Developmental Brain Disorder Gene Database

LoF Variant Gene

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Tier

1

KMT2C

HGNC:13726 (protein-coding gene)

lysine methyltransferase 2C

Unique Cases:
16
Disorders:
ID, ASD, ADHD, SCZ, BD
Last Updated:
November 4, 2024

Summary
Cases
Publications
External

Gene Summary:

DBD Genes Classification
KMT2C is a High Confidence candidate gene classified as Tier 1. Tier 1 genes have three or more de novo pathogenic loss-of-function variants.
Gene Function
Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) (PubMed:25561738). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:22266653, PubMed:24081332, PubMed:25561738). Likely plays a redundant role with KMT2D in enriching H3K4me1 mark on primed and active enhancer elements (PubMed:240813... (Source: Uniprot)
Previous symbols
MLL3
Alias symbols
KIAA1506, HALR
Chromosomal Location
7q36.1
Genomic Coordinates
GRCh37:chr7:151832010-152133090
GRCh38:chr7:152134925-152436642
Associated Disorders
Intellectual Disability, Autism, Attention Deficit Hyperactivity Disorder

Predictive Scores:

HI Score (Decipher)

53.58

pLI (gnomAD)

1.00

LOEUF (gnomAD)

0.2

Classifications from External Sources:

SFARI Score (SFARI)

1

DDG2P Classification (DDG2P)

No Classification

ClinGen Classification (ClinGen)

Definitive1

GenCC Classification (GenCC)

Moderate1 Strong2 Definitive3

Publications:

Howrigan DP et. al., Exome sequencing in schizophrenia-affected parent-offspring trios reveals risk conferred by protein-coding de novo mutations., Nat Neurosci, 2020
Kataoka M et. al., Exome sequencing for bipolar disorder points to roles of de novo loss-of-function and protein-altering mutations., Mol Psychiatry, 2016
Coe BP et. al., Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity., Nat Genet, 2019
Girirajan S et. al., Refinement and discovery of new hotspots of copy-number variation associated with autism spectrum disorder., Am J Hum Genet, 2013
Guo H et. al., Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model., Mol Autism, 2018
Wang T et. al., De novo genic mutations among a Chinese autism spectrum disorder cohort., Nat Commun, 2016
Nishioka M et. al., Systematic analysis of exonic germline and postzygotic de novo mutations in bipolar disorder., Nat Commun, 2021
Brea-Fernández AJ et. al., Trio-based exome sequencing reveals a high rate of the de novo variants in intellectual disability., Eur J Hum Genet, 2022
Whitford W et. al., A novel 11 base pair deletion in KMT2C resulting in Kleefstra syndrome 2., Mol Genet Genomic Med, 2023
Elliott AM et. al., Genome-wide sequencing and the clinical diagnosis of genetic disease: The CAUSES study., HGG Adv, 2022
Faundes V et. al., Histone Lysine Methylases and Demethylases in the Landscape of Human Developmental Disorders., Am J Hum Genet, 2018

NCBI: Gene

Integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
NCBI: Gene

Gene Reviews

An international point-of-care resource for busy clinicians, provides clinically relevant and medically actionable information for inherited conditions in a standardized journal-style format, covering diagnosis, management, and genetic counseling for patients and their families.
Gene Reviews

DECIPHER

DECIPHER (DatabasE of genomiC varIation and Phenotype in Humans using Ensembl Resources) is an interactive web-based database which incorporates a suite of tools designed to aid the interpretation of genomic variants. DECIPHER enhances clinical diagnosis by retrieving information from a variety of bioinformatics resources relevant to the variant found in the patient.
DECIPHER

SFARI

SFARI Gene is an evolving online database designed to permit quick entrée into the genetics of autism, and to help researchers track the ever-expanding genetic risk factors that emerge in the literature.
SFARI

ClinGen

ClinGen is a National Institutes of Health (NIH)-funded resource dedicated to building an authoritative central resource that defines the clinical relevance of genes and variants for use in precision medicine and research.
ClinGen

GenCC

The GenCC DB provides information pertaining to the validity of gene-disease relationships, with a current focus on Mendelian diseases.
GenCC

gnomAD

The Genome Aggregation Database (gnomAD) is a resource developed by an international coalition of investigators, with the goal of aggregating and harmonizing both exome and genome sequencing data from a wide variety of large-scale sequencing projects, and making summary data available for the wider scientific community.
gnomAD
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