CRHBP

Summary

CRHBP (corticotropin releasing hormone binding protein, HGNC:2356) is a protein-coding gene on chromosome 5q13.3, encoding Corticotropin-releasing factor-binding protein (P24387). Binds CRF and inactivates it.

Corticotropin-releasing hormone is a potent stimulator of synthesis and secretion of preopiomelanocortin-derived peptides. Although CRH concentrations in the human peripheral circulation are normally low, they increase throughout pregnancy and fall rapidly after parturition. Maternal plasma CRH probably originates from the placenta. Human plasma contains a CRH-binding protein which inactivates CRH and which may prevent inappropriate pituitary-adrenal stimulation in pregnancy.

Source: NCBI Gene 1393 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 31 total
• Druggable target: yes
• MANE Select transcript: NM_001882

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2356
Approved symbol	CRHBP
Name	corticotropin releasing hormone binding protein
Location	5q13.3
Locus type	gene with protein product
Status	Approved
Aliases	CRF-BP, CRFBP
Ensembl gene	ENSG00000145708
Ensembl biotype	protein_coding
OMIM	122559
Entrez	1393

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000274368, ENST00000503763, ENST00000506501, ENST00000512446, ENST00000514258, ENST00000909956, ENST00000909957

RefSeq mRNA: 1 — MANE Select: NM_001882 NM_001882

CCDS: CCDS4034

Canonical transcript exons

ENST00000274368 — 7 exons

Exon	Start	End
ENSE00000971778	76953601	76953694
ENSE00000971781	76958741	76958889
ENSE00001169777	76968728	76969471
ENSE00001169788	76953045	76953215
ENSE00003520846	76963343	76963460
ENSE00003543524	76954029	76954186
ENSE00003586142	76955653	76955863

Expression profiles

Bgee: expression breadth ubiquitous, 185 present calls, max score 89.96.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9316 / max 449.1848, expressed in 333 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
57166	2.1622	240
57170	0.2086	51
57168	0.1844	112
57167	0.1153	58
57164	0.1042	53
57163	0.0696	34
57169	0.0451	18
57165	0.0423	19

Top tissues by expression

284 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.96	gold quality
spleen	UBERON:0002106	89.80	gold quality
liver	UBERON:0002107	89.48	gold quality
right lobe of liver	UBERON:0001114	87.80	gold quality
prefrontal cortex	UBERON:0000451	86.13	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.81	gold quality
left adrenal gland cortex	UBERON:0035825	84.68	gold quality
right adrenal gland cortex	UBERON:0035827	84.64	gold quality
adult mammalian kidney	UBERON:0000082	84.42	gold quality
left adrenal gland	UBERON:0001234	84.03	gold quality
right adrenal gland	UBERON:0001233	83.96	gold quality
metanephros cortex	UBERON:0010533	83.95	gold quality
adrenal cortex	UBERON:0001235	83.06	gold quality
adrenal gland	UBERON:0002369	82.88	gold quality
metanephros	UBERON:0000081	82.23	gold quality
hypothalamus	UBERON:0001898	81.93	gold quality
metanephric glomerulus	UBERON:0004736	81.59	gold quality
cingulate cortex	UBERON:0003027	81.07	gold quality
adrenal tissue	UBERON:0018303	80.97	gold quality
anterior cingulate cortex	UBERON:0009835	80.95	gold quality
renal glomerulus	UBERON:0000074	80.52	gold quality
kidney	UBERON:0002113	78.62	gold quality
right atrium auricular region	UBERON:0006631	78.13	gold quality
cortex of kidney	UBERON:0001225	78.01	gold quality
buccal mucosa cell	CL:0002336	77.79	gold quality
Brodmann (1909) area 9	UBERON:0013540	77.52	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	77.38	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	76.75	gold quality
adipose tissue of abdominal region	UBERON:0007808	76.24	gold quality
frontal cortex	UBERON:0001870	76.22	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-MTAB-10553	yes	5005.84
E-MTAB-7407	yes	3160.02
E-HCAD-9	yes	3089.38
E-CURD-98	yes	2019.15
E-MTAB-8884	yes	1264.98
E-GEOD-76312	yes	1118.78
E-MTAB-8271	yes	1045.79
E-CURD-6	yes	859.22
E-ANND-5	yes	670.60
E-MTAB-10432	yes	409.95
E-HCAD-6	yes	245.35
E-HCAD-10	yes	37.61
E-MTAB-6701	yes	11.49
E-CURD-112	yes	10.88
E-ANND-3	yes	10.65

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR1, ESR2, TNF

miRNA regulators (miRDB)

67 targeting CRHBP, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349

Literature-anchored findings (GeneRIF, showing 31)

• Detected in myometrium. Widespread expression of CRH system in gestational tissue suggests paracrine role CRH in birth process (e.g. effects on macrophages and endothelial cells). (PMID:12784189)
• The corticotropin releasing hormone binding protein gene is likely to be involved in the genetic vulnerability for major depression. (PMID:14573312)
• The placenta was identified as the main site of the CRH-BP mRNA expression during the last weeks of pregnancy (PMID:15072543)
• analysis of regulation and function of CRH-BP [review] (PMID:16368564)
• We found a significant decrease in CRF-BP mRNA levels in the basolateral amygdala of male bipolar and male schizophrenic subjects and the lateral amygdala of male bipolar subjects compared to controls. (PMID:16482088)
• expression of CRH-BP, CRH-R1 and CRH-R2 in uterine tissues is down-regulated during pregnancy; the most pronounced down-regulation of CRH-BP and CRH-R2 occurred in laboring cervix, irrespective the length of gestation (PMID:16734917)
• Five single nucleotide polymorphisms (SNPs) and a deletion polymorphism in the CRF-BP gene were genotyped and the haplotype block structure of the gene was assessed. (PMID:17599466)
• An isolated Swedish population does not support a role for the CRF-BP gene in the vulnerability for bipolar disorder. (PMID:17728670)
• CRF-BP has distinct and separable binding surfaces for CRF and Ucn 1 (PMID:18234674)
• genotype analyses yielded significant association between CRHBP and suicide attempt (P = 0.035); interaction analysis showed significant interaction between CRH receptor type 1 and CRHBP in influencing suicide attempt and severity of suicidal behaviour (PMID:18838498)
• CRH-BP modulates CRH which influences cortical and hippocampal EEG activity and is the primary mediator of the neuroendocrine stress response. this suggest a likely role for CRH-BP in stress-related alcoholism. (PMID:18974851)
• In white women, non-smokers with the CT genotype at CRH-BP + 17487 have lower Nugent scores than non-smokers with the TT genotype; whereas smokers with the CT genotype have higher Nugent scores than smokers with the TT genotype (PMID:19131402)
• SNP rs10473984 affects response to citalopram in African American and Hispanic patients with major depressive disorder (PMID:20368512)
• results extend recent preclinical and clinical findings implicating the CRH-BP in stress-related alcoholism and confirm the role of the Asp40 allele of the OPRM1 gene in reward-driven alcohol phenotypes (PMID:21039637)
• interaction of CRHR1 SNP rs110402 and SNP rs3811939 predicts high risk of comorbid alcoholism in schizophrenic patients (PMID:21810631)
• CRHBP variation may predispose, independently and additively, to suicidal behavior in individuals who have experienced childhood trauma. (PMID:21978546)
• There was a significant association between the s/s homozygous genotype for the 5-HTTLPR polymorphism of SLC6A4 gene and restrained eating condition (p = 0.033 (PMID:22286724)
• A significant association was observed in Blacks, Hispanics and Whites between birth weight and maternal CRH-BP single nucleotide polymorphism genotypes. (PMID:22984453)
• Significant main effects on children’s cortisol reactivity were found for loci on CRHR1 and CRHBP. (PMID:23131710)
• Homozygosity for the CRHBP rs10055255 T allele was associated with significantly fewer post-ICU PTSD and depressive symptoms (PMID:24075295)
• Genetic polymorphism rs7718461 in the CRHBP gene showed significant association with overall pain severity during the year after motor vehicle collision. (PMID:26447706)
• A measure of stressful life events was significantly predictive of alcohol use/misuse. In addition, this association was significantly dependent upon the number of putative risk variants at rs1715749, a single-nucleotide polymorphism (SNP) in CRHBP. (PMID:26751645)
• These results suggest that the CRH and CRH-BP genes have no direct effect on Irritable bowel syndrome status. (PMID:26882083)
• We describe for the first time tumor specific epigenetic silencing of CRHBP and statistical association with aggressive tumors thus suggesting the CRH system to contribute to the development of kidney cancer. (PMID:27695045)
• found no differences in genotype distributions between heroin-dependent subjects and controls. However, identified a prominent interaction of one variant of the CRHBP gene predicting the risk of heroin relapse in the chronically stressed subjects. (PMID:29853227)
• Reduction in cocaine abuse among methadone maintenance treatment patients may be mediated by a genetic effect in a stress-related gene (CRHBP SNP rs1500 minor C allele). (PMID:30844877)
• Integrative analysis reveals CRHBP inhibits renal cell carcinoma progression by regulating inflammation and apoptosis. (PMID:31570754)
• The GCAG Haplotype of the CRHBP Gene May Decrease the Risk for Robbery Behavior Among the Han Chinese. (PMID:32551975)
• [Analysis of Correlation between Gene Polymorphisms of CRHBP in Yunnan Han Population and Schizophrenia and Aggressive Behavior]. (PMID:33295169)
• The Effect of CRHBP rs10062367 Polymorphism and Parenting Styles on Internalizing Problems in Preschoolers: The Moderating Effect of Sensory Processing Sensitivity. (PMID:36114994)
• Genetic Variation, Stress, and Physiological Stress Response in Adults With Food Allergy or Celiac Disease. (PMID:36280595)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	crhbp	ENSDARG00000024831
mus_musculus	Crhbp	ENSMUSG00000021680
rattus_norvegicus	Crhbp	ENSRNOG00000017890
drosophila_melanogaster	CG15537	FBGN0039770

Protein

Protein identifiers

Corticotropin-releasing factor-binding protein — P24387 (reviewed: P24387)

Alternative names: Corticotropin-releasing hormone-binding protein

All UniProt accessions (2): D6RHH7, P24387

UniProt curated annotations — full annotation on UniProt →

Function. Binds CRF and inactivates it. May prevent inappropriate pituitary-adrenal stimulation in pregnancy.

Subcellular location. Secreted.

Similarity. Belongs to the CRF-binding protein family.

RefSeq proteins (1): NP_001873* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008435	CRF-bd	Family
IPR035914	Sperma_CUB_dom_sf	Homologous_superfamily
IPR056177	CRF-BP_N	Domain
IPR056178	CRF-BP_C	Domain

Pfam: PF05428, PF23541

UniProt features (9 total): disulfide bond 5, signal peptide 1, chain 1, glycosylation site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P24387-F1	83.71	0.67

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (5): 60–81, 104–141, 183–205, 237–264, 277–318

Glycosylation sites (1): 204

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-373080	Class B/2 (Secretin family receptors)

MSigDB gene sets: 253 (showing top): TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_RESPONSE_TO_COCAINE, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOCC_SECRETORY_GRANULE, TTTGTAG_MIR520D, GOBP_ADULT_BEHAVIOR, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEGATIVE_REGULATION_OF_PEPTIDE_SECRETION

GO Biological Process (24): synaptic transmission, dopaminergic (GO:0001963), maternal aggressive behavior (GO:0002125), inflammatory response (GO:0006954), signal transduction (GO:0007165), female pregnancy (GO:0007565), learning or memory (GO:0007611), hormone-mediated signaling pathway (GO:0009755), cellular response to potassium ion (GO:0035865), hormone metabolic process (GO:0042445), regulated exocytosis (GO:0045055), behavioral response to ethanol (GO:0048149), regulation of corticotropin secretion (GO:0051459), negative regulation of corticotropin secretion (GO:0051460), cellular response to calcium ion (GO:0071277), cellular response to cocaine (GO:0071314), cellular response to cAMP (GO:0071320), cellular response to tumor necrosis factor (GO:0071356), cellular response to estrogen stimulus (GO:0071391), cellular response to estradiol stimulus (GO:0071392), cellular response to xenobiotic stimulus (GO:0071466), regulation of cellular response to stress (GO:0080135), cellular response to gonadotropin-releasing hormone (GO:0097211), negative regulation of corticotropin-releasing hormone receptor activity (GO:1900011), regulation of NMDA receptor activity (GO:2000310)

GO Molecular Function (3): peptide binding (GO:0042277), corticotropin-releasing hormone binding (GO:0051424), protein binding (GO:0005515)

GO Cellular Component (12): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), secondary lysosome (GO:0005767), multivesicular body (GO:0005771), microtubule (GO:0005874), secretory granule (GO:0030141), dendrite (GO:0030425), dense core granule (GO:0031045), varicosity (GO:0043196), perikaryon (GO:0043204), axon terminus (GO:0043679)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular response to oxygen-containing compound	3
cellular anatomical structure	3
cellular response to hormone stimulus	2
cellular response to metal ion	2
corticotropin secretion	2
binding	2
chemical synaptic transmission	1
aggressive behavior	1
defense response	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
multi-organism reproductive process	1
multi-multicellular organism process	1
behavior	1
cognition	1
signal transduction	1
response to potassium ion	1
metabolic process	1
regulation of hormone levels	1
exocytosis	1
adult behavior	1
response to ethanol	1
regulation of endocrine process	1
regulation of peptide hormone secretion	1
negative regulation of multicellular organismal process	1
regulation of corticotropin secretion	1
negative regulation of peptide hormone secretion	1
response to calcium ion	1
response to cocaine	1
cellular response to alkaloid	1
response to cAMP	1
cellular response to nitrogen compound	1
response to tumor necrosis factor	1
cellular response to cytokine stimulus	1
response to estrogen	1
response to estradiol	1
cellular response to lipid	1

Protein interactions and networks

STRING

660 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CRHBP	CRH	P06850	997
CRHBP	CRHR1	P34998	983
CRHBP	CRHR2	Q13324	973
CRHBP	UCN	P55089	967
CRHBP	UCN3	Q969E3	839
CRHBP	POMC	P01189	763
CRHBP	UCN2	Q96RP3	716
CRHBP	FKBP5	Q13451	615
CRHBP	NR3C1	P04150	571
CRHBP	NR3C2	P08235	471
CRHBP	SST	P01166	453
CRHBP	SLC6A4	P31645	447
CRHBP	MC2R	Q01718	441
CRHBP	OXT	P01178	436
CRHBP	MT1H	P80294	423

IntAct

8 interactions, top by confidence:

A	B	Type	Score
CRHBP	CCNB2	psi-mi:“MI:0914”(association)	0.640
PBK	TRIM37	psi-mi:“MI:0914”(association)	0.550
CRHBP	TNIP1	psi-mi:“MI:0914”(association)	0.530
IMPACT	CRHBP	psi-mi:“MI:0915”(physical association)	0.400
CRHBP		psi-mi:“MI:0914”(association)	0.350

BioGRID (31): TUBB1 (Affinity Capture-MS), TNIP1 (Affinity Capture-MS), CCNB2 (Affinity Capture-MS), PLS1 (Affinity Capture-MS), PHLDB3 (Affinity Capture-MS), EIF1AX (Affinity Capture-MS), SQSTM1 (Affinity Capture-MS), COA7 (Affinity Capture-MS), CRHBP (Two-hybrid), TNIP1 (Affinity Capture-MS), CCNB2 (Affinity Capture-MS), PHLDB3 (Affinity Capture-MS), TUBB1 (Affinity Capture-MS), COA7 (Affinity Capture-MS), SQSTM1 (Affinity Capture-MS)

ESM2 similar proteins: A7E2Z9, B3MFC2, B3NSF6, B4GAN3, B4HNI3, B4J8Z9, B4KR21, B4LQ44, B4MQJ1, B4P641, B4QBL6, B5A5T4, B5E022, C6K2K4, D3ZTT2, O13157, O88745, O94907, P01216, P24387, P43446, P68241, P68242, Q01974, Q26492, Q5R7F5, Q5RH73, Q66IA6, Q6DGP8, Q6FHJ7, Q76KF0, Q7YRN1, Q86Y78, Q8BNJ6, Q8BPP5, Q8CGD2, Q8JIE9, Q8NC67, Q8NFY4, Q99445

Diamond homologs: P24387, P24388, Q28557, Q60571, Q91653

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

31 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1167 predictions. Top by Δscore:

