KDM4D
protein-codinglysine demethylase 4D, the group of Lysine demethylases
Gene summary
Enables histone H3K9me2/H3K9me3 demethylase activity. Involved in inflammatory response. Acts upstream of or within several processes, including cellular response to ionizing radiation; double-strand break repair via homologous recombination; and positive regulation of double-strand break repair via nonhomologous end joining. Located in site of double-strand break. Biomarker of nephroblastoma. [provided by Alliance of Genome Resources, Jul 2025]
- JMJD2D
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~25.8 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 KDM4D variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018039.3. 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 | 0 | |||||
| missense | 60 | 1 | 2 | 63 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 60 | 1 | 2 | 63 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060509.2 | 1 | MANE Select | |
| Ensembl | ENSP00000334181.5 | 1 | MANE Select | |
| Ensembl | ENSP00000460897.1 | 1 | Standard | |
| Ensembl | ENSP00000460897.1 | 1 | 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
- negative regulation of transcription by RNA polymerase II
- double-strand break repair via homologous recombination
- regulation of protein phosphorylation
- chromatin remodeling
- histone H3-K9 demethylation
Molecular Function
- damaged DNA binding
- chromatin DNA binding
- histone demethylase activity
- histone demethylase activity (H3-K9 specific)
- metal ion binding
Cellular Component
- nucleus
- nucleoplasm
- pericentric heterochromatin
- histone methyltransferase complex
- site of double-strand break
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000335080
- Coding exons
- 1
- Length
- 25838
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.16 | 204 | 311 | 0.655 | 0.0000184 | 3416 |
| Missense (PolyPhen) | 34 | 102.42 | 0.33196 | 1273 | ||
| Synonymous | -0.377 | 119 | 114 | 1.04 | 0.00000612 | 1070 |
| Loss of Function | 1.07 | 0 | 1.34 | 0.00 | 5.46e-8 | 22 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Histone demethylase that specifically demethylates 'Lys- 9' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27', H3 'Lys-36' nor H4 'Lys-20'. Demethylates both di- and trimethylated H3 'Lys- 9' residue, while it has no activity on monomethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. {ECO:0000269|PubMed:16603238}.;
Recessive Scores
- pRec
- 0.101
Intolerance Scores
- LoFtool
- 0.414
- RVIS EVS
- 0.64
- RVIS percentile EVS
- 83.98
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.848
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |