KDM5B

Chr 1AR

lysine demethylase 5B

Also known as: CT31, JARID1B, MRT65, PLU-1, PLU1, PPP1R98, PUT1, RBBP2H1A

NCBI Gene: 10765ENSG00000117139UniProt: Q9UGL1

This gene encodes a lysine-specific histone demethylase that belongs to the jumonji/ARID domain-containing family of histone demethylases. The encoded protein is capable of demethylating tri-, di- and monomethylated lysine 4 of histone H3. This protein plays a role in the transcriptional repression or certain tumor suppressor genes and is upregulated in certain cancer cells. This protein may also play a role in genome stability and DNA repair. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal recessive 65MIM #618109
AR
1
Active trials
85
Pathogenic / LP
414
ClinVar variants
51
Pubs (1 yr)
1.8
Missense Z
0.57
LOEUF
Clinical Summary— KDM5B
🧬
Gene-Disease Validity (ClinGen)
intellectual disability · ARModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
85 Pathogenic / Likely Pathogenic· 252 VUS of 414 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.57LOEUF
pLI 0.000
Z-score 4.96
OE 0.44 (0.34–0.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.78Z-score
OE missense 0.83 (0.78–0.88)
701 obs / 846.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.44 (0.34–0.57)
0≤0.351.4
Missense OE0.83 (0.78–0.88)
0≤0.61.4
Synonymous OE0.94
0≤1.21.6
LoF obs/exp: 40 / 91.1Missense obs/exp: 701 / 846.6Syn Z: 0.82

ClinVar Variant Classifications

414 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic53
VUS252
Likely Benign60
Benign10
Conflicting7
32
Pathogenic
53
Likely Pathogenic
252
VUS
60
Likely Benign
10
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
1
18
0
32
Likely Pathogenic
27
6
20
0
53
VUS
7
227
18
0
252
Likely Benign
0
9
13
38
60
Benign
0
2
3
5
10
Conflicting
—7
Total472457243414

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

View in ClinVar →

KDM5B · protein map & ClinVar variants

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

Gene2Phenotype Curations

KDM5B-related neurodevelopmental disorder (monoallelic)

strong
ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. Disorders
G2P ↗

KDM5B-related neurodevelopmental disorder (biallelic)

strong
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. Disorders
G2P ↗

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

Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Ubiquitin-mediated stabilization of KDM5B drives chemoresistance via repression of dual-specificity phosphatase 4 in ovarian cancer.
Yoo J et al.·Signal Transduct Target Ther
2026
OTUD3-mediated deubiquitination licenses TEX264 to orchestrate ER-phagy for KDM5B degradation in teniposide lung cancer therapy.
Han N et al.·Eur J Pharmacol
2026
KDM5B cooperates with CRL4B complex to promote the tumorigenesis of ER+ breast cancer via regulating cholesterol metabolism.
Yang Y et al.·Cell Death Dis
2026Open Access
Integrated Multi-Omic Analysis Reveals KDM5B as a Regulator of Microglial Reactivity to Immunomodulatory Stimuli.
Wohlfahrt J et al.·J Proteome Res
2026
Suppressing the OTUD7A/KDM5B/GABPA axis enhances the sensitivity of cisplatin through inducing ferroptosis in KRAS-mutant LUAD.
Si R et al.·Cell Death Dis
2025Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients