SLC22A5

Chr 5AR

solute carrier family 22 member 5

Also known as: CDSP, OCTN2

NCBI Gene: 6584UniProt: O76082

Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. The encoded protein is a plasma integral membrane protein which functions both as an organic cation transporter and as a sodium-dependent high affinity carnitine transporter. The encoded protein is involved in the active cellular uptake of carnitine. Mutations in this gene are the cause of systemic primary carnitine deficiency (CDSP), an autosomal recessive disorder manifested early in life by hypoketotic hypoglycemia and acute metabolic decompensation, and later in life by skeletal myopathy or cardiomyopathy. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2015]

Primary Disease Associations & Inheritance

Carnitine deficiency, systemic primaryMIM #212140
AR
UniProtSystemic primary carnitine deficiency
1
Active trials
293
ClinVar variants
62
Pathogenic / LP
-0.4
Missense Z
1.36
LOEUF
12
Pubs (2 yr)
Clinical Summary— SLC22A5
🧬
Gene-Disease Validity (ClinGen)
short QT syndrome · ARDisputed

Disputed — evidence questions this relationship

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
62 Pathogenic / Likely Pathogenic· 71 VUS of 293 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
GeneReview available — SLC22A5
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

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.
1.36LOEUF
pLI 0.000
Z-score 0.16
OE 0.97 (0.70–1.36)
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.
-0.36Z-score
OE missense 1.06 (0.96–1.16)
332 obs / 314.2 exp
Tolerant

Tolerant to missense variation

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.0.97 (0.70–1.36)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.06 (0.96–1.16)
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.1.09
0≤1.21.6
LoF obs/exp: 24 / 24.9Missense obs/exp: 332 / 314.2Syn Z: -0.85

ClinVar Variant Classifications

293 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic28
VUS71
Likely Benign159
Conflicting1
34
Pathogenic
28
Likely Pathogenic
71
VUS
159
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
1
16
0
34
Likely Pathogenic
9
17
2
0
28
VUS
0
64
3
4
71
Likely Benign
0
0
73
86
159
Benign
0
0
0
0
0
Conflicting
—1
Total26829490293

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC22A5 · protein map & ClinVar variants

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

Gene2Phenotype Curations

SLC22A5-related primary systemic carnitine deficiency

definitive
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. DisordersCardiac
G2P ↗
stop gainedmissense variant

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Carnitine deficiency, systemic primary

MIM #212140

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Carnitine transport and fatty acid oxidation.
Longo N et al.·Biochim Biophys Acta
2016Review
Mapping the immune-genetic architecture of aging: A single-cell causal framework for biomarker discovery and therapeutic targeting.
Hong Y et al.·Ageing Res Rev
2025
Functional genomics of OCTN2 variants informs protein-specific variant effect predictor for Carnitine Transporter Deficiency.
Koleske ML et al.·Proc Natl Acad Sci U S A
2022Functional
Pharmacological and pathophysiological roles of carnitine/organic cation transporters (OCTNs: SLC22A4, SLC22A5 and Slc22a21).
Tamai I·Biopharm Drug Dispos
2013Review
The Human OCTN Sub-Family: Gene and Protein Structure, Expression, and Regulation.
Galluccio M et al.·Int J Mol Sci
2024Review
Unraveling sex differences in Alzheimer's disease and related endophenotypes with brain proteomes.
Mei Z et al.·Alzheimers Dement
2025
Dissection of immunotherapeutic predictive versus prognostic transcriptional programs identifies SLC22A5-centric carnitine metabolism-driven resistance to anti-PD-(L)1 treatment in non-small cell lung cancer.
Wang YZ et al.·Drug Resist Updat
2026
Newborn screening of primary carnitine deficiency: clinical and molecular genetic characteristics.
Hu H et al.·Ital J Pediatr
2025
Genes, diet and inflammatory bowel disease.
Ferguson LR et al.·Mutat Res
2007Review
Clinical Efficacy and Safety of the Ketogenic Diet in Patients with Genetic Confirmation of Drug-Resistant Epilepsy.
Na JH et al.·Nutrients
2025Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Integrated Genomic and GEO Data Analysis Reveals Therapeutic Targets for Rosacea
Deng X et al.·J Cosmet Dermatol
2025
Newborn Screening and Genetic Analysis Identify Six Novel Genetic Variants for Primary Carnitine Deficiency in Ningbo Area, China
Yang X et al.·Front Genet
2021
A report of a pedigree with compound heterozygous mutations in the SLC22A5 gene
Zhou Y et al.·Front Pediatr
2023
The global prevalence and genetic spectrum of primary carnitine deficiency
Sun L et al.·BMC Genom Data
2025
Systemic Primary Carnitine Deficiency: A Case Report with Homozygoys SLC22A5 Gene Mutation.
Yildiz D et al.·Klin Padiatr
2022Case report
Biochemical and genetic characteristics of patients with primary carnitine deficiency identified through newborn screening
Lin Y et al.·Orphanet J Rare Dis
2021Cohort
Broadening the Spectrum of SLC22A5 Phenotype: Primary Carnitine Deficiency Presenting with Focal Myoclonus
Khries M et al.·Child Neurol Open
2023
Glioma cells survival depends both on fatty acid oxidation and on functional carnitine transport by SLC22A5.
Juraszek B et al.·J Neurochem
2021Functional
Top 8 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Chronic Myeloid Leukemia, Chronic PhaseWithdrawal;Drug

Efficacy and Safety of TKIs' Withdrawal After a Two-step Dose Reduction in Patients with Chronic Myeloid Leukemia

ACTIVE NOT RECRUITING
NCT04147533Phase PHASE2Masaryk UniversityStarted 2020-06-16
Imatinib withdrawalDasatinibNilotinib

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients