CASR

Protein identityUniProt · HPA

UniProt accession

P41180

Gene

CASR

Ensembl

ENSG00000036828

Chromosome

3

Canonical length

1078 aa

Protein class

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

Quaternary structure

Homodimer

OverviewNCBI Gene

The protein encoded by this gene is a plasma membrane G protein-coupled receptor that senses small changes in circulating calcium concentration. The encoded protein couples this information to intracellular signaling pathways that modify parathyroid hormone secretion or renal cation handling, and thus this protein plays an essential role in maintaining mineral ion homeostasis. Mutations in this gene are a cause of familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcemia. [provided by RefSeq, Aug 2017]

Canonical amino-acid sequenceUniProt

1078 residues, UniProt reviewed canonical sequence.

>P41180|CASR
     1  MAFYSCCWVL LALTWHTSAY GPDQRAQKKG DIILGGLFPI HFGVAAKDQD LKSRPESVEC
    61  IRYNFRGFRW LQAMIFAIEE INSSPALLPN LTLGYRIFDT CNTVSKALEA TLSFVAQNKI
   121  DSLNLDEFCN CSEHIPSTIA VVGATGSGVS TAVANLLGLF YIPQVSYASS SRLLSNKNQF
   181  KSFLRTIPND EHQATAMADI IEYFRWNWVG TIAADDDYGR PGIEKFREEA EERDICIDFS
   241  ELISQYSDEE EIQHVVEVIQ NSTAKVIVVF SSGPDLEPLI KEIVRRNITG KIWLASEAWA
   301  SSSLIAMPQY FHVVGGTIGF ALKAGQIPGF REFLKKVHPR KSVHNGFAKE FWEETFNCHL
   361  QEGAKGPLPV DTFLRGHEES GDRFSNSSTA FRPLCTGDEN ISSVETPYID YTHLRISYNV
   421  YLAVYSIAHA LQDIYTCLPG RGLFTNGSCA DIKKVEAWQV LKHLRHLNFT NNMGEQVTFD
   481  ECGDLVGNYS IINWHLSPED GSIVFKEVGY YNVYAKKGER LFINEEKILW SGFSREVPFS
   541  NCSRDCLAGT RKGIIEGEPT CCFECVECPD GEYSDETDAS ACNKCPDDFW SNENHTSCIA
   601  KEIEFLSWTE PFGIALTLFA VLGIFLTAFV LGVFIKFRNT PIVKATNREL SYLLLFSLLC
   661  CFSSSLFFIG EPQDWTCRLR QPAFGISFVL CISCILVKTN RVLLVFEAKI PTSFHRKWWG
   721  LNLQFLLVFL CTFMQIVICV IWLYTAPPSS YRNQELEDEI IFITCHEGSL MALGFLIGYT
   781  CLLAAICFFF AFKSRKLPEN FNEAKFITFS MLIFFIVWIS FIPAYASTYG KFVSAVEVIA
   841  ILAASFGLLA CIFFNKIYII LFKPSRNTIE EVRCSTAAHA FKVAARATLR RSNVSRKRSS
   901  SLGGSTGSTP SSSISSKSNS EDPFPQPERQ KQQQPLALTQ QEQQQQPLTL PQQQRSQQQP
   961  RCKQKVIFGS GTVTFSLSFD EPQKNAMAHR NSTHQNSLEA QKSSDTLTRH EPLLPLQCGE
  1021  TDLDLTVQET GLQGPVGGDQ RPEVEDPEEL SPALVVSSSQ SFVISGGGST VTENVVNS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CASR 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

616 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CASR.

Disease | AllUniProt

Conditions CASR is implicated in, by any mechanism.

• Hypocalciuric hypercalcemia, familial 1 (HHC1) MIM:145980
• Hyperparathyroidism, neonatal severe (NSHPT) MIM:239200
• Hypocalcemia, autosomal dominant 1 (HYPOC1) MIM:601198
• Epilepsy, idiopathic generalized 8 (EIG8) MIM:612899

Disease | GeneticClinVar

327 pathogenic / likely-pathogenic of 3,105 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal dominant hypocalcemia 1
• Familial hypocalciuric hypercalcemia
• Familial hypocalciuric hypercalcemia 1
• Neonatal severe primary hyperparathyroidism
• Nephrolithiasis/nephrocalcinosis

Disease | AutoantibodyPubMed

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

• Polyendocrinopathies, Autoimmune 8

Showing 1 of 2 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for CASR 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. 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)

0.45

gnomAD pLI

0.05

gnomAD missense Z

3.12

DepMap mean gene effect

-0.05

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-inhibiting G protein-coupled receptor signaling pathway
• anatomical structure morphogenesis
• bile acid secretion
• branching morphogenesis of an epithelial tube
• cellular response to glucose stimulus
• cellular response to hepatocyte growth factor stimulus
• cellular response to hypoxia
• cellular response to low-density lipoprotein particle stimulus
• cellular response to peptide
• cellular response to vitamin D
• chemosensory behavior
• chloride transmembrane transport
• detection of calcium ion
• fat pad development
• G protein-coupled receptor signaling pathway
• intracellular calcium ion homeostasis
• JNK cascade
• ossification
• phospholipase C-activating G protein-coupled receptor signaling pathway
• positive regulation of calcium ion import
• positive regulation of cell population proliferation
• positive regulation of ERK1 and ERK2 cascade
• positive regulation of gene expression
• positive regulation of insulin secretion
• positive regulation of NLRP3 inflammasome complex assembly
• positive regulation of positive chemotaxis
• positive regulation of vasoconstriction
• regulation of calcium ion transport
• regulation of presynaptic membrane potential
• response to fibroblast growth factor
• response to ischemia
• vasodilation

Molecular functions

• amino acid binding
• calcium ion binding
• G protein-coupled receptor activity
• identical protein binding
• integrin binding
• protein homodimerization activity
• protein kinase binding
• transmembrane transporter binding

Cellular components

• apical plasma membrane
• axon terminus
• basolateral plasma membrane
• cell surface
• glutamatergic synapse
• neuronal cell body
• plasma membrane
• presynaptic membrane

Protein domainsUniProt · Pfam · InterPro

• GPCR, family 3, extracellular calcium-sensing receptor-related
• GPCR, family 3
• Receptor, ligand binding region
• GPCR, family 3, nine cysteines domain
• GPCR family 3, C-terminal
• GPCR, family 3, conserved site
• Periplasmic binding protein-like I
• GPCR, family 3, nine cysteines domain superfamily
• 7 transmembrane sweet-taste receptor of 3 GCPR
• Receptor family ligand binding region
• Nine Cysteines Domain of family 3 GPCR

KeywordsUniProt

• Calcium
• Cell membrane
• Disulfide bond
• Epilepsy
• G-protein coupled receptor
• Glycoprotein
• Membrane
• Metal-binding
• Phosphoprotein
• Receptor
• Signal
• Transducer
• Transmembrane
• Transmembrane helix
• Ubl conjugation

InteractionsUniProt · HPA

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

• ARRB1
• VCP
• TMED2
• RNF19A