KDM4B

Chr 19AD

lysine demethylase 4B

Also known as: JMJD2B, MRD65, TDRD14B

NCBI Gene: 23030ENSG00000127663UniProt: O94953

Enables histone H3K36 demethylase activity and histone H3K9me2/H3K9me3 demethylase activity. Predicted to be involved in brain development; chromatin remodeling; and regulation of gene expression. Located in cytosol and nucleoplasm. Implicated in autosomal dominant intellectual developmental disorder 65; breast cancer; colorectal cancer; malignant peripheral nerve sheath tumor; and stomach cancer. Biomarker of several diseases, including alopecia areata; lung cancer; medulloblastoma; prostate cancer; and stomach cancer. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 65MIM #619320
AD
436
ClinVar variants
45
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— KDM4B
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
45 Pathogenic / Likely Pathogenic· 282 VUS of 436 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.17LOEUF
pLI 1.000
Z-score 6.27
OE 0.07 (0.04–0.17)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
3.48Z-score
OE missense 0.64 (0.59–0.69)
469 obs / 734.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.07 (0.04–0.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.64 (0.59–0.69)
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.1.04
0≤1.21.6
LoF obs/exp: 4 / 53.5Missense obs/exp: 469 / 734.8Syn Z: -0.65

ClinVar Variant Classifications

436 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic27
VUS282
Likely Benign64
Benign12
Conflicting9
18
Pathogenic
27
Likely Pathogenic
282
VUS
64
Likely Benign
12
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
2
11
0
18
Likely Pathogenic
18
3
6
0
27
VUS
4
260
17
1
282
Likely Benign
1
19
4
40
64
Benign
0
1
4
7
12
Conflicting
—9
Total282854248412

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

View in ClinVar →

Protein Context — Lollipop Plot

KDM4B · protein map & ClinVar variants

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

Gene2Phenotype Curations

KDM4B-related developmental disorder

strong
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder, autosomal dominant 65

MIM #619320

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Heterozygous Variants in KDM4B Lead to Global Developmental Delay and Neuroanatomical Defects.
Duncan AR et al.·Am J Hum Genet
2020
Oncometabolites suppress DNA repair by disrupting local chromatin signalling.
Sulkowski PL et al.·Nature
2020
Human phenotype caused by biallelic KDM4B frameshift variant.
Takada S et al.·Clin Genet
2024
KDM4B mutations in human cancers.
Bush W et al.·Mutat Res
2024
KDM4B, a potential prognostic biomarker revealed by large-scale public databases and clinical samples in uterine corpus endometrial carcinoma.
Zhang M et al.·Mol Omics
2022
Targeting KDM4B that coactivates c-Myc-regulated metabolism to suppress tumor growth in castration-resistant prostate cancer.
Wu MJ et al.·Theranostics
2021
Strong KDM4B and KDM4D Expression Associates with Radioresistance and Aggressive Phenotype in Classical Hodgkin Lymphoma.
Bur H et al.·Anticancer Res
2016
KDM4B and KDM4A promote endometrial cancer progression by regulating androgen receptor, c-myc, and p27kip1.
Qiu MT et al.·Oncotarget
2015
KDM4B is a coactivator of c-Jun and involved in gastric carcinogenesis.
Wu MC et al.·Cell Death Dis
2019
Targeting KDM4 family epigenetically triggers antitumour immunity via enhancing tumour-intrinsic innate sensing and immunogenicity.
Sun M et al.·Clin Transl Med
2024
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