KMT2D
lysine methyltransferase 2D, the group of PHD finger proteins|SET domain containing|Lysine methyltransferases
Basic information
Region (hg38): 12:49018975-49060794
Previous symbols: [ "TNRC21", "MLL2" ]
Links
Phenotypes
GenCC
Source:
- Kabuki syndrome 1 (Definitive), mode of inheritance: AD
- Kabuki syndrome 1 (Definitive), mode of inheritance: AD
- Kabuki syndrome (Supportive), mode of inheritance: AD
- choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome (Moderate), mode of inheritance: AD
- Kabuki syndrome 1 (Definitive), mode of inheritance: AD
- Kabuki syndrome 1 (Strong), mode of inheritance: AD
- branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome (Strong), mode of inheritance: AD
- Kabuki syndrome 1 (Definitive), mode of inheritance: AD
- choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome; Kabuki syndrome 1 | AD | Audiologic/Otolaryngologic; Cardiovascular; Endocrine; Renal | Branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome can include hearing loss, and early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Individuals have been described with endocrine anomalies including hypothyroidism and growth hormone deficiency, and awareness may allow medical management; In Kabuki syndrome, congenital heart defects, as well as arrhythmias, are frequent in affected individuals, and surveillance may allow early diagnosis and treatment; Individuals may have renal anomalies and/or vesicoureteral reflux, and screening for renal anomalies (eg, with ultrasound and functional testing) may allow measures to help monitor and preserve renal function | Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Cardiovascular; Craniofacial; Dental; Endocrine; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Ophthalmologic; Renal | 3067577; 8048822; 10190924; 11343317; 11665999; 12002156; 15108197; 15887282; 20711175; 21671394; 21607748; 21882399; 22126750; 23535010; 23913813; 29321794; 31949313; 32083401 |
ClinVar
This is a list of variants' phenotypes submitted to
- Kabuki_syndrome (4751 variants)
- not_provided (1534 variants)
- Kabuki_syndrome_1 (1424 variants)
- KMT2D-related_disorder (819 variants)
- Choanal_atresia-athelia-hypothyroidism-delayed_puberty-short_stature_syndrome (587 variants)
- Inborn_genetic_diseases (437 variants)
- not_specified (385 variants)
- Intellectual_disability (24 variants)
- See_cases (8 variants)
- Branchial_cleft_anomaly (6 variants)
- Autism_spectrum_disorder (4 variants)
- Microcephaly (3 variants)
- Seizure (2 variants)
- Lung_cancer (2 variants)
- Neurodevelopmental_disorder (2 variants)
- Dystonia,_early-onset,_and/or_spastic_paraplegia (2 variants)
- Lymphoma (2 variants)
- Eccrine_porocarcinoma (1 variants)
- Left_ventricular_noncompaction (1 variants)
- Abnormal_pinna_morphology (1 variants)
- Complement_component_C1s_deficiency (1 variants)
- Multiple_myeloma (1 variants)
- Rare_genetic_intellectual_disability (1 variants)
- Congenital_anomaly_of_kidney_and_urinary_tract (1 variants)
- Stenosis_of_the_external_auditory_canal (1 variants)
- Amblyopia (1 variants)
- Autism_spectrum_disorder_due_to_AUTS2_deficiency (1 variants)
- Choanal_atresia (1 variants)
- Neurodevelopmental_abnormality (1 variants)
- Smith-Magenis_Syndrome-like (1 variants)
- Dandy-Walker_syndrome (1 variants)
- Rubinstein_Taybi_like_syndrome (1 variants)
- Astrocytoma (1 variants)
- CHARGE_syndrome (1 variants)
- Strabismus (1 variants)
- Familial_thoracic_aortic_aneurysm_and_aortic_dissection (1 variants)
- Neurodevelopmental_delay (1 variants)
- Autism (1 variants)
- VISS_syndrome (1 variants)
- Abnormality_of_the_nervous_system (1 variants)
- Connective_tissue_nevi (1 variants)
- Male_infertility_with_spermatogenesis_disorder (1 variants)
- Microtia (1 variants)
- Vein_of_Galen_aneurysmal_malformation (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the KMT2D gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003482.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 42 | 1195 | 230 | 1477 | ||
| missense | 42 | 89 | 1899 | 1017 | 487 | 3534 |
| nonsense | 214 | 61 | 11 | 287 | ||
| start loss | 1 | 1 | ||||
| frameshift | 377 | 116 | 500 | |||
| splice donor/acceptor (+/-2bp) | 49 | 43 | 102 | |||
| Total | 689 | 313 | 1968 | 2214 | 717 |
Highest pathogenic variant AF is 0.000021027565
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| KMT2D | protein_coding | protein_coding | ENST00000301067 | 54 | 40800 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 3.55e-26 | 124655 | 0 | 21 | 124676 | 0.0000842 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.73 | 2541 | 3.13e+3 | 0.812 | 0.000188 | 35136 |
| Missense in Polyphen | 553 | 854.32 | 0.6473 | 9611 | ||
| Synonymous | -1.43 | 1365 | 1.30e+3 | 1.05 | 0.0000776 | 12026 |
| Loss of Function | 13.0 | 15 | 224 | 0.0669 | 0.0000122 | 2432 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000557 | 0.000485 |
| Ashkenazi Jewish | 0.000201 | 0.000199 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000448 | 0.0000442 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000656 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Histone methyltransferase. Methylates 'Lys-4' of histone H3 (H3K4me). H3K4me represents a specific tag for epigenetic transcriptional activation. Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription. {ECO:0000269|PubMed:16603732, ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:17851529}.;
- Disease
- DISEASE: Kabuki syndrome 1 (KABUK1) [MIM:147920]: A congenital mental retardation syndrome with additional features, including postnatal dwarfism, a peculiar facies characterized by long palpebral fissures with eversion of the lateral third of the lower eyelids, a broad and depressed nasal tip, large prominent earlobes, a cleft or high-arched palate, scoliosis, short fifth finger, persistence of fingerpads, radiographic abnormalities of the vertebrae, hands, and hip joints, and recurrent otitis media in infancy. {ECO:0000269|PubMed:20711175, ECO:0000269|PubMed:21280141, ECO:0000269|PubMed:21607748, ECO:0000269|PubMed:21658225, ECO:0000269|PubMed:21671394, ECO:0000269|PubMed:22126750, ECO:0000269|PubMed:23320472, ECO:0000269|PubMed:23913813, ECO:0000269|PubMed:24739679}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Cushing,s syndrome - Homo sapiens (human);Lysine degradation - Homo sapiens (human);Histone Modifications;Signaling by WNT;Signal Transduction;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;Chromatin organization;Transcriptional regulation by RUNX1;Formation of the beta-catenin:TCF transactivating complex;TCF dependent signaling in response to WNT
(Consensus)
Recessive Scores
- pRec
- 0.105
Intolerance Scores
- loftool
- rvis_EVS
- -5.29
- rvis_percentile_EVS
- 0.06
Haploinsufficiency Scores
- pHI
- 0.693
- hipred
- Y
- hipred_score
- 0.637
- ghis
- 0.608
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- gene_indispensability_score
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Kmt2d
- Phenotype
- behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; embryo phenotype; neoplasm; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); 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); hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); skeleton phenotype; immune system phenotype; homeostasis/metabolism phenotype; cellular phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; craniofacial phenotype; muscle phenotype;
Zebrafish Information Network
- Gene name
- kmt2d
- Affected structure
- chondrocyte
- Phenotype tag
- abnormal
- Phenotype quality
- position
Gene ontology
- Biological process
- oocyte growth;chromatin silencing;regulation of transcription, DNA-templated;positive regulation of cell population proliferation;positive regulation of intracellular estrogen receptor signaling pathway;response to estrogen;regulation of megakaryocyte differentiation;positive regulation of transcription by RNA polymerase II;oogenesis;histone H3-K4 methylation;beta-catenin-TCF complex assembly
- Cellular component
- nucleus;nucleoplasm;histone methyltransferase complex;MLL3/4 complex
- Molecular function
- DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;transcription coactivator activity;protein binding;histone-lysine N-methyltransferase activity;histone binding;histone methyltransferase activity (H3-K4 specific);transcription regulatory region DNA binding;metal ion binding