OSR2

Chr 8

odd-skipped related transciption factor 2

NCBI Gene: 116039 ENSG00000164920 UniProt: Q8N2R0 OMIM: 611297

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.

OMIM ResearchSummary from RefSeq, UniProt

OSR2 is a mammalian homolog of the Drosophila odd-skipped family of transcription factors (Lan et al., 2004 [PubMed 15175245]).[supplied by OMIM, Mar 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.79

Clinical Summary— OSR2

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 26 VUS of 40 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.79LOEUF

pLI 0.130

Z-score 2.01

OE 0.31 (0.14–0.79)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.83Z-score

OE missense 0.62 (0.53–0.72)

115 obs / 185.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.31 (0.14–0.79)

0≤0.351.4

Missense OE?0.62 (0.53–0.72)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 3 / 9.8Missense obs/exp: 115 / 185.2Syn Z: -0.56

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

limitedOSR2-related radioulnar synostosisOTHERAD

This gene — mechanism propensity

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

40 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS26

Likely Benign5

Benign1

Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	2	0	2
Likely Pathogenic	0	0	0	0
VUS	26	0	0	26
Likely Benign	4	0	1	5
Benign	0	0	1	1
Total	30	2	2	34

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

View in ClinVar →

33 pathogenic / likely-pathogenic (of 44) ClinVar copy-number / structural variants overlap OSR2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →