KMT2D lysine methyltransferase 2D [Homo sapiens (human)] - Gene

Summary

Official Symbol: KMT2Dprovided by HGNC
Official Full Name: lysine methyltransferase 2Dprovided by HGNC
Primary source: HGNC:HGNC:7133
See related: Ensembl:ENSG00000167548 MIM:602113; AllianceGenome:HGNC:7133
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ALR; KMS; MLL2; MLL4; AAD10; BCAHH; KABUK1; TNRC21; CAGL114
Summary: The protein encoded by this gene is a histone methyltransferase that methylates the Lys-4 position of histone H3. The encoded protein is part of a large protein complex called ASCOM, which has been shown to be a transcriptional regulator of the beta-globin and estrogen receptor genes. Mutations in this gene have been shown to be a cause of Kabuki syndrome. [provided by RefSeq, Oct 2010]
Expression: Ubiquitous expression in bone marrow (RPKM 10.0), skin (RPKM 5.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 12q13.12

Exon count:: 55

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (49018978..49060794, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (48981150..49022967, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (49412761..49454577, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The histone methyltransferase KMT2D maintains cellular glucocorticoid responsiveness by shielding the glucocorticoid receptor from degradation.
Title: The histone methyltransferase KMT2D maintains cellular glucocorticoid responsiveness by shielding the glucocorticoid receptor from degradation.
Histone-methyltransferase KMT2D deficiency impairs the Fanconi anemia/BRCA pathway upon glycolytic inhibition in squamous cell carcinoma.
Title: Histone-methyltransferase KMT2D deficiency impairs the Fanconi anemia/BRCA pathway upon glycolytic inhibition in squamous cell carcinoma.
PI 3-Kinase and the Histone Methyl-Transferase KMT2D Collaborate to Induce Arp2/3-Dependent Migration of Mammary Epithelial Cells.
Title: PI 3-Kinase and the Histone Methyl-Transferase KMT2D Collaborate to Induce Arp2/3-Dependent Migration of Mammary Epithelial Cells.
Lysine Methyltransferase 2D Regulates Immune Response and Metastasis in Head and Neck Cancer.
Title: Lysine Methyltransferase 2D Regulates Immune Response and Metastasis in Head and Neck Cancer.
DNA methylation profiling in Kabuki syndrome: reclassification of germline KMT2D VUS and sensitivity in validating postzygotic mosaicism.
Title: DNA methylation profiling in Kabuki syndrome: reclassification of germline KMT2D VUS and sensitivity in validating postzygotic mosaicism.
Macular dystrophy in Kabuki syndrome due to de novo KMT2D variants: refining the phenotype with multimodal imaging and follow-up over 10 years: insight into pathophysiology.
Title: Macular dystrophy in Kabuki syndrome due to de novo KMT2D variants: refining the phenotype with multimodal imaging and follow-up over 10 years: insight into pathophysiology.
[Clinical and genetic characteristics of four children with Kabuki syndrome due to de novo variants of KMT2D gene].
Title: [Clinical and genetic characteristics of four children with Kabuki syndrome due to de novo variants of KMT2D gene].
KMT2D Deficiency Causes Sensorineural Hearing Loss in Mice and Humans.
Title: KMT2D Deficiency Causes Sensorineural Hearing Loss in Mice and Humans.
Hearing characteristics and otoradiological abnormalities in three patients with novel pathogenic variants of KMT2D-related Kabuki syndrome.
Title: Hearing characteristics and otoradiological abnormalities in three patients with novel pathogenic variants of KMT2D-related Kabuki syndrome.
EBF2 Links KMT2D-Mediated H3K4me1 to Suppress Pancreatic Cancer Progression via Upregulating KLLN.
Title: EBF2 Links KMT2D-Mediated H3K4me1 to Suppress Pancreatic Cancer Progression via Upregulating KLLN.

Submit: New GeneRIF Correction See all GeneRIFs (170)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Choanal atresia-athelia-hypothyroidism-delayed puberty-short stature syndrome MedGen: C5680310 OMIM: 620186 GeneReviews: Not available	Compare labs
Kabuki syndrome 1 MedGen: CN030661 OMIM: 147920 GeneReviews: Kabuki Syndrome	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2020-01-23) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2020-01-23) ClinGen Genome Curation PagePubMed

Variation

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See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-T90896 (e-PCR)
- UniSTS:54037

WIAF-1691 (e-PCR)
- UniSTS:29549

HSC1JE012 (e-PCR)
- UniSTS:81060

TKY027 (e-PCR)
- UniSTS:503992

TKY025 (e-PCR)
- UniSTS:504016

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	NAS Non-traceable Author Statement more info	PubMed
enables histone H3K4 methyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables histone H3K4 methyltransferase activity	ISS Inferred from Sequence or Structural Similarity more info
enables histone H3K4 methyltransferase activity	TAS Traceable Author Statement more info
enables histone H3K4 monomethyltransferase activity	IEA Inferred from Electronic Annotation more info
enables histone H3K4 trimethyltransferase activity	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transcription cis-regulatory region binding	IDA Inferred from Direct Assay more info	PubMed
enables transcription coactivator activity	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in beta-catenin-TCF complex assembly	TAS Traceable Author Statement more info
involved_in heterochromatin formation	ISS Inferred from Sequence or Structural Similarity more info
involved_in methylation	IEA Inferred from Electronic Annotation more info
involved_in oocyte growth	ISS Inferred from Sequence or Structural Similarity more info
involved_in oogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of intracellular estrogen receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of DNA-templated transcription	NAS Non-traceable Author Statement more info	PubMed
involved_in response to estrogen	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
part_of MLL3/4 complex	IBA Inferred from Biological aspect of Ancestor more info
part_of MLL3/4 complex	IDA Inferred from Direct Assay more info	PubMed
part_of MLL3/4 complex	IPI Inferred from Physical Interaction more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: histone-lysine N-methyltransferase 2D

Names: ALL1-related protein; Kabuki make-up syndrome; histone-lysine N-methyltransferase MLL2; lysine (K)-specific methyltransferase 2D; lysine N-methyltransferase 2D; myeloid/lymphoid or mixed-lineage leukemia 2; trinucleotide repeat containing 21

NP_003473.3

EC 2.1.1.364

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_027827.1 RefSeqGene

Range

5001..41350

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_003482.4 → NP_003473.3 histone-lysine N-methyltransferase 2D

See identical proteins and their annotated locations for NP_003473.3

Status: REVIEWED

Source sequence(s)

AC011603

Consensus CDS

CCDS44873.1

UniProtKB/Swiss-Prot

O14686, O14687

UniProtKB/TrEMBL

A0A8I5KSG1

Related

ENSP00000301067.7, ENST00000301067.12

Conserved Domains (11) summary

smart00398
Location:2021 → 2072

HMG; high mobility group

smart00542
Location:5240 → 5327

FYRC; FY-rich domain, C-terminal region

smart00317
Location:5397 → 5519

SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain

cd15509
Location:228 → 273

PHD1_KMT2C_like; PHD finger 1 found in Histone-lysine N-methyltransferase 2C (KMT2C) and 2D (KMT2D)

cd15513
Location:1429 → 1475

PHD5_KMT2C_like; PHD finger 5 found in Histone-lysine N-methyltransferase 2C (KMT2C) and PHD finger 4 found in KMT2D

cd15597
Location:1378 → 1428

PHD3_KMT2D; PHD finger 3 found in Histone-lysine N-methyltransferase 2D (KMT2D)

cd15601
Location:1506 → 1556

PHD5_KMT2D; PHD finger 5 found in Histone-lysine N-methyltransferase 2D (KMT2D)

cd15695
Location:134 → 217

ePHD1_KMT2D; Extended PHD finger 1 found in histone-lysine N-methyltransferase 2D (KMT2D)

cd15698
Location:5032 → 5138

ePHD2_KMT2D; Extended PHD finger 2 found in histone-lysine N-methyltransferase 2D (KMT2D)

pfam05964
Location:5182 → 5232

FYRN; F/Y-rich N-terminus

cl22851
Location:275 → 320

PHD_SF; PHD finger superfamily