REN

renin, the group of Peptidase family A1

Basic information

Region (hg38): 1:204154819-204190324

Links

ENSG00000143839 ∙ NCBI:5972 ∙ OMIM:179820 ∙ HGNC:9958 ∙ Uniprot:P00797 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• renal tubular dysgenesis of genetic origin (Supportive), mode of inheritance: AR
• familial juvenile hyperuricemic nephropathy type 2 (Supportive), mode of inheritance: AD
• familial juvenile hyperuricemic nephropathy type 2 (Definitive), mode of inheritance: AD
• familial juvenile hyperuricemic nephropathy type 2 (Strong), mode of inheritance: AD
• renal tubular dysgenesis of genetic origin (Strong), mode of inheritance: AR
• renal tubular dysgenesis of genetic origin (Definitive), mode of inheritance: AR
• familial juvenile hyperuricemic nephropathy type 2 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Tubulointerstitial kidney disease, autosomal dominant, 4	AD	Pharmacogenomic; Renal	Surveillance for hematologic (anemia) and renal (hyperuricemia, decreased renal function) disease may be beneficial to allow early medical management; Treatment of low plasma renin activity/low plasma concentration of aldosterone (eg, through management of sodium intake), as well as medical management of hyperkalemia (eg, with fludrocortisones, potassium restriction) may be beneficial, and may be indicated prior to the development of severe chronic kidney disease, though kidney transplantation may be necessary; Treatment of anemia (with erythropoietin) may be effective; Preventive treatment of hyperuricemia (eg, with allopurinol) and medical treatment of gout (eg, with prednisone, colchicines) may be effective; Certain agents should be avoided, including NSAIDS, ACE-inhibitors, dehydration, and specific dietary practices that can exacerbate gout	Renal	2017226; 7982942; 12634862; 16116425; 16164624; 19664745; 21084044; 21473025

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the REN gene.

• Renal tubular dysgenesis (2 variants)
• not provided (1 variants)
• Renal tubular dysgenesis of genetic origin;Familial juvenile hyperuricemic nephropathy type 2 (1 variants)
• Familial juvenile hyperuricemic nephropathy type 2;Renal tubular dysgenesis of genetic origin (1 variants)
• Familial juvenile hyperuricemic nephropathy type 2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the REN gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				19	3	22
missense		2	62	4		68
nonsense	3					3
start loss						0
frameshift						0
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)		2				2
splice region			5	7		12
non coding			5	10	21	36
Total	3	5	68	33	24

Highest pathogenic variant AF is 0.0000263

Variants in REN

This is a list of pathogenic ClinVar variants found in the REN region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-204155017-C-A			Uncertain significance (Apr 22, 2022)
1-204155021-G-A		Hepatoblastoma	Uncertain significance (Jun 20, 2023)
1-204155041-C-T		Inborn genetic diseases	Uncertain significance (Jul 14, 2023)
1-204155050-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 27, 2023)
1-204155051-G-A		Familial juvenile hyperuricemic nephropathy type 2	Uncertain significance (-)
1-204155053-C-T		Familial juvenile hyperuricemic nephropathy type 2	Uncertain significance (Oct 10, 2023)
1-204155054-G-A		Inborn genetic diseases	Uncertain significance (Oct 30, 2023)
1-204155054-G-T			Likely benign (May 03, 2018)
1-204155061-C-T			Likely benign (Nov 20, 2022)
1-204155077-C-T		Inborn genetic diseases • Familial juvenile hyperuricemic nephropathy type 2	Uncertain significance (Feb 22, 2023)
1-204155078-G-A		Hyperproreninemia, familial	Pathogenic (Dec 02, 1994)
1-204155086-G-T		Inborn genetic diseases	Uncertain significance (Jun 07, 2023)
1-204155107-G-A		Inborn genetic diseases	Uncertain significance (Jun 10, 2024)
1-204155119-G-A		Familial juvenile hyperuricemic nephropathy type 2 • Renal tubular dysgenesis	Conflicting classifications of pathogenicity (Jan 12, 2018)
1-204155121-C-T			Likely benign (Oct 29, 2023)
1-204155136-G-A			Likely benign (Jan 23, 2022)
1-204155152-C-T		Familial juvenile hyperuricemic nephropathy type 2	Uncertain significance (Mar 22, 2023)
1-204155161-T-A		Familial juvenile hyperuricemic nephropathy type 2 • Renal tubular dysgenesis • Inborn genetic diseases	Conflicting classifications of pathogenicity (May 30, 2023)
1-204155242-AC-A			Benign (May 15, 2021)
1-204155417-A-G			Benign (Jun 21, 2021)
1-204155737-C-T			Benign (May 14, 2021)
1-204155803-G-C			Likely benign (Feb 08, 2023)
1-204155810-C-T			Likely benign (Apr 18, 2023)
1-204155825-A-T		Inborn genetic diseases	Uncertain significance (Jun 07, 2024)
1-204155847-C-T		Familial juvenile hyperuricemic nephropathy type 2 • Renal tubular dysgenesis	Conflicting classifications of pathogenicity (Aug 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
REN	protein_coding	protein_coding	ENST00000272190	10	11522

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.43e-7	0.908	125684	0	64	125748	0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.797	199	233	0.853	0.0000144	2643
Missense in Polyphen		47	75.491	0.62259		893
Synonymous	-0.889	108	96.9	1.11	0.00000683	810
Loss of Function	1.71	14	22.8	0.614	0.00000135	242

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000355	0.000355
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000708	0.000707
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000231	0.000229
Middle Eastern	0.000708	0.000707
South Asian	0.000340	0.000327
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Renin is a highly specific endopeptidase, whose only known function is to generate angiotensin I from angiotensinogen in the plasma, initiating a cascade of reactions that produce an elevation of blood pressure and increased sodium retention by the kidney.
• Disease: DISEASE: Renal tubular dysgenesis (RTD) [MIM:267430]: Autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype). {ECO:0000269|PubMed:16116425}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Familial juvenile hyperuricemic nephropathy 2 (HNFJ2) [MIM:613092]: A renal disease characterized by juvenile onset of hyperuricemia, slowly progressive renal failure and anemia. {ECO:0000269|PubMed:19664745}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics;Renin-angiotensin system - Homo sapiens (human);Renin secretion - Homo sapiens (human);ACE Inhibitor Pathway, Pharmacodynamics;Temocapril Action Pathway;Olmesartan Action Pathway;Losartan Action Pathway;Irbesartan Action Pathway;Forasartan Action Pathway;Valsartan Action Pathway;Telmisartan Action Pathway;Angiotensin Metabolism;Spirapril Action Pathway;Trandolapril Action Pathway;Ramipril Action Pathway;Rescinnamine Action Pathway;Perindopril Action Pathway;Quinapril Action Pathway;Lisinopril Action Pathway;Moexipril Action Pathway;Candesartan Action Pathway;Eprosartan Action Pathway;Fosinopril Action Pathway;Enalapril Action Pathway;Benazepril Action Pathway;Cilazapril Action Pathway;Captopril Action Pathway;ACE Inhibitor Pathway;Peptide hormone metabolism;Metabolism of proteins;Metabolism of Angiotensinogen to Angiotensins (Consensus)

Recessive Scores

• pRec: 0.891

Intolerance Scores

• loftool: 0.728
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.73

Haploinsufficiency Scores

• pHI: 0.0901
• hipred: N
• hipred_score: 0.353
• ghis: 0.421

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.752

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ren1
• Phenotype: normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; muscle phenotype

Gene ontology

• Biological process: kidney development;mesonephros development;angiotensin maturation;renin-angiotensin regulation of aldosterone production;proteolysis;regulation of blood pressure;male gonad development;hormone-mediated signaling pathway;response to lipopolysaccharide;cellular response to drug;response to immobilization stress;drinking behavior;regulation of MAPK cascade;cell maturation;amyloid-beta metabolic process;response to cAMP;response to cGMP
• Cellular component: extracellular region;extracellular space;cytoplasm;plasma membrane;apical part of cell
• Molecular function: aspartic-type endopeptidase activity;signaling receptor binding;insulin-like growth factor receptor binding;protein binding;peptidase activity