TSHR

Protein identityUniProt · HPA

UniProt accession

P16473

Gene

TSHR

Ensembl

ENSG00000165409

Chromosome

14

Canonical length

764 aa

Protein class

Cancer-related genes, Disease related genes, FDA approved drug targets, G-protein coupled receptors, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins

Secretome location

Intracellular and membrane

OverviewNCBI Gene

The protein encoded by this gene is a membrane protein and a major controller of thyroid cell metabolism. The encoded protein is a receptor for thyrothropin and thyrostimulin, and its activity is mediated by adenylate cyclase. Defects in this gene are a cause of several types of hyperthyroidism. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

Canonical amino-acid sequenceUniProt

764 residues, UniProt reviewed canonical sequence.

>P16473|TSHR
     1  MRPADLLQLV LLLDLPRDLG GMGCSSPPCE CHQEEDFRVT CKDIQRIPSL PPSTQTLKLI
    61  ETHLRTIPSH AFSNLPNISR IYVSIDVTLQ QLESHSFYNL SKVTHIEIRN TRNLTYIDPD
   121  ALKELPLLKF LGIFNTGLKM FPDLTKVYST DIFFILEITD NPYMTSIPVN AFQGLCNETL
   181  TLKLYNNGFT SVQGYAFNGT KLDAVYLNKN KYLTVIDKDA FGGVYSGPSL LDVSQTSVTA
   241  LPSKGLEHLK ELIARNTWTL KKLPLSLSFL HLTRADLSYP SHCCAFKNQK KIRGILESLM
   301  CNESSMQSLR QRKSVNALNS PLHQEYEENL GDSIVGYKEK SKFQDTHNNA HYYVFFEEQE
   361  DEIIGFGQEL KNPQEETLQA FDSHYDYTIC GDSEDMVCTP KSDEFNPCED IMGYKFLRIV
   421  VWFVSLLALL GNVFVLLILL TSHYKLNVPR FLMCNLAFAD FCMGMYLLLI ASVDLYTHSE
   481  YYNHAIDWQT GPGCNTAGFF TVFASELSVY TLTVITLERW YAITFAMRLD RKIRLRHACA
   541  IMVGGWVCCF LLALLPLVGI SSYAKVSICL PMDTETPLAL AYIVFVLTLN IVAFVIVCCC
   601  YVKIYITVRN PQYNPGDKDT KIAKRMAVLI FTDFICMAPI SFYALSAILN KPLITVSNSK
   661  ILLVLFYPLN SCANPFLYAI FTKAFQRDVF ILLSKFGICK RQAQAYRGQR VPPKNSTDIQ
   721  VQKVTHEMRQ GLHNMEDVYE LIENSHLTPK KQGQISEEYM QTVL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TSHR can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

7

Mean surface accessibility (rSASA)

0.35

Highest tissue expression

257 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TSHR.

Disease | AllUniProt

Conditions TSHR is implicated in, by any mechanism.

• Hypothyroidism, congenital, non-goitrous, 1 (CHNG1) MIM:275200
• Familial gestational hyperthyroidism (HTFG) MIM:603373
• Hyperthyroidism, non-autoimmune (HTNA) MIM:609152

Disease | GeneticClinVar

109 pathogenic / likely-pathogenic of 622 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hypothyroidism due to TSH receptor mutations
• Familial hyperthyroidism due to mutations in TSH receptor
• Familial gestational hyperthyroidism
• TSHR-related disorder
• Ovarian cancer

Disease | ImmuneIEDB

Conditions an epitope on TSHR was assayed in.

• Graves' disease B and T cell
• autoimmune thyroiditis B and T cell
• nodular goiter T cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against TSHR are reported. Each links to that disease's full target list.

• Graves Disease 824
• Thyroiditis, Autoimmune 154
• Hyperthyroidism 149
• Hypothyroidism 116
• Hashimoto Disease 55
• Thyroiditis 23
• Diabetes Mellitus, Type 1 10
• Hepatitis C 7
• Arthritis, Rheumatoid 5
• COVID-19 5
• Hepatitis C, Chronic 5
• HIV Infections 5
• Lupus Erythematosus, Systemic 5
• Abortion, Spontaneous 4
• Celiac Disease 4
• Urticaria 4
• Myasthenia Gravis 3
• Pre-Eclampsia 3
• Sjogren's Syndrome 3

Showing 19 of 40 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for TSHR from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.26

gnomAD pLI

0

gnomAD missense Z

0.33

DepMap mean gene effect

0.16

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adenylate cyclase-activating G protein-coupled receptor signaling pathway
• cell surface receptor signaling pathway
• cell-cell signaling
• cellular response to glycoprotein
• G protein-coupled receptor signaling pathway
• G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
• hormone-mediated signaling pathway
• positive regulation of cell population proliferation
• positive regulation of cold-induced thermogenesis
• cellular response to thyrotropin-releasing hormone
• thyroid-stimulating hormone signaling pathway

Molecular functions

• G protein-coupled peptide receptor activity
• G protein-coupled receptor activity
• protein-containing complex binding
• signaling receptor activity
• thyroid-stimulating hormone receptor activity

Cellular components

• basolateral plasma membrane
• cell surface
• plasma membrane
• receptor complex

Protein domainsUniProt · Pfam · InterPro

• G protein-coupled receptor, rhodopsin-like
• Glycoprotein hormone receptor family
• GPCR, rhodopsin-like, 7TM
• BspA-type LRR region
• Leucine-rich repeat domain superfamily
• 7 transmembrane receptor (rhodopsin family)
• BspA type Leucine rich repeat region (6 copies)
• Thyrotropin receptor

KeywordsUniProt

• Cell membrane
• Congenital hypothyroidism
• Disulfide bond
• G-protein coupled receptor
• Glycoprotein
• Leucine-rich repeat
• Membrane
• Receptor
• Repeat
• Signal
• Sulfation
• Transducer
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of TSHR in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GNAS
• ADORA1
• MID1IP1
• SCRIB
• SYT1