KMT5B

Chr 11AD

lysine methyltransferase 5B

Also known as: CGI-85, CGI85, MRD51, SUV420H1

NCBI Gene: 51111ENSG00000110066UniProt: Q4FZB7OMIM: 610881

The protein is a histone methyltransferase that specifically methylates lysine-20 of histone H4 to regulate transcriptional repression, heterochromatin formation, and DNA repair. Heterozygous loss-of-function mutations cause autosomal dominant intellectual developmental disorder through haploinsufficiency. The gene is highly intolerant to loss-of-function variants, consistent with dominant negative effects from reduced histone methylation activity.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.081 OMIM phenotype
Clinical Summary— KMT5B
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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.
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ClinVar Variants
83 unique Pathogenic / Likely Pathogenic· 124 VUS of 278 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.08LOEUF
pLI 1.000
Z-score 5.72
OE 0.00 (0.00–0.08)
Highly constrained

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

Missense Constraint
2.79Z-score
OE missense 0.64 (0.58–0.70)
306 obs / 477.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.08)
0≤0.351.4
Missense OE0.64 (0.58–0.70)
0≤0.61.4
Synonymous OE0.86
0≤1.21.6
LoF obs/exp: 0 / 38.1Missense obs/exp: 306 / 477.5Syn Z: 1.46
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveKMT5B-related intellectual developmental disorderLOFAD
DN
0.2099th %ile
GOF
0.1699th %ile
LOF
0.88top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 69% of P/LP variants are LoF · LOEUF 0.08

Literature Evidence

LOFWe provide evidence to firmly associate KMT2C, ASH1L, and KMT5B haploinsufficiency with dominant developmental disorders.PMID:29276005

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

278 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic46
VUS124
Likely Benign47
Benign6
Conflicting8
37
Pathogenic
46
Likely Pathogenic
124
VUS
47
Likely Benign
6
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
28
2
7
0
37
Likely Pathogenic
29
12
5
0
46
VUS
8
105
11
0
124
Likely Benign
1
23
3
20
47
Benign
0
3
1
2
6
Conflicting
—8
Total661452722268

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

View in ClinVar →

Protein Context — Lollipop Plot

KMT5B · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
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
Catalytic activity of KMT5B promotes ciliogenesis without affecting global chromatin accessibility.
Tait J et al.·Life Sci Alliance
2026Open Access
Novel KMT5B De Novo Variants Disrupt DNA Damage Response in Intellectual Disability.
Hu X et al.·QJM
2025
Combined Histological and Proteomic Analysis Reveals Muscle Denervation in KMT5B-Related Neurodevelopmental Disorder: A Case Report.
Aksel Kilicarslan O et al.·J Clin Med
2025Open AccessCase report
A Novel KMT5B Frameshift Variant Presenting with Autism and Psychiatric Features: Intrafamilial Phenotypic Variation - A Case Report.
Özcan S et al.·Mol Syndromol
2025Case report
Bridging Genotype to Phenotype in KMT5B-Related Syndrome: Evidence from RNA-Seq, 18FDG-PET, Clinical Deep Phenotyping in Two New Cases, and a Literature Review.
Politano D et al.·Genes (Basel)
2025Open AccessReview
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