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clpC1

ATP-dependent ATPase involved in protein degradation

NCBI Pathogen Isolates

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NCBI Reference Gene Catalog

Known alleles and reference sequences

Protein entries specific to clpC1

Browse AMR rules for clpC1

Validation StatusSupported

Overview

Mechanism: mutation-induced resistance
Validation Method: whole-genome sequencing and Sanger DNA sequencing
Drug Classes: Pyrazinamide
Organisms: Mycobacterium tuberculosis H37Rv, Mycobacterium tuberculosis H37Ra, Mycobacterium tuberculosis, Mycobacterium abscessus, Mycobacterium smegmatis, Mycobacterium marinum, Mycobacterium bovis
Papers: 7
Databases: Reslit
Mutations: 5

Mutations

Protein Change	Nucleotide Change	Mechanism	Organism	Resistance To	Database	Validation Status
G99D	-	-	Mycobacterium tuberculosis	Pyrazinamide	Reslit	Candidate
V63A	-	-	Mycobacterium tuberculosis	Pyrazinamide	Reslit	Candidate
K209E	-	impairs PanD degradation	Mycobacterium bovis, Mycobacterium tuberculosis	Pyrazinamide

Papers7

1

Mutation in clpC1 encoding an ATP-dependent ATPase involved in protein degradation is associated with pyrazinamide resistance in Mycobacterium tuberculosis.

PMID 28196969 · 2017

A single mutation in the clpC1 gene (G296T, resulting in G99D) was identified as a potential new mechanism of pyrazinamide resistance in Mycobacterium tuberculosis, in addition to known resistance genes pncA, rpsA, and panD.

Gene Information

Gene Name: clpC1
Allele: clpC1
Encodes: ATP-dependent ATPase involved in protein degradation
Source Database: Reslit
Mechanism: mutation-induced resistance
Confers Resistance To: Pyrazinamide
Organisms Tested In: • Mycobacterium tuberculosis H37Rv
• Mycobacterium tuberculosis H37Ra
Validation Method: whole-genome sequencing and Sanger DNA sequencing

2

Atypical Genetic Basis of Pyrazinamide Resistance in Monoresistant Mycobacterium tuberculosis.

PMID 33722890 · 2021

Gene Information

Gene Name: clpC1
Allele: clpC1
Encodes: AAA+ ATPase that acts as the chaperone for the cytoplasmic Clp protease
Source Database: Reslit
Mechanism: Mutations in the N terminus (Val63Ala) and promoter (clpC1p -C138) confer low-level pyrazinamide resistance
Confers Resistance To: Pyrazinamide
Organisms Tested In: • Mycobacterium tuberculosis
Validation Method: Long-read sequencing and phenotypic drug susceptibility testing

3

Overcoming the Challenges of Pyrazinamide Susceptibility Testing in Clinical Mycobacterium tuberculosis Isolates.

PMID 33972244 · 2021

Gene Information

Gene Name: clpC1
Allele: clpC1
Encodes: ATP-dependent ATPase
Source Database: Reslit
Mechanism: mutational resistance
Confers Resistance To: Pyrazinamide
Organisms Tested In: • Mycobacterium tuberculosis
Validation Method: whole-genome sequencing

4

Mutations in ClpC1 or ClpX subunit of caseinolytic protease confer resistance to ilamycins in mycobacteria.

PMID 40804467 · 2025

Mutations in clpC1 and clpX confer resistance to ilamycins (ILE and ILF) in mycobacteria. Specific mutations such as F80I, F80V, F80L, F80C, F2L, F2C, M1-FERF-F2, Q17R, H77D, L88R, L88P, F5I, F80S, and P30H were identified as responsible for resistance.

Gene Information

Gene Name: clpC1
Allele: clpC1
Encodes: protease subunit
Source Database: Reslit
Organisms Tested In: • Mycobacterium tuberculosis
• Mycobacterium abscessus
• Mycobacterium smegmatis
• Mycobacterium marinum
Validation Method: gene editing and mutational analysis