SLC25A20

Chr 3

solute carrier family 25 member 20

Also known as: CAC, CACT

NCBI Gene: 788ENSG00000178537UniProt: O43772

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. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

UniProtCarnitine-acylcarnitine translocase deficiency
375
ClinVar variants
96
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC25A20
🧬
Gene-Disease Validity (ClinGen)
carnitine-acylcarnitine translocase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
96 Pathogenic / Likely Pathogenic· 114 VUS of 375 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.17LOEUF
pLI 0.000
Z-score 1.04
OE 0.73 (0.48–1.17)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.30Z-score
OE missense 0.93 (0.82–1.07)
152 obs / 163.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.73 (0.48–1.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.93 (0.82–1.07)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88
0≤1.21.6
LoF obs/exp: 13 / 17.7Missense obs/exp: 152 / 163.0Syn Z: 0.72

ClinVar Variant Classifications

375 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic53
Likely Pathogenic43
VUS114
Likely Benign150
Benign5
Conflicting10
53
Pathogenic
43
Likely Pathogenic
114
VUS
150
Likely Benign
5
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
22
3
28
0
53
Likely Pathogenic
23
7
13
0
43
VUS
1
91
20
2
114
Likely Benign
0
2
82
66
150
Benign
0
0
5
0
5
Conflicting
—10
Total4610314868375

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SLC25A20 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SLC25A20-related carnitine-acylcarnitine translocase deficiency

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — SLC25A20
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Loss-of-function SLC25A20 variant causes carnitine-acylcarnitine translocase deficiency by reducing SLC25A20 protein stability.
Gan Z et al.·Gene
2025
[Clinical and genetic analysis of two pedigrees affected with Carnitine-acylcarnitine translocase deficiency due to variant of SLC25A20 gene].
Zhang Q et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2024
In Silico Analysis of the Structural Dynamics and Substrate Recognition Determinants of the Human Mitochondrial Carnitine/Acylcarnitine SLC25A20 Transporter.
Pasquadibisceglie A et al.·Int J Mol Sci
2023
Carnitine-acylcarnitine translocase deficiency caused by SLC25A20 gene heterozygous variants in twins: a case report.
Zhang L et al.·J Int Med Res
2023Case report
Chronic acidosis rewires cancer cell metabolism through PPARα signaling.
Rolver MG et al.·Int J Cancer
2023
Molecular and functional analysis of SLC25A20 mutations causing carnitine-acylcarnitine translocase deficiency.
Iacobazzi V et al.·Hum Mutat
2004Case report
Development and validation of a carnitine cycle and transport disorders (CCD) panel: an ONT-compatible multi-gene diagnostic kit for newborn and selective screening.
Akan G et al.·Orphanet J Rare Dis
2025
The mitochondrial carnitine/acylcarnitine carrier: function, structure and physiopathology.
Indiveri C et al.·Mol Aspects Med
2011Review
A Comprehensive LOVD Database for Fatty Acid Oxidation Disorders in Chinese Populations.
Zhang T et al.·Hum Mutat
2023
Clinical and molecular characteristics of carnitine-acylcarnitine translocase deficiency: Experience with six patients in Guangdong China.
Tang C et al.·Clin Chim Acta
2019Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
HLX and SLC25A20: Immunologic regulators bridging ankylosing spondylitis and uveitis via multi-omics integration and machine learning.
Cai W et al.·PLoS One
2025🔓 Open Access
Successful Improvement of Cardiac Function in Late-Onset Dilated Cardiomyopathy Due to the SLC25A20 c.199-10T>G Mutation.
Nguyen HT et al.·JACC Case Rep
2025🔓 Open Access
Dietary supplementation with L-carnitine elevates intracellular carnitine levels and affects gene expression of SLC25A20 and COX4I1, as well as non-mitochondrial respiration of bovine blood cells during systemic immune challenge.
Seemann L et al.·Front Immunol
2025🔓 Open Access
Successful Management by Selective Embryo in the Carnitine-acylcarnitine Translocase Deficiency with SLC25A20 C.199-10T>G Variation: The First Case Report from Vietnam and Literature Review.
Trinh NB et al.·Oman Med J
2025Review
Loss of SLC25A20 in Pancreatic Adenocarcinoma Reversed the Tumor-Promoting Effects of a High-Fat Diet.
Woo SM et al.·Theranostics
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools