TSHB (thyroid stimulating hormone subunit beta)

Gene

• Entrez ID: 7252
• Gene name: Thyroid stimulating hormone subunit beta
• Gene symbol: TSHB
• Synonyms (NCBI Gene): TSH-B, TSH-BETA
• Chromosome: 1
• Chromosome location: 1p13.2
• Summary: The four human glycoprotein hormones chorionic gonadotropin (CG), luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH) are dimers consisting of alpha and beta subunits that are associated noncovalently. The a

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121918668	G>A	Pathogenic	Upstream transcript variant, missense variant, genic upstream transcript variant, coding sequence variant
rs121918669	G>A,T	Pathogenic	Missense variant, stop gained, coding sequence variant, upstream transcript variant, genic upstream transcript variant
rs121918670	C>T	Likely-pathogenic	Stop gained, coding sequence variant
rs755485552	T>-	Pathogenic, likely-pathogenic	Frameshift variant, coding sequence variant
rs868637545	G>A	Pathogenic	Intron variant, genic upstream transcript variant, upstream transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT030150	hsa-miR-26b-5p	Microarray	19088304

Transcription factors

Transcription factor	Regulation	Reference
GATA2	Unknown	17244762
LHX2	Activation	22535646
POU1F1	Activation	7529501
POU1F1	Unknown	12655183;16901973;9167960;9207961

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005102	Function	Signaling receptor binding	IEA
GO:0005179	Function	Hormone activity	IEA
GO:0005179	Function	Hormone activity	TAS	2792087
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA
GO:0005737	Component	Cytoplasm	IBA
GO:0007165	Process	Signal transduction	IEA
GO:0007186	Process	G protein-coupled receptor signaling pathway	IBA
GO:0007186	Process	G protein-coupled receptor signaling pathway	TAS	2792087
GO:0007267	Process	Cell-cell signaling	TAS	2792087
GO:0009653	Process	Anatomical structure morphogenesis	TAS	2792087

Other IDs

• MIM: 188540
• HGNC: 12372
• e!Ensembl: ENSG00000134200

Protein

• UniProt ID: P01222
• Protein name: Thyrotropin subunit beta (Thyroid-stimulating hormone subunit beta) (TSH-B) (TSH-beta) (Thyrotropin beta chain) (Thyrotropin alfa)
• Protein function: Indispensable for the control of thyroid structure and metabolism.
• PDB: 7T9I, 7UTZ, 7XW5
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00007	Cys_knot	19 → 125	Cystine-knot domain	Domain

• Sequence:

  MTALFLMSMLFGLTCGQAMSFCIPTEYTMHIERRECAYCLTINTTICAGYCMTRDINGKL
  FLPKYALSQDVCTYRDFIYRTVEIPGCPLHVAPYFSYPVALSCKCGKCNTDYSDCIHEAI
  KTNYCTKPQKSYLVGFSV

• Sequence length: 138

Pathways

KEGG:

cAMP signaling pathway
Neuroactive ligand-receptor interaction
Hormone signaling
Thyroid hormone synthesis
Regulation of lipolysis in adipocytes
Autoimmune thyroid disease

Reactome:

Glycoprotein hormones
Thyroxine biosynthesis
Hormone ligand-binding receptors
G alpha (s) signalling events
ADORA2B mediated anti-inflammatory cytokines production

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
Isolated thyroid-stimulating hormone deficiency	Likely pathogenic; Pathogenic	rs2101008674, rs121918668, rs121918669, rs121918670, rs868637545, rs771834192, rs755485552	RCV001353349 RCV000013521 RCV000013522 RCV000013524 RCV000013525 RCV005013026 RCV000503516	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Pituitary hypothyroidism	Pathogenic	rs755485552	RCV002463363	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
TSHB-related disorder	Likely pathogenic; Pathogenic	rs121918670	RCV003415693	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
BIPOLAR DISORDER	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BIPOLAR I DISORDER, MOST RECENT EPISODE MANIC	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL ABSENCE OF THYROID GLAND	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL ATROPHY OF THYROID	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Congenital hypothyroidism	Benign	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
CONGENITAL HYPOTHYROIDISM WITHOUT GOITER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DEPRESSION, BIPOLAR	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GRAVES DISEASE	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOTHYROIDISM	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MIXED BIPOLAR I DISORDER	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Autoimmune thyroiditis	Autoimmune Thyroiditis	BEFREE	22752807, 8664977		★☆☆☆☆ Found in Text Mining only
Bipolar Disorder	Bipolar Disorder	CTD_human_DG	6455462		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Central hypothyroidism	Central hypothyroidism	BEFREE	11297590, 12566717, 16804796, 22851492, 27362444, 29794369		★☆☆☆☆ Found in Text Mining only
Central hypothyroidism	Central hypothyroidism	CTD_human_DG	18031379, 24729111		★☆☆☆☆ Found in Text Mining only
Congenital central hypothyroidism	Congenital Central Hypothyroidism	BEFREE	16804796, 23363888, 25950606		★☆☆☆☆ Found in Text Mining only
Congenital exomphalos	Congenital Exomphalos	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital Hypothyroidism	Congenital Hypothyroidism	GENOMICS_ENGLAND_DG	27362444		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Congenital Hypothyroidism	Congenital hypothyroidism	Pubtator	27362444, 31914441, 34200080	Associate	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Congenital Hypothyroidism	Congenital Hypothyroidism	HPO_DG			★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
Congenital omphalocele	Congenital omphalocele	HPO_DG			★☆☆☆☆ Found in Text Mining only
Depression, Bipolar	Bipolar Disorder	CTD_human_DG	6455462		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Dyssomnias	Dyssomnia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Generalized Thyroid Hormone Resistance	Thyroid Hormone Resistance	BEFREE	8175956		★☆☆☆☆ Found in Text Mining only
Hashimoto Disease	Hashimoto Disease	BEFREE	22752807, 26170068, 8664977		★☆☆☆☆ Found in Text Mining only
Hyperthyroidism	Hyperthyroidism	BEFREE	9039330		★☆☆☆☆ Found in Text Mining only
Hypothyroidism	Hypothyroidism	CTD_human_DG	18031379, 24729111		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypothyroidism	Hypothyroidism	Pubtator	23363888, 25950606, 26735259, 27362444, 27603907, 28515030, 31166470, 31703413, 31914441, 8636437	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypothyroidism	Hypothyroidism	BEFREE	30448824, 8664977, 9039330		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypothyroidism	Hypothyroidism	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hypothyroidism, Congenital, Nongoitrous, 4	Congenital hypothyroidism, nongoitrous	CLINVAR_DG	11297590, 11549695		★☆☆☆☆ Found in Text Mining only
Hypothyroidism, Congenital, Nongoitrous, 4	Congenital hypothyroidism, nongoitrous	ORPHANET_DG	12930599, 20537182, 22851492		★☆☆☆☆ Found in Text Mining only
Hypothyroidism, Congenital, Nongoitrous, 4	Congenital hypothyroidism, nongoitrous	GENOMICS_ENGLAND_DG	27362444, 2792087		★☆☆☆☆ Found in Text Mining only
Hypothyroidism, Congenital, Nongoitrous, 4	Congenital hypothyroidism, nongoitrous	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Isolated thyroid-stimulating hormone deficiency	Isolated Thyroid-Stimulating Hormone Deficiency	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Liver carcinoma	Liver carcinoma	BEFREE	20532728, 24151232		★☆☆☆☆ Found in Text Mining only
Macroglossia	Macroglossia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Manic	Manic Disorder	CTD_human_DG	6455462		★☆☆☆☆ Found in Text Mining only
Manic Disorder	Manic Disorder	CTD_human_DG	6455462		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	25867808, 2723029		★☆☆☆☆ Found in Text Mining only
Ovarian Failure, Premature	Ovarian Failure	BEFREE	24366283		★☆☆☆☆ Found in Text Mining only
Pituitary Diseases	Pituitary Diseases	BEFREE	9828108		★☆☆☆☆ Found in Text Mining only
Premature Menopause	Premature Menopause	BEFREE	24366283		★☆☆☆☆ Found in Text Mining only
Primary Hypothyroidism	Hypothyroidism	CTD_human_DG	18031379, 24729111		★☆☆☆☆ Found in Text Mining only
Secondary hypothyroidism	Hypothyroidism	ORPHANET_DG	12930599, 20537182, 22851492		★☆☆☆☆ Found in Text Mining only
Secondary hypothyroidism	Hypothyroidism	CTD_human_DG	18031379, 24729111		★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sleep Disorders	Sleep Disorders	HPO_DG			★☆☆☆☆ Found in Text Mining only
Thyroid Dysgenesis	Thyroid Dysgenesis	BEFREE	31797737		★☆☆☆☆ Found in Text Mining only
Thyrotropin deficiency, isolated	Hypothyroidism	ORPHANET_DG	12930599, 20537182, 22851492		★☆☆☆☆ Found in Text Mining only
Turner Syndrome	Turner Syndrome	BEFREE	8664977		★☆☆☆☆ Found in Text Mining only