Human Gene Module / Chromosome 12 / KMT2D

KMT2Dlysine methyltransferase 2D

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
13 / 13
Rare Variants / Common Variants
20 / 0
Aliases
-
Associated Syndromes
Kabuki syndrome 1, ASD, DD, ID, Kabuki syndrome 1, ASD, DD, ID, epilepsy/seizures
Chromosome Band
12q13.12
Associated Disorders
-
Relevance to Autism

Shangguan et al., 2025 assembled genotype and phenotype data for 9 affected individuals from 9 unrelated families with predicted deleterious KMT2D variants through literature (Parisi et al., 2015; Sertelik et al., 2016; Luo et al., 2021) and two web-based databases (ClinVar and DECIPHER); all 9 probands were diagnosed with autism and presented with intellectual disability and dysmorphic facial features. In the same report, the authors observed that selective knockdown of Kmt2d in the mouse hippocampus resulted in defects in social behaviors and increased repetitive behavior, as well as decreased excitatory and increased inhibitory synaptic transmission. De novo variants in the KMT2D gene, including a loss-of-function variant and several potentially deleterious missense variants, have also been identified in ASD probands from the Simons Simplex Collection, the SPARK cohort, the Autism Sequencing Consortium, the MSSNG cohort, and a Korean ASD cohort (Iossifov et al., 2014; Yuen et al., 2017; Krupp et al., 2017; Satterstrom et al., 2020; Zhou et al., 2022; Kim et al., 2024; Tan et al., 2024).

Molecular Function

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.

External Links
Gene CardPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser
Reports related to KMT2D (13 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support The contribution of de novo coding mutations to autism spectrum disorder Iossifov I et al. (2014) Yes -
2 Support - L Parisi et al. (2015) Yes -
3 Support Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder C Yuen RK et al. (2017) Yes -
4 Support - Mehmet Sertçelik et al. (2016) Yes -
5 Support Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder Krupp DR , et al. (2017) Yes -
6 Support Family-based exome sequencing and case-control analysis implicate CEP41 as an ASD gene Patowary A , et al. (2019) Yes -
7 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
8 Support - Jianhua Luo et al. (2021) Yes -
9 Support - Zhou X et al. (2022) Yes -
10 Support - Ana Karen Sandoval-Talamantes et al. (2023) Yes -
11 Support - Soo-Whee Kim et al. (2024) Yes -
12 Support - Senwei Tan et al. () Yes -
13 Primary - Huakun Shangguan et al. (2025) Yes -
Rare Variants   (20)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
C>T p.? splice_site_variant De novo - Simplex 39472663 Senwei Tan et al. ()
c.9397C>T p.Gln3133Ter stop_gained De novo - - 40883562 Huakun Shangguan et al. (2025)
c.181G>A p.Gly61Ser missense_variant De novo - - 31981491 Satterstrom FK et al. (2020)
c.1712G>A p.Arg571His missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.5356C>T p.Arg1786Cys missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.14653G>T p.Ala4885Ser missense_variant De novo - - 39334436 Soo-Whee Kim et al. (2024)
c.12066G>T p.Thr4022= synonymous_variant De novo - Unknown 35982159 Zhou X et al. (2022)
c.15928G>A p.Gly5310Arg missense_variant De novo - - 31981491 Satterstrom FK et al. (2020)
c.13398A>G p.Leu4466= synonymous_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.7753G>C p.Gly2585Arg missense_variant De novo - Simplex 28867142 Krupp DR , et al. (2017)
c.3103C>A p.Gln1035Lys missense_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.4389C>T p.Thr1463= synonymous_variant De novo - Multiplex 28263302 C Yuen RK et al. (2017)
c.16529A>G p.Tyr5510Cys missense_variant De novo - Simplex 25363768 Iossifov I et al. (2014)
c.13058delG p.Pro4353ArgfsTer31 frameshift_variant De novo - - 34487531 Jianhua Luo et al. (2021)
c.1530del p.Pro511LeufsTer419 frameshift_variant De novo - - 40883562 Huakun Shangguan et al. (2025)
c.6597del p.Pro2200LeufsTer64 frameshift_variant De novo - - 40883562 Huakun Shangguan et al. (2025)
c.1769dupT p.Met590fs frameshift_variant Familial Maternal - 40883562 Huakun Shangguan et al. (2025)
c.15634G>C p.Ala5212Pro missense_variant De novo - Simplex 28373809 Mehmet Sertçelik et al. (2016)
c.8156G>C p.Ser2719Thr missense_variant Familial - Extended multiplex 30664616 Patowary A , et al. (2019)
c.13885A>C p.Thr4629Pro missense_variant Unknown - - 38003033 Ana Karen Sandoval-Talamantes et al. (2023)
Common Variants  

No common variants reported.

Submit New Gene

Report an Error