KDM8
protein-codinglysine demethylase 8, the group of Lysine demethylases
Gene summary
This gene likely encodes a histone lysine demethylase. Studies of a similar protein in mouse indicate a potential role for this protein as a tumor suppressor. Alternatively spliced transcript variants have been described.[provided by RefSeq, Feb 2009]
- JMJD5
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~18.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KDM8 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024773.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 62 | 8 | 70 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 66 | 9 | 0 | 75 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_079049.2 | 7 | MANE Select | |
| Ensembl | ENSP00000286096.5 | 7 | MANE Select | |
| RefSeq | NP_001138820.1 | 8 | Standard | |
| Ensembl | ENSP00000398410.2 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- HDMs demethylate histones
- Chromatin modifying enzymes
- Chromatin organization
Biological Process
- G2/M transition of mitotic cell cycle
- proteolysis
- positive regulation of transcription, DNA-templated
- oxidation-reduction process
- histone H3-K36 demethylation
Molecular Function
- chromatin binding
- peptidase activity
- 2-oxoglutarate-dependent dioxygenase activity
- histone demethylase activity
- metal ion binding
Cellular Component
- nucleus
- nucleoplasm
- chromosome
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000441782
- Coding exons
- 8
- Length
- 18283
- Individuals with no LoFs
- 125696
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 52
- Defined
- 125748
- p
- 0.000207
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.615 | 247 | 276 | 0.896 | 0.0000168 | 2965 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000071 | 0.000070 | rare |
| South Asian | 0.0011 | 0.0010 | notable |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
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}.;
Recessive Scores
- pRec
- 0.105
Intolerance Scores
- RVIS EVS
- -0.6
- RVIS percentile EVS
- 18.06
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |