.1293 / max 121.5895, expressed in 615 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142969	1.0500	405
142968	0.3636	226
142967	0.2784	117
142971	0.1222	48
142972	0.1127	40
142974	0.0750	19
142970	0.0716	29
142973	0.0558	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.43	gold quality
stromal cell of endometrium	CL:0002255	69.88	gold quality
mucosa of stomach	UBERON:0001199	68.97	gold quality
popliteal artery	UBERON:0002250	68.44	gold quality
tibial artery	UBERON:0007610	68.43	gold quality
lower esophagus mucosa	UBERON:0035834	67.18	gold quality
adrenal tissue	UBERON:0018303	66.77	gold quality
bone marrow	UBERON:0002371	65.07	gold quality
aorta	UBERON:0000947	64.77	gold quality
right testis	UBERON:0004534	64.43	gold quality
calcaneal tendon	UBERON:0003701	64.14	gold quality
esophagus mucosa	UBERON:0002469	64.08	gold quality
testis	UBERON:0000473	64.05	gold quality
esophagus	UBERON:0001043	63.47	gold quality
smooth muscle tissue	UBERON:0001135	63.43	gold quality
islet of Langerhans	UBERON:0000006	63.37	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	63.26	gold quality
left testis	UBERON:0004533	63.14	gold quality
body of stomach	UBERON:0001161	62.98	gold quality
lower esophagus	UBERON:0013473	62.86	gold quality
lower esophagus muscularis layer	UBERON:0035833	62.82	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	62.78	gold quality
right hemisphere of cerebellum	UBERON:0014890	62.53	gold quality
muscle of leg	UBERON:0001383	61.95	gold quality
right coronary artery	UBERON:0001625	61.89	gold quality
cerebellar hemisphere	UBERON:0002245	61.78	gold quality
descending thoracic aorta	UBERON:0002345	61.65	gold quality
cerebellar cortex	UBERON:0002129	61.43	gold quality
gastrocnemius	UBERON:0001388	61.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

197 targeting SLC25A21, 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-3924	100.00	72.09	2394
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
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-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-146A-5P	99.96	68.93	988

Literature-anchored findings (GeneRIF, showing 3)

• Compares and contrasts all the known human SLC25A* genes and includes functional information. (PMID:23266187)
• We identified a novel pathogenic variant in a patient by whole-exome sequencing. The pathogenicity of the mutation was studied by transport assays, computer modeling, followed by targeted metabolic testing and in vitro studies in human fibroblasts and neurons (PMID:29517768)
• SLC25A21 downregulation promotes KRAS-mutant colorectal cancer progression by increasing glutamine anaplerosis. (PMID:37937641)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc25a21	ENSDARG00000060564
mus_musculus	Slc25a21	ENSMUSG00000035472
rattus_norvegicus	Slc25a21	ENSRNOG00000008931
drosophila_melanogaster	CG9582	FBGN0032090
drosophila_melanogaster	CG5254	FBGN0040383
caenorhabditis_elegans		WBGENE00011226

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), SLC25A4 (ENSG00000151729), SLC25A27 (ENSG00000153291), SLC25A28 (ENSG00000155287), SLC25A44 (ENSG00000160785), SLC25A45 (ENSG00000162241), SLC25A34 (ENSG00000162461), SLC25A32 (ENSG00000164933), SLC25A6 (ENSG00000169100), SLC25A33 (ENSG00000171612), SLC25A30 (ENSG00000174032), UCP3 (ENSG00000175564)

Protein

Protein identifiers

Mitochondrial 2-oxodicarboxylate carrier — Q9BQT8 (reviewed: Q9BQT8)

Alternative names: Mitochondrial 2-oxoadipate carrier, Solute carrier family 25 member 21

All UniProt accessions (1): Q9BQT8

UniProt curated annotations — full annotation on UniProt →

Function. Transports dicarboxylates across the inner membranes of mitochondria by a counter-exchange mechanism. Can transport 2-oxoadipate (2-oxohexanedioate), 2-oxoglutarate, adipate (hexanedioate), glutarate, and to a lesser extent, pimelate (heptanedioate), 2-oxopimelate (2-oxoheptanedioate), 2-aminoadipate (2-aminohexanedioate), oxaloacetate, and citrate. Plays a central role in catabolism of lysine, hydroxylysine, and tryptophan, by transporting common metabolite intermediates (such as 2-oxoadipate) into the mitochondria, where it is converted into acetyl-CoA and can enter the citric acid (TCA) cycle.

Subcellular location. Mitochondrion inner membrane.

Tissue specificity. Expressed in placenta, gall bladder and colon.

Disease relevance. Mitochondrial DNA depletion syndrome 18 (MTDPS18) [MIM:618811] An autosomal recessive mitochondrial disorder characterized by early-onset progressive weakness and atrophy of the distal limb muscles, loss of ambulation, and atrophy of the intrinsic hand muscles with clawed hands. Additional features include scoliosis, hypo- or hyperreflexia, and decreased pulmonary vital capacity. Examination of skeletal muscle shows mitochondrial respiratory chain deficiencies involving complexes I and IV, associated with mtDNA depletion. The disease may be 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?
Q9BQT8-1	1	yes
Q9BQT8-2	2

RefSeq proteins (2): NP_001164641, NP_085134* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002067	MCP	Family
IPR018108	MCP_transmembrane	Repeat
IPR023395	MCP_dom_sf	Homologous_superfamily
IPR051752	Mito_2-oxodicarb_carrier	Family

Pfam: PF00153

Catalyzed reactions (Rhea), 7 shown:

• 2-oxoadipate(in) + 2-oxoglutarate(out) = 2-oxoadipate(out) + 2-oxoglutarate(in) (RHEA:71739)
• hexanedioate(in) + 2-oxoglutarate(out) = hexanedioate(out) + 2-oxoglutarate(in) (RHEA:71743)
• L-2-aminoadipate(in) + 2-oxoglutarate(out) = L-2-aminoadipate(out) + 2-oxoglutarate(in) (RHEA:71747)
• glutarate(in) + 2-oxoglutarate(out) = glutarate(out) + 2-oxoglutarate(in) (RHEA:71751)
• 2-oxoheptanedioate(in) + 2-oxoglutarate(out) = 2-oxoheptanedioate(out) + 2-oxoglutarate(in) (RHEA:71755)
• heptanedioate(in) + 2-oxoglutarate(out) = heptanedioate(out) + 2-oxoglutarate(in) (RHEA:71759)
• citrate(in) + 2-oxoglutarate(out) = citrate(out) + 2-oxoglutarate(in) (RHEA:71763)

UniProt features (13 total): transmembrane region 6, repeat 3, sequence variant 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQT8-F1	88.91	0.56

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-71064	Lysine catabolism

MSigDB gene sets: 698 (showing top): ELVIDGE_HYPOXIA_DN, chr2p25, HORIUCHI_WTAP_TARGETS_DN, PAL_PRMT5_TARGETS_UP, ENK_UV_RESPONSE_KERATINOCYTE_UP, GCANCTGNY_MYOD_Q6, TTTGTAG_MIR520D, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, YANG_BREAST_CANCER_ESR1_LASER_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_GLUTAMINE_FAMILY_AMINO_ACID_METABOLIC_PROCESS, GOLDRATH_ANTIGEN_RESPONSE, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP

GO Biological Process (4): obsolete lysine catabolic process (GO:0006554), lipid transport (GO:0006869), mitochondrial alpha-ketoglutarate transmembrane transport (GO:1990550), transmembrane transport (GO:0055085)

GO Molecular Function (2): alpha-ketoglutarate transmembrane transporter activity (GO:0015139), antiporter activity (GO:0015297)

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

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
transport	2
alpha-ketoglutarate transport	2
lipid localization	1
carboxylic acid transmembrane transport	1
cellular process	1
dicarboxylic acid transmembrane transporter activity	1
secondary active transmembrane transporter activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

808 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC25A21	MIPOL1	Q8TD10	731
SLC25A21	PAX9	P55771	534
SLC25A21	KLHL18	O94889	473
SLC25A21	SLC25A10	Q9UBX3	435
SLC25A21	SLC25A26	Q70HW3	418
SLC25A21	SEMA6D	Q8NFY4	414
SLC25A21	MRPL57	Q9BQC6	412
SLC25A21	NEURL1	O76050	412
SLC25A21	ZCCHC14	Q8WYQ9	398
SLC25A21	CCDC74A	Q96AQ1	389
SLC25A21	TIMM10B	Q9Y5J6	386
SLC25A21	NKX2-8	O15522	384
SLC25A21	OTUD7A	Q8TE49	373
SLC25A21	CCDC70	Q6NSX1	371
SLC25A21	DUOXA2	Q1HG44	359

IntAct

32 interactions, top by confidence:

A	B	Type	Score
	PMPCB	psi-mi:“MI:0914”(association)	0.640
SLC1A1	AGPAT2	psi-mi:“MI:0914”(association)	0.640
SLC25A21	DNASE1L2	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
RIPK4	VWA8	psi-mi:“MI:0914”(association)	0.350
COQ9	NDUFS8	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
SLC25A21	BLVRA	psi-mi:“MI:0914”(association)	0.350
FFAR1	SLC12A8	psi-mi:“MI:0914”(association)	0.350
A4GNT	CLGN	psi-mi:“MI:0914”(association)	0.350
CD80	RIMOC1	psi-mi:“MI:0914”(association)	0.350
MICB	LGALS8	psi-mi:“MI:0914”(association)	0.350
SLC2A12	NBAS	psi-mi:“MI:0914”(association)	0.350
VSIG4	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC25A21	HMGN3	psi-mi:“MI:0914”(association)	0.350
SLC10A4	ILVBL	psi-mi:“MI:0914”(association)	0.350
SLC1A2	UBXN8	psi-mi:“MI:0914”(association)	0.350
SLC35G2	GPR89A	psi-mi:“MI:0914”(association)	0.350
SLC39A2	AGPAT2	psi-mi:“MI:0914”(association)	0.350
SLC45A4	EIF3CL	psi-mi:“MI:0914”(association)	0.350
SV2C	TIMM23	psi-mi:“MI:0914”(association)	0.350
P/V	ESYT2	psi-mi:“MI:0914”(association)	0.350
NRAS	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
KRAS	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
KRAS		psi-mi:“MI:0914”(association)	0.350
AGGF1	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
PPIL4	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
U2AF1	MED19	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	RPSA2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (37): TBX20 (Affinity Capture-MS), NOSIP (Affinity Capture-MS), DNASE1L2 (Affinity Capture-MS), PPIE (Affinity Capture-MS), TBX20 (Affinity Capture-MS), DNASE1L2 (Affinity Capture-MS), PPIE (Affinity Capture-MS), SLC25A21 (Affinity Capture-MS), SLC25A21 (Affinity Capture-MS), SLC25A21 (Affinity Capture-MS), SLC25A21 (Synthetic Lethality), SLC25A21 (Affinity Capture-MS), SLC25A21 (Affinity Capture-MS), SLC25A21 (Affinity Capture-MS), BLVRA (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K5L2, A0JN87, G3XP90, G3YAF3, O04619, O77792, O95847, O97562, P55851, P55916, P56499, P56500, P56501, P70406, Q08DK4, Q1LZB3, Q29RM1, Q2YDD9, Q3SZI5, Q3TZX3, Q3V132, Q4V9P0, Q505J6, Q5IS35, Q5NVC1, Q5R5A8, Q5RD81, Q5RFB7, Q5ZKP7, Q6DG32, Q6P036, Q6PGY3, Q7K566, Q8BZ09, Q922G0, Q96CQ1, Q99JD3, Q9BQT8, Q9BSK2, Q9C5M0

Diamond homologs: A0JN87, A2A3V2, A4RPU0, F1LZW6, G3YAF3, G3YFS7, O04200, O43772, O77792, O95258, O97649, P16260, P33303, P39953, P97521, Q03028, Q08DK7, Q12482, Q3ZBJ8, Q54FE6, Q54RB9, Q54S10, Q55GE2, Q5HZE0, Q5RFB7, Q68F18, Q6GLJ0, Q6PGY3, Q75AH6, Q7DNC3, Q86AV5, Q86I81, Q8BL03, Q8BZ09, Q8HXW2, Q8HXY2, Q8WUT9, Q93XM7, Q99297, Q99JD3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	92
Likely benign	53
Benign	15

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
827876	NM_030631.4(SLC25A21):c.695A>G (p.Lys232Arg)	Pathogenic

SpliceAI

5286 predictions. Top by Δscore:

Variant	Effect	Δscore
14:36684742:AC:A	donor_gain	1.0000
14:36684743:CC:C	donor_gain	1.0000
14:36684750:T:TA	donor_gain	1.0000
14:36711314:TTACC:T	donor_loss	1.0000
14:36711315:TACCT:T	donor_loss	1.0000
14:36711478:GGTTG:G	acceptor_gain	1.0000
14:36711479:GTTG:G	acceptor_gain	1.0000
14:36711480:TTG:T	acceptor_gain	1.0000
14:36711481:TG:T	acceptor_gain	1.0000
14:36711483:C:CA	acceptor_loss	1.0000
14:36711483:C:CC	acceptor_gain	1.0000
14:36711484:T:G	acceptor_loss	1.0000
14:36726544:T:C	donor_gain	1.0000
14:36813916:AC:A	donor_gain	1.0000
14:36813917:CC:C	donor_gain	1.0000
14:36824934:C:A	donor_gain	1.0000
14:36825838:T:TA	donor_gain	1.0000
14:37172275:CCTTA:C	donor_loss	1.0000
14:37172276:CTTAC:C	donor_loss	1.0000
14:37172277:TTA:T	donor_loss	1.0000
14:37172278:TA:T	donor_loss	1.0000
14:37172280:C:CT	donor_loss	1.0000
2:10440866:TGCCT:T	acceptor_loss	1.0000
2:10440867:GCC:G	acceptor_loss	1.0000
2:10440869:C:CC	acceptor_gain	1.0000
2:10440869:CTGA:C	acceptor_loss	1.0000
2:10441503:A:AC	donor_gain	1.0000
2:10441503:ACTT:A	donor_loss	1.0000
2:10441504:C:CC	donor_gain	1.0000
2:10441504:CTTA:C	donor_gain	1.0000

AlphaMissense

1933 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:36684833:T:A	K232N	0.998
14:36684833:T:G	K232N	0.998
14:36711360:A:C	F187L	0.998
14:36711360:A:T	F187L	0.998
14:36711362:A:G	F187L	0.998
14:36711375:G:C	F182L	0.998
14:36711375:G:T	F182L	0.998
14:36711377:A:G	F182L	0.998
14:36725661:C:T	G116E	0.998
14:36729564:A:C	F91L	0.998
14:36729564:A:T	F91L	0.998
14:36729566:A:G	F91L	0.998
14:36683861:C:G	G269R	0.997
14:36711388:C:G	R178P	0.997
14:36711410:C:G	G171R	0.997
14:36711410:C:T	G171R	0.997
14:36725606:T:A	K134N	0.997
14:36725606:T:G	K134N	0.997
14:36725649:C:T	G120E	0.997
14:36734519:T:A	K86N	0.997
14:36734519:T:G	K86N	0.997
14:36874972:C:G	D35H	0.997
14:37172289:C:T	G21D	0.997
14:37172292:C:T	G20D	0.997
14:36684827:C:A	R234S	0.996
14:36684827:C:G	R234S	0.996
14:36684830:A:C	S233R	0.996
14:36684830:A:T	S233R	0.996
14:36684832:T:G	S233R	0.996
14:36684854:G:C	N225K	0.996

dbSNP variants (sampled 300 via entrez): RS1000021322 (14:37133986 G>T), RS1000024470 (14:37156794 G>T), RS1000027869 (14:36935598 C>G), RS1000028926 (14:36980212 C>A,T), RS1000038003 (14:37140249 A>C,T), RS1000040019 (14:36724922 G>C), RS1000047019 (14:37022270 T>C), RS1000052917 (14:36688243 T>C), RS1000059893 (14:36892537 C>T), RS1000060840 (14:36852404 G>A), RS1000061302 (14:37009029 G>A,C), RS1000072580 (14:36899416 T>C), RS1000082492 (14:36819759 T>C), RS1000087280 (14:36934954 A>G), RS1000134603 (14:37008737 A>G)

Disease associations

OMIM: gene MIM:607571 | disease phenotypes: MIM:618811

GenCC curated gene-disease

Disease	Classification	Inheritance
mitochondrial DNA depletion syndrome 18	Moderate	Autosomal recessive

Mondo (2): mitochondrial DNA depletion syndrome 18 (MONDO:0032932), kidney disorder (MONDO:0005240)

Orphanet (0):

HPO phenotypes

94 total (30 of 94 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000256	Macrocephaly
HP:0000278	Retrognathia
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000348	High forehead
HP:0000378	Cupped ear
HP:0000384	Preauricular skin tag
HP:0000400	Macrotia
HP:0000407	Sensorineural hearing impairment
HP:0000414	Bulbous nose
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000561	Absent eyelashes
HP:0000581	Blepharophimosis
HP:0000653	Sparse eyelashes
HP:0000708	Atypical behavior
HP:0000718	Aggressive behavior
HP:0000750	Delayed speech and language development
HP:0000902	Rib fusion
HP:0000958	Dry skin
HP:0000960	Sacral dimple
HP:0001182	Tapered finger
HP:0001250	Seizure

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST001937_20	Breast cancer	2.000000e-13
GCST004525_9	Subclinical trait of interstitial lung disease (basilar peel-core ratio of high attentuation areas on CT scan)	3.000000e-09
GCST005194_67	Coronary artery disease	7.000000e-06
GCST006485_9	Telomere length	1.000000e-06
GCST008839_562	Height	7.000000e-15
GCST90002385_23	High light scatter reticulocyte count	3.000000e-15
GCST90002386_166	High light scatter reticulocyte percentage of red cells	8.000000e-12
GCST90002390_261	Mean corpuscular hemoglobin	3.000000e-35
GCST90002392_448	Mean corpuscular volume	6.000000e-39
GCST90002397_73	Mean spheric corpuscular volume	2.000000e-30
GCST90002405_366	Reticulocyte count	2.000000e-14
GCST90002406_419	Reticulocyte fraction of red cells	2.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007627	airway imaging measurement
EFO:0007986	reticulocyte count
EFO:0004527	mean corpuscular hemoglobin

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4680040 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 14,806 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL359965	ALLICIN	2	14,806

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs28362380	ODC1, SNORA80B		0.00	0
rs2302615	ODC1, SNORA80B		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — Mitochondrial di- and tri-carboxylic acid transporter subfamily

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.96	IC50	11	nM	ALLICIN

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
3-prop-2-enylsulfinylsulfanylprop-1-ene	1675137: Inhibition of ODC (unknown origin) expressed in Escherichia coli after 30 mins in presence of [1-14C] L-ornithine by liquid scintillation counter analysis	ic50	0.0110	uM

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	5
Valproic Acid	affects expression, affects cotreatment, decreases expression	5
Aflatoxin B1	affects expression, decreases expression, decreases methylation	5
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
methyleugenol	decreases expression	1
propionaldehyde	decreases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
belinostat	decreases expression	1
bisphenol B	decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
jinfukang	decreases expression	1
Irinotecan	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Aldehydes	decreases expression	1
Estradiol	increases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Quercetin	decreases expression	1
Thimerosal	affects cotreatment, increases expression	1
Urethane	decreases expression	1
Vanadates	decreases expression	1
Zidovudine	increases expression	1
Cadmium Chloride	increases expression	1
Particulate Matter	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
CHEMBL4669553	Binding	Inhibition of ODC (unknown origin) expressed in Escherichia coli after 30 mins in presence of [1-14C] L-ornithine by liquid scintillation counter analysis	Allicin, a Potent New Ornithine Decarboxylase Inhibitor in Neuroblastoma Cells. — 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_D4ET	1321N1-SLC25A21-KO-c13	Cancer cell line	Male
CVCL_D4EU	1321N1-SLC25A21-KO-c7	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00067990	PHASE4	COMPLETED	Angiotensin II Blockade for Chronic Allograft Nephropathy
NCT00117078	PHASE4	COMPLETED	Aranesp® Monthly Preference Study - 2
NCT00117130	PHASE4	COMPLETED	Study to Evaluate Effectiveness of Aranesp®
NCT00132431	PHASE4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00140985	PHASE4	COMPLETED	Antiproteinuric Efficacy of Losartan Potassium in Patients With Non-Diabetic Proteinuric Renal Diseases (0954-213)
NCT00246129	PHASE4	COMPLETED	CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation
NCT00275535	PHASE4	COMPLETED	The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients
NCT00282217	PHASE4	COMPLETED	Study Evaluating Sirolimus in the Treatment of Kidney Transplant
NCT00289614	PHASE4	COMPLETED	Patients With Renal Impairment and Diabetes Undergoing Computed Tomography (CT)
NCT00290069	PHASE4	UNKNOWN	Renal Function Optimization With Mycophenolate Mofetil (MMF) Immunosuppressor Regimes (ALHAMBRA)
NCT00338468	PHASE4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00368901	PHASE4	COMPLETED	STAAR-2 Clinical Study
NCT00369733	PHASE4	COMPLETED	STAAR-3 Clinical Study
NCT00369772	PHASE4	COMPLETED	STAAR-1 Clinical Study
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00443508	PHASE4	UNKNOWN	Reduction or Discontinuation of CNI’s With Conversion to Everolimus-Based Immunosuppresion
NCT00452478	PHASE4	TERMINATED	Conversion From Standard Phosphate Binder Therapy to Fosrenol® (Lanthanum Carbonate) in Chronic Kidney Disease Stage 5
NCT00492518	PHASE4	COMPLETED	Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy
NCT00505102	PHASE4	UNKNOWN	Safe Renal Function In Long Term Heart Transplanted Patients
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00688480	PHASE4	COMPLETED	Do Xanthine Oxidase Inhibitors Reduce Both Left Ventricular Hypertrophy and Endothelial Dysfunction in Cardiovascular Patients With Renal Dysfunction?
NCT00863707	PHASE4	COMPLETED	A Study of the Safety and Tolerance of Regadenoson in Subjects With Renal Impairment
NCT01101698	PHASE4	UNKNOWN	Vitamin K2 and Vessel Calcification in Chronic Kidney Disease Patients
NCT01150201	PHASE4	COMPLETED	Aliskiren Combined With Losartan in Proteinuric, Non-diabetic Chronic Kidney Disease
NCT01155141	PHASE4	COMPLETED	Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
NCT01228279	PHASE4	COMPLETED	Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis
NCT01334333	PHASE4	COMPLETED	Comparison of Medication Adherence Between Once and Twice Daily Tacrolimus in Stable Renal Transplant Recipients
NCT01437943	PHASE4	TERMINATED	Effect of Short Term Aliskiren Treatment in Kidney Transplant Patients
NCT01545479	PHASE4	COMPLETED	Increased Renal Oxygenation and Angiotensin Converting Enzyme Inhibition
NCT01614431	PHASE4	COMPLETED	N Acetyl Cysteine for Cystinosis Patients
NCT01631149	PHASE4	COMPLETED	Effect of Deep BLock on Intraoperative Surgical Conditions
NCT01722513	PHASE4	UNKNOWN	Efficacy and Safety of Alprostadil Prevent Contrast Induced Nephropathy
NCT01985360	PHASE4	COMPLETED	ISCHEMIA-Chronic Kidney Disease Trial
NCT02311010	PHASE4	UNKNOWN	Practical Use of Advagraf de Novo After Kidney Transplantation According to Recipient Genetic Polymorphism
NCT02413073	PHASE4	COMPLETED	Whole Body Vibration in Kidney Disease
NCT02444013	PHASE4	UNKNOWN	Folic Acid for Prevention of Contrast Induced Nephropathy
NCT02663713	PHASE4	COMPLETED	A Randomized, Pharmacodynamic Comparison of Low Dose Ticagrelor to Clopidogrel in Patients With Prior Myocardial Infarction
NCT02707809	PHASE4	COMPLETED	Effects of Dexmedetomidine on Microcirculation of Kidney Transplant Recipient
NCT02761577	PHASE4	COMPLETED	A Prospective Study on Incidence and Prevention of Contrast-induced Nephropathy in Croatia
NCT03029351	PHASE4	TERMINATED	GLP-1 Receptor Agonist Therapy and Albuminuria in Patients With Type 2 Diabetes