Gene

KMT2C

lysine methyltransferase 2C

Explore in graph →CI-GENE-00007113HGNC:13726 ENSG00000055609 NCBI 58508 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (9)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 1–9 of 9 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
KMT2C Loss1
Aromatase Inhibitor	Malignant Breast Neoplasm	Predictive	B	Supports Resistance	3	accepted	EID6484

Cohorts

Alteration frequency by cohort (200)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved200 cohort rows (showing 50, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Cutaneous Squamous Cell Carcinoma (UOW, Front Oncol 2022) cscc_ranson_2022	Skin Squamous Cell Carcinoma	Ssm

Literature

Linked publications (3)

25 per page, newest first.

pubmedPublishedShowing 1–3 of 3 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

KMT2A/C mutations function as a potential predictive biomarker for immunotherapy in solid tumors.
· Biomark Res · 2020 · PMID 33298164 · validated civic_curation pubmed
Mutational landscape of aggressive cutaneous squamous cell carcinoma.
· Clin Cancer Res · 2014 · PMID 25303977 · validated civic_curation pubmed
KMT2C mediates the estrogen dependence of breast cancer through regulation of ERα enhancer function.
· Oncogene · 2018 · PMID 29755131 · validated civic_curation pubmed

KMT2C Loss-of-function2
(functional)	—UNRESOLVED	Functional	B	Supports Loss Of Function	2	submitted	EID12772 In a bladder cancer cohort with matched tumor–normal samples (n = 104), KMT2C expression was significantly reduced in tumors compared to normal tissue (71/104 pairs; p < 0.001). shRNA-mediated KMT2C … (full text at CIViC) PMID 30665945 · Rampias et al., 2019 · Open in CIViC	civic
Olaparib	Bladder Carcinoma	Predictive	D	Supports Sensitivity Response	2	submitted	EID12773 In preclinical xenograft models derived from KMT2C-deficient tumors (HTB9 BC, H1437 NSCLC, T84 COAD, Cal-33 HNSCC), PARP1/2 inhibition with olaparib significantly reduced tumor growth compared to KMT2… (full text at CIViC) PMID 30665945 · Rampias et al., 2019 · Open in CIViC	civic

KMT2C Loss-of-function2

(functional)

—UNRESOLVED

Functional

Supports Loss Of Function

submitted

EID12772

In a bladder cancer cohort with matched tumor–normal samples (n = 104), KMT2C expression was significantly reduced in tumors compared to normal tissue (71/104 pairs; p < 0.001). shRNA-mediated KMT2C … (full text at CIViC)

PMID 30665945 · Rampias et al., 2019 · Open in CIViC

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Olaparib

Bladder Carcinoma

Predictive

Supports Sensitivity Response

submitted

EID12773

In preclinical xenograft models derived from KMT2C-deficient tumors (HTB9 BC, H1437 NSCLC, T84 COAD, Cal-33 HNSCC), PARP1/2 inhibition with olaparib significantly reduced tumor growth compared to KMT2… (full text at CIViC)

PMID 30665945 · Rampias et al., 2019 · Open in CIViC

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KMT2C Mutation2
(prognostic)	Skin Squamous Cell Carcinoma	Prognostic	B	Supports Poor Outcome	3	accepted	EID1696 Evaluation of 39 aggressive cutaneous squamous cell carcinomas revealed that tumors with a KMT2C mutation were 5x more likely to invade the bone (53% versus 10%; p=0.008). Patients with KMT2C mutatio… (full text at CIViC) PMID 25303977 · Pickering et al., 2014 · Open in CIViC	civic
(oncogenic)	Diffuse Large B-Cell LymphomaCURATED_BROADER	Oncogenic	E	Supports Oncogenicity	2	submitted	EID11959 The rate of KMT2C/MLL3 mutations reported in DLBCL was above 20% in the Zhang study but much lower in other studies (around 5%). Although the mutations do continue to be observed, the relevance and fr… (full text at CIViC) PMID 23292937 · Zhang et al., 2013 · Open in CIViC	civic

KMT2C Mutation2

(prognostic)

Skin Squamous Cell Carcinoma

Prognostic

Supports Poor Outcome

accepted

EID1696

Evaluation of 39 aggressive cutaneous squamous cell carcinomas revealed that tumors with a KMT2C mutation were 5x more likely to invade the bone (53% versus 10%; p=0.008). Patients with KMT2C mutatio… (full text at CIViC)

PMID 25303977 · Pickering et al., 2014 · Open in CIViC

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(oncogenic)

Diffuse Large B-Cell LymphomaCURATED_BROADER

Oncogenic

Supports Oncogenicity

submitted

EID11959

The rate of KMT2C/MLL3 mutations reported in DLBCL was above 20% in the Zhang study but much lower in other studies (around 5%). Although the mutations do continue to be observed, the relevance and fr… (full text at CIViC)

PMID 23292937 · Zhang et al., 2013 · Open in CIViC

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KMT2A Mutation + KMT2C MutationKMT2C KMT2A1
Immunotherapy	Malignant NeoplasmALIAS	Predictive	B	Supports Sensitivity Response	4	accepted	EID12031 This study examined the role of KMT2A/C mutations as a potential biomarker for predicting the effectiveness of immunotherapy. In the primary ICI-treated cohort (n = 546), the researchers observed that… (full text at CIViC) PMID 33298164 · Zhang et al., 2020 · Open in CIViC	civic

KMT2A Mutation + KMT2C MutationKMT2C KMT2A1

Immunotherapy

Malignant NeoplasmALIAS

Predictive

Supports Sensitivity Response

accepted

EID12031

This study examined the role of KMT2A/C mutations as a potential biomarker for predicting the effectiveness of immunotherapy. In the primary ICI-treated cohort (n = 546), the researchers observed that… (full text at CIViC)

PMID 33298164 · Zhang et al., 2020 · Open in CIViC

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KMT2A Mutation + KMT2B Mutation + KMT2C Mutation + KMT2D mutationKMT2C KMT2D KMT2A KMT2B2
Immune Checkpoint Inhibitor	Melanoma	Predictive	B	Supports Sensitivity Response	2	submitted	EID12592 In a retrospective pan-cancer analysis of four immune checkpoint therapy (ICT)–treated cohorts (melanoma n = 287; NSCLC n = 131; total n = 418), KMT2 family mutations were associated with improved ICT… (full text at CIViC) PMID 33653367 · Zhang et al., 2021 · Open in CIViC	civic
〃	Lung Non-Small Cell CarcinomaCURATED_BROADER	Predictive	B	Supports Sensitivity Response	2	submitted	EID12593 In a retrospective pan-cancer analysis of four immune checkpoint therapy (ICT)–treated cohorts (melanoma n = 287; NSCLC n = 131; total n = 418), KMT2 family mutations were associated with improved ICT… (full text at CIViC) PMID 33653367 · Zhang et al., 2021 · Open in CIViC	civic

KMT2A Mutation + KMT2B Mutation + KMT2C Mutation + KMT2D mutationKMT2C KMT2D KMT2A KMT2B2

Immune Checkpoint Inhibitor

Melanoma

Predictive

Supports Sensitivity Response

submitted

EID12592

In a retrospective pan-cancer analysis of four immune checkpoint therapy (ICT)–treated cohorts (melanoma n = 287; NSCLC n = 131; total n = 418), KMT2 family mutations were associated with improved ICT… (full text at CIViC)

PMID 33653367 · Zhang et al., 2021 · Open in CIViC

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〃

Lung Non-Small Cell CarcinomaCURATED_BROADER

Predictive

Supports Sensitivity Response

submitted

EID12593

PMID 33653367 · Zhang et al., 2021 · Open in CIViC

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KMT2C Loss-of-function + KMT2D Loss-of-functionKMT2D KMT2C1
Afatinib + GefitinibSubstitutes	Urothelial Carcinoma	Predictive	D	Supports Sensitivity Response	2	submitted	EID12775 In preclinical urothelial carcinoma (UC) models, combined loss of KMT2C/KMT2D increased sensitivity to EGFR inhibitors, with Kmt2c/d-deficient cells showing significantly reduced IC50 values for afati… (full text at CIViC) PMID 39806204 · Wang et al., 2025 · Open in CIViC	civic

KMT2C Loss-of-function + KMT2D Loss-of-functionKMT2D KMT2C1

Afatinib + GefitinibSubstitutes

Urothelial Carcinoma

Predictive

Supports Sensitivity Response

submitted

EID12775

In preclinical urothelial carcinoma (UC) models, combined loss of KMT2C/KMT2D increased sensitivity to EGFR inhibitors, with Kmt2c/d-deficient cells showing significantly reduced IC50 values for afati… (full text at CIViC)

PMID 39806204 · Wang et al., 2025 · Open in CIViC

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