KMT2D Loss-of-function

CI-VAR-00002522Explore in graph →CIViC 167

Curated evidence

Evidence by cancer (5 items)

Grouped by cancer context first, then therapy. The same variant can be sensitizing in one cancer and irrelevant in another — contexts are never merged. 50 items per page; a cancer group may continue on the next page.

civicCuratedShowing 1–5 of 5 evidence items across 4 cancer contexts on this page · levels, directions and significance as curated at the source; each row links to its CIViC record.

Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Colorectal Adenocarcinoma2
KMT2D Loss-of-function	Immune Checkpoint Inhibitor	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
KMT2D Loss-of-function	WRN Inhibitor HRO761 + WRN Inhibitor RO7589831Substitutes	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)

ClinVar

Clinical significance (0)

ClinVar interpretations are shown as structured records — significance, review status, star rating, conditions — never flattened into one word.

Data not yet available

No ClinVar interpretation attached to this variant.

Follicular Lymphoma1
KMT2D Loss-of-function	(diagnostic)	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

Lung Adenocarcinoma1
KMT2D Loss-of-function	2-Deoxy-D-glucose	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

Urothelial Carcinoma1
KMT2D Loss-of-function OR KMT2C Loss-of-function	Afatinib + GefitinibSubstitutes	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