KDM5B

lysine demethylase 5B, the group of AT-rich interaction domain containing|PHD finger proteins|Lysine demethylases

Basic information

Region (hg38): 1:202724495-202808487

Previous symbols: [ "JARID1B" ]

Links

ENSG00000117139 ∙ NCBI:10765 ∙ OMIM:605393 ∙ HGNC:18039 ∙ Uniprot:Q9UGL1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Tourette syndrome (No Known Disease Relationship), mode of inheritance: Unknown
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• intellectual disability, autosomal recessive 65 (Limited), mode of inheritance: AD
• intellectual disability, autosomal recessive 65 (Strong), mode of inheritance: AR
• intellectual disability (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 65	AR	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	29276005; 30409806
Heterozygous variants appear to be able to cause an incompletely penetrant phenotype

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KDM5B gene.

• not provided (12 variants)
• Inborn genetic diseases (7 variants)
• Intellectual disability, autosomal recessive 65 (5 variants)
• Neurodevelopmental disorder (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 KDM5B 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				34	9	43
missense		3	161	5	1	170
nonsense	9	15	5			29
start loss						0
frameshift	14	9	8			31
inframe indel			1			1
splice donor/acceptor (+/-2bp)	2	10	3			15
splice region			4	2	1	7
non coding	1		2	4	3	10
Total	26	37	180	43	13

Variants in KDM5B

This is a list of pathogenic ClinVar variants found in the KDM5B region.

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

Position	Type	Phenotype	Significance	ClinVar
1-202729046-C-G		Inborn genetic diseases	Uncertain significance (Jul 27, 2024)
1-202729066-A-T		Intellectual disability, autosomal recessive 65	Uncertain significance (Feb 02, 2022)
1-202729084-GTCT-G			Uncertain significance (Apr 26, 2024)
1-202729085-T-C			Uncertain significance (Apr 02, 2024)
1-202729093-C-G		Inborn genetic diseases	Uncertain significance (Mar 08, 2022)
1-202729097-GC-G			Uncertain significance (Mar 01, 2023)
1-202729106-G-T		Inborn genetic diseases	Uncertain significance (Jul 15, 2021)
1-202729161-G-A			Uncertain significance (Jan 05, 2021)
1-202729710-A-T		Inborn genetic diseases	Uncertain significance (Nov 01, 2024)
1-202729721-G-A			Uncertain significance (Apr 10, 2023)
1-202729753-T-C		Inborn genetic diseases	Uncertain significance (Dec 17, 2023)
1-202729754-C-G		KDM5B-related disorder	Uncertain significance (Jan 22, 2024)
1-202729778-C-T		Inborn genetic diseases	Uncertain significance (Mar 07, 2023)
1-202729786-G-A		Inborn genetic diseases	Uncertain significance (Dec 26, 2023)
1-202729793-C-CT			Uncertain significance (Jul 24, 2019)
1-202729807-T-C		Intellectual disability, autosomal recessive 65	Uncertain significance (Sep 13, 2021)
1-202729822-C-T		Inborn genetic diseases • KDM5B-related disorder	Likely benign (Nov 19, 2021)
1-202729840-C-T		Bladder exstrophy-epispadias-cloacal extrophy complex	Uncertain significance (-)
1-202729842-C-T			Likely benign (Jul 01, 2022)
1-202729851-T-C		KDM5B-related disorder	Benign (Dec 31, 2019)
1-202729907-G-A		KDM5B-related disorder	Uncertain significance (May 20, 2024)
1-202729907-G-T		Inborn genetic diseases	Uncertain significance (May 18, 2021)
1-202729913-G-A		Inborn genetic diseases	Uncertain significance (Mar 21, 2023)
1-202729922-TA-T			Likely pathogenic (Sep 24, 2024)
1-202729928-G-A		Inborn genetic diseases	Pathogenic/Likely pathogenic (Nov 01, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KDM5B	protein_coding	protein_coding	ENST00000367265	27	82073

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.91e-15	1.00	125620	0	128	125748	0.000509

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.78	701	847	0.828	0.0000454	10098
Missense in Polyphen		226	331.32	0.68212		3976
Synonymous	0.822	294	312	0.941	0.0000159	2954
Loss of Function	4.96	40	91.1	0.439	0.00000581	989

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000542	0.000538
Ashkenazi Jewish	0.000404	0.000397
East Asian	0.00245	0.00245
Finnish	0.000232	0.000231
European (Non-Finnish)	0.000436	0.000431
Middle Eastern	0.00245	0.00245
South Asian	0.000266	0.000261
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Histone demethylase that demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code (PubMed:24952722, PubMed:27214403, PubMed:28262558). Does not demethylate histone H3 'Lys-9' or H3 'Lys-27'. Demethylates trimethylated, dimethylated and monomethylated H3 'Lys-4'. Acts as a transcriptional corepressor for FOXG1B and PAX9. Favors the proliferation of breast cancer cells by repressing tumor suppressor genes such as BRCA1 and HOXA5 (PubMed:24952722). In contrast, may act as a tumor suppressor for melanoma. Represses the CLOCK-ARNTL/BMAL1 heterodimer-mediated transcriptional activation of the core clock component PER2 (By similarity). {ECO:0000250|UniProtKB:Q80Y84, ECO:0000269|PubMed:12657635, ECO:0000269|PubMed:16645588, ECO:0000269|PubMed:17320161, ECO:0000269|PubMed:17363312, ECO:0000269|PubMed:24952722, ECO:0000269|PubMed:26645689, ECO:0000269|PubMed:26741168, ECO:0000269|PubMed:27214403, ECO:0000269|PubMed:28262558}.
• Pathway: Gene expression (Transcription);Generic Transcription Pathway;HDMs demethylate histones;RNA Polymerase II Transcription;Chromatin modifying enzymes;Chromatin organization;TFAP2 (AP-2) family regulates transcription of cell cycle factors;Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors (Consensus)

Recessive Scores

• pRec: 0.128

Intolerance Scores

• loftool: 0.176
• rvis_EVS: -1.72
• rvis_percentile_EVS: 2.48

Haploinsufficiency Scores

• pHI: 0.693
• hipred: Y
• hipred_score: 0.648
• ghis: 0.560

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.636

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kdm5b
• 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); reproductive system phenotype; homeostasis/metabolism 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

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;chromatin remodeling;regulation of transcription by RNA polymerase II;single fertilization;post-embryonic development;positive regulation of gene expression;positive regulation of mammary gland epithelial cell proliferation;histone H3-K4 demethylation;histone H3-K4 demethylation, trimethyl-H3-K4-specific;cellular response to fibroblast growth factor stimulus;negative regulation of transcription, DNA-templated;rhythmic process;oxidation-reduction process;branching involved in mammary gland duct morphogenesis;mammary duct terminal end bud growth;response to fungicide;uterus morphogenesis;lens fiber cell differentiation;cellular response to leukemia inhibitory factor;regulation of estradiol secretion
• Cellular component: nucleus;nucleoplasm;cytosol;histone methyltransferase complex
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;transcription corepressor activity;protein binding;zinc ion binding;histone demethylase activity;histone demethylase activity (H3-K4 specific);histone demethylase activity (H3-trimethyl-K4 specific);histone demethylase activity (H3-dimethyl-K4 specific);histone binding;dioxygenase activity;sequence-specific double-stranded DNA binding