KMT2C

lysine methyltransferase 2C, the group of PHD finger proteins|SET domain containing|Lysine methyltransferases

Basic information

Region (hg38): 7:152134922-152436644

Previous symbols: [ "MLL3" ]

Links

ENSG00000055609NCBI:58508OMIM:606833HGNC:13726Uniprot:Q8NEZ4AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • Kleefstra syndrome 2 (Moderate), mode of inheritance: AD
  • Kleefstra syndrome 2 (Strong), mode of inheritance: AD
  • syndromic intellectual disability (Definitive), mode of inheritance: AD
  • Kleefstra syndrome 2 (Definitive), mode of inheritance: AD
  • Kleefstra syndrome 2 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Kleefstra syndrome 2ADGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCraniofacial; Musculoskeletal; Neurologic22726846; 29069077

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KMT2C gene.

  • KMT2C-related NDD (39 variants)
  • not provided (20 variants)
  • Kleefstra syndrome 2 (17 variants)
  • Inborn genetic diseases (6 variants)
  • Kleefstra syndrome 1 (1 variants)
  • Neurodevelopmental abnormality (1 variants)
  • Kleefstra syndrome (1 variants)
  • Neurodevelopmental disorder (1 variants)
  • Neurodevelopmental delay (1 variants)
  • Autism spectrum disorder (1 variants)
  • Kleefstra syndrome due to a point mutation (1 variants)
  • Intellectual disability (1 variants)
  • Rare genetic intellectual disability (1 variants)
  • KMT2C-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KMT2C gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
3
clinvar
222
clinvar
85
clinvar
310
missense
12
clinvar
691
clinvar
286
clinvar
94
clinvar
1083
nonsense
25
clinvar
17
clinvar
4
clinvar
1
clinvar
2
clinvar
49
start loss
0
frameshift
48
clinvar
18
clinvar
2
clinvar
68
inframe indel
15
clinvar
1
clinvar
16
splice donor/acceptor (+/-2bp)
4
clinvar
7
clinvar
4
clinvar
1
clinvar
1
clinvar
17
splice region
2
18
48
18
86
non coding
2
clinvar
90
clinvar
25
clinvar
117
Total 77 54 721 601 207

Variants in KMT2C

This is a list of pathogenic ClinVar variants found in the KMT2C region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
7-152136861-C-A Autism spectrum disorder Likely benign (-)2430043
7-152136891-C-G Uncertain significance (May 03, 2024)3373233
7-152136899-A-T Kleefstra syndrome 2 Uncertain significance (Oct 05, 2022)872355
7-152136909-T-G Benign (May 11, 2023)3011549
7-152136911-T-C Uncertain significance (Jul 24, 2023)3361498
7-152136917-T-C Uncertain significance (Jun 26, 2019)1306759
7-152136932-C-T Likely benign (May 01, 2023)2193125
7-152136934-G-A Likely benign (Aug 30, 2024)2898459
7-152138827-C-T Uncertain significance (Jun 01, 2023)3362170
7-152138860-A-G Likely benign (Jun 20, 2022)1498934
7-152138869-G-A Likely benign (Dec 27, 2022)2824185
7-152138874-A-G Likely benign (Jan 06, 2025)1569606
7-152138879-T-C Uncertain significance (Dec 06, 2019)1310711
7-152138887-C-T Kleefstra syndrome 2 Uncertain significance (Jan 04, 2024)1704687
7-152138889-C-T Likely benign (Jan 01, 2024)1639812
7-152138896-T-C KMT2C-related disorder Uncertain significance (Dec 19, 2022)2635223
7-152138902-T-C Kleefstra syndrome 2 Uncertain significance (Sep 20, 2022)2661909
7-152138908-C-T Likely benign (May 15, 2024)2993823
7-152138915-C-T Benign (Nov 07, 2024)1600332
7-152139169-G-A not specified Likely benign (Mar 14, 2025)1988743
7-152139171-T-A not specified Likely benign (Mar 19, 2024)3233864
7-152139172-C-G Likely benign (Dec 27, 2021)2062788
7-152139175-C-A Likely benign (Dec 27, 2021)2062791
7-152139179-G-A Likely benign (Jul 17, 2023)1569665
7-152139191-G-A Likely benign (Jul 01, 2024)3257047

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
KMT2Cprotein_codingprotein_codingENST00000262189 59301081
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.003.49e-2312478409641257480.00384
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.1422262.53e+30.8800.00013331901
Missense in Polyphen6801069.80.6356213392
Synonymous-0.5309198991.020.00004749586
Loss of Function12.6182190.08210.00001222645

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.01020.00894
Ashkenazi Jewish0.002430.00218
East Asian0.002690.00229
Finnish0.002460.00222
European (Non-Finnish)0.003790.00331
Middle Eastern0.002690.00229
South Asian0.01010.00840
Other0.004600.00408

dbNSFP

Source: dbNSFP

Function
FUNCTION: Histone methyltransferase. Methylates 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Central component of the MLL2/3 complex, a coactivator complex of nuclear receptors, involved in transcriptional coactivation. KMT2C/MLL3 may be a catalytic subunit of this complex. May be involved in leukemogenesis and developmental disorder. {ECO:0000269|PubMed:17500065}.;
Disease
DISEASE: Kleefstra syndrome 2 (KLEFS2) [MIM:617768]: A form of Kleefstra syndrome, an autosomal dominant disease characterized by variable mental retardation, psychomotor developmental delay, seizures, behavioral abnormalities, and facial dysmorphisms. {ECO:0000269|PubMed:22726846, ECO:0000269|PubMed:29069077}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Lysine degradation - Homo sapiens (human);Histone Modifications;Pathways Affected in Adenoid Cystic Carcinoma;Gene expression (Transcription);Generic Transcription Pathway;PKMTs methylate histone lysines;RNA Polymerase II Transcription;RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function;Chromatin modifying enzymes;Lysine metabolism;Chromatin organization;Transcriptional regulation by RUNX1 (Consensus)

Recessive Scores

pRec
0.106

Intolerance Scores

loftool
rvis_EVS
-2.52
rvis_percentile_EVS
0.91

Haploinsufficiency Scores

pHI
0.469
hipred
Y
hipred_score
0.683
ghis
0.600

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
essential_gene_gene_trap
H
gene_indispensability_pred
gene_indispensability_score

Gene Damage Prediction

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

Mouse Genome Informatics

Gene name
Kmt2c
Phenotype
cellular phenotype; growth/size/body region phenotype; vision/eye phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);

Gene ontology

Biological process
regulation of megakaryocyte differentiation;positive regulation of transcription by RNA polymerase II;histone H3-K4 methylation
Cellular component
nucleus;nucleoplasm;histone methyltransferase complex;MLL3/4 complex
Molecular function
DNA binding;transcription coactivator activity;RNA binding;protein binding;transferase activity, transferring acyl groups;histone-lysine N-methyltransferase activity;histone binding;histone methyltransferase activity (H3-K4 specific);metal ion binding