SOX4
protein-codingSRY-box transcription factor 4, the group of SRY-box transcription factors
Gene summary
This intronless 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, such as syndecan binding protein (syntenin). The protein may function in the apoptosis pathway leading to cell death as well as to tumorigenesis and may mediate downstream effects of parathyroid hormone (PTH) and PTH-related protein (PTHrP) in bone development. The solution structure has been resolved for the HMG-box of a similar mouse protein. [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 ~4.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0032791
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0015452
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0004981
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0032791
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0032791
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0032791
Submitter: Illumina
Inheritance Pattern: AD
Disease ID:MONDO:0032791
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular; Craniofacial; Musculoskeletal; Neurologic
Intervention: Cardiovascular
Rationale: The condition can involve congenital cardiac anomalies, and awareness may allow early management
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SOX4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003107.3. 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 | 1 | 42 | 1 | 44 | ||
| missense | 2 | 15 | 175 | 12 | 1 | 205 |
| nonsense | 4 | 3 | 6 | 13 | ||
| start loss | 0 | |||||
| frameshift | 2 | 5 | 13 | 2 | 22 | |
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 8 | 23 | 195 | 54 | 4 | 284 |
Highest pathogenic variant AF is 6.864492e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003098.1 | 1 | MANE Select | |
| Ensembl | ENSP00000244745.1 | 1 | MANE Select |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| sox4b | Danio rerio | Structure: glucagon secreting cell Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- MicroRNAs in cancer - Homo sapiens (human)
- H19 action Rb-E2F1 signaling and CDK-β-catenin activity
- Signaling by WNT
- Signal Transduction
- Deactivation of the beta-catenin transactivating complex
Biological Process
- skeletal system development
- neural tube formation
- pro-B cell differentiation
- mitral valve morphogenesis
- cardiac ventricle formation
Molecular Function
- transcription regulatory region sequence-specific DNA binding
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- mitochondrion
- nuclear transcription factor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000244745
- Coding exons
- 1
- Length
- 4876
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.17 | 150 | 196 | 0.765 | 0.00000902 | 2971 |
| Missense (PolyPhen) | 9 | 50.031 | 0.17989 | 563 | ||
| Synonymous | -5.14 | 157 | 93.7 | 1.67 | 0.00000469 | 1027 |
| Loss of Function | 2.68 | 0 | 8.34 | 0.00 | 3.61e-7 | 117 |
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 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional activator that binds with high affinity to the T-cell enhancer motif 5'-AACAAAG-3' motif.;
Recessive Scores
- pRec
- 0.260
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.903
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |