SOX18 (SRY-box transcription factor 18)

Gene

• Entrez ID: 54345
• Gene name: SRY-box transcription factor 18
• Gene symbol: SOX18
• Synonyms (NCBI Gene): HLTRS, HLTS
• Chromosome: 20
• Chromosome location: 20q13.33
• 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 for

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT018859	hsa-miR-335-5p	Microarray	18185580

Transcription factors

Transcription factor	Regulation	Reference
EGR1	Unknown	20054233
NFYA	Activation	18496767
NFYB	Activation	18496767
NFYC	Activation	18496767
SP3	Repression	18496767
ZNF148	Repression	18496767

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000122	Process	Negative regulation of transcription by RNA polymerase II	IDA	22292085
GO:0000785	Component	Chromatin	IDA	22292085
GO:0000785	Component	Chromatin	ISA
GO:0000976	Function	Transcription cis-regulatory region binding	IDA	18065521
GO:0000976	Function	Transcription cis-regulatory region binding	IEA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA	22292085
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IEA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IBA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	22292085
GO:0001525	Process	Angiogenesis	IBA
GO:0001525	Process	Angiogenesis	IEA
GO:0001525	Process	Angiogenesis	IEP	16882943
GO:0001568	Process	Blood vessel development	IEA
GO:0001570	Process	Vasculogenesis	IBA
GO:0001570	Process	Vasculogenesis	IEA
GO:0001570	Process	Vasculogenesis	ISS
GO:0001701	Process	In utero embryonic development	IEA
GO:0001942	Process	Hair follicle development	IEA
GO:0001944	Process	Vasculature development	IEA
GO:0001944	Process	Vasculature development	ISS
GO:0001945	Process	Lymph vessel development	IEA
GO:0001946	Process	Lymphangiogenesis	IBA
GO:0001946	Process	Lymphangiogenesis	IEA
GO:0001946	Process	Lymphangiogenesis	IMP	12740761
GO:0001947	Process	Heart looping	ISS
GO:0003151	Process	Outflow tract morphogenesis	ISS
GO:0003677	Function	DNA binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IEA
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	18065521
GO:0005634	Component	Nucleus	IEA
GO:0005667	Component	Transcription regulator complex	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0007507	Process	Heart development	IEA
GO:0009888	Process	Tissue development	IEA
GO:0022405	Process	Hair cycle process	IMP	12740761
GO:0035050	Process	Embryonic heart tube development	IEA
GO:0035050	Process	Embryonic heart tube development	ISS
GO:0043534	Process	Blood vessel endothelial cell migration	IEP	16882943
GO:0043565	Function	Sequence-specific DNA binding	IEA
GO:0045892	Process	Negative regulation of DNA-templated transcription	IEA
GO:0045892	Process	Negative regulation of DNA-templated transcription	ISS
GO:0045893	Process	Positive regulation of DNA-templated transcription	IEA
GO:0045893	Process	Positive regulation of DNA-templated transcription	ISS
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IBA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	18065521, 22292085
GO:0048469	Process	Cell maturation	IEA
GO:0048646	Process	Anatomical structure formation involved in morphogenesis	IEA
GO:0048866	Process	Stem cell fate specification	IEA
GO:0060214	Process	Endocardium formation	IEA
GO:0060214	Process	Endocardium formation	ISS
GO:0060836	Process	Lymphatic endothelial cell differentiation	IEA
GO:0060836	Process	Lymphatic endothelial cell differentiation	ISS
GO:0060956	Process	Endocardial cell differentiation	IEA
GO:0060956	Process	Endocardial cell differentiation	ISS
GO:0061028	Process	Establishment of endothelial barrier	IMP	18065521
GO:0072091	Process	Regulation of stem cell proliferation	IEA
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

Other IDs

• MIM: 601618
• HGNC: 11194
• e!Ensembl: ENSG00000203883

Protein

• UniProt ID: P35713
• Protein name: Transcription factor SOX-18
• Protein function: Transcriptional activator that binds to the consensus sequence 5'-AACAAAG-3' in the promoter of target genes and plays an essential role in embryonic cardiovascular development and lymphangiogenesis. Activates transcription of PROX1 and other ge
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00505	HMG_box	85 → 153	HMG (high mobility group) box	Domain
  PF12067	Sox17_18_mid	197 → 249	Sox 17/18 central domain	Family

• Tissue specificity: TISSUE SPECIFICITY: Detected in heart, lung, placenta, skeletal muscle, liver, kidney, spleen, prostate, ovary, msosmall intestine and colon. {ECO:0000269|PubMed:10807548, ECO:0000269|PubMed:11130989}.
• Sequence:

  MQRSPPGYGAQDDPPARRDCAWAPGHGAAADTRGLAAGPAALAAPAAPASPPSPQRSPPR
  SPEPGRYGLSPAGRGERQAADESRIRRPMNAFMVWAKDERKRLAQQNPDLHNAVLSKMLG
  KAWKELNAAEKRPFVEEAERLRVQHLRDHPNYKYRPRRKKQARKARRLEPGLLLPGLAPP
  QPPPEPFPAASGSARAFRELPPLGAEFDGLGLPTPERSPLDGLEPGEAAFFPPPAAPEDC
  ALRPFRAPYAPTELSRDPGGCYGAPLAEALRTAPPAAPLAGLYYGTLGTPGPYPGPLSPP
  PEAPPLESAEPLGPAADLWADVDLTEFDQYLNCSRTRPDAPGLPYHVALAKLGPRAMSCP
  EESSLISALSDASSAVYYSACISG

• Sequence length: 384

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Hypotrichosis-lymphedema-telangiectasia syndrome	Likely pathogenic; Pathogenic	rs794728015, rs28936692, rs28936693	RCV000184062 RCV000008464 RCV000008465	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome	Likely pathogenic; Pathogenic	rs74315430, rs1210062863	RCV000008466 RCV000590995	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
BLADDER EXSTROPHY AND EPISPADIAS COMPLEX	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Bladder exstrophy-epispadias-cloacal extrophy complex	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARCINOMA, BASAL CELL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DERMATOLOGIC DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SKIN DISEASES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SKIN DISEASES, GENETIC	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SOX18-related disorder	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Absent eyebrow	Absent eyebrow	HPO_DG			★☆☆☆☆ Found in Text Mining only
Adenocarcinoma	Adenocarcinoma	BEFREE	25310193, 29115529		★☆☆☆☆ Found in Text Mining only
Adenocarcinoma of lung (disorder)	Lung adenocarcinoma	BEFREE	29115529		★☆☆☆☆ Found in Text Mining only
Alopecia	Alopecia	HPO_DG			★☆☆☆☆ Found in Text Mining only
ANOPHTHALMIA AND PULMONARY HYPOPLASIA	Syndromic microphthalmia	BEFREE	29408481		★☆☆☆☆ Found in Text Mining only
Arsenic Encephalopathy	Arsenic Encephalopathy	CTD_human_DG	16835338		★☆☆☆☆ Found in Text Mining only
Arteriosclerosis	Arteriosclerosis	BEFREE	16179596, 27666488		★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	BEFREE	16179596, 27666488		★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	LHGDN	16179596		★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	Pubtator	20054233	Associate	★☆☆☆☆ Found in Text Mining only
Bladder Neoplasm	Bladder Neoplasm	BEFREE	31260682		★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	16882943, 24065215, 27108946, 28137359		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	27188720	Inhibit	★☆☆☆☆ Found in Text Mining only
Carcinoma Ductal Breast	Ductal carcinoma of breast	Pubtator	31427562	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	26151573, 31427562, 35465267	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma of bladder	Bladder carcinoma	BEFREE	31260682		★☆☆☆☆ Found in Text Mining only
Carcinoma of lung	Lung carcinoma	BEFREE	15911247, 25310193, 27666488, 29115529		★☆☆☆☆ Found in Text Mining only
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	25075026, 31427562		★☆☆☆☆ Found in Text Mining only
Cardiomyopathy, Familial Idiopathic	Cardiomyopathy	BEFREE	24065215		★☆☆☆☆ Found in Text Mining only
Cardiovascular Abnormalities	Cardiovascular abnormalities	Pubtator	12740761	Associate	★☆☆☆☆ Found in Text Mining only
Central Nervous System Diseases	Central nervous system disease	Pubtator	36672963	Associate	★☆☆☆☆ Found in Text Mining only
Cholestasis	Cholelithiasis	Pubtator	27230943	Associate	★☆☆☆☆ Found in Text Mining only
Chronic Kidney Diseases	Kidney Disease	HPO_DG			★☆☆☆☆ Found in Text Mining only
Class III malocclusion	Malocclusion	HPO_DG			★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	30555240		★☆☆☆☆ Found in Text Mining only
Congenital Epicanthus	Congenital Epicanthus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital hypotrichia	Congenital Hypotrichia	BEFREE	12740761, 19429912, 19515696, 29307792		★☆☆☆☆ Found in Text Mining only
Conventional (Clear Cell) Renal Cell Carcinoma	Renal Carcinoma	BEFREE	31527225		★☆☆☆☆ Found in Text Mining only
Cushing's symphalangism	Proximal symphalangism	Pubtator	12740761	Associate	★☆☆☆☆ Found in Text Mining only
Cutis marmorata	Cutis marmorata	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dermatologic disorders	Dermatologic Disorders	CTD_human_DG	16835338		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Early infantile epileptic encephalopathy with suppression bursts	Epileptic Encephalopathy	BEFREE	29266413		★☆☆☆☆ Found in Text Mining only
Endometrial Carcinoma	Endometrial carcinoma	BEFREE	30935961		★☆☆☆☆ Found in Text Mining only
Endometrial Neoplasms	Endometrial neoplasm	Pubtator	30935961	Associate	★☆☆☆☆ Found in Text Mining only
Generalized hypotrichosis	Hypotrichosis	CLINVAR_DG	29307792		★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	21211035		★☆☆☆☆ Found in Text Mining only
Glomerulonephritis, Membranoproliferative	Glomerulonephritis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hemangioma	Hemangioma	BEFREE	31358114		★☆☆☆☆ Found in Text Mining only
Hydrops Fetalis	Hydrops fetalis	Pubtator	12740761	Associate	★☆☆☆☆ Found in Text Mining only
Hydrops Fetalis	Hydrops Fetalis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hydrops Fetalis, Non-Immune	Hydrops Fetalis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	BEFREE	30549413		★☆☆☆☆ Found in Text Mining only
Hypotrichosis	Hypotrichosis	BEFREE	12740761, 19429912, 19515696, 29307792		★☆☆☆☆ Found in Text Mining only
Hypotrichosis	Hypotrichosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypotrichosis, lymphedema, telangiectasia, renal defect syndrome	Hypotrichosis-Lymphedema-Telangiectasia-Renal Defect Syndrome	GENOMICS_ENGLAND_DG	12740761		★☆☆☆☆ Found in Text Mining only
Hypotrichosis, lymphedema, telangiectasia, renal defect syndrome	Hypotrichosis-Lymphedema-Telangiectasia-Renal Defect Syndrome	ORPHANET_DG	24697860		★☆☆☆☆ Found in Text Mining only
Hypotrichosis, lymphedema, telangiectasia, renal defect syndrome	Hypotrichosis-Lymphedema-Telangiectasia-Renal Defect Syndrome	CLINVAR_DG	29307792		★☆☆☆☆ Found in Text Mining only
Hypotrichosis, lymphedema, telangiectasia, renal defect syndrome	Hypotrichosis-Lymphedema-Telangiectasia-Renal Defect Syndrome	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
HYPOTRICHOSIS-LYMPHEDEMA-TELANGIECTASIA SYNDROME	Hypotrichosis-Lymphedema-Telangiectasia-Renal Defect Syndrome	GENOMICS_ENGLAND_DG	12740761		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HYPOTRICHOSIS-LYMPHEDEMA-TELANGIECTASIA SYNDROME	Hypotrichosis-Lymphedema-Telangiectasia-Renal Defect Syndrome	UNIPROT_DG	12740761		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HYPOTRICHOSIS-LYMPHEDEMA-TELANGIECTASIA SYNDROME	Hypotrichosis-Lymphedema-Telangiectasia-Renal Defect Syndrome	CLINVAR_DG	12740761, 24697860, 26148450		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HYPOTRICHOSIS-LYMPHEDEMA-TELANGIECTASIA SYNDROME	Hypotrichosis-Lymphedema-Telangiectasia-Renal Defect Syndrome	BEFREE	19429912, 24697860, 26148450, 26631803, 29307792, 30549413		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
HYPOTRICHOSIS-LYMPHEDEMA-TELANGIECTASIA SYNDROME	Hypotrichosis-Lymphedema-Telangiectasia-Renal Defect Syndrome	CTD_human_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hypotrichosis-lymphedema-telangiectasia-renal defect syndrome	Hypotrichosis-Lymphedema-Telangiectasia-Renal Defect Syndrome	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Infantile hemangioma	Hemangioma	BEFREE	31358114		★☆☆☆☆ Found in Text Mining only
Invasive Ductal Breast Carcinoma	Invasive Duct and Lobular Carcinoma	BEFREE	24065215, 29345290, 31427562		★☆☆☆☆ Found in Text Mining only
Kidney Failure	Kidney Failure	BEFREE	24697860		★☆☆☆☆ Found in Text Mining only
Laryngeal Neoplasms	Laryngeal neoplasm	Pubtator	31189744	Associate	★☆☆☆☆ Found in Text Mining only
Leiomyosarcoma	Leiomyosarcoma	Pubtator	22419440	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	29428447		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	26151573, 31427562, 31529503		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	37511076	Associate	★☆☆☆☆ Found in Text Mining only
Lymphedema	Lymphedema	Pubtator	12740761, 18564920	Associate	★☆☆☆☆ Found in Text Mining only
Lymphoma, T-Cell, Cutaneous	Lymphoma	BEFREE	27230943		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	16882943, 24065215, 27108946, 28137359		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of endometrium	Endometrial Cancer	BEFREE	30935961		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of lung	Lung Cancer	BEFREE	15911247, 25310193, 27666488, 29115529		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of ovary	Ovarian cancer	BEFREE	25075026, 31427562		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	27922675		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of urinary bladder	Urinary bladder cancer	BEFREE	31260682		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	24065215, 25075026, 26151573, 27922675, 30008814, 30914279, 31260682, 31527225		★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	BEFREE	16882943		★☆☆☆☆ Found in Text Mining only
Milroy Disease	Milroy Disease	BEFREE	18564920, 29307792		★☆☆☆☆ Found in Text Mining only
Mycosis Fungoides	Mycosis fungoides	Pubtator	27230943	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	16882943, 21211035, 21796627, 26573263, 27922675, 29115529, 30604758		★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	25310193, 27666488, 29115529		★☆☆☆☆ Found in Text Mining only
Opitz GBBB Syndrome, X-Linked	Opitz GBBB Syndrome, X-Linked	BEFREE	29266413		★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	BEFREE	26573263, 29184419		★☆☆☆☆ Found in Text Mining only
Osteosarcoma	Osteosarcoma	Pubtator	32196572, 36053455	Associate	★☆☆☆☆ Found in Text Mining only
ovarian neoplasm	Ovarian neoplasm	BEFREE	25075026, 31427562		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	31427562, 31825847	Associate	★☆☆☆☆ Found in Text Mining only
Pancreatic Ductal Adenocarcinoma	Pancreatic adenocarcinoma	BEFREE	29408481		★☆☆☆☆ Found in Text Mining only
Pleural effusion disorder	Pleural effusion	HPO_DG			★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	27922675		★☆☆☆☆ Found in Text Mining only
Sarcoma Kaposi	Sarcoma	Pubtator	32518203	Associate	★☆☆☆☆ Found in Text Mining only
Seizures	Seizures	Pubtator	36672963	Associate	★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of lung	Lung carcinoma	BEFREE	27666488		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	26396173, 31881968	Associate	★☆☆☆☆ Found in Text Mining only
Strawberry nevus of skin	Strawberry Nevus Of Skin	BEFREE	31358114		★☆☆☆☆ Found in Text Mining only
Testicular Hydrocele	Testicular Hydrocele	HPO_DG			★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	32449280	Associate	★☆☆☆☆ Found in Text Mining only
Uterine Cervical Neoplasms	Uterine neoplasm	Pubtator	26588701	Associate	★☆☆☆☆ Found in Text Mining only
Vascular Diseases	Vascular Diseases	BEFREE	31358114		★☆☆☆☆ Found in Text Mining only