KDM4C

Chr 9

lysine demethylase 4C

Also known as: GASC1, JHDM3C, JMJD2C, TDRD14C

NCBI Gene: 23081ENSG00000107077UniProt: Q9H3R0

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]

407
ClinVar variants
14
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— KDM4C
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 87 VUS of 407 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.54LOEUF
pLI 0.000
Z-score 4.34
OE 0.37 (0.27–0.54)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.49Z-score
OE missense 1.06 (0.99–1.13)
622 obs / 588.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.37 (0.27–0.54)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.06 (0.99–1.13)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.21
0≤1.21.6
LoF obs/exp: 21 / 56.1Missense obs/exp: 622 / 588.6Syn Z: -2.39

ClinVar Variant Classifications

407 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
VUS87
Likely Benign6
14
Pathogenic
87
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
0
0
0
VUS
1
81
5
0
87
Likely Benign
0
3
0
3
6
Benign
0
0
0
0
0
Total184193107

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

KDM4C · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Novel germline variant in the histone demethylase and transcription regulator KDM4C induces a multi-cancer phenotype.
Katainen R et al.·J Med Genet
2022
KDM4C works in concert with GATA1 to regulate heme metabolism in head and neck squamous cell carcinoma.
Wu MJ et al.·Cell Mol Life Sci
2025
Cross-phenotype analysis of Immunochip data identifies KDM4C as a relevant locus for the development of systemic vasculitis.
Ortiz-Fernández L et al.·Ann Rheum Dis
2018Meta-analysis
Essential Roles of the Histone Demethylase KDM4C in Renal Development and Acute Kidney Injury.
Pan HC et al.·Int J Mol Sci
2022
Wnt-Induced Stabilization of KDM4C Is Required for Wnt/β-Catenin Target Gene Expression and Glioblastoma Tumorigenesis.
Chen Y et al.·Cancer Res
2020
Rare genetic variants in the gene encoding histone lysine demethylase 4C (KDM4C) and their contributions to susceptibility to schizophrenia and autism spectrum disorder.
Kato H et al.·Transl Psychiatry
2020
Whole-genome sequencing reveals individual and cohort level insights into chromosome 9p syndromes.
Wang Y et al.·Genome Med
2025Cohort
KDM4C-mediated senescence defense is a targetable vulnerability in gastric cancer harboring TP53 mutations.
Wang K et al.·Clin Epigenetics
2023
Rare KDM4C variants and reduced expression underlie epigenetic dysregulation in rheumatoid arthritis.
Oner DA et al.·Immunol Res
2026
KDM4A, KDM4B and KDM4C in non-small cell lung cancer.
Soini Y et al.·Int J Clin Exp Pathol
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools