KDM8

lysine demethylase 8, the group of Lysine demethylases

Basic information

Region (hg38): 16:27203508-27221768

Previous symbols: [ "JMJD5" ]

Links

ENSG00000155666 ∙ NCBI:79831 ∙ OMIM:611917 ∙ HGNC:25840 ∙ Uniprot:Q8N371 ∙ 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 KDM8 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KDM8 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				1		1
missense			16	3		19
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			7	1		8
Total	0	0	23	5	0

Variants in KDM8

This is a list of pathogenic ClinVar variants found in the KDM8 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-27204117-G-T		not specified	Uncertain significance (Nov 28, 2023)
16-27204142-G-C		not specified	Uncertain significance (Mar 23, 2023)
16-27204159-C-G		not specified	Uncertain significance (Dec 06, 2022)
16-27210096-C-A		not specified	Uncertain significance (Jan 05, 2022)
16-27210097-G-A		not specified	Uncertain significance (Apr 07, 2022)
16-27210104-A-C		not specified	Uncertain significance (Jul 12, 2022)
16-27210115-G-A		not specified	Likely benign (Dec 08, 2023)
16-27210128-C-A		not specified	Uncertain significance (Sep 27, 2021)
16-27210203-C-T		not specified	Uncertain significance (Sep 14, 2021)
16-27210206-A-G		not specified	Uncertain significance (Jan 26, 2022)
16-27210221-T-A		not specified	Uncertain significance (Sep 13, 2023)
16-27210370-A-G		not specified	Uncertain significance (Jan 23, 2024)
16-27210401-G-A		not specified	Likely benign (Apr 25, 2023)
16-27210412-A-G			Likely benign (Jul 26, 2017)
16-27210491-G-A		Coffin-Siris syndrome	Uncertain significance (Nov 16, 2020)
16-27210584-C-T		not specified	Uncertain significance (Mar 29, 2023)
16-27210589-C-T		not specified	Uncertain significance (Jan 31, 2022)
16-27214890-A-G		not specified	Uncertain significance (Mar 16, 2022)
16-27214908-G-A		not specified	Uncertain significance (Jan 23, 2023)
16-27215957-G-A		not specified	Uncertain significance (Mar 16, 2022)
16-27220403-G-T			Uncertain significance (Nov 01, 2023)
16-27220427-C-T		not specified	Uncertain significance (Dec 13, 2022)
16-27220462-C-T		not specified	Uncertain significance (Jan 10, 2023)
16-27220478-C-T		not specified	Uncertain significance (Feb 13, 2024)
16-27220479-G-A			Likely benign (Jul 26, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KDM8	protein_coding	protein_coding	ENST00000441782	8	18283

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000252	0.983	125696	0	52	125748	0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.615	247	276	0.896	0.0000168	2965
Missense in Polyphen		69	81.982	0.84165		859
Synonymous	-0.0399	123	122	1.00	0.00000865	892
Loss of Function	2.14	11	21.8	0.505	0.00000110	238

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000304	0.000301
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.000218	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.0000709	0.0000703
Middle Eastern	0.000218	0.000217
South Asian	0.00107	0.00105
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Histone demethylase required for G2/M phase cell cycle progression (PubMed:20457893). Specifically demethylates dimethylated 'Lys-36' (H3K36me2) of histone H3, an epigenetic repressive mark, thereby acting as a transcription activator (PubMed:20457893). Regulates expression of CCNA1 (cyclin-A1), leading to regulate cancer cell proliferation (PubMed:20457893). In a complex with coregulator RCCD1, is also able to demethylate trimethylated 'Lys-36' (H3K36me3) of histone H3 (PubMed:24981860). Plays a role in transcriptional repression of satellite repeats, possibly by regulating H3K36 methylation levels in centromeric regions together with RCCD1 (PubMed:24981860). Possibly together with RCCD1, involved in proper mitotic spindle organization and chromosome segregation (PubMed:24981860). Plays a role in regulating alpha-tubulin acetylation and cytoskeletal microtubule stability (PubMed:28455245). Might function as a protein hydroxylase (PubMed:22851697, PubMed:24100311). Under stress conditions that cause a DNA damage response, acts as a histone protease by cleaving the N-terminal tail of histone H3 at the carboxyl side of monomethyl-lysine (Kme1) residues, preferably at monomethylated 'Lys-9' (H3K9me1) (PubMed:28982940). The histone variant H3F3A is the major target for cleavage (PubMed:28982940). {ECO:0000269|PubMed:20457893, ECO:0000269|PubMed:24981860, ECO:0000269|PubMed:28455245, ECO:0000269|PubMed:28982940, ECO:0000303|PubMed:22851697, ECO:0000303|PubMed:24100311}.
• Pathway: HDMs demethylate histones;Chromatin modifying enzymes;Chromatin organization (Consensus)

Recessive Scores

• pRec: 0.105

Intolerance Scores

• rvis_EVS: -0.6
• rvis_percentile_EVS: 18.06

Haploinsufficiency Scores

• pHI: 0.0804
• hipred: N
• hipred_score: 0.236
• ghis: 0.545

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kdm8
• Phenotype: hematopoietic system 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); 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; pigmentation phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; growth/size/body region 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); homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;proteolysis;positive regulation of transcription, DNA-templated;oxidation-reduction process;histone H3-K36 demethylation
• Cellular component: nucleus;nucleoplasm;chromosome;cytosol
• Molecular function: chromatin binding;peptidase activity;2-oxoglutarate-dependent dioxygenase activity;histone demethylase activity;metal ion binding;histone demethylase activity (H3-K36 specific)