Protein / target

Histone-lysine N-methyltransferase KMT5B

Encoded byKMT5BQ4FZB7Homo sapiensSwiss-Prot

UniProt: Q4FZB7 Ensembl: ENSG00000110066 HGNC: HGNC:24283 NCBI Gene: 51111

Small-molecule tractable

Druggability

Structure with Ligand

Research papers

Protein at a glance

Biological role

Histone H4K20 monomethyltransferase

Strongest disease association

Genetic Diseases, Inborn

Via encoding gene KMT5B · Genetic evidence · score 0.85

Research activity

Emerging research

4 papers · latest 2025

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

View complete UniProt function annotation

Histone methyltransferase that specifically methylates monomethylated 'Lys-20' (H4K20me1) and dimethylated 'Lys-20' (H4K20me2) of histone H4 to produce respectively dimethylated 'Lys-20' (H4K20me2) and trimethylated 'Lys-20' (H4K20me3) and thus regulates transcription and maintenance of genome integrity (PubMed:24396869, PubMed:28114273). In vitro also methylates unmodified 'Lys-20' (H4K20me0) of histone H4 and nucleosomes (PubMed:24396869). H4 'Lys-20' trimethylation represents a specific tag for epigenetic transcriptional repression. Mainly functions in pericentric heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin in these regions. KMT5B is targeted to histone H3 via its interaction with RB1 family proteins (RB1, RBL1 and RBL2) (By similarity). Plays a role in myogenesis by regulating the expression of target genes, such as EID3 (PubMed:23720823). Facilitates TP53BP1 foci formation upon DNA damage and proficient non-homologous end-joining (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (PubMed:28114273). May play a role in class switch reconbination by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (By similarity)

Subcellular location

NucleusChromosome

Domains and Gene Ontology detail (19)

Domains & features

SET

Gene Ontology

Ccondensed chromosome, centromeric region
Cfibrillar center
Cnucleoplasm
Cnucleus
Fchromatin binding
Fhistone H4 methyltransferase activity
Fhistone H4K20 methyltransferase activity
Fhistone H4K20 monomethyltransferase activity
Fhistone H4K20me methyltransferase activity
Fhistone methyltransferase activity
Fmetal ion binding
FS-adenosyl-L-methionine binding

885 aa · 99 kDa · 3 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Transcriptional regulationUniProt · GOMetabolic enzyme activityGO

View supporting evidence

Transcriptional regulation

·Histone methyltransferase that specifically methylates monomethylated 'Lys-20' (H4K20me1…
·DNA-templated transcription

Metabolic enzyme activity

·histone H4 methyltransferase activity
·histone H4K20 methyltransferase activity
·histone H4K20 monomethyltransferase activity
·histone H4K20me methyltransferase activity

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene KMT5B

Gene-level evidence surfaced through the gene KMT5Bthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Genetic Diseases, Inborn

0.85Well supported

Genetic evidence dominant · Open Targets 0.52

Neural Tube Defects

0.56Moderately supported

Genetic evidence dominant · Open Targets 0.34

Complex neurodevelopmental disorder

0.49Limited support

Genetic literature evidence dominant · Open Targets 0.37

Poisoning

0.45Limited support

Genetic evidence dominant · Open Targets 0.28

Autism Spectrum Disorder

0.45Limited support

Genetic evidence dominant · Open Targets 0.33

View evidence synthesis (5)

Genetic Diseases, InbornWell supported

0.85

agreement 0.73–0.97

Genetic100%

Open Targets aggregate 0.52 · 1 independent evidence family

Neural Tube DefectsModerately supported

0.56

agreement 0.44–0.68

Genetic100%

Open Targets aggregate 0.34 · 1 independent evidence family

Complex neurodevelopmental disorderLimited support

0.49

agreement 0.33–0.64

Genetic literature100%

Open Targets aggregate 0.37 · 1 independent evidence family

PoisoningLimited support

0.45

agreement 0.33–0.57

Genetic100%

Open Targets aggregate 0.28 · 1 independent evidence family

Autism Spectrum DisorderLimited support

0.45

agreement 0.31–0.59

Genetic97%Literature3%

Open Targets aggregate 0.33 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Genetic Diseases, Inborn0.52

Complex neurodevelopmental disorder0.37

Neural Tube Defects0.34

Autism Spectrum Disorder0.33

Poisoning0.28

Tractability

Small molecules — Emerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

Antibodies — Emerging

Feasibility evidence (go cc high conf and human protein atlas loc) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (7)

SM · Structure with LigandSM · High-Quality LigandAB · GO CC high confAB · Human Protein Atlas locPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule Binder

Raw Open Targets tractability assessment buckets, by modality.