KMT5B

Chr 11AD

lysine methyltransferase 5B

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

NCBI Gene: 51111ENSG00000110066UniProt: Q4FZB7

This gene encodes a protein that contains a SET domain. SET domains appear to be protein-protein interaction domains that mediate interactions with a family of proteins that display similarity with dual-specificity phosphatases (dsPTPases). The function of this gene has not been determined. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 51MIM #617788
AD
265
ClinVar variants
83
Pathogenic / LP
1.00
pLI score· haploinsufficient
2
Active trials
Clinical Summary— KMT5B
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · 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
83 Pathogenic / Likely Pathogenic· 125 VUS of 265 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.08LOEUF
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?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.
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?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.0.00 (0.00–0.08)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.64 (0.58–0.70)
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.0.86
0≤1.21.6
LoF obs/exp: 0 / 38.1Missense obs/exp: 306 / 477.5Syn Z: 1.46

ClinVar Variant Classifications

265 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic44
VUS125
Likely Benign43
Benign7
Conflicting7
39
Pathogenic
44
Likely Pathogenic
125
VUS
43
Likely Benign
7
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
19
2
18
0
39
Likely Pathogenic
19
11
14
0
44
VUS
7
103
15
0
125
Likely Benign
1
21
4
17
43
Benign
0
2
3
2
7
Conflicting
—7
Total461395419265

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.

Gene2Phenotype Curations

KMT5B-related intellectual developmental disorder

definitive
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

Intellectual developmental disorder, autosomal dominant 51

MIM #617788

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.
Stessman HA et al.·Nat Genet
2017
Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.
Sheppard SE et al.·Sci Adv
2023Functional
Histone Lysine Methylases and Demethylases in the Landscape of Human Developmental Disorders.
Faundes V et al.·Am J Hum Genet
2018
H4K20me3-Mediated Repression of Inflammatory Genes Is a Characteristic and Targetable Vulnerability of Persister Cancer Cells.
Ramponi V et al.·Cancer Res
2025
Loss-of-function of KMT5B leads to neurodevelopmental disorder and impairs neuronal development and neurogenesis.
Chen G et al.·J Genet Genomics
2022
Bridging Genotype to Phenotype in KMT5B-Related Syndrome: Evidence from RNA-Seq, (18)FDG-PET, Clinical Deep Phenotyping in Two New Cases, and a Literature Review.
Politano D et al.·Genes (Basel)
2025Review
Persistence and/or Senescence: Not So Lasting at Last?
Schmitt CA·Cancer Res
2025
Neurodevelopmental disorder caused by an inherited novel KMT5B variant: case report.
Odak L et al.·Croat Med J
2023Case report
Novel pathogenic variants and multiple molecular diagnoses in neurodevelopmental disorders.
Trinh J et al.·J Neurodev Disord
2019
Histone methyltransferase SUV420H1/KMT5B contributes to poor prognosis in hepatocellular carcinoma.
Kato H et al.·Cancer Sci
2024
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
NAFLD

Target of Suv420h1/2 in Hepatocytes

RECRUITING
NCT06332677Phase NAFondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoStarted 2023-03-01
the main genes and expression by comparing the transcriptomic lipidomic profile

External Resources

Links to major genomics databases and tools