EBF2

Chr 8

EBF transcription factor 2

Also known as: COE2, EBF-2, O/E-3, OE-3

EBF2 encodes a transcription factor that regulates bone development by activating TNFRSF11B in osteoblasts, which controls osteoclast differentiation and bone remodeling. Mutations cause autosomal dominant hypodontia and delayed tooth eruption. This gene is highly constrained against loss-of-function variants (pLI=1.0, LOEUF=0.19), indicating that such mutations are likely pathogenic.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
14
Pubs (1 yr)
82
P/LP submissions
0%
P/LP missense
0.19
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryEBF2
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
82 unique Pathogenic / Likely Pathogenic· 65 VUS of 159 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.19LOEUF
pLI 1.000
Z-score 4.97
OE 0.06 (0.020.19)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.11Z-score
OE missense 0.67 (0.600.75)
221 obs / 328.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.06 (0.020.19)
00.351.4
Missense OE0.67 (0.600.75)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 2 / 32.6Missense obs/exp: 221 / 328.6Syn Z: -0.43
DN
0.4587th %ile
GOF
0.3887th %ile
LOF
0.81top 5%

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

LOFprediction above median · LOEUF 0.19

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

159 submitted variants in ClinVar

Classification Summary

Pathogenic78
Likely Pathogenic4
VUS65
Benign2
78
Pathogenic
4
Likely Pathogenic
65
VUS
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
78
0
78
Likely Pathogenic
0
0
4
0
4
VUS
0
61
4
0
65
Likely Benign
0
0
0
0
0
Benign
0
0
1
1
2
Total061871149

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

View in ClinVar →

Protein Context — Lollipop Plot

EBF2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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