SOX18

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

Basic information

Region (hg38): 20:64047582-64049639

Links

ENSG00000203883 ∙ NCBI:54345 ∙ OMIM:601618 ∙ HGNC:11194 ∙ Uniprot:P35713 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypotrichosis-lymphedema-telangiectasia syndrome; Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome	AD/AR	General	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	Cardiovascular; Craniofacial; Dermatologic; Genitourinary; Neurologic; Renal	2484451; 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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				29	1	30
missense	2		134	11	1	148
nonsense	1	2	2			5
start loss						0
frameshift		3	1			4
splice donor/acceptor (+/-2bp)						0
Total	3	5	137	40	2

Highest pathogenic variant AF is 0.0000066492

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SOX18	protein_coding	protein_coding	ENST00000340356	2	1919

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.151	0.784	111033	0	1	111034	0.00000450

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.860	104	132	0.789	0.00000611	2355
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000994	0.00000994
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

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
• 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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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