OSR1
protein-codingodd-skipped related transcription factor 1, the group of Zinc fingers C2H2-type
Gene summary
Enables sequence-specific double-stranded DNA binding activity. Involved in negative regulation of sodium ion transmembrane transport; positive regulation of gastrulation; and pronephros development. Located in nucleus. [provided by Alliance of Genome Resources, Jun 2026]
- ODD
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005453
Submitter: ClinGen
*OSR1* was first reported in relation to autosomal dominant congenital heart disease in 2016 (Zhang et al 2016., PMID: 26744331). This gene-disease relationship is supported by a mouse model that showed the histology of *Tbx5* and *Osr1* transgenic mouse embryo hearts at E13.5 with missing structures of atrial septation (PMID: 26744331). In summary, the evidence supporting the relationship between *OSR1* and autosomal dominant congenital heart disease has been disputed and no valid evidence remains to support the claim. More evidence is needed to either support or entirely refute the role *OSR1* plays in this disease. This classification was approved by the ClinGen Congenital Heart Disease GCEP on the meeting date April 8th, 2024 (SOP Version 10).
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to OSR1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_145260.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 4 | ||||
| missense | 34 | 34 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 34 | 4 | 0 | 38 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_660303.1 | 2 | MANE Select | |
| Ensembl | ENSP00000272223.2 | 2 | MANE Select | |
| Ensembl | ENSP00000522293.1 | 2 | Standard | |
| Ensembl | ENSP00000522294.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| osr1 | Danio rerio | Structure: anterior lateral plate mesoderm Quality: morphology abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of transcription by RNA polymerase II
- urogenital system development
- ureteric bud development
- mesonephros development
- chondrocyte differentiation
Molecular Function
- RNA polymerase II regulatory region sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- metal ion binding
Cellular Component
- nucleus
- cytosol
- extrinsic component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000536433
- Coding exons
- 2
- Length
- 7169
- Individuals with no LoFs
- 125744
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 125745
- p
- 0.00000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.74 | 101 | 164 | 0.618 | 0.00000959 | 1719 |
| Missense (PolyPhen) | 20 | 56.256 | 0.35552 | 599 | ||
| Synonymous | 0.306 | 73 | 76.4 | 0.955 | 0.00000489 | 570 |
| Loss of Function | 2.36 | 0 | 6.51 | 0.00 | 3.18e-7 | 84 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcription factor that plays a role in the regulation of embryonic heart and urogenital development. {ECO:0000250}.;
Intolerance Scores
- LoFtool
- 0.0916
- RVIS EVS
- 0.04
- RVIS percentile EVS
- 56.92
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.921
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |