REN

Protein identityUniProt · HPA

UniProt accession

P00797

Gene

REN

Ensembl

ENSG00000143839

Chromosome

1

Canonical length

406 aa

Protein class

Candidate cardiovascular disease genes, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Predicted intracellular proteins, Predicted secreted proteins

Secretome location

Secreted to blood

OverviewNCBI Gene

This gene encodes renin, an aspartic protease that is secreted by the kidneys. Renin is a part of the renin-angiotensin-aldosterone system involved in regulation of blood pressure, and electrolyte balance. This enzyme catalyzes the first step in the activation pathway of angiotensinogen by cleaving angiotensinogen to form angiotensin I, which is then converted to angiotensin II by angiotensin I converting enzyme. This cascade can result in aldosterone release, narrowing of blood vessels, and increase in blood pressure as angiotension II is a vasoconstrictive peptide. Transcript variants that encode different protein isoforms and that arise from alternative splicing and the use of alternative promoters have been described, but their full-length nature has not been determined. Mutations in this gene have been shown to cause hyperuricemic nephropathy familial juvenile 2, familial hyperproreninemia, and renal tubular dysgenesis. [provided by RefSeq, May 2020]

Canonical amino-acid sequenceUniProt

406 residues, UniProt reviewed canonical sequence.

>P00797|REN
     1  MDGWRRMPRW GLLLLLWGSC TFGLPTDTTT FKRIFLKRMP SIRESLKERG VDMARLGPEW
    61  SQPMKRLTLG NTTSSVILTN YMDTQYYGEI GIGTPPQTFK VVFDTGSSNV WVPSSKCSRL
   121  YTACVYHKLF DASDSSSYKH NGTELTLRYS TGTVSGFLSQ DIITVGGITV TQMFGEVTEM
   181  PALPFMLAEF DGVVGMGFIE QAIGRVTPIF DNIISQGVLK EDVFSFYYNR DSENSQSLGG
   241  QIVLGGSDPQ HYEGNFHYIN LIKTGVWQIQ MKGVSVGSST LLCEDGCLAL VDTGASYISG
   301  STSSIEKLME ALGAKKRLFD YVVKCNEGPT LPDISFHLGG KEYTLTSADY VFQESYSSKK
   361  LCTLAIHAMD IPPPTGPTWA LGATFIRKFY TEFDRRNNRI GFALAR

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against REN 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

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.27

Highest tissue expression

135 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about REN.

Disease | AllUniProt

Conditions REN is implicated in, by any mechanism.

• Renal tubular dysgenesis (RTD) MIM:267430
• Tubulointerstitial kidney disease, autosomal dominant 4 (ADTKD4) MIM:613092

Disease | GeneticClinVar

22 pathogenic / likely-pathogenic of 259 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Familial juvenile hyperuricemic nephropathy type 2
• Renal tubular dysgenesis of genetic origin
• Renal tubular dysgenesis
• HYPERPRORENINEMIA, FAMILIAL
• Inborn genetic diseases

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)

0.96

gnomAD pLI

0

gnomAD missense Z

0.8

DepMap mean gene effect

-0.13

DepMap dependency class

selective

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

• amyloid-beta metabolic process
• angiotensin maturation
• cell maturation
• cellular response to xenobiotic stimulus
• drinking behavior
• hormone-mediated signaling pathway
• juxtaglomerular apparatus development
• kidney development
• male gonad development
• mesonephros development
• proteolysis
• regulation of blood pressure
• regulation of MAPK cascade
• renin-angiotensin regulation of aldosterone production
• response to cAMP
• response to cGMP
• response to immobilization stress
• response to lipopolysaccharide

Molecular functions

• aspartic-type endopeptidase activity
• insulin-like growth factor receptor binding
• peptidase activity
• signaling receptor binding

Cellular components

• apical part of cell
• extracellular region
• extracellular space
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Aspartic peptidase A1
• Aspartic peptidase, active site
• Aspartic peptidase, N-terminal
• Aspartic peptidase domain superfamily
• Peptidase family A1 domain
• Eukaryotic aspartyl protease
• A1 Propeptide
• Renin-like domain

KeywordsUniProt

• Aspartyl protease
• Cleavage on pair of basic residues
• Disulfide bond
• Glycoprotein
• Hydrolase
• Membrane
• Protease
• Secreted
• Signal
• Zymogen

InteractionsUniProt · HPA

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

• ATP6AP2
• AGT