KDM5A

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

Basic information

Region (hg38): 12:280057-389320

Previous symbols: [ "RBBP2", "JARID1A" ]

Links

ENSG00000073614 ∙ NCBI:5927 ∙ OMIM:180202 ∙ HGNC:9886 ∙ Uniprot:P29375 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital heart disease (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
El Hayek-Chahrour neurodevelopmental syndrome	AR	Cardiovascular	Among other findings, the condition may involve congenital cardiovascular anomalies, and awareness may allow early identification and management	Cardiovascular; Neurologic	33350388

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KDM5A gene.

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KDM5A 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				7	5	12
missense		1	81	2	8	92
nonsense			2			2
start loss		1				1
frameshift	1		2			3
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region				6	1	7
non coding						0
Total	1	2	86	9	13

Variants in KDM5A

This is a list of pathogenic ClinVar variants found in the KDM5A region.

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

Position	Type	Phenotype	Significance	ClinVar
12-285482-T-C		not specified	Likely benign (Mar 20, 2024)
12-285484-G-A		not specified	Uncertain significance (May 30, 2023)
12-285551-T-C		not specified	Uncertain significance (Jan 08, 2024)
12-285554-C-T			Uncertain significance (Mar 03, 2022)
12-285599-A-C		not specified	Uncertain significance (May 15, 2024)
12-292941-T-C		not specified	Uncertain significance (Jun 24, 2022)
12-292952-T-A		KDM5A-related disorder	Benign (Jun 05, 2018)
12-293068-T-A		See cases	Uncertain significance (Apr 08, 2022)
12-293103-G-A			not provided (-)
12-293147-G-A		not specified	Uncertain significance (Mar 30, 2024)
12-293162-C-A		KDM5A-related disorder	Uncertain significance (Sep 01, 2022)
12-293162-C-G			Uncertain significance (Feb 16, 2023)
12-293167-A-T		not specified	Uncertain significance (Feb 11, 2022)
12-295567-C-A		KDM5A-related disorder	Likely benign (Apr 21, 2022)
12-295588-G-C		not specified	Uncertain significance (Mar 18, 2024)
12-295608-G-T			Benign (Dec 31, 2019)
12-295632-A-G		not specified	Uncertain significance (Jan 17, 2023)
12-295632-A-AT			Uncertain significance (Jan 26, 2024)
12-295655-G-T		not specified	Uncertain significance (Feb 02, 2024)
12-295682-A-G		not specified	Uncertain significance (Dec 21, 2022)
12-295692-C-G		KDM5A-related disorder	Benign (Dec 31, 2019)
12-295714-T-G			Likely benign (Nov 16, 2018)
12-295730-G-A		not specified	Uncertain significance (Oct 26, 2022)
12-295745-C-A		Seizure;Intellectual disability	Likely pathogenic (Mar 02, 2023)
12-295754-A-G		not specified	Uncertain significance (Aug 16, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KDM5A	protein_coding	protein_coding	ENST00000399788	28	109326

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	3.78e-9	125178	0	16	125194	0.0000639

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.25	718	909	0.790	0.0000507	11118
Missense in Polyphen		134	271.67	0.49325		3412
Synonymous	-2.66	384	323	1.19	0.0000169	3216
Loss of Function	7.94	8	88.7	0.0902	0.00000509	1047

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000290	0.0000290
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000797	0.0000793
Middle Eastern	0.00	0.00
South Asian	0.000131	0.000131
Other	0.000331	0.000329

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Histone demethylase that specifically demethylates 'Lys- 4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. Regulates specific gene transcription through DNA-binding on 5'-CCGCCC-3' motif (PubMed:18270511). May stimulate transcription mediated by nuclear receptors. Involved in transcriptional regulation of Hox proteins during cell differentiation (PubMed:19430464). May participate in transcriptional repression of cytokines such as CXCL12. Plays a role in the regulation of the circadian rhythm and in maintaining the normal periodicity of the circadian clock. In a histone demethylase-independent manner, acts as a coactivator of the CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER1/2 and other clock-controlled genes and increases histone acetylation at PER1/2 promoters by inhibiting the activity of HDAC1 (By similarity). Seems to act as a transcriptional corepressor for some genes such as MT1F and to favor the proliferation of cancer cells (PubMed:27427228). {ECO:0000250|UniProtKB:Q3UXZ9, ECO:0000269|PubMed:11358960, ECO:0000269|PubMed:15949438, ECO:0000269|PubMed:17320160, ECO:0000269|PubMed:17320161, ECO:0000269|PubMed:17320163, ECO:0000269|PubMed:18270511, ECO:0000269|PubMed:19430464, ECO:0000269|PubMed:27427228}.
• Pathway: HDMs demethylate histones;Chromatin modifying enzymes;Chromatin organization (Consensus)

Recessive Scores

• pRec: 0.161

Intolerance Scores

• loftool: 0.0591
• rvis_EVS: -0.74
• rvis_percentile_EVS: 13.79

Haploinsufficiency Scores

• pHI: 0.604
• hipred: Y
• hipred_score: 0.793
• ghis: 0.571

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.835

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kdm5a
• Phenotype: cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; immune system phenotype; neoplasm; hematopoietic 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); 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;spermatogenesis;male gonad development;circadian regulation of gene expression;histone H3-K9 demethylation;histone H3-K4 demethylation;histone H3-K4 demethylation, trimethyl-H3-K4-specific;positive regulation of transcription, DNA-templated;regulation of DNA-binding transcription factor activity;oxidation-reduction process;negative regulation of histone deacetylase activity
• Cellular component: nucleus;nucleoplasm;nucleolus;protein-DNA complex;histone methyltransferase complex
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;core promoter sequence-specific DNA binding;DNA binding;DNA-binding transcription factor activity;transcription coactivator activity;protein binding;zinc ion binding;chromatin DNA binding;histone demethylase activity;histone demethylase activity (H3-K9 specific);histone demethylase activity (H3-trimethyl-K4 specific);histone demethylase activity (H3-dimethyl-K4 specific);methylated histone binding;histone binding;dioxygenase activity