GeneBe

KDM4B

protein-coding

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

Gene summary

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 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, Jun 2026]

Previous symbols:
  • JMJD2B

MANE transcript

NM_015015.3

Inheritance

AD

ClinVar variants

P:40U:318B:97

Top phenotype

Intellectual developmental disorder, autosomal dominant 65

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr19:4,969,113-5,153,611

External References & Databases

Ensembl (ENSG00000127663)NCBI Gene (23030)OMIM (609765)HGNC:29136GenCCUniProt (O94953)AlphaFoldClinVar (KDM4B)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~184.5 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder, autosomal dominant 65STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0023657

Submitter: G2P

syndromic intellectual disabilitySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0000508

Submitter: Orphanet

complex neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Illumina

intellectual developmental disorder, autosomal dominant 65STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0023657

Submitter: ClinGen

The *KDM4B* gene is located on chromosome 19 at 19p13.3 and is a histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a role in histone code. The *KDM4B* gene was first reported in relation to intellectual developmental disorder, autosomal dominant 65 in 2020 (Duncan et al. 2020, PMID: 33232677). This disorder is characterized by global developmental delay, intellectual disability, language delays, structural brain anomalies, characteristic facial features, and clinodactyly.. Ten unique variants (4 missense, 4 insertion/deletion, 1 splice-site, 1 synonymous) that have been reported in 10 individuals from 2 publications are included in this curation (PMIDs: 33232677, 38270710). In seven of the ten individuals, variants were reported as de novo occurrences. The mechanism of pathogenicity appears to be loss of function. This gene-disease relationship is also supported by experimental evidence including biochemical function and two mouse models recapitulating the human phenotype (PMIDs: 35186950, 27023172, 33232677). In summary, there is strong evidence to support the relationship between *KDM4B* and Intellectual developmental disorder, autosomal dominant 65. Three years must elapse from the first proposal of the assertion to reach a definitive classification without any valid contradictory evidence. We will re-evaluate this gene-disease relationship at that time to determine if an upgraded classification of definitive is warranted. This classification was approved by the ClinGen Syndromic Disorders GCEP on the meeting date November 6th, 2024 (SOP Version 11).

intellectual developmental disorder, autosomal dominant 65STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0023657

Submitter: Labcorp Genetics (formerly Invitae)

intellectual developmental disorder, autosomal dominant 65STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0023657

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Intellectual developmental disorder, autosomal dominant 65AD

Manifestation: Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision making, and avoidance of unnecessary testing

Refs: 33232677Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KDM4B variants in ClinVar

11 Conditions Cataloged
not providedTotal: 232
Inborn genetic diseasesTotal: 168
Intellectual developmental disorder, autosomal dominant 65Total: 64
not specifiedTotal: 43
KDM4B-related disorderTotal: 36
Neurodevelopmental delayTotal: 2
See casesTotal: 2
Neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015015.3. 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
1
clinvar
7
clinvar
59
clinvar
5
clinvar
 72
missense
2
clinvar
4
clinvar
298
clinvar
33
clinvar
 337
nonsense
3
clinvar
8
clinvar
1
clinvar
 12
start loss
1
clinvar
 1
frameshift
5
clinvar
8
clinvar
2
clinvar
 15
splice donor/acceptor (+/-2bp)
1
clinvar
8
clinvar
9
clinvar
 18
Total1129318925455

Highest pathogenic variant AF is 0.000025030826

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 66 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_015015.3RefSeqNP_055830.121MANE Select
ENST00000159111.9EnsemblENSP00000159111.321MANE Select
NM_001370093.1RefSeqNP_001357022.110Standard
NM_001370094.1RefSeqNP_001357023.19Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • DNA Repair
  • Signal Transduction
  • DNA Double-Strand Break Repair
  • HDMs demethylate histones
  • Chromatin modifying enzymes

Biological Process

  • negative regulation of transcription by RNA polymerase II
  • chromatin remodeling
  • histone H3-K9 demethylation
  • oxidation-reduction process
  • histone H3-K36 demethylation

Molecular Function

  • histone demethylase activity
  • histone demethylase activity (H3-K9 specific)
  • metal ion binding
  • histone demethylase activity (H3-K36 specific)

Cellular Component

  • nucleus
  • nucleoplasm
  • histone methyltransferase complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000159111
Coding exons
21
Length
184482
Individuals with no LoFs
125717
Homozygous LoFs
0
Heterozygous LoFs
8
Defined
125725
p
0.0000318
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense3.484697350.6380.00005227054
Missense (PolyPhen)69187.010.368961599
Synonymous-0.6453533381.040.00002802183
Loss of Function6.27453.50.07470.00000256600

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian0.0000540.000054rare
Finnish00.0absent
European (Non-Finnish)0.0000550.000053rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Histone demethylase that specifically demethylates 'Lys- 9' of histone H3, thereby playing a role in histone code. Does not demethylate histone H3 'Lys-4', H3 'Lys-27', H3 'Lys-36' nor H4 'Lys-20'. Only able to demethylate trimethylated H3 'Lys-9', with a weaker activity than KDM4A, KDM4C and KDM4D. Demethylation of Lys residue generates formaldehyde and succinate. {ECO:0000269|PubMed:16603238, ECO:0000269|PubMed:28262558}.;

Recessive Scores

pRec
0.114

Intolerance Scores

LoFtool
0.0736
RVIS EVS
-2.57
RVIS percentile EVS
0.84

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
S
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.806

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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