SLC25A20

Summary

SLC25A20 (solute carrier family 25 member 20, HGNC:1421) is a protein-coding gene on chromosome 3p21.31, encoding Mitochondrial carnitine/acylcarnitine carrier protein (O43772). Mediates the electroneutral exchange of acylcarnitines (O-acyl-(R)-carnitine or L-acylcarnitine) of different acyl chain lengths (ranging from O-acetyl-(R)-carnitine to long-chain O-acyl-(R)-carnitines) with free carnitine ((R)-carnitine or L-carnitine) across the mitochondrial….

This gene product is one of several closely related mitochondrial-membrane carrier proteins that shuttle substrates between cytosol and the intramitochondrial matrix space. This protein mediates the transport of acylcarnitines into mitochondrial matrix for their oxidation by the mitochondrial fatty acid-oxidation pathway. Mutations in this gene are associated with carnitine-acylcarnitine translocase deficiency, which can cause a variety of pathological conditions such as hypoglycemia, cardiac arrest, hepatomegaly, hepatic dysfunction and muscle weakness, and is usually lethal in new born and infants.

Source: NCBI Gene 788 — RefSeq curated summary.

At a glance

• Gene–disease (curated): carnitine-acylcarnitine translocase deficiency (Definitive, ClinGen)
• GWAS associations: 13
• Clinical variants (ClinVar): 362 total — 42 pathogenic, 28 likely-pathogenic
• Phenotypes (HPO): 45
• Druggable target: yes
• MANE Select transcript: NM_000387

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1421
Approved symbol	SLC25A20
Name	solute carrier family 25 member 20
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	CAC
Ensembl gene	ENSG00000178537
Ensembl biotype	protein_coding
OMIM	613698
Entrez	788

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000319017, ENST00000430379, ENST00000440964, ENST00000479050, ENST00000880877, ENST00000880878, ENST00000946112

RefSeq mRNA: 1 — MANE Select: NM_000387 NM_000387

CCDS: CCDS2779

Canonical transcript exons

ENST00000319017 — 9 exons

Exon	Start	End
ENSE00001743152	48898690	48898882
ENSE00001802486	48856926	48857772
ENSE00003476151	48883997	48884124
ENSE00003490092	48858507	48858631
ENSE00003511295	48862542	48862659
ENSE00003518376	48859092	48859201
ENSE00003521086	48879358	48879448
ENSE00003571937	48859555	48859627
ENSE00003641024	48891980	48892072

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 96.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.1212 / max 168.5189, expressed in 1737 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42178	7.6132	1732
42177	0.5080	138

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	96.61	gold quality
mucosa of transverse colon	UBERON:0004991	96.41	gold quality
apex of heart	UBERON:0002098	95.62	gold quality
ileal mucosa	UBERON:0000331	95.53	gold quality
liver	UBERON:0002107	95.25	gold quality
granulocyte	CL:0000094	95.03	gold quality
heart left ventricle	UBERON:0002084	94.75	gold quality
gastrocnemius	UBERON:0001388	94.70	gold quality
cardiac ventricle	UBERON:0002082	94.63	gold quality
duodenum	UBERON:0002114	94.22	gold quality
jejunal mucosa	UBERON:0000399	93.87	gold quality
muscle of leg	UBERON:0001383	93.82	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.29	gold quality
monocyte	CL:0000576	93.09	gold quality
left adrenal gland	UBERON:0001234	93.06	gold quality
right adrenal gland	UBERON:0001233	93.01	gold quality
leukocyte	CL:0000738	92.98	gold quality
left adrenal gland cortex	UBERON:0035825	92.92	gold quality
mononuclear cell	CL:0000842	92.91	gold quality
right adrenal gland cortex	UBERON:0035827	92.87	gold quality
heart	UBERON:0000948	92.56	gold quality
heart right ventricle	UBERON:0002080	92.35	gold quality
muscle organ	UBERON:0001630	92.32	gold quality
jejunum	UBERON:0002115	92.30	gold quality
adrenal cortex	UBERON:0001235	92.29	gold quality
right atrium auricular region	UBERON:0006631	92.15	gold quality
rectum	UBERON:0001052	91.86	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.78	gold quality
gluteal muscle	UBERON:0002000	91.77	gold quality
body of pancreas	UBERON:0001150	91.74	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-110499	yes	311.34
E-ANND-3	no	3.10

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PPARA, PPARD, SP1

miRNA regulators (miRDB)

50 targeting SLC25A20, 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-6873-3P	100.00	71.42	2626
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-4279	99.19	66.70	2437

Literature-anchored findings (GeneRIF, showing 18)

• A deficiency in CACT was treated with a carnitine diet and administration of medium-chain triglycerides. (PMID:15057979)
• The clinical, biochemical, & molecular features of 6 CACT-deficient patients from Italy, Spain, & North America who had significant clinical heterogeneity are reported. 5 novel & 3 previously reported mutations were found. (PMID:15365988)
• The modulation of CACT expression has consequences for CPT 1 activity, while the biologic effects of acetyl-carnitine are not associated with a generic supply of energy compounds but to the anaplerotic property of the molecule. (PMID:15515015)
• Report the outcome of two siblings with CACT deficiency. (PMID:17508264)
• Functional analysis of mutations of residues Pro278 and Ala279 in A. nidulans, together with kinetic data in reconstituted liposomes, suggest a predominant structural role for these amino acids. (PMID:18307102)
• PPARalpha regulates the expression of human SLC25A20 via the peroxisome proliferator responsive element. (PMID:19748481)
• These results show that FOXA and Sp1 sites in HepG2 cells and only the Sp1 site in HEK293 and SK-N-SH cells have a critical role in the transcriptional regulation of the CAC proximal promoter. (PMID:21130740)
• Results show Steroid Receptor Coactivator-3 (SRC-3) plays a central role in long chain fatty acid metabolism by directly regulating carnitine/acyl-carnitine translocase (CACT) gene expression. (PMID:22560224)
• Compares and contrasts all the known human SLC25A* genes and includes functional information. (PMID:23266187)
• CPT2 and CACT are crucial for mitochondrial acylcarnitine formation and export to the extracellular fluids in mitochondrial fatty acid beta-oxidation disorders. (PMID:23322164)
• C.576G>A, c.106-2a>t and c.516T>C are novel CACT gene mutations. (PMID:24088670)
• The antiport mode of transport, typical of mitochondrial carriers such as CAC, results from coupling of uniport reactions in opposite directions mediated by specific amino acid residues. (PMID:25325845)
• We provide evidence that the downregulation of hsa-miR-124-3p, hsa-miR-129-5p and hsa-miR-378 induced an increase in both expression and activity of CPT1A, CACT and CrAT in malignant prostate cells. (PMID:28671672)
• we report the first 2 cases of CACTD identified from the mainland China. Apart from a founder mutation c.199-10T>G, we have identified a novel c.1A>G mutation. Patients with Carnitine-acylcarnitine translocase deficiency with a genotype of c.199-10T>G mutation usually presents with a severe clinical phenotype. Early recognition and appropriate treatment is crucial in this highly lethal disorder. (PMID:29137068)
• Clinical and molecular characteristics of carnitineacylcarnitine translocase deficiency with c.270delC and a novel c.408C>A variant. (PMID:34449152)
• Novel mutations associated with carnitine-acylcarnitine translocase and carnitine palmitoyl transferase 2 deficiencies in Malaysia. (PMID:34626609)
• Inhibition of the Mitochondrial Carnitine/Acylcarnitine Carrier by Itaconate through Irreversible Binding to Cysteine 136: Possible Pathophysiological Implications. (PMID:37371573)
• [Clinical and genetic analysis of two pedigrees affected with Carnitine-acylcarnitine translocase deficiency due to variant of SLC25A20 gene]. (PMID:38565514)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	slc25a20	ENSDARG00000040401
mus_musculus	Slc25a20	ENSMUSG00000032602
rattus_norvegicus	Slc25a20	ENSRNOG00000020288

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 carnitine/acylcarnitine carrier protein — O43772 (reviewed: O43772)

Alternative names: Carnitine/acylcarnitine translocase, Solute carrier family 25 member 20

All UniProt accessions (3): O43772, C9JPE1, F8WEF6

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the electroneutral exchange of acylcarnitines (O-acyl-(R)-carnitine or L-acylcarnitine) of different acyl chain lengths (ranging from O-acetyl-(R)-carnitine to long-chain O-acyl-(R)-carnitines) with free carnitine ((R)-carnitine or L-carnitine) across the mitochondrial inner membrane, via a ping-pong mechanism. Key player in the mitochondrial oxidation pathway, it translocates the fatty acids in the form of acylcarnitines into the mitochondrial matrix, where the carnitine palmitoyltransferase 2 (CPT-2) activates them to undergo fatty acid beta-oxidation. Catalyzes the unidirectional transport (uniport) of carnitine at lower rates than the antiport (exchange).

Subcellular location. Mitochondrion inner membrane.

Disease relevance. Carnitine-acylcarnitine translocase deficiency (CACTD) [MIM:212138] A rare long-chain fatty acid oxidation disorder. Metabolic consequences include hypoketotic hypoglycemia under fasting conditions, hyperammonemia, elevated creatine kinase and transaminases, dicarboxylic aciduria, very low free carnitine and abnormal acylcarnitine profile with marked elevation of the long-chain acylcarnitines. Clinical features include neurologic abnormalities, cardiomyopathy, arrhythmias, skeletal muscle damage, liver dysfunction and episodes of life-threatening coma, which eventually lead to death. Most patients become symptomatic in the neonatal period with a rapidly progressive deterioration and a high mortality rate. The disease is caused by variants affecting the gene represented in this entry.

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

RefSeq proteins (1): NP_000378* (*=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), 6 shown:

• (R)-carnitine(in) = (R)-carnitine(out) (RHEA:34959)
• O-acetyl-(R)-carnitine(in) + (R)-carnitine(out) = O-acetyl-(R)-carnitine(out) + (R)-carnitine(in) (RHEA:49908)
• O-propanoyl-(R)-carnitine(in) + (R)-carnitine(out) = O-propanoyl-(R)-carnitine(out) + (R)-carnitine(in) (RHEA:49912)
• O-hexadecanoyl-(R)-carnitine(in) + (R)-carnitine(out) = O-hexadecanoyl-(R)-carnitine(out) + (R)-carnitine(in) (RHEA:49916)
• O-octanoyl-(R)-carnitine(in) + (R)-carnitine(out) = O-octanoyl-(R)-carnitine(out) + (R)-carnitine(in) (RHEA:49920)
• an O-acyl-(R)-carnitine(in) + (R)-carnitine(out) = an O-acyl-(R)-carnitine(out) + (R)-carnitine(in) (RHEA:49924)

UniProt features (28 total): topological domain 7, transmembrane region 6, modified residue 5, repeat 3, sequence variant 3, sequence conflict 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43772-F1	89.02	0.64

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 (5): 2, 148, 157, 170, 170

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-200425	Carnitine shuttle
R-HSA-1430728	Metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-8978868	Fatty acid metabolism

MSigDB gene sets: 294 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, ZHAN_MULTIPLE_MYELOMA_MF_UP, GOBP_MODIFIED_AMINO_ACID_TRANSPORT, STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, LUCAS_HNF4A_TARGETS_UP, GOBP_MITOCHONDRIAL_TRANSPORT, GOBP_AMINO_ACID_BETAINE_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, GOBP_MITOCHONDRIAL_TRANSMEMBRANE_TRANSPORT, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_QUATERNARY_AMMONIUM_GROUP_TRANSPORT

GO Biological Process (6): in utero embryonic development (GO:0001701), mitochondrial transport (GO:0006839), carnitine shuttle (GO:0006853), carnitine transmembrane transport (GO:1902603), lipid transport (GO:0006869), O-acyl-L-carnitine transmembrane transport (GO:1902616)

GO Molecular Function (3): carnitine:O-acyl-L-carnitine antiporter activity (GO:0005476), O-acyl-L-carnitine transmembrane transporter activity (GO:0015227), protein binding (GO:0005515)

GO Cellular Component (6): mitochondrion (GO:0005739), mitochondrial envelope (GO:0005740), mitochondrial inner membrane (GO:0005743), cytosol (GO:0005829), membrane (GO:0016020), mitochondrial membrane (GO:0031966)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Fatty acid metabolism	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transmembrane transport	2
cytoplasm	2
mitochondrion	2
cellular anatomical structure	2
chordate embryonic development	1
intracellular transport	1
long-chain fatty acid transport	1
intracellular lipid transport	1
fatty acid transmembrane transport	1
mitochondrial transmembrane transport	1
carnitine transport	1
transport	1
lipid localization	1
quaternary ammonium group transport	1
carnitine transmembrane transporter activity	1
O-acyl-L-carnitine transmembrane transporter activity	1
antiporter activity	1
quaternary ammonium group transmembrane transporter activity	1
O-acyl-L-carnitine transmembrane transport	1
binding	1
intracellular membrane-bounded organelle	1
organelle envelope	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrial envelope	1
organelle membrane	1

Protein interactions and networks

STRING

1628 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLC25A20	CPT2	P23786	993
SLC25A20	CPT1C	Q8TCG5	924
SLC25A20	CPT1B	Q92523	924
SLC25A20	CPT1A	P50416	920
SLC25A20	AASDH	Q4L235	914
SLC25A20	CRAT	P43155	760
SLC25A20	ACADS	P16219	741
SLC25A20	ACADVL	P49748	716
SLC25A20	PPARA	Q07869	709
SLC25A20	SLC22A5	O76082	656
SLC25A20	HADHA	P40939	634
SLC25A20	ACADM	P11310	620
SLC25A20	ETFDH	Q16134	616
SLC25A20	ACADL	P28330	597
SLC25A20	HADHB	P55084	589

IntAct

50 interactions, top by confidence:

A	B	Type	Score
POLR3E	POLR3A	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
LAMP2	SLC25A20	psi-mi:“MI:0915”(physical association)	0.560
ARL15	SLC25A20	psi-mi:“MI:0914”(association)	0.530
MRAP2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
ISLR	BCKDK	psi-mi:“MI:0914”(association)	0.530
MMP26	SLC25A20	psi-mi:“MI:0914”(association)	0.530
PLEC	SLC25A20	psi-mi:“MI:0915”(physical association)	0.400
Washc1	COX7A2	psi-mi:“MI:0914”(association)	0.350
SGTB	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
HNRNPD	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
SYNCRIP	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
Tbc1d7	SLC25A20	psi-mi:“MI:0914”(association)	0.350
CLEC2D	TMEM120B	psi-mi:“MI:0914”(association)	0.350
GLMP	RTL8C	psi-mi:“MI:0914”(association)	0.350
ISLR	DDX11L8	psi-mi:“MI:0914”(association)	0.350
NIT1	NUDT19	psi-mi:“MI:0914”(association)	0.350
MRAP2	GOSR1	psi-mi:“MI:0914”(association)	0.350
MMP26	NME4	psi-mi:“MI:0914”(association)	0.350
POLR3E	POLR3A	psi-mi:“MI:0914”(association)	0.350
KLK15	SLC25A20	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
LRRC25	POTEF	psi-mi:“MI:0914”(association)	0.350
MGARP	RTL8C	psi-mi:“MI:0914”(association)	0.350

BioGRID (79): SLC25A20 (Affinity Capture-MS), SLC25A20 (Affinity Capture-MS), SLC25A20 (Affinity Capture-MS), SLC25A20 (Co-fractionation), SLC25A20 (Co-fractionation), SLC25A20 (Affinity Capture-MS), SLC25A20 (Affinity Capture-MS), SLC25A20 (Affinity Capture-MS), SLC25A20 (Affinity Capture-MS), SLC25A20 (Affinity Capture-MS), SLC25A20 (Affinity Capture-MS), SLC25A20 (Affinity Capture-MS), SLC25A20 (Affinity Capture-MS), SLC25A20 (Affinity Capture-MS), SLC25A20 (Affinity Capture-MS)

