OSR2

Chr 8

odd-skipped related transciption factor 2

OSR2 encodes a transcription factor that is involved in mandibular molar tooth development during the bud stage. Mutations cause isolated tooth agenesis, which follows an autosomal dominant inheritance pattern. The gene shows relatively low constraint against loss-of-function variants, suggesting some tolerance to functional disruption.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
9
Pubs (1 yr)
35
P/LP submissions
0%
P/LP missense
0.79
LOEUF
DN
Mechanism· predicted
Clinical SummaryOSR2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
35 unique Pathogenic / Likely Pathogenic· 37 VUS of 84 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.79LOEUF
pLI 0.130
Z-score 2.01
OE 0.31 (0.140.79)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.83Z-score
OE missense 0.62 (0.530.72)
115 obs / 185.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.31 (0.140.79)
00.351.4
Missense OE0.62 (0.530.72)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 3 / 9.8Missense obs/exp: 115 / 185.2Syn Z: -0.56
DN
0.78top 25%
GOF
0.5563th %ile
LOF
0.55top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

84 submitted variants in ClinVar

Classification Summary

Pathogenic35
VUS37
Likely Benign5
Benign1
35
Pathogenic
37
VUS
5
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
35
0
35
Likely Pathogenic
0
0
0
0
0
VUS
0
26
11
0
37
Likely Benign
0
4
0
1
5
Benign
0
0
0
1
1
Total03046278

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

View in ClinVar →

Protein Context — Lollipop Plot

OSR2 · 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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