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
El Hayek-Chahrour neurodevelopmental disorder (Limited), mode of inheritance: AR
neurodevelopmental disorder (Limited), mode of inheritance: AD
neurodevelopmental disorder (Limited), mode of inheritance: AR

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_specified (139 variants)
not_provided (81 variants)
KDM5A-related_disorder (15 variants)
El_Hayek-Chahrour_neurodevelopmental_disorder (7 variants)
Seizure (3 variants)
Intellectual_disability (3 variants)
See_cases (2 variants)
KDM5A-associated_neurodevelopmental_syndrome (1 variants)
KDM5A-related_Neurodevelopmental_disorder_with_autism (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. These statistics are base on transcript: NM_001042603.3. 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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	12 clinvar	3 clinvar	18
missense	1 clinvar	1 clinvar	184 clinvar	5 clinvar	5 clinvar	196
nonsense	1 clinvar	2 clinvar	4 clinvar			7
start loss		1				1
frameshift	1 clinvar		6 clinvar			7
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	14 clinvar			16
Total	4	5	211	17	8

Highest pathogenic variant AF is 0.000015497744

Loading clinvar variants...

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