ESM2 similar proteins: A0JN87, A6QR09, F1R4U0, F1RFX9, O22261, O43772, O43808, O70579, O77792, O95258, O97562, O97649, P55851, P55916, P56499, P56501, P70406, P97521, Q08DK4, Q287T7, Q3SZI5, Q4V9P0, Q5R5A8, Q5RD81, Q5RFB7, Q5U680, Q5ZKP7, Q641C8, Q66H23, Q6DG32, Q6GLA2, Q6IZB5, Q70HW3, Q8BMG8, Q8HXY2, Q8R0Z5, Q920G8, Q922G0, Q95J75, Q96A46

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

2 interactions.

A	Effect	B	Mechanism
PPARD	“up-regulates quantity by expression”	SLC25A20	“transcriptional regulation”
PPARA	“up-regulates quantity by expression”	SLC25A20	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	42
Likely pathogenic	28
Uncertain significance	112
Likely benign	146
Benign	5

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
12132	NM_000387.6(SLC25A20):c.897dup (p.Asn300fs)	Pathogenic
12133	NM_000387.6(SLC25A20):c.200_326+1del	Pathogenic
12134	SLC25A20, 110-BP DEL	Pathogenic
12135	NM_000387.6(SLC25A20):c.496C>T (p.Arg166Ter)	Pathogenic
12136	NM_000387.6(SLC25A20):c.84del (p.His29fs)	Pathogenic
12137	NM_000387.6(SLC25A20):c.199-10T>G	Pathogenic
12138	NM_000387.6(SLC25A20):c.713A>G (p.Gln238Arg)	Pathogenic
126507	NM_000387.6(SLC25A20):c.576G>A (p.Trp192Ter)	Pathogenic
126508	NM_000387.6(SLC25A20):c.106-2A>T	Pathogenic
1301321	NM_000387.6(SLC25A20):c.528del (p.Met177fs)	Pathogenic
1377642	NM_000387.6(SLC25A20):c.48del (p.Gly17fs)	Pathogenic
2031549	NM_000387.6(SLC25A20):c.106-2A>G	Pathogenic
2422997	NC_000003.11:g.(?48929393)(48929525_?)del	Pathogenic
2422998	NC_000003.11:g.(?48916771)(48921577_?)del	Pathogenic
2678861	NM_000387.6(SLC25A20):c.706C>T (p.Arg236Ter)	Pathogenic
2678867	NM_000387.6(SLC25A20):c.843+4_843+50del	Pathogenic
2678875	NM_000387.6(SLC25A20):c.191_192del (p.Leu63_Phe64insTer)	Pathogenic
2705051	NM_000387.6(SLC25A20):c.510_514dup (p.Thr172fs)	Pathogenic
2729645	NM_000387.6(SLC25A20):c.1A>G (p.Met1Val)	Pathogenic
2734532	NM_000387.6(SLC25A20):c.718+1G>C	Pathogenic
2734533	NM_000387.6(SLC25A20):c.180del (p.Lys61fs)	Pathogenic
2751691	NM_000387.6(SLC25A20):c.170_173del (p.Asp57fs)	Pathogenic
2781289	NM_000387.6(SLC25A20):c.394G>T (p.Glu132Ter)	Pathogenic
2787313	NM_000387.6(SLC25A20):c.729del (p.Lys244fs)	Pathogenic
2822351	NM_000387.6(SLC25A20):c.211del (p.Leu71fs)	Pathogenic
2871198	NM_000387.6(SLC25A20):c.415C>T (p.Gln139Ter)	Pathogenic
2894019	NM_000387.6(SLC25A20):c.306_315del (p.His103fs)	Pathogenic
2918004	NM_000387.6(SLC25A20):c.301C>T (p.Gln101Ter)	Pathogenic
3246861	NC_000003.11:g.(?48921410)(48921577_?)del	Pathogenic
3246863	NC_000003.11:g.(?48929393)(48936227_?)del	Pathogenic

SpliceAI

1681 predictions. Top by Δscore:

Variant	Effect	Δscore
3:48858499:CTACT:C	donor_loss	1.0000
3:48858501:ACT:A	donor_loss	1.0000
3:48858502:CTC:C	donor_loss	1.0000
3:48858503:TCACC:T	donor_loss	1.0000
3:48858504:CA:C	donor_loss	1.0000
3:48858505:A:AC	donor_gain	1.0000
3:48858506:C:CC	donor_gain	1.0000
3:48858506:C:G	donor_loss	1.0000
3:48858506:CCG:C	donor_gain	1.0000
3:48858506:CCGCA:C	donor_gain	1.0000
3:48859084:CCACT:C	donor_loss	1.0000
3:48859085:CACTC:C	donor_loss	1.0000
3:48859086:ACTCA:A	donor_loss	1.0000
3:48859087:CTCA:C	donor_loss	1.0000
3:48859088:TCA:T	donor_loss	1.0000
3:48859089:CA:C	donor_loss	1.0000
3:48859090:A:C	donor_loss	1.0000
3:48859091:C:CA	donor_loss	1.0000
3:48859091:CCAGT:C	donor_gain	1.0000
3:48859200:CC:C	acceptor_gain	1.0000
3:48859201:CC:C	acceptor_gain	1.0000
3:48862539:TACCT:T	donor_loss	1.0000
3:48862540:A:C	donor_loss	1.0000
3:48862564:C:CA	donor_gain	1.0000
3:48862655:TGAAT:T	acceptor_gain	1.0000
3:48862657:AAT:A	acceptor_gain	1.0000
3:48862658:AT:A	acceptor_gain	1.0000
3:48862660:C:CC	acceptor_gain	1.0000
3:48879352:CCTTA:C	donor_loss	1.0000
3:48879353:CTTAC:C	donor_loss	1.0000

AlphaMissense

1954 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:48858547:C:T	G268E	0.999
3:48858548:C:G	G268R	0.999
3:48858548:C:T	G268R	0.999
3:48859108:C:A	K234N	0.999
3:48859108:C:G	K234N	0.999
3:48859119:C:G	D231H	0.999
3:48859151:C:T	G220E	0.999
3:48859160:C:T	G217D	0.999
3:48859163:C:T	G216E	0.999
3:48859612:C:T	G184E	0.999
3:48862566:C:G	G171R	0.999
3:48862566:C:T	G171R	0.999
3:48879370:C:A	K135N	0.999
3:48879370:C:G	K135N	0.999
3:48879377:C:G	R133P	0.999
3:48898700:T:A	D32V	0.999
3:48898701:C:G	D32H	0.999
3:48898728:A:G	C23R	0.999
3:48857771:G:T	A282D	0.998
3:48858509:C:G	A281P	0.998
3:48858548:C:A	G268W	0.998
3:48859110:T:C	K234E	0.998
3:48859140:A:G	W224R	0.998
3:48859140:A:T	W224R	0.998
3:48859152:C:A	G220W	0.998
3:48859152:C:G	G220R	0.998
3:48859152:C:T	G220R	0.998
3:48859154:G:T	A219E	0.998
3:48859161:C:G	G217R	0.998
3:48859164:C:A	G216W	0.998

dbSNP variants (sampled 300 via entrez): RS1000015578 (3:48891769 C>G,T), RS1000222156 (3:48872792 T>G), RS1000247182 (3:48878568 G>A), RS1000266578 (3:48885298 G>A), RS1000310008 (3:48857511 T>G), RS1000360189 (3:48894325 G>C), RS1000381560 (3:48865503 T>C), RS1000412668 (3:48865329 T>C), RS1000414178 (3:48894744 T>A,C), RS1000482931 (3:48899344 T>C), RS1000484876 (3:48865087 T>C,G), RS1000713586 (3:48864000 G>A), RS1000716706 (3:48878914 C>A,T), RS1000744537 (3:48863799 G>A), RS1000829692 (3:48886098 T>C)

Disease associations

OMIM: gene MIM:613698 | disease phenotypes: MIM:212138

GenCC curated gene-disease

Disease	Classification	Inheritance
carnitine-acylcarnitine translocase deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
carnitine-acylcarnitine translocase deficiency	Definitive	AR

Mondo (1): carnitine-acylcarnitine translocase deficiency (MONDO:0008918)

Orphanet (1): Carnitine-acylcarnitine translocase deficiency (Orphanet:159)

HPO phenotypes

45 total (30 of 45 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000639	Nystagmus
HP:0000737	Irritability
HP:0000961	Cyanosis
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001259	Coma
HP:0001263	Global developmental delay
HP:0001290	Generalized hypotonia
HP:0001298	Encephalopathy
HP:0001324	Muscle weakness
HP:0001397	Hepatic steatosis
HP:0001399	Hepatic failure
HP:0001638	Cardiomyopathy
HP:0001662	Bradycardia
HP:0001678	Atrioventricular block
HP:0001695	Cardiac arrest
HP:0001714	Ventricular hypertrophy
HP:0001943	Hypoglycemia
HP:0001985	Hypoketotic hypoglycemia
HP:0001987	Hyperammonemia
HP:0001998	Neonatal hypoglycemia
HP:0002045	Hypothermia
HP:0002093	Respiratory insufficiency
HP:0002240	Hepatomegaly
HP:0002615	Hypotension
HP:0002882	Sudden episodic apnea
HP:0002910	Elevated circulating hepatic transaminase concentration

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST009391_1377	Metabolite levels	7.000000e-06
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13
GCST90002382_566	Eosinophil percentage of white cells	1.000000e-14
GCST90002387_69	Immature fraction of reticulocytes	1.000000e-16
GCST90002405_11	Reticulocyte count	2.000000e-13
GCST90002406_29	Reticulocyte fraction of red cells	3.000000e-16

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0010367	lysophosphatidylethanolamine 18:0 measurement
EFO:0004346	neuroimaging measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007986	reticulocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562812	Carnitine-Acylcarnitine Translocase Deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2216740 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.30	IC50	5000	nM	CHEMBL2216788

PubChem BioAssay actives

1 with measured affinity, of 3 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
(3S)-3-decanoyloxy-4-(trimethylazaniumyl)butanoate	719716: Inhibition of CACT	ic50	5.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases methylation, affects cotreatment, increases expression, affects expression	6
Cyclosporine	decreases expression	3
perfluorooctanoic acid	increases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
Calcitriol	increases expression, affects cotreatment	2
Cisplatin	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Fenofibrate	increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
chloroacetaldehyde	increases expression	1
methylmercuric chloride	decreases activity, decreases reaction	1
fenofibric acid	affects binding, increases expression	1
glycidyl methacrylate	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
trichostatin A	affects expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression	1
GW 4064	affects cotreatment, decreases expression	1
GW 7647	affects cotreatment, increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2217068	Binding	Inhibition of CACT	Carnitine palmitoyltransferase (CPT) modulators: a medicinal chemistry perspective on 35 years of research. — J Med Chem

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2FP	Abcam HeLa SLC25A20 KO	Cancer cell line	Female
CVCL_D4SL	HuH7-SLC25A20-KO-c1	Cancer cell line	Male
CVCL_D4SM	HuH7-SLC25A20-KO-c6	Cancer cell line	Male
CVCL_TM21	HAP1 SLC25A20 (-) 1	Cancer cell line	Male
CVCL_TM22	HAP1 SLC25A20 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02214160	PHASE2	COMPLETED	Long-Chain Fatty Acid Oxidation Disorders (LC-FAOD) Extension Study for Subjects Previously Enrolled in Triheptanoin Studies
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT05687474	Not specified	COMPLETED	Baby Detect : Genomic Newborn Screening
NCT05910151	Not specified	UNKNOWN	Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in Kazakhstan