KDM5D
protein-codinglysine demethylase 5D, the group of AT-rich interaction domain containing|PHD finger proteins|Minor histocompatibility antigens|Lysine demethylases
Gene summary
This gene encodes a protein containing zinc finger domains. A short peptide derived from this protein is a minor histocompatibility antigen which can lead to graft rejection of male donor cells in a female recipient. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]
- HYA
- HY
- SMCY
- JARID1D
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~41.1 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 KDM5D variants in ClinVar
No annotated ClinVar phenotypes.
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004653.5. 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 | 7 | 7 | ||||
| missense | 21 | 21 | ||||
| nonsense | 4 | 4 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 8 | 8 | ||||
| Total | 0 | 0 | 40 | 0 | 0 | 40 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004644.2 | 26 | MANE Select | |
| Ensembl | ENSP00000322408.4 | 26 | MANE Select | |
| RefSeq | NP_001140177.1 | 27 | Standard | |
| RefSeq | NP_001140178.1 | 25 | 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
- T cell antigen processing and presentation
- chromatin remodeling
- histone H3-K4 demethylation
- histone H3-K4 demethylation, trimethyl-H3-K4-specific
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA binding
- protein binding
- histone demethylase activity
- histone demethylase activity (H3-K4 specific)
Cellular Component
- fibrillar center
- cellular_component
- nucleus
- nucleoplasm
- histone methyltransferase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000317961
- Coding exons
- 26
- Length
- 41075
- Individuals with no LoFs
- 67931
- Homozygous LoFs
- 13
- Heterozygous LoFs
- 0
- Defined
- 67944
- p
- 0.0000957
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.372 | 259 | 243 | 1.07 | 0.0000401 | 10069 |
| Missense (PolyPhen) | 56 | 83.025 | 0.67449 | 3352 | ||
| Synonymous | -2.81 | 118 | 85.0 | 1.39 | 0.0000131 | 3059 |
| Loss of Function | 3.71 | 3 | 21.6 | 0.139 | 0.00000362 | 844 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00014 | 0.000070 | rare |
| Ashkenazi Jewish | 0.00039 | 0.00019 | rare |
| East Asian | 0.00022 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00023 | 0.00011 | rare |
| South Asian | 0.00017 | 0.000087 | rare |
| Other | 0.00072 | 0.00031 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Histone demethylase that specifically demethylates 'Lys- 4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9', H3 'Lys-27', H3 'Lys-36', H3 'Lys-79' or H4 'Lys-20'. Demethylates trimethylated and dimethylated but not monomethylated H3 'Lys-4'. May play a role in spermatogenesis. Involved in transcriptional repression of diverse metastasis-associated genes; in this function seems to cooperate with ZMYND8. Suppresses prostate cancer cell invasion. Regulates androgen receptor (AR) transcriptional activity by demethylating H3K4me3 active transcription marks. {ECO:0000269|PubMed:17320160, ECO:0000269|PubMed:17320162, ECO:0000269|PubMed:17351630, ECO:0000269|PubMed:26747897, ECO:0000269|PubMed:27185910, ECO:0000269|PubMed:27427228, ECO:0000269|PubMed:27477906}.;
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.163
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |