KDM4A

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

Basic information

Region (hg38): 1:43650148-43705518

Previous symbols: [ "JMJD2", "JMJD2A" ]

Links

ENSG00000066135 ∙ NCBI:9682 ∙ OMIM:609764 ∙ HGNC:22978 ∙ Uniprot:O75164 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the KDM4A gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KDM4A 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				2	4	6
missense			41		1	42
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					1	1
Total	0	0	41	2	6

Variants in KDM4A

This is a list of pathogenic ClinVar variants found in the KDM4A region.

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

Position	Type	Phenotype	Significance	ClinVar
1-43653205-C-T			Benign (Apr 19, 2018)
1-43653219-T-C		not specified	Uncertain significance (Dec 08, 2023)
1-43653223-C-A			Benign (Aug 02, 2017)
1-43653297-G-A		not specified	Uncertain significance (Mar 28, 2023)
1-43655680-G-T			Benign (May 30, 2018)
1-43655718-A-G		not specified	Uncertain significance (Dec 16, 2022)
1-43660338-C-T		not specified	Uncertain significance (Feb 05, 2024)
1-43660364-C-A		not specified	Uncertain significance (Dec 28, 2023)
1-43662990-C-G		not specified	Uncertain significance (Apr 24, 2023)
1-43665700-T-A		not specified	Uncertain significance (Apr 22, 2022)
1-43667056-C-T		not specified	Uncertain significance (Jun 16, 2023)
1-43667078-A-G		not specified	Uncertain significance (Jun 01, 2023)
1-43667086-G-C		not specified	Uncertain significance (May 14, 2024)
1-43667878-T-C		not specified	Uncertain significance (Jan 06, 2023)
1-43667884-A-G		not specified	Uncertain significance (May 18, 2023)
1-43667950-A-G		not specified	Uncertain significance (Apr 26, 2023)
1-43667976-A-G			Benign (May 30, 2018)
1-43669114-G-A		not specified	Uncertain significance (Sep 14, 2022)
1-43669153-C-T		not specified	Uncertain significance (Jan 31, 2024)
1-43669229-G-A			Likely benign (May 14, 2018)
1-43669269-C-T		not specified	Uncertain significance (Aug 02, 2023)
1-43669270-G-A		not specified	Uncertain significance (Jun 29, 2023)
1-43671620-G-A			Benign (May 30, 2018)
1-43671631-G-A		not specified	Uncertain significance (Jun 29, 2023)
1-43671633-C-T		not specified	Uncertain significance (Aug 13, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KDM4A	protein_coding	protein_coding	ENST00000372396	21	55358

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	3.80e-7	125738	0	10	125748	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.68	351	606	0.579	0.0000344	7021
Missense in Polyphen		110	247.69	0.4441		2730
Synonymous	0.797	201	216	0.931	0.0000120	1999
Loss of Function	6.62	4	58.7	0.0681	0.00000329	669

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000121	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000364	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000383	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Histone demethylase that specifically demethylates 'Lys- 9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code (PubMed:26741168). Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. Participates in transcriptional repression of ASCL2 and E2F-responsive promoters via the recruitment of histone deacetylases and NCOR1, respectively. {ECO:0000269|PubMed:16024779, ECO:0000269|PubMed:16603238, ECO:0000269|PubMed:26741168}.
• Pathway: DNA Repair;DNA Double-Strand Break Repair;HDMs demethylate histones;Chromatin modifying enzymes;Chromatin organization;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.274
• rvis_EVS: -0.02
• rvis_percentile_EVS: 52.25

Haploinsufficiency Scores

• pHI: 0.181
• hipred: Y
• hipred_score: 0.794
• ghis: 0.520

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.920

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kdm4a
• Phenotype: homeostasis/metabolism phenotype; muscle phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;chromatin remodeling;negative regulation of autophagy;positive regulation of gene expression;negative regulation of gene expression;cardiac muscle hypertrophy in response to stress;viral process;histone demethylation;response to nutrient levels;histone H3-K9 demethylation;positive regulation of neuron differentiation;negative regulation of transcription, DNA-templated;negative regulation of astrocyte differentiation;oxidation-reduction process;negative regulation of cell death;histone H3-K36 demethylation;negative regulation of histone H3-K9 trimethylation
• Cellular component: fibrillar center;nucleus;nucleoplasm;pericentric heterochromatin;cytosol;histone methyltransferase complex
• Molecular function: protein binding;zinc ion binding;ubiquitin protein ligase binding;histone demethylase activity;histone demethylase activity (H3-K9 specific);methylated histone binding;histone demethylase activity (H3-K36 specific)