KDM3B

Chr 5AD

lysine demethylase 3B

Also known as: 5qNCA, C5orf7, DIJOS, JMJD1B, NET22

NCBI Gene: 51780ENSG00000120733UniProt: Q7LBC6

Predicted to enable chromatin DNA binding activity; histone H3K9 demethylase activity; and transcription coregulator activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. Biomarker of acute lymphoblastic leukemia; breast cancer; colorectal cancer; and lung non-small cell carcinoma. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Diets-Jongmans syndromeMIM #618846
AD
436
ClinVar variants
54
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— KDM3B
🧬
Gene-Disease Validity (ClinGen)
syndromic intellectual disability · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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
54 Pathogenic / Likely Pathogenic· 279 VUS of 436 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
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.
0.06LOEUF
pLI 1.000
Z-score 8.17
OE 0.01 (0.00–0.06)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

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.
4.98Z-score
OE missense 0.55 (0.51–0.59)
524 obs / 957.6 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.0.01 (0.00–0.06)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.55 (0.51–0.59)
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.0.98
0≤1.21.6
LoF obs/exp: 1 / 79.7Missense obs/exp: 524 / 957.6Syn Z: 0.24

ClinVar Variant Classifications

436 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic19
VUS279
Likely Benign75
Benign18
Conflicting10
35
Pathogenic
19
Likely Pathogenic
279
VUS
75
Likely Benign
18
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
8
22
0
35
Likely Pathogenic
6
7
6
0
19
VUS
2
265
10
2
279
Likely Benign
0
37
6
32
75
Benign
0
6
3
9
18
Conflicting
—10
Total133234743436

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

View in ClinVar →

Protein Context — Lollipop Plot

KDM3B · protein map & ClinVar variants

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

Gene2Phenotype Curations

KDM3B-related Diets-Jongmans syndrome

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

Diets-Jongmans syndrome

MIM #618846

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — KDM3B
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Epigenetic balance ensures mechanistic control of MLL amplification and rearrangement.
Gray ZH et al.·Cell
2023
De Novo and Inherited Pathogenic Variants in KDM3B Cause Intellectual Disability, Short Stature, and Facial Dysmorphism.
Diets IJ et al.·Am J Hum Genet
2019
Two patients with KDM3B variants and new presentations of Diets-Jongmans syndrome.
Zhao X et al.·Neurogenetics
2023Case report
A rare presentation of childhood interstitial lung disease attributed to KDM3B gene mutation: a case report.
Benslimane Z et al.·Pan Afr Med J
2023Case report
KDM3B suppresses castration-resistance prostate cancer cell proliferation by promoting PTEN expression.
Zhang P et al.·Eur J Med Res
2025
Histone demethylase KDM3B regulates the transcriptional network of cell-cycle genes in hepatocarcinoma HepG2 cells.
An MJ et al.·Biochem Biophys Res Commun
2019
Unraveling the Complexity of Chikungunya Virus Infection Immunological and Genetic Insights in Acute and Chronic Patients.
Fritsch H et al.·Genes (Basel)
2024Cohort
N(6) -methyladenosine-modified FAM111A-DT promotes hepatocellular carcinoma growth via epigenetically activating FAM111A.
Pu J et al.·Cancer Sci
2023
Histone demethylase KDM3B mediates matrix stiffness-induced osteogenic differentiation of adipose-derived stem cells.
Ma H et al.·Arch Biochem Biophys
2024
Systematic characterization of chromatin modifying enzymes identifies KDM3B as a critical regulator in castration resistant prostate cancer.
Saraç H et al.·Oncogene
2020
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
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools