GeneBe

KDM4C

protein-coding

lysine demethylase 4C, the group of Tudor domain containing|Lysine demethylases

Gene summary

This gene is a member of the Jumonji domain 2 (JMJD2) family. The encoded protein is a trimethylation-specific demethylase, and converts specific trimethylated histone residues to the dimethylated form. This enzymatic action regulates gene expression and chromosome segregation. Chromosomal aberrations and changes in expression of this gene may be found in tumor cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

Previous symbols:
  • JMJD2C

MANE transcript

NM_015061.6

Inheritance

—

ClinVar variants

U:176B:17

Top phenotype

KDM4C-related disorder

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr9:6,720,863-7,175,648

External References & Databases

Ensembl (ENSG00000107077)NCBI Gene (23081)OMIM (605469)HGNC:17071GenCCUniProt (Q9H3R0)AlphaFoldClinVar (KDM4C)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~454.8 kb
Loading mutation effect viewer...

GenCC 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 KDM4C variants in ClinVar

5 Conditions Cataloged
not specifiedTotal: 155
not providedTotal: 11
KDM4C-related disorderTotal: 6
EnchondromatosisTotal: 1
Maffucci syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015061.6. 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.

EffectPLPVUSLBBSum
synonymous
6
clinvar
4
clinvar
5
clinvar
 15
missense
163
clinvar
7
clinvar
1
clinvar
 171
nonsense
3
clinvar
 3
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
4
clinvar
 4
Total00176116193
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 65 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_015061.6RefSeqNP_055876.221MANE Select
ENST00000381309.8EnsemblENSP00000370710.321MANE Select
NM_001146695.4RefSeqNP_001140167.117Standard
NM_001146696.2RefSeqNP_001140168.118Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Signal Transduction
  • HDMs demethylate histones
  • Chromatin modifying enzymes
  • AndrogenReceptor
  • Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3

Biological Process

  • negative regulation of transcription by RNA polymerase II
  • blastocyst formation
  • chromatin remodeling
  • regulation of transcription by RNA polymerase II
  • positive regulation of cell population proliferation

Molecular Function

  • zinc ion binding
  • enzyme binding
  • histone demethylase activity
  • histone demethylase activity (H3-K9 specific)
  • androgen receptor binding

Cellular Component

  • nuclear chromatin
  • nucleus
  • nucleoplasm
  • pericentric heterochromatin
  • histone methyltransferase complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000381309
Coding exons
21
Length
454786
Individuals with no LoFs
125711
Homozygous LoFs
0
Heterozygous LoFs
37
Defined
125748
p
0.000147
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.4896225891.060.00003106985
Missense (PolyPhen)138195.380.706332277
Synonymous-2.392622171.210.00001251908
Loss of Function4.342156.10.3750.00000282704

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000120.00012rare
Latino/Admixed American0.000200.00020rare
Ashkenazi Jewish0.000200.00020rare
East Asian0.000110.00011rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.000190.00018rare
South Asian0.0000660.000065rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Histone demethylase that specifically demethylates 'Lys- 9' and 'Lys-36' residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27' nor H4 'Lys-20'. Demethylates trimethylated H3 'Lys-9' and H3 'Lys-36' residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. {ECO:0000269|PubMed:16603238, ECO:0000269|PubMed:28262558}.;

Intolerance Scores

LoFtool
0.689
RVIS EVS
-0.34
RVIS percentile EVS
29.62

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.948

Gene Damage Prediction

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh
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