KDM6B

lysine demethylase 6B, the group of Lysine demethylases

Basic information

Region (hg38): 17:7834217-7854796

Previous symbols: [ "JMJD3" ]

Links

ENSG00000132510 ∙ NCBI:23135 ∙ OMIM:611577 ∙ HGNC:29012 ∙ Uniprot:O15054 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities (Strong), mode of inheritance: AD
• neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities (Strong), mode of inheritance: AD
• neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities (Strong), mode of inheritance: AD
• syndromic intellectual disability (Limited), mode of inheritance: AR
• syndromic intellectual disability (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Stolerman neurodevelopmental syndrome	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	31124279

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KDM6B gene.

• Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities (10 variants)
• not provided (9 variants)
• Inborn genetic diseases (2 variants)
• Neurodevelopmental abnormality (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KDM6B gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	57	8	68
missense		7	198	43	13	261
nonsense	10	6	5			21
start loss						0
frameshift	7	3	8			18
inframe indel			10	7	9	26
splice donor/acceptor (+/-2bp)		4	1			5
splice region	1		6	6	1	14
non coding			2	2	1	5
Total	17	20	227	109	31

Variants in KDM6B

This is a list of pathogenic ClinVar variants found in the KDM6B region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-7845559-A-G		Inborn genetic diseases	Uncertain significance (Oct 05, 2023)
17-7845582-GC-G		Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities	Likely pathogenic (Dec 27, 2021)
17-7845591-G-T			Uncertain significance (May 05, 2022)
17-7845595-G-A		KDM6B-related disorder	Likely benign (Jan 27, 2023)
17-7845609-C-T		KDM6B-related disorder	Uncertain significance (Aug 13, 2024)
17-7845616-G-A			Uncertain significance (Feb 01, 2024)
17-7845634-C-T		Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities	Uncertain significance (May 04, 2022)
17-7845649-C-T			Uncertain significance (Jan 21, 2020)
17-7845664-C-T		KDM6B-related disorder • Inborn genetic diseases	Uncertain significance (Mar 18, 2024)
17-7845670-G-C		Inborn genetic diseases	Likely benign (May 31, 2023)
17-7845864-C-G			Likely benign (Apr 16, 2018)
17-7845870-A-G		Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities	Likely pathogenic (Sep 09, 2022)
17-7845871-G-A		Inborn genetic diseases • Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities	Likely pathogenic (Jul 05, 2019)
17-7845872-A-G		KDM6B-related disorder	Likely benign (Jan 23, 2023)
17-7845894-C-T		Inborn genetic diseases	Uncertain significance (Oct 03, 2022)
17-7845897-C-T		Inborn genetic diseases	Uncertain significance (Jul 30, 2024)
17-7845898-C-G		Inborn genetic diseases	Uncertain significance (Dec 28, 2023)
17-7845899-G-A		KDM6B-related disorder	Benign (Dec 13, 2018)
17-7845916-C-T			Uncertain significance (Dec 16, 2022)
17-7845917-C-T			Likely benign (Apr 24, 2018)
17-7845918-C-A			Uncertain significance (Nov 08, 2022)
17-7845918-C-G		Inborn genetic diseases	Uncertain significance (Apr 12, 2022)
17-7845918-C-T		Inborn genetic diseases	Likely benign (Sep 17, 2021)
17-7845931-G-A		Inborn genetic diseases	Uncertain significance (Mar 19, 2024)
17-7845954-C-T		Inborn genetic diseases	Uncertain significance (Sep 17, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KDM6B	protein_coding	protein_coding	ENST00000254846	19	14893

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	3.34e-8	125730	0	17	125747	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.32	924	1.04e+3	0.885	0.0000708	10584
Missense in Polyphen		59	195.02	0.30253		2094
Synonymous	-5.07	570	435	1.31	0.0000293	3740
Loss of Function	7.02	4	65.2	0.0613	0.00000402	677

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000325	0.000304
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000164	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.0000650	0.0000527
Middle Eastern	0.000164	0.000163
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Histone demethylase that specifically demethylates 'Lys- 27' of histone H3, thereby playing a central role in histone code (PubMed:17825402, PubMed:17851529, PubMed:17713478, PubMed:18003914). Demethylates trimethylated and dimethylated H3 'Lys-27' (PubMed:17825402, PubMed:17851529, PubMed:17713478, PubMed:18003914). Plays a central role in regulation of posterior development, by regulating HOX gene expression (PubMed:17851529). Involved in inflammatory response by participating in macrophage differentiation in case of inflammation by regulating gene expression and macrophage differentiation (PubMed:17825402). Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression by acting as a link between T-box factors and the SMARCA4-containing SWI/SNF remodeling complex (By similarity). {ECO:0000250|UniProtKB:Q5NCY0, ECO:0000269|PubMed:17713478, ECO:0000269|PubMed:17825402, ECO:0000269|PubMed:17851529, ECO:0000269|PubMed:18003914, ECO:0000269|PubMed:28262558}.
• Pathway: Oxidative Stress Induced Senescence;Pathways Affected in Adenoid Cystic Carcinoma;Oxidative Stress Induced Senescence;Cellular Senescence;Cellular responses to stress;HDMs demethylate histones;Chromatin modifying enzymes;Cellular responses to external stimuli;Chromatin organization (Consensus)

Recessive Scores

• pRec: 0.127

Intolerance Scores

• loftool: 0.200
• rvis_EVS: -1.32
• rvis_percentile_EVS: 4.79

Haploinsufficiency Scores

• pHI: 0.206
• hipred: Y
• hipred_score: 0.572
• ghis: 0.514

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.609

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Kdm6b
• Phenotype: skeleton phenotype; immune system phenotype; limbs/digits/tail 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); reproductive system phenotype; 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); hematopoietic system phenotype; respiratory system phenotype; cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: kdm6bb
• Affected structure: definitive hemopoiesis
• Phenotype tag: abnormal
• Phenotype quality: disrupted

Gene ontology

• Biological process: inflammatory response to antigenic stimulus;chromatin remodeling;response to activity;hippocampus development;cell fate commitment;endothelial cell differentiation;positive regulation of transcription by RNA polymerase II;mesodermal cell differentiation;cardiac muscle cell differentiation;oxidation-reduction process;response to fungicide;cellular response to hydrogen peroxide;histone H3-K27 demethylation;positive regulation of cold-induced thermogenesis
• Cellular component: nucleus;nucleoplasm;MLL3/4 complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;chromatin binding;protein binding;beta-catenin binding;chromatin DNA binding;histone demethylase activity;sequence-specific DNA binding;metal ion binding;dioxygenase activity;histone demethylase activity (H3-K27 specific)