KDM4B

lysine demethylase 4B, the group of Lysine demethylases|Tudor domain containing

Basic information

Region (hg38): 19:4969112-5153598

Previous symbols: [ "JMJD2B" ]

Links

ENSG00000127663 ∙ NCBI:23030 ∙ OMIM:609765 ∙ HGNC:29136 ∙ Uniprot:O94953 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• syndromic intellectual disability (Supportive), mode of inheritance: AD
• complex neurodevelopmental disorder (Strong), mode of inheritance: AD
• intellectual developmental disorder, autosomal dominant 65 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 65	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision making, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	33232677

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KDM4B gene.

• not provided (85 variants)
• Inborn genetic diseases (44 variants)
• Intellectual developmental disorder, autosomal dominant 65 (21 variants)
• KDM4B-related condition (7 variants)
• not specified (2 variants)
• See cases (2 variants)
• Neurodevelopmental disorder (1 variants)
• Neurodevelopmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KDM4B 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				21	8	29
missense		2	86	8		96
nonsense	2	2				4
start loss			1			1
frameshift		4		1		5
inframe indel			4	1		5
splice donor/acceptor (+/-2bp)		4	1			5
splice region			2	1	2	5
non coding				2	3	5
Total	2	12	92	33	11

Highest pathogenic variant AF is 0.00000657

Variants in KDM4B

This is a list of pathogenic ClinVar variants found in the KDM4B region.

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

Position	Type	Phenotype	Significance	ClinVar
19-5032892-T-C		Intellectual developmental disorder, autosomal dominant 65	Uncertain significance (May 03, 2023)
19-5032916-A-G			Uncertain significance (Feb 16, 2022)
19-5032941-G-A			Likely benign (Feb 01, 2023)
19-5032945-C-T		KDM4B-related disorder	Uncertain significance (Sep 05, 2023)
19-5032946-G-A		Inborn genetic diseases	Uncertain significance (Aug 05, 2023)
19-5032955-T-C		KDM4B-related disorder	Uncertain significance (Dec 18, 2023)
19-5032976-A-G		not specified	Uncertain significance (Nov 04, 2022)
19-5032982-A-G			Uncertain significance (Mar 09, 2023)
19-5039838-C-G			Uncertain significance (Mar 09, 2023)
19-5039861-C-T		Intellectual developmental disorder, autosomal dominant 65 • not specified	Uncertain significance (Mar 18, 2024)
19-5039863-C-T		Inborn genetic diseases	Uncertain significance (Nov 17, 2021)
19-5039889-C-T			Likely benign (Feb 01, 2023)
19-5039901-G-A			Likely benign (Feb 01, 2023)
19-5039903-C-T			Uncertain significance (Mar 31, 2023)
19-5039982-C-T		Syndromic global developmental delay	Likely pathogenic (Oct 30, 2020)
19-5040007-G-A		Intellectual developmental disorder, autosomal dominant 65	Uncertain significance (Jan 14, 2022)
19-5041150-C-T		KDM4B-related disorder	Uncertain significance (Aug 31, 2023)
19-5041167-T-C			Benign (Sep 17, 2019)
19-5041169-A-G		KDM4B-related disorder	Uncertain significance (Dec 09, 2022)
19-5041178-G-A		See cases	Uncertain significance (Dec 20, 2021)
19-5041252-G-A		Inborn genetic diseases	Likely pathogenic (Sep 19, 2023)
19-5041252-G-GT			Uncertain significance (Sep 26, 2019)
19-5041256-G-T		Inborn genetic diseases	Uncertain significance (Feb 22, 2023)
19-5047472-A-G			Benign/Likely benign (Mar 01, 2024)
19-5047474-A-G			Uncertain significance (May 05, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KDM4B	protein_coding	protein_coding	ENST00000159111	21	184482

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.00000264	125717	0	8	125725	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.48	469	735	0.638	0.0000522	7054
Missense in Polyphen		69	187.01	0.36896		1599
Synonymous	-0.645	353	338	1.04	0.0000280	2183
Loss of Function	6.27	4	53.5	0.0747	0.00000256	600

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000549	0.0000528
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Histone demethylase that specifically demethylates 'Lys- 9' of histone H3, thereby playing a role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27', H3 'Lys-36' nor H4 'Lys-20'. Only able to demethylate trimethylated H3 'Lys-9', with a weaker activity than KDM4A, KDM4C and KDM4D. Demethylation of Lys residue generates formaldehyde and succinate. {ECO:0000269|PubMed:16603238, ECO:0000269|PubMed:28262558}.
• Pathway: DNA Repair;Signal Transduction;DNA Double-Strand Break Repair;HDMs demethylate histones;Chromatin modifying enzymes;Signaling by Nuclear Receptors;Chromatin organization;Estrogen-dependent gene expression;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response;ESR-mediated signaling (Consensus)

Recessive Scores

• pRec: 0.114

Intolerance Scores

• loftool: 0.0736
• rvis_EVS: -2.57
• rvis_percentile_EVS: 0.84

Haploinsufficiency Scores

• pHI: 0.434
• hipred: Y
• hipred_score: 0.774
• ghis: 0.651

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.806

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Kdm4b
• Phenotype: endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;chromatin remodeling;histone H3-K9 demethylation;oxidation-reduction process;histone H3-K36 demethylation
• Cellular component: nucleus;nucleoplasm;histone methyltransferase complex
• Molecular function: histone demethylase activity;histone demethylase activity (H3-K9 specific);metal ion binding;histone demethylase activity (H3-K36 specific)