KDM6A

lysine demethylase 6A, the group of Lysine demethylases|Tetratricopeptide repeat domain containing

Basic information

Region (hg38): X:44873188-45112779

Previous symbols: [ "UTX" ]

Links

ENSG00000147050NCBI:7403OMIM:300128HGNC:12637Uniprot:O15550AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • Kabuki syndrome 2 (Strong), mode of inheritance: XL
  • Kabuki syndrome 2 (Strong), mode of inheritance: XL
  • Kabuki syndrome (Supportive), mode of inheritance: AD
  • Kabuki syndrome 2 (Definitive), mode of inheritance: XL
  • Kabuki syndrome 2 (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Kabuki syndrome 2XLCardiovascularThe condition can involve congenital cardiac anomalies, and awareness may allow early managementCardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic22197486; 23076834; 24633898

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KDM6A gene.

  • Kabuki_syndrome_2 (822 variants)
  • not_provided (357 variants)
  • Inborn_genetic_diseases (94 variants)
  • KDM6A-related_disorder (59 variants)
  • not_specified (40 variants)
  • Kabuki_syndrome_1 (12 variants)
  • Intellectual_disability (11 variants)
  • Malignant_tumor_of_urinary_bladder (9 variants)
  • Neurodevelopmental_disorder (2 variants)
  • See_cases (2 variants)
  • Prostate_cancer (2 variants)
  • CHARGE_syndrome (1 variants)
  • Anemia (1 variants)
  • Autism_spectrum_disorder (1 variants)
  • Kabuki_Syndrome_-_KDM6A (1 variants)
  • Tremor,_hereditary_essential,_6 (1 variants)
  • Primary_dilated_cardiomyopathy (1 variants)
  • Peripheral_precocious_puberty (1 variants)
  • Multiple_congenital_anomalies/dysmorphic_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KDM6A gene is commonly pathogenic or not. These statistics are base on transcript: NM_001291415.2. 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.

EffectPLPVUSLBBSum
synonymous
16
clinvar
140
clinvar
21
clinvar
177
missense
4
clinvar
19
clinvar
459
clinvar
61
clinvar
11
clinvar
554
nonsense
34
clinvar
12
clinvar
4
clinvar
50
start loss
0
frameshift
44
clinvar
11
clinvar
9
clinvar
64
splice donor/acceptor (+/-2bp)
14
clinvar
16
clinvar
8
clinvar
1
clinvar
39
Total 96 58 496 202 32

Highest pathogenic variant AF is 0.00000896282

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
KDM6Aprotein_codingprotein_codingENST00000377967 29239091
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.007.20e-7125723051257280.0000199
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.953175030.6300.00003559172
Missense in Polyphen45147.270.305562860
Synonymous0.09501861880.9910.00001372687
Loss of Function6.51457.00.07020.00000443926

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.00007220.0000544
Finnish0.000.00
European (Non-Finnish)0.00005020.0000352
Middle Eastern0.00007220.0000544
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Histone demethylase that specifically demethylates 'Lys- 27' of histone H3, thereby playing a central role in histone code (PubMed:17851529, PubMed:17713478, PubMed:17761849). Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-27' (PubMed:17851529, PubMed:17713478, PubMed:17761849). Plays a central role in regulation of posterior development, by regulating HOX gene expression (PubMed:17851529). Demethylation of 'Lys-27' of histone H3 is concomitant with methylation of 'Lys-4' of histone H3, and regulates the recruitment of the PRC1 complex and monoubiquitination of histone H2A (PubMed:17761849). Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression (By similarity). {ECO:0000250|UniProtKB:O70546, ECO:0000269|PubMed:17713478, ECO:0000269|PubMed:17761849, ECO:0000269|PubMed:17851529, ECO:0000269|PubMed:18003914}.;
Disease
DISEASE: Kabuki syndrome 2 (KABUK2) [MIM:300867]: 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:22197486}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Transcriptional misregulation in cancer - Homo sapiens (human);Mesodermal Commitment Pathway;Pathways Affected in Adenoid Cystic Carcinoma;HDMs demethylate histones;Chromatin modifying enzymes;Chromatin organization (Consensus)

Recessive Scores

pRec
0.168

Intolerance Scores

loftool
0.187
rvis_EVS
-0.07
rvis_percentile_EVS
48.78

Haploinsufficiency Scores

pHI
0.983
hipred
Y
hipred_score
0.729
ghis
0.525

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
H
gene_indispensability_pred
E
gene_indispensability_score
0.897

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Kdm6a
Phenotype
neoplasm; 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); normal phenotype; 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); respiratory system phenotype; embryo phenotype; skeleton phenotype; immune system 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); muscle phenotype; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype;

Zebrafish Information Network

Gene name
kdm6a
Affected structure
ceratobranchial cartilage
Phenotype tag
abnormal
Phenotype quality
decreased size

Gene ontology

Biological process
in utero embryonic development;neural tube closure;heart morphogenesis;respiratory system process;chromatin remodeling;positive regulation of gene expression;somite rostral/caudal axis specification;multicellular organism growth;mesodermal cell differentiation;notochord morphogenesis;histone H3-K4 methylation;oxidation-reduction process;canonical Wnt signaling pathway;histone H3-K27 demethylation;cardiovascular system development
Cellular component
nucleus;nucleoplasm;histone methyltransferase complex;MLL3/4 complex
Molecular function
RNA polymerase II proximal promoter sequence-specific DNA binding;chromatin binding;chromatin DNA binding;histone demethylase activity;identical protein binding;sequence-specific DNA binding;metal ion binding;dioxygenase activity;histone demethylase activity (H3-K27 specific)