CPT1C

Chr 19AD

carnitine palmitoyltransferase 1C

NCBI Gene: 126129ENSG00000169169UniProt: Q8TCG5

Palmitoyl thioesterase specifically expressed in the endoplasmic reticulum of neurons. Modulates the trafficking of the glutamate receptor, AMPAR, to plasma membrane through depalmitoylation of GRIA1 (PubMed:30135643). Also regulates AMPR trafficking through the regulation of SACM1L phosphatidylinositol-3-phosphatase activity by interaction in a malonyl-CoA dependent manner (By similarity). Binds malonyl-CoA and couples malonyl-CoA to ceramide levels, necessary for proper spine maturation and contributing to systemic energy homeostasis and appetite control (PubMed:16651524). Binds to palmitoyl-CoA, but does not have carnitine palmitoyltransferase 1 catalytic activity or at very low levels (PubMed:25751282, PubMed:30135643)

Primary Disease Associations & Inheritance

?Spastic paraplegia 73, autosomal dominantMIM #616282
AD
448
ClinVar variants
27
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CPT1C
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
27 Pathogenic / Likely Pathogenic· 227 VUS of 448 total submissions

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.
0.69LOEUF
pLI 0.000
Z-score 3.20
OE 0.49 (0.35–0.69)
Tolerant

Typical tolerance to LoF variation

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.
1.31Z-score
OE missense 0.83 (0.77–0.91)
419 obs / 501.9 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.0.49 (0.35–0.69)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.77–0.91)
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.1.06
0≤1.21.6
LoF obs/exp: 22 / 45.2Missense obs/exp: 419 / 501.9Syn Z: -0.69

ClinVar Variant Classifications

448 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic11
VUS227
Likely Benign156
Benign17
Conflicting10
16
Pathogenic
11
Likely Pathogenic
227
VUS
156
Likely Benign
17
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
12
0
16
Likely Pathogenic
3
2
6
0
11
VUS
6
201
16
4
227
Likely Benign
0
12
51
93
156
Benign
0
2
7
8
17
Conflicting
—10
Total1221892105437

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

View in ClinVar →

Protein Context — Lollipop Plot

CPT1C · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Spastic paraplegia 73, autosomal dominant

MIM #616282

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
CPT1A-mediated Fat Oxidation, Mechanisms, and Therapeutic Potential.
Schlaepfer IR et al.·Endocrinology
2020Review
To be or not to be a fat burner, that is the question for cpt1c in cancer cells.
Fadó R et al.·Cell Death Dis
2023Review
A novel miR-1291-ERRα-CPT1C axis modulates tumor cell proliferation, metabolism and tumorigenesis.
Chen Y et al.·Theranostics
2020Meta-analysis
CPT1C-positive cancer-associated fibroblast facilitates immunosuppression through promoting IL-6-induced M2-like phenotype of macrophage.
Wei R et al.·Oncoimmunology
2024
Hereditary ataxias and paraparesias: clinical and genetic update.
Parodi L et al.·Curr Opin Neurol
2018Review
CPT1C-mediated fatty acid oxidation facilitates colorectal cancer cell proliferation and metastasis.
Li J et al.·Acta Biochim Biophys Sin (Shanghai)
2023
Expression of Carnitine Palmitoyltransferase I Isotypes in Gingival Tissues of Human Periodontitis.
Shen Y et al.·Int Dent J
2025
APC/C-regulated CPT1C promotes tumor progression by upregulating the energy supply and accelerating the G1/S transition.
Zhao H et al.·Cell Commun Signal
2024
International Union of Basic and Clinical Pharmacology. CXIX. Fundamental insights and clinical relevance regarding the carnitine palmitoyltransferase family of enzymes.
Rodríguez-Rodríguez R et al.·Pharmacol Rev
2025Review
Metabolic Flux Analysis Reveals the Roles of Stearate and Oleate on CPT1C-mediated Tumor Cell Senescence.
Chen P et al.·Int J Biol Sci
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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