CPT1C

Chr 19AD

carnitine palmitoyltransferase 1C

Also known as: CATL1, CPT I-C, CPT1-B, CPT1P, CPTI-B, CPTIC, SPG73

The encoded protein is a palmitoyl thioesterase that regulates AMPA receptor trafficking to the plasma membrane through depalmitoylation and contributes to systemic energy homeostasis and appetite control. Mutations cause spastic paraplegia 73 with autosomal dominant inheritance. This gene is not highly constrained against loss-of-function variants (pLI near zero), suggesting the pathogenic variants may not simply eliminate protein function.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 0.691 OMIM phenotype
Clinical SummaryCPT1C
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Gene-Disease Validity (ClinGen)
hereditary spastic paraplegia · ADLimited

Limited evidence — not for standalone diagnostic reporting

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📖
GeneReview available — CPT1C
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.69LOEUF
pLI 0.000
Z-score 3.20
OE 0.49 (0.350.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.31Z-score
OE missense 0.83 (0.770.91)
419 obs / 501.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.49 (0.350.69)
00.351.4
Missense OE0.83 (0.770.91)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 22 / 45.2Missense obs/exp: 419 / 501.9Syn Z: -0.69
DN
0.7229th %ile
GOF
0.6052th %ile
LOF
0.2386th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median · 1 literature citation
GOF1 literature citation

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

DNWe also observed a reduction of mean (SD) lipid droplets in primary cortical neurons isolated from Cpt1c−/− mice as compared with wild-type mice (1.0 [0.12] vs 0.44 [0.05]; P < .001), suggesting a dominant negative mechanism for the mutation.PMID:25751282
GOFCarnitine palmitoyltransferase-1c gain-of-function in the brain results in postnatal microencephalyPMID:21592121

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