KDM8
lysine demethylase 8, the group of Lysine demethylases
Basic information
Region (hg38): 16:27203508-27221768
Previous symbols: [ "JMJD5" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (63 variants)
- not_provided (3 variants)
- Coffin-Siris_syndrome (2 variants)
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. These statistics are base on transcript: NM_000024773.3. 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 | 1 | |||||
| missense | 54 | 61 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 54 | 8 | 0 |
Loading clinvar variants...
GnomAD
Source:
| 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:
- 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
- loftool
- 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_indispensability_pred
- gene_indispensability_score
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)