CRHR2

Chr 7

corticotropin releasing hormone receptor 2

Also known as: CRF-RB, CRF2, CRFR2, HM-CRF

NCBI Gene: 1395ENSG00000106113UniProt: Q13324

The protein encoded by this gene belongs to the G-protein coupled receptor 2 family, and the subfamily of corticotropin releasing hormone receptor. This receptor shows high affinity for corticotropin releasing hormone (CRH), and also binds CRH-related peptides such as urocortin. CRH is synthesized in the hypothalamus, and plays an important role in coordinating the endocrine, autonomic, and behavioral responses to stress and immune challenge. Studies in mice suggest that this receptor maybe involved in mediating cardiovascular homeostasis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jan 2011]

112
ClinVar variants
23
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— CRHR2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
23 Pathogenic / Likely Pathogenic· 81 VUS of 112 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.28LOEUF
pLI 0.000
Z-score 0.38
OE 0.92 (0.68–1.28)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.75Z-score
OE missense 0.87 (0.78–0.97)
229 obs / 263.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.92 (0.68–1.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.78–0.97)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.83
0≤1.21.6
LoF obs/exp: 26 / 28.2Missense obs/exp: 229 / 263.2Syn Z: 1.35

ClinVar Variant Classifications

112 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic4
VUS81
Likely Benign6
Benign2
19
Pathogenic
4
Likely Pathogenic
81
VUS
6
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
19
0
19
Likely Pathogenic
0
0
4
0
4
VUS
0
68
12
1
81
Likely Benign
0
5
1
0
6
Benign
0
1
0
1
2
Total074362112

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CRHR2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Corticotropin-Releasing Hormone Family and Their Receptors in the Cardiovascular System.
Takefuji M et al.·Circ J
2019Review
Association between genetic variant rs2267716 of CRHR2 gene with colorectal cancer.
Ramírez-Guerrero AA et al.·J Investig Med
2022
Novel corticotropin-releasing hormone receptor genes (CRHR1 and CRHR2) linkage to and association with polycystic ovary syndrome.
Amin M et al.·J Ovarian Res
2023
Urocortin2 measurement for heart failure assessment.
Inukai K et al.·Sci Rep
2025
The Role of Urocortins in Intracerebral Hemorrhage.
Choy KW et al.·Biomolecules
2020Review
The urocortin peptides: biological relevance and laboratory aspects of UCN3 and its receptor.
Alghamdi NJ et al.·Crit Rev Clin Lab Sci
2022Review
Cross species association examination of UCN3 and CRHR2 as potential pharmacological targets for antiobesity drugs.
Jiang Z et al.·PLoS One
2006
CRH Receptor Signalling: Potential Roles in Pathophysiology.
Grammatopoulos DK et al.·Curr Mol Pharmacol
2017Review
The Neuropeptide System and Colorectal Cancer Liver Metastases: Mechanisms and Management.
Kasprzak A et al.·Int J Mol Sci
2020Review
Lidocaine ameliorates intestinal barrier dysfunction in irritable bowel syndrome by modulating corticotropin-releasing hormone receptor 2.
Wang Y et al.·Neurogastroenterol Motil
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Paraphilic DisordersSexual AddictionParasomnia

Paraphilic Disorders and Other Conditions With Risk for Sexual Violence: a Case-control Study

RECRUITING
NCT05861752Region StockholmStarted 2022-10-19
Treatment as usual

External Resources

Links to major genomics databases and tools