SOX7
protein-codingSRY-box transcription factor 7, the group of SRY-box transcription factors
Gene summary
This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins. The protein may play a role in tumorigenesis. A similar protein in mice is involved in the regulation of the wingless-type MMTV integration site family (Wnt) pathway. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005453
Submitter: ClinGen
*SOX7* was first reported in relation to autosomal dominant congenital heart disease in 2013 (Long et al., PMID: 24009689). At least two unique variants (1 missense, 1 nonsense) that were reported in two individuals with CHD (PMID: 35422912, 37406974) were included in this curation. There are other individuals reported with variants in *SOX7* in the literature, however they were not included due to inconsistent mechanism of pathogenicity or high frequencies in gnomAD v4 (PMIDs: 24009689, 35260939). Of note, several individuals with CHD were also identified with CNVs that included *SOX7* and other genes including *GATA4* (PMID: 22318994, 33846290, 36816019). This gene-disease relationship is also supported by evidence of biochemical function studies, expression in embryonic human and mouse heart, protein interaction with *GATA4*, and a knockout mouse model replicating the disease phenotype (PMIDs: 35260939, 33846290, 37000005). In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This classification was approved by the ClinGen Congenital Heart Disease GCEP on the meeting date October 1st, 2024 (SOP Version 11).
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SOX7 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_031439.4. 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 | 5 | 3 | 8 | |||
| missense | 84 | 2 | 1 | 87 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 85 | 7 | 4 | 96 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_113627.1 | 2 | MANE Select | |
| Ensembl | ENSP00000301921.1 | 2 | MANE Select | |
| Ensembl | ENSP00000805530.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| sox7 | Danio rerio | Structure: trunk Quality: decreased occurrence abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endoderm Differentiation
- Signaling by WNT
- Signal Transduction
- Deactivation of the beta-catenin transactivating complex
- TCF dependent signaling in response to WNT
Biological Process
- negative regulation of transcription by RNA polymerase II
- endoderm formation
- regulation of transcription, DNA-templated
- negative regulation of cell population proliferation
- cell differentiation
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- protein binding
- sequence-specific DNA binding
- transcription regulatory region DNA binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- nuclear transcription factor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000304501
- Coding exons
- 2
- Length
- 116080
- Individuals with no LoFs
- 125733
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 125742
- p
- 0.0000358
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.744 | 289 | 256 | 1.13 | 0.0000165 | 2449 |
| Missense (PolyPhen) | 83 | 88.422 | 0.93868 | 882 | ||
| Synonymous | -2.29 | 156 | 124 | 1.26 | 0.00000889 | 836 |
| Loss of Function | 2.37 | 2 | 10.2 | 0.197 | 4.33e-7 | 118 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000090 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000020 | 0.000018 | rare |
| South Asian | 0.000069 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds to and activates the CDH5 promoter, hence plays a role in the transcriptional regulation of genes expressed in the hemogenic endothelium and blocks further differentiation into blood precursors (By similarity). May be required for the survival of both hematopoietic and endothelial precursors during specification (By similarity). Competes with GATA4 for binding and activation of the FGF3 promoter (By similarity). Represses Wnt/beta-catenin-stimulated transcription, probably by targeting CTNNB1 to proteasomal degradation. Binds the DNA sequence 5'- AACAAT-3'. {ECO:0000250, ECO:0000269|PubMed:18819930}.;
Recessive Scores
- pRec
- 0.138
Intolerance Scores
- LoFtool
- 0.0872
- RVIS EVS
- -0.42
- RVIS percentile EVS
- 25.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.162
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |