Gene

KMT2D

lysine methyltransferase 2D

Explore in graph →CI-GENE-00007119HGNC:7133 ENSG00000167548 NCBI 8085 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (15)

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

civicCuratedShowing 1–15 of 15 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
KMT2A Mutation + KMT2B Mutation + KMT2C Mutation + KMT2D mutationKMT2C KMT2D KMT2A KMT2B2
Immune Checkpoint Inhibitor

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 (1)

25 per page, newest first.

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

Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma.
· Nature · 2011 · PMID 21796119 · validated civic_curation pubmed

KMT2D Loss3
Carboplatin + Doxorubicin + OlaparibSubstitutes	Malignant Prostate Neoplasm	Predictive	D	Supports Sensitivity Response	2	submitted	EID12806 In prostate cancer (PCa) cell models (PC-3 and DU145; shRNA/siRNA knockdown of KMT2D), loss of enhancer activity markers H3K4me1/H3K27ac reduced FOXO3 protein abundance and DNA binding and suppressed … (full text at CIViC) PMID 31232159 · Lv et al., 2019 · Open in CIViC	civic
HDAC Inhibitor REC-2282	Kabuki SyndromeUNRESOLVED	Predictive	D	Supports Sensitivity Response	3	submitted	EID5993 In a mouse model of Kabuki syndrome with a heterozygous deletion in the gene encoding the lysine-specific methyltransferase 2D (Kmt2d), reduction in histone 4 acetylation and histone 3 lysine 4 trimet… (full text at CIViC) PMID 25273096 · Bjornsson et al., 2014 · Open in CIViC	civic
Afatinib + SHP2 InhibitorCombination	Lung Squamous Cell Carcinoma	Predictive	D	Supports Sensitivity Response	3	submitted	EID12776 In preclinical lung squamous cell carcinoma models, KMT2D loss increased sensitivity to SHP2 inhibition (SHP099) and pan-ERBB inhibition (afatinib). Enhanced growth suppression was observed in Kmt2d-d… (full text at CIViC) PMID 36525973 · Pan et al., 2023 · Open in CIViC	civic

KMT2D Loss3

Carboplatin + Doxorubicin + OlaparibSubstitutes

Malignant Prostate Neoplasm

Predictive

Supports Sensitivity Response

submitted

EID12806

In prostate cancer (PCa) cell models (PC-3 and DU145; shRNA/siRNA knockdown of KMT2D), loss of enhancer activity markers H3K4me1/H3K27ac reduced FOXO3 protein abundance and DNA binding and suppressed … (full text at CIViC)

PMID 31232159 · Lv et al., 2019 · Open in CIViC

civic

HDAC Inhibitor REC-2282

Kabuki SyndromeUNRESOLVED

Predictive

Supports Sensitivity Response

submitted

EID5993

In a mouse model of Kabuki syndrome with a heterozygous deletion in the gene encoding the lysine-specific methyltransferase 2D (Kmt2d), reduction in histone 4 acetylation and histone 3 lysine 4 trimet… (full text at CIViC)

PMID 25273096 · Bjornsson et al., 2014 · Open in CIViC

civic

Afatinib + SHP2 InhibitorCombination

Lung Squamous Cell Carcinoma

Predictive

Supports Sensitivity Response

submitted

EID12776

In preclinical lung squamous cell carcinoma models, KMT2D loss increased sensitivity to SHP2 inhibition (SHP099) and pan-ERBB inhibition (afatinib). Enhanced growth suppression was observed in Kmt2d-d… (full text at CIViC)

PMID 36525973 · Pan et al., 2023 · Open in CIViC

civic

KMT2D Loss-of-function4
(diagnostic)	Follicular Lymphoma	Diagnostic	B	Supports Positive	3	accepted	EID435 MLL2 was found to be the most frequently mutated gene in a sample of 31/35 follicular lymphoma patients and was not mutated in normal centroblast samples. Furthermore, MLL2 mutations were as frequentl… (full text at CIViC) PMID 21796119 · Morin et al., 2011 · Open in CIViC	civic
2-Deoxy-D-glucose	Lung Adenocarcinoma	Predictive	D	Supports Sensitivity Response	2	submitted	EID12778 In preclinical lung adenocarcinoma (LUAD) models, loss-of-function KMT2D (truncating/inactivating) was associated with greater sensitivity to glycolysis inhibition, most consistently 2-deoxy-D-glucose… (full text at CIViC) PMID 32243837 · Alam et al., 2020 · Open in CIViC	civic
Immune Checkpoint Inhibitor	Colorectal Adenocarcinoma	Predictive	B	Supports Sensitivity Response	3	submitted	EID12583 In a retrospective TCGA cohort of microsatellite-instable colorectal adenocarcinoma (n = 43; KMT2D LOF = 16, WT = 27), KMT2D loss of function was associated with higher TMB (p < 0.001), higher neoanti… (full text at CIViC) PMID 39578878 · Takemon et al., 2024 · Open in CIViC	civic
WRN Inhibitor HRO761 + WRN Inhibitor RO7589831Substitutes	Colorectal Adenocarcinoma	Predictive	D	Supports Sensitivity Response	2	submitted	EID12584 In microsatellite-instable (MSI) colorectal carcinoma cell-line assays, KMT2D loss of function (LOF) stratified sensitivity to WRN perturbation. In DepMap viability data, WRN knockout was lethal in MS… (full text at CIViC) PMID 39578878 · Takemon et al., 2024 · Open in CIViC	civic

KMT2D Loss-of-function4

(diagnostic)

Follicular Lymphoma

Diagnostic

Supports Positive

accepted

EID435

MLL2 was found to be the most frequently mutated gene in a sample of 31/35 follicular lymphoma patients and was not mutated in normal centroblast samples. Furthermore, MLL2 mutations were as frequentl… (full text at CIViC)

PMID 21796119 · Morin et al., 2011 · Open in CIViC

civic

2-Deoxy-D-glucose

Lung Adenocarcinoma

Predictive

Supports Sensitivity Response

submitted

EID12778

In preclinical lung adenocarcinoma (LUAD) models, loss-of-function KMT2D (truncating/inactivating) was associated with greater sensitivity to glycolysis inhibition, most consistently 2-deoxy-D-glucose… (full text at CIViC)

PMID 32243837 · Alam et al., 2020 · Open in CIViC

civic

Immune Checkpoint Inhibitor

Colorectal Adenocarcinoma

Predictive

Supports Sensitivity Response

submitted

EID12583

In a retrospective TCGA cohort of microsatellite-instable colorectal adenocarcinoma (n = 43; KMT2D LOF = 16, WT = 27), KMT2D loss of function was associated with higher TMB (p < 0.001), higher neoanti… (full text at CIViC)

PMID 39578878 · Takemon et al., 2024 · Open in CIViC

civic

WRN Inhibitor HRO761 + WRN Inhibitor RO7589831Substitutes

Colorectal Adenocarcinoma

Predictive

Supports Sensitivity Response

submitted

EID12584

In microsatellite-instable (MSI) colorectal carcinoma cell-line assays, KMT2D loss of function (LOF) stratified sensitivity to WRN perturbation. In DepMap viability data, WRN knockout was lethal in MS… (full text at CIViC)

PMID 39578878 · Takemon et al., 2024 · Open in CIViC

civic

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

civic

KMT2D mutation5
(oncogenic)	Diffuse Large B-Cell LymphomaCURATED_BROADER	Oncogenic	E	Supports Oncogenicity	4	submitted	EID11836 One of the most common mutations in DLBCL PMID 21796119 · Morin et al., 2011 · Open in CIViC	civic
〃	Burkitt Lymphoma	Oncogenic	E	Supports Oncogenicity	3	submitted	EID11835 More common in DLBCL but also mutated in BL PMID 30617194 · Grande et al., 2019 · Open in CIViC	civic
〃	Mantle Cell Lymphoma	Oncogenic	E	Supports Oncogenicity	3	submitted	EID11871 [the study] identified 25 significantly mutated genes, including known drivers such as ataxia-telangectasia mutated (ATM), cyclin D1 (CCND1), and the tumor suppressor TP53; mutated genes encoding the … (full text at CIViC) PMID 24145436 · Beà et al., 2013 · Open in CIViC	civic
〃	Mantle Cell Lymphoma	Oncogenic	E	Supports Oncogenicity	3	submitted	EID11892 Through a meta-analysis of exome and whole genome sequencing data, this study identified 18 genes that were significantly enriched for mutations in MCL (including KMT2D). PMID 32160292 · Pararajalingam et al., 2020 · Open in CIViC	civic
(prognostic)	Mantle Cell Lymphoma	Prognostic	E	Does Not Support Poor Outcome	3	submitted	EID11896 This study did not confirm a previous reported association between KMT2D mutation status and outcome (Supplemental Figure 5) PMID 32160292 · Pararajalingam et al., 2020 · Open in CIViC	civic

KMT2D mutation5

(oncogenic)

Diffuse Large B-Cell LymphomaCURATED_BROADER

Oncogenic

Supports Oncogenicity

submitted

EID11836

One of the most common mutations in DLBCL

PMID 21796119 · Morin et al., 2011 · Open in CIViC

civic

〃

Burkitt Lymphoma

Oncogenic

Supports Oncogenicity

submitted

EID11835

More common in DLBCL but also mutated in BL

PMID 30617194 · Grande et al., 2019 · Open in CIViC

civic

〃

Mantle Cell Lymphoma

Oncogenic

Supports Oncogenicity

submitted

EID11871

[the study] identified 25 significantly mutated genes, including known drivers such as ataxia-telangectasia mutated (ATM), cyclin D1 (CCND1), and the tumor suppressor TP53; mutated genes encoding the … (full text at CIViC)

PMID 24145436 · Beà et al., 2013 · Open in CIViC

civic

〃

Mantle Cell Lymphoma

Oncogenic

Supports Oncogenicity

submitted

EID11892

Through a meta-analysis of exome and whole genome sequencing data, this study identified 18 genes that were significantly enriched for mutations in MCL (including KMT2D).

PMID 32160292 · Pararajalingam et al., 2020 · Open in CIViC

civic

(prognostic)

Mantle Cell Lymphoma

Prognostic

Does Not Support Poor Outcome

submitted

EID11896

This study did not confirm a previous reported association between KMT2D mutation status and outcome (Supplemental Figure 5)

PMID 32160292 · Pararajalingam et al., 2020 · Open in CIViC

civic