GeneBe

KDM3B

protein-coding

lysine demethylase 3B, the group of Lysine demethylases

Gene summary

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]

Previous symbols:
  • C5orf7
  • JMJD1B

MANE transcript

NM_016604.4

Inheritance

AD

ClinVar variants

P:49U:345B:95

Top phenotype

Diets-Jongmans syndrome

gnomAD constraint

pLI —, LoF o/e 0.01

Max pathogenic AF

—

Genomic locus

chr5:138,352,685-138,437,028

External References & Databases

Ensembl (ENSG00000120733)NCBI Gene (51780)OMIM (609373)HGNC:1337GenCCUniProt (Q7LBC6)AlphaFoldClinVar (KDM3B)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~84.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Diets-Jongmans syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030012

Submitter: G2P

Diets-Jongmans syndromeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0030012

Submitter: Ambry Genetics

Diets-Jongmans syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030012

Submitter: Labcorp Genetics (formerly Invitae)

syndromic intellectual disabilityDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0000508

Submitter: ClinGen

*KDM3B* encodes a histone demethylase involved in H3K9 demethylation, a critical process in chromatin modification required for transcriptional regulation. *KDM3B* was first reported in relation to autosomal dominant syndromic intellectual disability in 2019 (Diets et al., PMID: 30929739). The disorder is characterized by developmental delay, mild to moderate intellectual disability, and facial dysmorphisms. Additional phenotypic features include feeding difficulties in infancy, hypotonia, joint hypermobility, short stature, and behavior problems, including autism spectrum disorder and ADHD. Eighteen variants (missense, nonsense, frameshift, and splice site) that have been reported in 19 probands in 5 publications (PMIDs: 28135719, 30885698, 30929739, 36274669, 36757469) are included in this curation. Most variants occur *de novo*, but can also be inherited from similarly affected parents. The mechanism of pathogenicity is loss of function. This gene-disease relationship is also supported by experimental evidence, including biochemical function, protein interaction, and a mouse model (PMIDs: 22615488, 29276005, 34217333). Several other genes encoding lysine demethylases have been implicated in intellectual disability and autism. In summary, there is definitive evidence supporting the relationship between *KDM3B* and autosomal dominant syndromic intellectual disability. This has been repeatedly demonstrated in both research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on February 21, 2024 (SOP Version 10).

Diets-Jongmans syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030012

Submitter: Illumina

Diets-Jongmans syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0030012

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Diets-Jongmans syndromeAD

Manifestation: Audiologic/Otolaryngologic; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic; Oncologic; Ophthalmologic

Intervention: Audiologic/Otolaryngologic; Oncologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Multiple patients were ascertained from a cohort of children with cancer, and a potential elevated risk of cancer may indicate that awareness may allow early diagnosis and management of oncologic sequelae

Refs: 29351919; 30929739Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KDM3B variants in ClinVar

13 Conditions Cataloged
not providedTotal: 199
Inborn genetic diseasesTotal: 191
Diets-Jongmans syndromeTotal: 63
KDM3B-related disorderTotal: 59
not specifiedTotal: 28
See casesTotal: 5
Developmental disorderTotal: 4
Neurodevelopmental disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016604.4. 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
9
clinvar
44
clinvar
2
clinvar
 55
missense
7
clinvar
10
clinvar
326
clinvar
46
clinvar
3
clinvar
 392
nonsense
10
clinvar
6
clinvar
1
clinvar
 17
start loss
0
frameshift
6
clinvar
6
clinvar
1
clinvar
 13
splice donor/acceptor (+/-2bp)
4
clinvar
8
clinvar
 12
Total2326345905489

Highest pathogenic variant AF is 0.0000013706347

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_016604.4RefSeqNP_057688.324MANE Select
ENST00000314358.10EnsemblENSP00000326563.524MANE Select
ENST00000507996.5EnsemblENSP00000423012.12Standard
ENST00000510866.5EnsemblENSP00000425186.17Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Thermogenesis - Homo sapiens (human)
  • HDMs demethylate histones
  • Chromatin modifying enzymes
  • Chromatin organization

Biological Process

  • histone H3-K9 demethylation
  • oxidation-reduction process
  • response to cisplatin
  • cellular oxidant detoxification

Molecular Function

  • transcription regulatory region sequence-specific DNA binding
  • antioxidant activity
  • chromatin DNA binding
  • histone demethylase activity
  • histone demethylase activity (H3-K9 specific)

Cellular Component

  • chromatin
  • nucleus
  • nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000314358
Coding exons
24
Length
84433
Individuals with no LoFs
125742
Homozygous LoFs
0
Heterozygous LoFs
4
Defined
125746
p
0.0000159
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense4.985249580.5470.000052511457
Missense (PolyPhen)86301.080.285643608
Synonymous0.2453613670.9840.00002043620
Loss of Function8.17179.70.01250.00000481863

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian0.0000540.000054rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.0000180.0000088rare
South Asian00.0absent
Other0.000160.00016rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Histone demethylase that specifically demethylates 'Lys- 9' of histone H3, thereby playing a central role in histone code. Demethylation of Lys residue generates formaldehyde and succinate. May have tumor suppressor activity. {ECO:0000269|PubMed:16603237}.;

Recessive Scores

pRec
0.0982

Intolerance Scores

RVIS EVS
-0.75
RVIS percentile EVS
13.74

Essentials

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

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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