SFMBT2
Chr 10Scm like with four mbt domains 2
Encodes a transcriptional repressor that binds histones and specifically represses HOXB13 gene expression. Biallelic mutations cause developmental and epileptic encephalopathy with microcephaly. This gene is highly constrained against loss-of-function variation (pLI 0.999, LOEUF 0.252), consistent with autosomal recessive inheritance where complete loss of function is pathogenic.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
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
182 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 22 | 0 | 22 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 121 | 10 | 0 | 131 |
Likely Benign | 0 | 7 | 0 | 2 | 9 |
Benign | 0 | 0 | 2 | 0 | 2 |
| Total | 0 | 128 | 35 | 2 | 165 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SFMBT2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools