KDM5C
Lysine Demethylase 5C: A Histone Demethylase Implicated in X-Linked Intellectual Disability and Cancer
Gene Information Card
| Symbol | KDM5C |
|---|---|
| Full Name | Lysine Demethylase 5C |
| Gene Type | Protein coding |
| Chromosomal Location | Xp11.22 |
| NCBI Gene ID | 8242 ncbi.nlm.nih.gov/gene/8242 |
| Ensembl ID | ENSG00000126012 |
| UniProt ID | P41229 |
| OMIM ID | 314690 |
| HGNC ID | 11114 |
| Aliases | JARID1C, SMCX, MRXJ, MRXSCJ |
Description
KDM5C (lysine demethylase 5C) encodes a histone demethylase that specifically demethylates lysine 4 of histone H3 (H3K4me3 and H3K4me2), acting as a transcriptional repressor. It is involved in neuronal development, chromatin remodeling, and cell cycle regulation. Mutations in KDM5C are associated with X-linked intellectual disability (XLID) and have been implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked intellectual disability (XLID) | Loss-of-function mutations impair H3K4 demethylation, leading to dysregulated gene expression in neurons. | ClinVar, OMIM |
| Cancer (e.g., breast, lung, renal) | Altered KDM5C expression or mutation affects chromatin state, promoting tumorigenesis or therapy resistance. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.2 | Low |
| Kidney | 6.1 | Low |
| Liver | 4.3 | Low |
| Heart | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.0 | Embryonic kidney cells |
| HeLa | 10.5 | Cervical cancer cells |
| SH-SY5Y | 18.2 | Neuroblastoma cells |
| MCF7 | 7.8 | Breast cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1091C>T (p.Ala364Val) | Missense | Rare | Reduced demethylase activity; associated with XLID |
| c.2T>C (p.Met1Thr) | Start loss | Rare | Loss of protein function; XLID |
| c.1265G>A (p.Arg422Gln) | Missense | Rare | Impaired H3K4me3 binding; XLID |
| c.1687C>T (p.Arg563*) | Nonsense | Rare | Truncated protein; loss of function; XLID |
Mutation functional classification
Loss of Function (LOF)
Most XLID-associated mutations (missense, nonsense, frameshift) reduce or abolish H3K4 demethylase activity, leading to increased H3K4me3 levels and altered transcription.
Gain of Function (GOF)
Not well documented; some cancer-associated mutations may alter substrate specificity or increase activity, but evidence is limited.
Dominant Negative (DN)
Not reported for KDM5C; XLID is X-linked recessive, and heterozygous females are usually unaffected.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Chromatin modifying enzymes
• Transcriptional regulation by histone demethylation
Protein Summary
KDM5C is a 1560-amino acid protein containing a JmjC domain responsible for demethylase activity, a JmjN domain, ARID domain, and PHD fingers. It demethylates H3K4me3/me2, repressing transcription. The protein is predominantly nuclear and interacts with transcription factors and chromatin remodelers. Mutations in the JmjC domain impair catalytic activity, linking to intellectual disability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KDM5C Knockout HEK293 Cell Line | EDJ-KQ2967 | Human | 8242 | Details Get a Quote |
| KDM5C Knockout A-549 Cell Line | EDJ-KQ24122 | Human | 8242 | Details Get a Quote |
| KDM5C Knockout HCT 116 Cell Line | EDJ-KQ24123 | Human | 8242 | Details Get a Quote |
| KDM5C Knockout HeLa Cell Line | EDJ-KQ24124 | Human | 8242 | Details Get a Quote |
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