DNMT3B

Chr 20Digenic dominantAR

DNA methyltransferase 3 beta

Also known as: FSHD4, ICF, ICF1, M.HsaIIIB

CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a DNA methyltransferase which is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes primarily to the nucleus and its expression is developmentally regulated. Mutations in this gene cause the immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome. Eight alternatively spliced transcript variants have been described. The full length sequences of variants 4 and 5 have not been determined. [provided by RefSeq, May 2011]

Primary Disease Associations & Inheritance

Facioscapulohumeral muscular dystrophy 4, digenicMIM #619478
Digenic dominant
Immunodeficiency-centromeric instability-facial anomalies syndrome 1MIM #242860
AR
1
Active trials
0
Pathogenic / LP
0
ClinVar variants
152
Pubs (1 yr)
1.5
Missense Z
0.38
LOEUF
Clinical SummaryDNMT3B
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Gene-Disease Validity (ClinGen)
immunodeficiency-centromeric instability-facial anomalies syndrome 1 · ARStrong

Strong evidence — appropriate for clinical testing

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
GeneReview available — DNMT3B
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.38LOEUF
pLI 0.200
Z-score 5.26
OE 0.24 (0.150.38)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.50Z-score
OE missense 0.81 (0.750.88)
418 obs / 513.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.24 (0.150.38)
00.351.4
Missense OE0.81 (0.750.88)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 13 / 55.2Missense obs/exp: 418 / 513.7Syn Z: -0.16

ClinVar Variant Classifications

0 submitted variants in ClinVar

DNMT3B · protein map & ClinVar variants

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

Gene2Phenotype Curations

DNMT3B-related immunodeficiency-centromeric instability-facial anomalies syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Literature
Landmark / reviewRecent case evidence