SOX18

SRY-box transcription factor 18, the group of SRY-box transcription factors

Basic information

Region (hg38): 20:64047582-64049639

Links

ENSG00000203883NCBI:54345OMIM:601618HGNC:11194Uniprot:P35713AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • hypotrichosis-lymphedema-telangiectasia-renal defect syndrome (Strong), mode of inheritance: AD
  • hypotrichosis-lymphedema-telangiectasia syndrome (Strong), mode of inheritance: AR
  • hypotrichosis-lymphedema-telangiectasia syndrome (grouping) (Supportive), mode of inheritance: AD
  • hypotrichosis-lymphedema-telangiectasia syndrome (Moderate), mode of inheritance: AD
  • hypotrichosis-lymphedema-telangiectasia syndrome (Limited), mode of inheritance: AR
  • hypotrichosis-lymphedema-telangiectasia-renal defect syndrome (Strong), mode of inheritance: AD
  • hypotrichosis-lymphedema-telangiectasia syndrome (Limited), mode of inheritance: AR
  • hypotrichosis-lymphedema-telangiectasia-renal defect syndrome (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Hypotrichosis-lymphedema-telangiectasia syndrome; Hypotrichosis-lymphedema-telangiectasia-renal defect syndromeAD/ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingCardiovascular; Craniofacial; Dermatologic; Genitourinary; Neurologic; Renal2484451; 12740761; 24697860
Renal transplantation has been described in Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SOX18 gene.

  • not_provided (93 variants)
  • Inborn_genetic_diseases (75 variants)
  • Hypotrichosis-lymphedema-telangiectasia-renal_defect_syndrome (69 variants)
  • Hypotrichosis-lymphedema-telangiectasia_syndrome (68 variants)
  • SOX18-related_disorder (6 variants)
  • not_specified (3 variants)
  • Bladder_exstrophy-epispadias-cloacal_extrophy_complex (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SOX18 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018419.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
29
clinvar
1
clinvar
30
missense
2
clinvar
134
clinvar
11
clinvar
1
clinvar
148
nonsense
1
clinvar
2
clinvar
2
clinvar
5
start loss
0
frameshift
3
clinvar
1
clinvar
4
splice donor/acceptor (+/-2bp)
0
Total 3 5 137 40 2

Highest pathogenic variant AF is 0.0000066492

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SOX18protein_codingprotein_codingENST00000340356 21919
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.1510.784111033011110340.00000450
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.8601041320.7890.000006112355
Missense in Polyphen2534.5970.72261587
Synonymous-0.0008106060.01.000.00000289856
Loss of Function1.5025.970.3352.54e-7107

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.000009940.00000994
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

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

Haploinsufficiency Scores

pHI
0.206
hipred
hipred_score
ghis
0.584

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.965

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Sox18
Phenotype
behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; pigmentation phenotype; digestive/alimentary phenotype; immune system phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype;

Zebrafish Information Network

Gene name
sox18
Affected structure
vascular lymphangioblast
Phenotype tag
abnormal
Phenotype quality
decreased amount

Gene ontology

Biological process
negative regulation of transcription by RNA polymerase II;angiogenesis;vasculogenesis;in utero embryonic development;hair follicle development;vasculature development;lymphangiogenesis;heart looping;outflow tract morphogenesis;regulation of transcription, DNA-templated;hair cycle process;cell differentiation;embryonic heart tube development;mRNA transcription by RNA polymerase II;blood vessel endothelial cell migration;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;cell maturation;stem cell fate specification;endocardium formation;lymphatic endothelial cell differentiation;endocardial cell differentiation;establishment of endothelial barrier;regulation of stem cell proliferation
Cellular component
nuclear chromatin;nucleus;nuclear transcription factor complex
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