SOX18
protein-codingSRY-box transcription factor 18, 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. This protein plays a role in hair, blood vessel, and lymphatic vessel development. Mutations in this gene have been associated with recessive and dominant forms of hypotrichosis-lymphedema-telangiectasia. [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 ~2.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0011914
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0019073
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0007670
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0011914
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0011914
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0019073
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0019073
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0011914
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0011914
Submitter: Genomics England PanelApp
Inheritance Pattern: AD
Disease ID:MONDO:0019073
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Neurologic; Renal
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
Comments: Renal transplantation has been described in Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SOX18 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018419.3. 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 | 40 | 2 | 42 | |||
| missense | 2 | 147 | 12 | 1 | 162 | |
| nonsense | 1 | 3 | 1 | 5 | ||
| start loss | 0 | |||||
| frameshift | 3 | 2 | 5 | |||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 3 | 6 | 150 | 52 | 3 | 214 |
Highest pathogenic variant AF is 0.0000066492016
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060889.1 | 2 | MANE Select | |
| Ensembl | ENSP00000341815.7 | 2 | MANE Select | |
| Ensembl | ENSP00000807952.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| sox18 | Danio rerio | Structure: vascular lymphangioblast Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of transcription by RNA polymerase II
- angiogenesis
- vasculogenesis
- in utero embryonic development
- hair follicle development
Molecular Function
- 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
- transcription regulatory region DNA binding
- protein heterodimerization activity
Cellular Component
- nuclear chromatin
- nucleus
- nuclear transcription factor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000340356
- Coding exons
- 2
- Length
- 1919
- Individuals with no LoFs
- 111033
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 111034
- p
- 0.00000450
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.860 | 104 | 132 | 0.789 | 0.00000611 | 2355 |
| Missense (PolyPhen) | 25 | 34.597 | 0.72261 | 587 | ||
| Synonymous | -0.000810 | 60 | 60.0 | 1.00 | 0.00000289 | 856 |
| Loss of Function | 1.50 | 2 | 5.97 | 0.335 | 2.54e-7 | 107 |
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) | 0.0000099 | 0.0000099 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds to the consensus sequence 5'-AACAAAG-3' and is able to trans-activate transcription via this site. {ECO:0000250}.;
- Disease
- DISEASE: Hypotrichosis-lymphedema-telangiectasia syndrome (HLTS) [MIM:607823]: A syndrome characterized by absent eyebrows and eyelashes, lymphatic edemas of the inferior members or eyelids, and peripheral vein anomalies. {ECO:0000269|PubMed:12740761}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome (HLTRS) [MIM:137940]: A syndrome characterized by sparse hair, lymphatic edemas, peripheral vein anomalies, and renal disease. {ECO:0000269|PubMed:12740761, ECO:0000269|PubMed:24697860}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.147
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.965
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |