SERPINA7 (serpin family A member 7)

Gene

• Entrez ID: 6906
• Gene name: Serpin family A member 7
• Gene symbol: SERPINA7
• Synonyms (NCBI Gene): TBG, TBGQTL
• Chromosome: X
• Chromosome location: Xq22.3
• Summary: There are three proteins including thyroxine-binding globulin (TBG), transthyretin and albumin responsible for carrying the thyroid hormones thyroxine (T4) and 3,5,3`-triiodothyronine (T3) in the bloodstream. This gene encodes the major thyroid hormone tr

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1050086	C>G,T	Pathogenic	Coding sequence variant, missense variant
rs1804495	C>A,T	Pathogenic	Coding sequence variant, missense variant, synonymous variant
rs2234036	C>T	Pathogenic, benign, uncertain-significance	Coding sequence variant, missense variant
rs28933689	A>T	Pathogenic	Coding sequence variant, missense variant
rs61754490	T>A,C	Pathogenic	Coding sequence variant, missense variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IBA
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IEA
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	TAS	3094014
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	NAS	14718574
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IEA
GO:0005615	Component	Extracellular space	TAS	7499319
GO:0070062	Component	Extracellular exosome	HDA	19056867, 23533145
GO:0070327	Process	Thyroid hormone transport	IMP	19415532

Other IDs

• MIM: 314200
• HGNC: 11583
• e!Ensembl: ENSG00000123561

Protein

• UniProt ID: P05543
• Protein name: Thyroxine-binding globulin (Serpin A7) (T4-binding globulin)
• Protein function: Major thyroid hormone transport protein in serum.
• PDB: 2CEO, 2RIV, 2RIW, 2XN3, 2XN5, 2XN6, 2XN7, 4X30, 4YIA
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00079	Serpin	44 → 412	Serpin (serine protease inhibitor)	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma.
• Sequence:

  MSPFLYLVLLVLGLHATIHCASPEGKVTACHSSQPNATLYKMSSINADFAFNLYRRFTVE
  TPDKNIFFSPVSISAALVMLSFGACCSTQTEIVETLGFNLTDTPMVEIQHGFQHLICSLN
  FPKKELELQIGNALFIGKHLKPLAKFLNDVKTLYETEVFSTDFSNISAAKQEINSHVEMQ
  TKGKVVGLIQDLKPNTIMVLVNYIHFKAQWANPFDPSKTEDSSSFLIDKTTTVQVPMMHQ
  MEQYYHLVDMELNCTVLQMDYSKNALALFVLPKEGQMESVEAAMSSKTLKKWNRLLQKGW
  VDLFVPKFSISATYDLGATLLKMGIQHAYSENADFSGLTEDNGLKLSNAAHKAVLHIGEK
  GTEAAAVPEVELSDQPENTFLHPIIQIDRSFMLLILERSTRSILFLGKVVNPTEA

• Sequence length: 415

Pathways

KEGG:

Thyroid hormone synthesis

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
Thyroxine-binding globulin deficiency, partial	Pathogenic	rs28933689	RCV000010454	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Thyroxine-binding globulin quantitative trait locus	Pathogenic	rs2147841568	RCV001784958	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Thyroxine-binding globulin, Chicago	Pathogenic	rs61754490	RCV000010459	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Thyroxine-binding globulin, slow	Pathogenic	rs1050086	RCV000010444	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Adrenocortical carcinoma, hereditary	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colorectal cancer	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER CIRRHOSIS, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pancreatic adenocarcinoma	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SERPINA7-related disorder	Conflicting classifications of pathogenicity; Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroxine-binding globulin deficiency	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroxine-binding globulin, variant A	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroxine-binding globulin, variant P	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
X-LINKED REDUCTION OF THYROXINE-BINDING GLOBULIN	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma, Clear Cell	Adenocarcinoma	BEFREE	26091520		★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	6092383	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Ovarian Epithelial	Epithelial ovarian carcinoma	Pubtator	26091520	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Renal Cell	Renal cell carcinoma	Pubtator	26091520	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma, Ovarian Epithelial	Ovarian Epithelial carcinoma	BEFREE	26091520		★☆☆☆☆ Found in Text Mining only
Cholangiocarcinoma	Cholangiocarcinoma	BEFREE	26627606		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Chronic Obstructive Airway Disease	Chronic Obstructive Pulmonary Disease	BEFREE	28579773		★☆☆☆☆ Found in Text Mining only
Congenital central hypothyroidism	Congenital Central Hypothyroidism	BEFREE	28910808		★☆☆☆☆ Found in Text Mining only
Congenital Hypothyroidism	Congenital Hypothyroidism	BEFREE	27362444		★☆☆☆☆ Found in Text Mining only
Depressive Disorder Major	Major depressive disorder	Pubtator	33451315	Associate	★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	BEFREE	3128768		★☆☆☆☆ Found in Text Mining only
Emphysema	Emphysema	Pubtator	25306249	Associate	★☆☆☆☆ Found in Text Mining only
Epilepsies Partial	Partial epilepsy	Pubtator	36475360	Associate	★☆☆☆☆ Found in Text Mining only
Epithelial ovarian cancer	Ovarian cancer	BEFREE	26091520		★☆☆☆☆ Found in Text Mining only
Familial hypercholesterolemia - homozygous	Hypercholesterolemia	BEFREE	28319445, 28319449		★☆☆☆☆ Found in Text Mining only
Fibrosis, Liver	Liver Fibrosis	BEFREE	29138513		★☆☆☆☆ Found in Text Mining only
Graves Disease	Graves Disease	BEFREE	402376		★☆☆☆☆ Found in Text Mining only
Hepatoblastoma	Hepatoblastoma	BEFREE	1323058, 8391424		★☆☆☆☆ Found in Text Mining only
Hypertensive disease	Hypertension	BEFREE	27613724, 28295976		★☆☆☆☆ Found in Text Mining only
Hyperthyroidism	Hyperthyroidism	BEFREE	1249194, 31636683		★☆☆☆☆ Found in Text Mining only
Hyperthyroidism	Hyperthyroidism	Pubtator	1294376, 7647413	Associate	★☆☆☆☆ Found in Text Mining only
Hyperthyroxinemia, Familial Dysalbuminemic	Hyperthyroxinemia, Dysalbuminemic	BEFREE	15068631, 3110251, 3112186, 3129213, 3138040, 3142912		★☆☆☆☆ Found in Text Mining only
Hypogammaglobulinemia	Hypogammaglobulinemia	BEFREE	6406111		★☆☆☆☆ Found in Text Mining only
Hypothyroidism	Hypothyroidism	Pubtator	1901689, 33554479, 34126618, 36475360	Associate	★☆☆☆☆ Found in Text Mining only
Hypothyroidism	Hypothyroidism	BEFREE	2106883		★☆☆☆☆ Found in Text Mining only
Inborn Errors of Metabolism	Inborn Errors Of Metabolism	CTD_human_DG	2155256		★☆☆☆☆ Found in Text Mining only
Insulin-Like Growth Factor I Deficiency	Insulin-Like Growth Factor I Deficiency	BEFREE	28295976		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	2837662, 6092383		★☆☆☆☆ Found in Text Mining only
Liver neoplasms	Liver neoplasms	BEFREE	6092383		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	24867250		★☆☆☆☆ Found in Text Mining only
Maturity onset diabetes mellitus in young	Mason type diabetes	BEFREE	29182332		★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	BEFREE	56342		★☆☆☆☆ Found in Text Mining only
Muscular Dystrophy Duchenne	Duchenne muscular dystrophy	Pubtator	10580756	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	1323058, 28335614		★☆☆☆☆ Found in Text Mining only
NON RARE IN EUROPE: Congenital isolated thyroxine-binding globulin deficiency	Congenital Isolated Thyroxine-Binding Globulin Deficiency	Orphanet			★☆☆☆☆ Found in Text Mining only
Polyneuropathy	Polyneuropathy	BEFREE	14558921		★☆☆☆☆ Found in Text Mining only
Pulmonary Disease Chronic Obstructive	Chronic obstructive pulmonary disease	Pubtator	28579773	Stimulate	★☆☆☆☆ Found in Text Mining only
Renal glomerular disease	Renal Glomerular Disease	BEFREE	28176633		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of the head and neck	Carcinoma Of The Head And Neck	BEFREE	24867250		★☆☆☆☆ Found in Text Mining only
Thyrotoxicosis	Thyrotoxicosis	BEFREE	3142912, 56342		★☆☆☆☆ Found in Text Mining only
X-linked reduction of thyroxine-binding globulin	Reduction Of Thyroxine-Binding Globulin X-Linked	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations