CRHR1

corticotropin releasing hormone receptor 1

Nominated Target, Selected for Target Enabling Resource Development

This gene encodes a G-protein coupled receptor that binds neuropeptides of the corticotropin releasing hormone family that are major regulators of the hypothalamic-pituitary-adrenal pathway. The encoded protein is essential for the activation of signal transduction pathways that regulate diverse physiological processes including stress, reproduction, immune response and obesity. Alternative splicing results in multiple transcript variants. Naturally-occurring readthrough transcription between this gene and upstream GeneID:147081 results in transcripts that encode isoforms that share similarity with the products of this gene.

provided by RefSeq


Biological Domains

Endolysosome, Immune Response, Synapse

Pharos Class

Tclin

Also known as

ENSG00000120088 (Ensembl Release 113)

UNIPROTKB P34998

CRF-R-1, CRH-R1, CRH-R-1, CRHR1L, CRFR-1, CRF1, CRFR1, CRHR, CRF-R, CRF-R1

Summary of Evidence

This tab shows an overview of how the selected gene is associated with AD.

  • Genetic Association with LOAD

    Indicates whether or not this gene shows significant genetic association with Late Onset AD (LOAD) based on evidence from multiple studies compiled by the ADSP Gene Verification Committee
    False
  • Brain eQTL

    Indicates whether or not this gene locus has a significant expression Quantitative Trait Locus (eQTL) based on an AMP-AD consortium study
    True
  • RNA Expression Change in AD Brain

    Indicates whether or not this gene shows significant differential expression in at least one brain region based on AMP-AD consortium work. See ‘EVIDENCE’ tab.
    True
  • Protein Expression Change in AD Brain

    Indicates whether or not this gene shows significant differential protein expression in at least one brain region based on AMP-AD consortium work. See ‘EVIDENCE’ tab.
    No data
  • Nominated Target

    Indicates whether or not this gene has been submitted as a nominated target to Agora.
    True

AD Risk Scores

About AD Risk Scores

The TREAT-AD Center at Emory-Sage-SGC has developed a Target Risk Score (TRS) to objectively rank the potential involvement of specific genes in AD. The TRS is derived by summing two component risk scores, the Genetic Risk Score and the Multi-omic Risk Score, each of which is derived from a meta-analysis of multiple harmonized data sets. More information about the methodology used to define these risk scores is available here.

AD Risk Scores for CRHR1

The TRS for CRHR1, along with the component Genetic and Multi-omic Risk Scores, is shown here. The scores for CRHR1 are superimposed on the genome-wide score distributions. If No Data is Currently Available is displayed for a score, that score was not calculated for CRHR1.

Target Risk Score

1.0800.511.522.533.544.505001,0001,5002,0002,5003,0003,5004,0004,500GENE SCORENUMBER OF GENES

Genetic Risk Score

1.0800.30.60.91.21.51.82.12.42.705001,0001,5002,0002,5003,0003,5004,0004,5005,000GENE SCORENUMBER OF GENES

Multi-omic Risk Score

0.0000.20.40.60.811.21.41.61.801,0002,0003,0004,0005,0006,0007,0008,0009,00010,000GENE SCORENUMBER OF GENES

Biological Domain Classification

About Biological Domains

A biological domain represents a standardized area of biology defined by a set of discrete, biologically coherent GO terms. The TREAT-AD Center at Emory-Sage-SGC has defined nineteen biological domains associated with AD, and objectively mapped genes to those biological domains using GO term annotations. More information about the methodology used to define AD biological domains, and to generate genome-wide biological domain mappings, is available here.

Biological Domains for CRHR1

Select a biological domain on the left to see the list of GO terms that link CRHR1 to it on the right. The percentage value displayed next to the currently selected biological domain indicates the proportion of CRHR1's total unique GO terms that map to the biological domain. The ratio displayed on the right indicates how many of the biological domain's total GO terms CRHR1 is annotated with.

BIOLOGICAL DOMAIN MAPPINGS

EndolysosomeImmune ResponseSynapseApoptosisAPP MetabolismAutophagyCell CycleDNA RepairEpigeneticLipid MetabolismMetal Binding and HomeostasisMitochondrial MetabolismMyelinationOxidative StressProteostasisRNA SpliceosomeStructural StabilizationTau HomeostasisVasculature33.3%

LINKING GO TERMS FOR ENDOLYSOSOME (1/202)

  • Endosome

RNA Expression

The results shown on this page are derived from a harmonized RNA-seq analysis of post-mortem brains from AD cases and controls. The samples were obtained from three human cohort studies across a total of nine different brain regions.


Overall Expression of CRHR1 Across Brain Regions

This plot depicts the median expression of the selected gene across brain regions, as measured by RNA-seq read counts per million (CPM) reads. Meaningful expression is considered to be a log2 CPM greater than log2(5), depicted by the red line in the plot.

1.010.000.230.190.14CBEFPPCCPHGSTG0.00.10.20.30.40.50.60.70.80.91.01.1Brain regionLOG2 CPM

Filter the following charts by statistical model

AD Diagnosis (males and females)

Differential Expression of CRHR1 Across Brain Regions

After selecting a statistical model, you will be able to see whether the selected gene is differentially expressed between AD cases and controls. The box plot depicts how the differential expression of the selected gene of interest (purple dot) compares with expression of other genes in a given tissue. Summary statistics for each tissue can be viewed by hovering over the purple dots. Meaningful differential expression is considered to be a log2 fold change value greater than 0.263, or less than -0.263.

AD Diagnosis (males and females)

ACCCBEDLPFCFPIFGPCCPHGSTGTCX−1.0−0.50.00.51.0LOG 2 FOLD CHANGE
Brain region

Consistency of Change in Expression

This forest plot indicates the estimate of the log fold change with standard errors across the brain regions in the model chosen using the filter above. Genes that show consistent patterns of differential expression will have similar log-fold change value across brain regions.

AD Diagnosis (males and females)

ACCCBEDLPFCFPIFGPCCPHGSTGTCX
−0.4−0.3−0.2−0.10.00.10.20.30.4false-0.0950.35false-0.280.063false-0.34-0.042false-0.310.025false-0.280.064false-0.210.10false-0.100.25false-0.0710.29false-0.380.085
LOG 2 FOLD CHANGE

Correlation of CRHR1 with Hallmarks of AD

This plot depicts the association between expression levels of the selected gene in the DLPFC and three phenotypic measures of AD. An odds ratio > 1 indicates a positive correlation and an odds ratio < 1 indicates a negative correlation. Statistical significance and summary statistics for each phenotype can be viewed by hovering over the dots.

Phenotype
No data is currently available.

Similarly Expressed Genes

The network diagram below is based on a coexpression network analysis of RNA-seq data from AD cases and controls. The network analysis uses an ensemble methodology to identify genes that show similar coexpression across individuals.

The color of the edges and nodes indicates how frequently significant coexpression was identified. Each node represents a different gene and the amount of edges within the network. Darker edges represent coexpression in more brain regions.

Filter by Number of Edges

>0
>1
CRHR1MAPT-AS1SLC27A2CAMTA2
Current gene
Selected gene
2-3 Edges
4-5 Edges
6-7 Edges

CRHR1

This gene encodes a G-protein coupled receptor that binds neuropeptides of the corticotropin releasing hormone family that are major regulators of the hypothalamic-pituitary-adrenal pathway. The encoded protein is essential for the activation of signal transduction pathways that regulate diverse physiological processes including stress, reproduction, immune response and obesity. Alternative splicing results in multiple transcript variants. Naturally-occurring readthrough transcription between this gene and upstream GeneID:147081 results in transcripts that encode isoforms that share similarity with the products of this gene. [provided by RefSeq, Aug 2016].

Genetic Association with LOAD
False
Brain eQTL
True
RNA Expression Change in AD Brain
True
Protein Expression Change in AD Brain
No data
Nominated target
True

Proteomics

Proteomic analyses of post-mortem brains show whether protein products of CRHR1 are differentially expressed between AD cases and controls. Each box plot depicts how the differential expression of the protein(s) of interest (purple dot) compares with expression of other proteins in a given brain region. Summary statistics for each tissue can be viewed by hovering over the purple dots.


Targeted SRM Differential Protein Expression

Selected Reaction Monitoring (SRM) data was generated from the DLPFC region of post-mortem brains of over 1000 individuals from multiple human cohort studies.

Note that only a single SRM result is available for a given gene, as the probes used for this experiment were designed to match multiple protein products derived from each targeted gene.

Brain tissue
No data is currently available.

Genome-wide Differential Protein Expression

Select a protein from the dropdown menu to see whether it is differentially expressed between AD cases and controls.

Select a protein

The assay-specific box plots below depict how the differential expression of the selected protein of interest (purple dot) compares with expression of other proteins in each brain region that was assayed. Assay-specific summary statistics for each brain region can be viewed by hovering over the purple dot.

Multiple proteins may map to a single gene. Results from both TMT and LFQ assays are provided, however results for some proteins may be available for only one of the assays.


TMT Differential Protein Expression

Tandem mass tagged (TMT) data was generated from the DLPFC region of post-mortem brains of 400 individuals from the ROSMAP cohort.

Note that proteins may not be detected in this brain region; for these proteins, the plot will show no data.

Brain tissue
No data is currently available.

LFQ Differential Protein Expression

Liquid-free quantification (LFQ) data was generated from post-mortem brains of more than 500 individuals. Samples were taken from four human cohort studies, representing four different brain regions.

Note that proteins may not be detected in all four brain regions; for these proteins, the plot will show fewer than four brain regions.

Brain tissue
No data is currently available.

Metabolomics

The results shown on this page are derived from an analysis of metabolite levels from AD cases and controls. The samples were obtained from approximately 1400 individuals from the ADNI study. Metabolites are associated with genes using genetic mapping and the metabolite with the highest genetic association is shown for each gene.


Mapping of Metabolites to CRHR1

No metabolomic data is currently available.


Levels of Metabolite by Disease Status

This plot shows differences in metabolite levels in AD cases and controls.

Diagnosis
No data is currently available.

Target Enabling Resources

Use these links to discover the Target Enabling Resources for CRHR1 that are currently available, under development, or planned.

Target Enabling Resources
View the openly available TREAT-AD resources for experimental validation of CRHR1 in the AD Knowledge Portal.
AD Informer Set
View information about the development and distribution of the AD Informer Set.

Drug Development Resources

These external sites provide information and resources related to drug development.

Chemical Probes
View expert reviews and evaluations of any chemical probes that are available for this target.
Open Targets
View evidence on the validity of this therapeutic target based on genome-scale experiments and analysis.
PharmGKB
Search for information on gene-drug and gene-phenotype relationships.
Pharos
View information about this target in the Knowledge Management Center for the Illuminating the Druggable Genome program.
Probe Miner
Search for information on chemical probes based on large-scale, publicly available, medicinal chemistry data.
Protein Data Bank
Search for experimental and computed 3D protein structure information.

Additional Resources

These external sites provide additional information about therapeutic targets for AD and related dementias.

AD Atlas
Perform interactive network and enrichment analyses on this target using a heterogenous network of multiomic, association, and endophenotypic data.
Alzforum
Visit Alzforum for news and information resources about AD and related disorders.
AlzPED
Search for information on preclinical efficacy studies of candidate AD therapeutics.
AMP-PD Target Explorer
View evidence about whether this target is associated with Parkinson's Disease.
Brain Knowledge Platform
View single nucleus RNAseq results for this target using the Allen Institute SEA-AD Comparative Viewer.
Gene Ontology
View the GO terms associated with this target and explore ontology-related tools.
GeneCards
View integrated information about this target gathered from a comprehensive collection of public sources.
Genomics DB
View information about this target on the National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) Genomics Database.
Pub AD
View dementia-related publication information for this target.
Reactome Pathways
View the reactome pathway information for this target on Ensembl.
SEA-AD
Explore the Seattle Alzheimer’s Disease Brain Cell Atlas resources from the Allen Institute.
UniProtKB
View protein sequence and functional information about this target.

Evidence Supporting the Nomination of CRHR1

This gene has been nominated as a potential target for AD. Nominated targets are obtained from several sources, including the National Institute on Aging's Accelerating Medicines Partnership in Alzheimer's Disease (AMP-AD) consortium. Targets have been identified using computational analyses of high-dimensional genomic, proteomic and/or metabolomic data derived from human samples.


AMP-AD: The Mayo Clinic - University of Florida - The Institute for Systems Biology

The Mayo-UFL-ISB AMP-AD team, led by Nilufer Ertekin-Taner, Todd Golde, Nathan Price, and Steven Younkin, includes three institutions: the University of Florida, the Institute for Systems Biology, and the Mayo Clinic Jacksonville. The focus of the team is to identify therapeutic targets within the innate immune signaling cascade in Alzheimer's disease that can be safely manipulated to provide disease modification.

Why was the target selected?

Stress response targets

Predicted therapeutic direction

Antagonism predicted to reduce disease progression

The type of data used and analyses done to identify target

AD vs Control (Simple, TCX) synaptic module, Down in AD (DEG significant TCX, simple and not significant comprehensive)

Cohort study data: Mayo

Initial date of nomination

2018

Planned Experimental Validation

not prioritized for experimental validation

Learn more about the target nomination process