NR3C2 (nuclear receptor subfamily 3 group C member 2)

Gene

• Entrez ID: 4306
• Gene name: Nuclear receptor subfamily 3 group C member 2
• Gene symbol: NR3C2
• Synonyms (NCBI Gene): MCR, MLR, MR, NR3C2VIT
• Chromosome: 4
• Chromosome location: 4q31.23
• Summary: This gene encodes the mineralocorticoid receptor, which mediates aldosterone actions on salt and water balance within restricted target cells. The protein functions as a ligand-dependent transcription factor that binds to mineralocorticoid response elemen

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs41511344	G>A,T	Pathogenic	Stop gained, intron variant, missense variant, coding sequence variant
rs121912562	G>A,C	Pathogenic	Stop gained, coding sequence variant, non coding transcript variant, missense variant
rs121912563	A>G	Pathogenic	Missense variant, coding sequence variant, genic downstream transcript variant, non coding transcript variant
rs121912564	G>T	Pathogenic	Stop gained, coding sequence variant, non coding transcript variant
rs121912565	T>C	Pathogenic	Missense variant, coding sequence variant, intron variant
rs121912566	C>T	Pathogenic	Missense variant, coding sequence variant, non coding transcript variant
rs121912567	A>G	Pathogenic	Missense variant, coding sequence variant, genic downstream transcript variant, non coding transcript variant
rs121912568	G>C	Pathogenic	Stop gained, coding sequence variant, non coding transcript variant
rs121912569	G>A	Pathogenic	Stop gained, coding sequence variant, genic downstream transcript variant, non coding transcript variant
rs121912570	A>T	Pathogenic	Stop gained, coding sequence variant, non coding transcript variant
rs121912571	G>A	Likely-pathogenic	Stop gained, coding sequence variant, intron variant
rs121912572	G>C	Pathogenic	Stop gained, coding sequence variant, intron variant
rs121912573	G>A,T	Pathogenic	Stop gained, missense variant, coding sequence variant, intron variant
rs121912574	T>C	Pathogenic	Missense variant, coding sequence variant, genic downstream transcript variant, non coding transcript variant
rs748573472	G>-,GGGGGGGGGG	Likely-pathogenic	Frameshift variant, intron variant, coding sequence variant, inframe insertion
rs879255348	G>T	Pathogenic	Coding sequence variant, stop gained, non coding transcript variant
rs1131691568	G>A	Pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs1131691921	G>A	Likely-pathogenic	Coding sequence variant, non coding transcript variant, stop gained
rs1553986377	G>A	Likely-pathogenic	Non coding transcript variant, stop gained, coding sequence variant, genic downstream transcript variant
rs1560735659	->A	Pathogenic	Stop gained, non coding transcript variant, coding sequence variant
rs1560910156	->G	Pathogenic	Genic downstream transcript variant, frameshift variant, non coding transcript variant, coding sequence variant
rs1560928649	A>C	Likely-pathogenic	Genic downstream transcript variant, non coding transcript variant, coding sequence variant, missense variant
rs1560949756	T>-	Pathogenic	Intron variant
rs1578859390	->A	Likely-pathogenic	Non coding transcript variant, coding sequence variant, genic downstream transcript variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT001167	hsa-miR-135a-5p	Luciferase reporter assay, qRT-PCR	19944075
MIRT001168	hsa-miR-124-3p	Luciferase reporter assay, qRT-PCR	19944075
MIRT017785	hsa-miR-335-5p	Microarray	18185580
MIRT019372	hsa-miR-148b-3p	Microarray	17612493
MIRT001164	hsa-miR-19b-3p	Sequencing	20371350
MIRT441973	hsa-miR-944	PAR-CLIP	22100165
MIRT732560	hsa-miR-301b-3p	Luciferase reporter assay, qRT-PCR, Western blot	27197190
MIRT732560	hsa-miR-301b-3p	Luciferase reporter assay, qRT-PCR, Western blot	27197190
MIRT732560	hsa-miR-301b-3p	Luciferase reporter assay, qRT-PCR, Western blot	27197190
MIRT732560	hsa-miR-301b-3p	Luciferase reporter assay, qRT-PCR, Western blotting	33542733
MIRT732560	hsa-miR-301b-3p	Luciferase reporter assay, qRT-PCR, Western blotting	33063403
MIRT734708	hsa-miR-4260	Luciferase reporter assay, Western blotting, Microarray, Immunoprecipitaion (IP), qRT-PCR	32338183
MIRT736360	hsa-miR-1204	Luciferase reporter assay, Western blotting, Immunoprecipitaion (IP)	32280303
MIRT732560	hsa-miR-301b-3p	Luciferase reporter assay, Western blotting, qRT-PCR	33542733
MIRT441973	hsa-miR-944	PAR-CLIP	22100165
MIRT1192760	hsa-miR-1914	CLIP-seq
MIRT1192761	hsa-miR-210	CLIP-seq
MIRT1192762	hsa-miR-3120-3p	CLIP-seq
MIRT1192763	hsa-miR-4717-3p	CLIP-seq
MIRT1192764	hsa-miR-545	CLIP-seq
MIRT1192765	hsa-miR-548ac	CLIP-seq
MIRT1192766	hsa-miR-548ae	CLIP-seq
MIRT1192767	hsa-miR-548aj	CLIP-seq
MIRT1192768	hsa-miR-548am	CLIP-seq
MIRT1192769	hsa-miR-548d-3p	CLIP-seq
MIRT1192770	hsa-miR-548p	CLIP-seq
MIRT1192771	hsa-miR-548u	CLIP-seq
MIRT1192772	hsa-miR-548x	CLIP-seq
MIRT1192773	hsa-miR-548z	CLIP-seq
MIRT1192774	hsa-miR-671-3p	CLIP-seq
MIRT1192775	hsa-miR-3148	CLIP-seq
MIRT1192776	hsa-miR-3978	CLIP-seq
MIRT1192777	hsa-miR-4760-5p	CLIP-seq
MIRT1192778	hsa-miR-889	CLIP-seq
MIRT2055985	hsa-miR-101	CLIP-seq
MIRT2055986	hsa-miR-144	CLIP-seq
MIRT2055987	hsa-miR-205	CLIP-seq
MIRT1192762	hsa-miR-3120-3p	CLIP-seq
MIRT2055988	hsa-miR-3143	CLIP-seq
MIRT2055989	hsa-miR-4494	CLIP-seq
MIRT2055990	hsa-miR-499a-5p	CLIP-seq
MIRT2055988	hsa-miR-3143	CLIP-seq
MIRT2439074	hsa-miR-576-5p	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	IBA
GO:0000785	Component	Chromatin	ISA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0003677	Function	DNA binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IEA
GO:0003700	Function	DNA-binding transcription factor activity	TAS	3037703
GO:0003707	Function	Nuclear steroid receptor activity	TAS	9662404
GO:0004879	Function	Nuclear receptor activity	IBA
GO:0005496	Function	Steroid binding	IEA
GO:0005515	Function	Protein binding	IPI	11518808, 24907116
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	IEA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IEA
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005789	Component	Endoplasmic reticulum membrane	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0007165	Process	Signal transduction	IEA
GO:0007165	Process	Signal transduction	TAS	3037703
GO:0008270	Function	Zinc ion binding	IEA
GO:0008289	Function	Lipid binding	IEA
GO:0016020	Component	Membrane	IEA
GO:0017025	Function	TBP-class protein binding	IPI	20685853
GO:0030518	Process	Nuclear receptor-mediated steroid hormone signaling pathway	IBA
GO:0032870	Process	Cellular response to hormone stimulus	IEA
GO:0033993	Process	Response to lipid	IEA
GO:0034056	Function	Estrogen response element binding	IBA
GO:0043235	Component	Receptor complex	IDA	23382219
GO:0043565	Function	Sequence-specific DNA binding	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:1901224	Process	Positive regulation of non-canonical NF-kappaB signal transduction	IMP	30769772
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IEA

Other IDs

• MIM: 600983
• HGNC: 7979
• e!Ensembl: ENSG00000151623

Protein

• UniProt ID: P08235
• Protein name: Mineralocorticoid receptor (MR) (Nuclear receptor subfamily 3 group C member 2)
• Protein function: Receptor for both mineralocorticoids (MC) such as aldosterone and glucocorticoids (GC) such as corticosterone or cortisol. Binds to mineralocorticoid response elements (MRE) and transactivates target genes. The effect of MC is to increase ion an
• PDB: 1Y9R, 1YA3, 2A3I, 2AA2, 2AA5, 2AA6, 2AA7, 2AAX, 2AB2, 2ABI, 2OAX, 3VHU, 3VHV, 3WFF, 3WFG, 4PF3, 4TNT, 4UDA, 4UDB, 5HCV, 5L7E, 5L7G, 5L7H, 5MWP, 5MWY, 6GEV, 6GG8, 6GGG, 6L88
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00105	zf-C4	601 → 670	Zinc finger, C4 type (two domains)	Domain
  PF00104	Hormone_recep	757 → 946	Ligand-binding domain of nuclear hormone receptor	Domain

• Tissue specificity: TISSUE SPECIFICITY: Ubiquitous. Highly expressed in distal tubules, convoluted tubules and cortical collecting duct in kidney, and in sweat glands. Detected at lower levels in cardiomyocytes, in epidermis and in colon enterocytes. {ECO:0000269|PubMed:1151
• Sequence:

  METKGYHSLPEGLDMERRWGQVSQAVERSSLGPTERTDENNYMEIVNVSCVSGAIPNNST
  QGSSKEKQELLPCLQQDNNRPGILTSDIKTELESKELSATVAESMGLYMDSVRDADYSYE
  QQNQQGSMSPAKIYQNVEQLVKFYKGNGHRPSTLSCVNTPLRSFMSDSGSSVNGGVMRAV
  VKSPIMCHEKSPSVCSPLNMTSSVCSPAGINSVSSTTASFGSFPVHSPITQGTPLTCSPN
  VENRGSRSHSPAHASNVGSPLSSPLSSMKSSISSPPSHCSVKSPVSSPNNVTLRSSVSSP
  ANINNSRCSVSSPSNTNNRSTLSSPAASTVGSICSPVNNAFSYTASGTSAGSSTLRDVVP
  SPDTQEKGAQEVPFPKTEEVESAISNGVTGQLNIVQYIKPEPDGAFSSSCLGGNSKINSD
  SSFSVPIKQESTKHSCSGTSFKGNPTVNPFPFMDGSYFSFMDDKDYYSLSGILGPPVPGF
  DGNCEGSGFPVGIKQEPDDGSYYPEASIPSSAIVGVNSGGQSFHYRIGAQGTISLSRSAR
  DQSFQHLSSFPPVNTLVESWKSHGDLSSRRSDGYPVLEYIPENVSSSTLRSVSTGSSRPS
  KICLVCGDEASGCHYGVVTCGSCKVFFKRAVEGQHNYLCAGRNDCIIDKIRRKNCPACRL
  QKCLQAGMNLGARKSKKLGKLKGIHEEQPQQQQPPPPPPPPQSPEEGTTYIAPAKEPSVN
  TALVPQLSTISRALTPSPVMVLENIEPEIVYAGYDSSKPDTAENLLSTLNRLAGKQMIQV
  VKWAKVLPGFKNLPLEDQITLIQYSWMCLSSFALSWRSYKHTNSQFLYFAPDLVFNEEKM
  HQSAMYELCQGMHQISLQFVRLQLTFEEYTIMKVLLLLSTIPKDGLKSQAAFEEMRTNYI
  KELRKMVTKCPNNSGQSWQRFYQLTKLLDSMHDLVSDLLEFCFYTFRESHALKVEFPAML
  VEIISDQLPKVESGNAKPLYFHRK

• Sequence length: 984

Pathways

KEGG:

Aldosterone-regulated sodium reabsorption

Reactome:

HSP90 chaperone cycle for steroid hormone receptors (SHR)
Nuclear Receptor transcription pathway
SUMOylation of intracellular receptors

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Autism spectrum disorder	Pathogenic	rs121912562	RCV000754683
Autosomal dominant pseudohypoaldosteronism type 1	Likely pathogenic; Pathogenic	rs1553986374, rs2149871784, rs2126657667, rs2149871751, rs1560928649, rs1553990750, rs2531829170, rs2531825719, rs121912562, rs1560949756, rs1560910156, rs121912563, rs1560735659, rs2531835861, rs121912564, rs121912565, rs121912566, rs121912567, rs121912568, rs121912569, rs121912570, rs121912571, rs121912572, rs121912573, rs121912574, rs2531826011, rs2530538343, rs1131691921, rs748573472, rs1553986377	RCV001375996 RCV001823793 RCV001839229 RCV002225053 RCV002288415 RCV003320392 RCV000009084 RCV000009085 RCV000009086 RCV000009087 RCV000009089 RCV000009090 RCV000009091 RCV000009092 RCV000009093 RCV000009094 RCV000009095 RCV000009096 RCV000009097 RCV000009098 RCV000009099 RCV000009100 RCV000009101 RCV000009102 RCV000009103 RCV003315122 RCV005863894 RCV001332610 RCV000625641 RCV000761320 RCV000761556
Cervical cancer	Likely pathogenic; Pathogenic	rs2530538343	RCV005939006
NR3C2-related disorder	Likely pathogenic; Pathogenic	rs2530538343, rs1131691921, rs1553986377	RCV004532127 RCV004535554 RCV004702396
Pseudohyperaldosteronism type 2	Pathogenic	rs121912569, rs1131691921	RCV002496310 RCV001535946
Pseudohypoaldosteronism	Pathogenic	rs879255348	RCV000239160

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Benign; Likely benign	rs61763143, rs5527	RCV005891359 RCV005897762
Familial cancer of breast	Conflicting classifications of pathogenicity	rs184268528	RCV005913901
Familial pancreatic carcinoma	Benign	rs61763143	RCV005891354
Gastric cancer	Benign; Likely benign	rs61763143, rs5527	RCV005891356 RCV005897761
Hepatocellular carcinoma	Benign; Likely benign	rs5527	RCV005897759
Hypertension, early-onset, autosomal dominant, with exacerbation in pregnancy	Uncertain significance	rs41511344	RCV000009088
Lung cancer	Benign	rs61763143, rs72648712	RCV005891358 RCV005891349
Malignant tumor of esophagus	Benign	rs61763143	RCV005891350
Myoepithelial tumor	Uncertain significance	rs771642215	RCV002463926
Nonpapillary renal cell carcinoma	Benign	rs61763143	RCV005891351
Ovarian serous cystadenocarcinoma	Benign	rs61763143	RCV005891357
Sarcoma	Benign	rs61763143	RCV005891355
See cases	Uncertain significance	rs1364162260	RCV001420625
Uveal melanoma	Benign	rs61763143	RCV005891353

Associations from Text Mining
Disease Name	Relationship Type	References
Abortion Spontaneous	Associate	26260058
Adenocarcinoma	Associate	36829221
Adenoma	Associate	24516561
Adenoma	Inhibit	35270010
Adenomatous Polyposis Coli	Associate	24191286
Alzheimer Disease	Associate	21653223
Anxiety	Associate	31908177
Arrhythmias Cardiac	Associate	36612333
Asthma	Associate	23334005
Atherosclerosis	Associate	18467630, 20508287, 28555959
Atrial Fibrillation	Associate	20063294
Atrioventricular Block	Associate	36612333
Autistic Disorder	Associate	26749308
Bipolar Disorder	Inhibit	14741058
Brain Ischemia	Associate	15718497
Breast Neoplasms	Associate	31908177, 33148314, 33564687
Carcinogenesis	Associate	38081950
Carcinoma Hepatocellular	Inhibit	26082033
Carcinoma Renal Cell	Associate	28349958, 31746384, 33838279, 35078194, 36741922, 36919662, 37919459
Cardiovascular Diseases	Associate	15718497, 37525257, 37798313
Central Serous Chorioretinopathy	Associate	28334414, 31815877, 35052395
Cognitive Dysfunction	Associate	32558353
Colorectal Neoplasms	Associate	23555666, 24516561, 36267311, 36532065
Colorectal Neoplasms	Inhibit	35191517, 36950803
Coronary Artery Disease	Associate	26941570
Coronary Artery Disease	Stimulate	36919662
Depressive Disorder	Associate	20528958, 25686805, 31908177
Depressive Disorder Major	Associate	25765757
Diabetes Mellitus	Associate	29751399, 31506348
Diabetes Mellitus Type 2	Associate	29781558
Diabetic Nephropathies	Associate	29781558, 32922187
Drug Related Side Effects and Adverse Reactions	Associate	34579671
Erectile Dysfunction	Associate	23614907
Fetal Diseases	Associate	36585686
Fibrosis	Associate	20063294, 28555959
Glioblastoma	Associate	34769089
Glioma	Associate	31734653, 34769089
Heart Failure	Associate	15722665, 25000480, 25356826, 28555959, 33549556, 37798313
Heart Failure Diastolic	Associate	34569641
Heart Murmurs	Associate	34569641
Hemostatic Disorders	Associate	28323995
Hyperaldosteronism	Associate	34243750
Hyperkalemia	Associate	40441250
Hypertension	Associate	15117605, 21042587, 21342026, 22723323, 23665601, 25820244, 26203193, 31028470, 31072402, 31373631, 32222724, 37827440, 38437868, 40441250
Hypertension Pregnancy Induced	Associate	15117605, 31852079
Hypoxia	Associate	23555666
Infarction	Inhibit	25356826
Inflammation	Associate	28555959, 36919662, 37827440
Inflammation	Stimulate	37525257
Insulin Resistance	Associate	36808340
Kidney Diseases	Associate	12969137
Learning Disabilities	Associate	20528958
Leukemia Myeloid Acute	Inhibit	32338183
Lymphatic Metastasis	Associate	21319141
Lymphoma Follicular	Associate	2049326
Mental Disorders	Associate	14741058
Mineralocorticoid Excess Syndrome Apparent	Associate	23665601
Mitral Valve Insufficiency	Stimulate	30581499
Multiple Sclerosis	Associate	39201568
Myocardial Infarction	Associate	36612333
Neglected Diseases	Associate	22407082
Neoplasm Metastasis	Inhibit	36950803
Neoplasms	Associate	21179495, 23555666, 25188500, 31659097, 33148314, 33564687, 35191517, 37065760
Neoplasms	Inhibit	26082033
Organizing Pneumonia	Stimulate	23614907
Organizing Pneumonia	Associate	28555959
Pituitary ACTH Hypersecretion	Associate	35270010, 37065760
Polycystic Ovary Syndrome	Associate	36808340
Premature Birth	Associate	26260058
Pseudohypoaldosteronism	Associate	23762408, 25188500, 40091330, 40441250
Renal Insufficiency Chronic	Associate	36142571, 37525257
Ring Chromosome 20 Syndrome	Associate	31556305
Schizophrenia	Inhibit	14741058
Stomach Neoplasms	Associate	38081950
Substance Related Disorders	Associate	40441250
Syndrome	Associate	37537162
Taste Disorders	Associate	34243750
Urinary Bladder Neoplasms	Associate	23567325
Uterine Cervical Neoplasms	Associate	21319141
Vascular Diseases	Associate	36142571
Vascular Remodeling	Associate	31373631
Ventricular Dysfunction Left	Associate	34569641, 36612333
Ventricular Remodeling	Associate	36612333
Wounds and Injuries	Associate	32558353