Variant	Effect	Δscore
5:76953693:GC:G	donor_gain	1.0000
5:76953695:G:GG	donor_gain	1.0000
5:76954023:CCCCA:C	acceptor_loss	1.0000
5:76954024:CCCA:C	acceptor_loss	1.0000
5:76954025:CCA:C	acceptor_loss	1.0000
5:76954026:CA:C	acceptor_loss	1.0000
5:76954027:A:AG	acceptor_gain	1.0000
5:76954027:AG:A	acceptor_gain	1.0000
5:76954027:AGG:A	acceptor_gain	1.0000
5:76954028:G:A	acceptor_gain	1.0000
5:76954028:G:GG	acceptor_gain	1.0000
5:76954028:GGG:G	acceptor_gain	1.0000
5:76954028:GGGT:G	acceptor_gain	1.0000
5:76954185:AGGT:A	donor_loss	1.0000
5:76954187:G:A	donor_loss	1.0000
5:76955820:A:T	donor_gain	1.0000
5:76955864:G:GG	donor_gain	1.0000
5:76955919:T:TA	donor_gain	1.0000
5:76955920:A:AA	donor_gain	1.0000
5:76958735:A:AG	acceptor_gain	1.0000
5:76958736:C:G	acceptor_gain	1.0000
5:76958737:A:AG	acceptor_gain	1.0000
5:76958738:A:G	acceptor_gain	1.0000
5:76958885:TAAAG:T	donor_loss	1.0000
5:76958886:AAAG:A	donor_loss	1.0000
5:76958889:GGT:G	donor_loss	1.0000
5:76958890:G:T	donor_loss	1.0000
5:76958891:T:G	donor_loss	1.0000
5:76968717:A:AG	acceptor_gain	1.0000
5:76968718:T:G	acceptor_gain	1.0000

AlphaMissense

2124 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:76955665:T:A	W116R	0.999
5:76955665:T:C	W116R	0.999
5:76958812:A:C	S206R	0.999
5:76958814:C:A	S206R	0.999
5:76958814:C:G	S206R	0.999
5:76955828:T:C	F170S	0.998
5:76968764:G:C	R283P	0.998
5:76955667:G:C	W116C	0.997
5:76955667:G:T	W116C	0.997
5:76955687:T:G	F123C	0.997
5:76955686:T:C	F123L	0.996
5:76955688:C:A	F123L	0.996
5:76955688:C:G	F123L	0.996
5:76955784:T:A	N155K	0.996
5:76955784:T:G	N155K	0.996
5:76954096:C:G	C81W	0.995
5:76955663:G:A	G115D	0.995
5:76955687:T:C	F123S	0.995
5:76958809:T:C	C205R	0.995
5:76954062:T:C	F70S	0.994
5:76954095:G:A	C81Y	0.994
5:76955690:C:A	P124H	0.994
5:76958809:T:A	C205S	0.994
5:76958810:G:C	C205S	0.994
5:76954031:T:C	C60R	0.993
5:76954094:T:C	C81R	0.993
5:76958811:C:G	C205W	0.993
5:76954031:T:A	C60S	0.992
5:76954032:G:C	C60S	0.992
5:76954094:T:A	C81S	0.992

dbSNP variants (sampled 300 via entrez): RS1000017236 (5:76974829 A>C), RS1000158126 (5:76963230 T>C), RS1000266830 (5:76955984 A>C,G,T), RS1000454365 (5:76974313 G>A,C), RS1000646927 (5:76971131 T>C), RS1000702488 (5:76970697 T>A,C), RS1000814329 (5:76977797 G>C), RS1000828589 (5:76967681 A>G), RS1001214489 (5:76954833 A>G), RS1001373990 (5:76967760 G>A), RS1001483609 (5:76974563 A>G), RS1001615304 (5:76966068 G>A,T), RS1001687755 (5:76973174 T>C), RS1001779814 (5:76961506 C>T), RS1002009891 (5:76971460 G>C,T)

Disease associations

OMIM: gene MIM:122559 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006585_1803	Blood protein levels	3.000000e-79
GCST007576_416	Chronotype	1.000000e-07
GCST009268_10	Dental caries (decayed, missing and filled tooth surfaces)	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3885546 (PROTEIN COMPLEX), CHEMBL5930 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10055255	Toxicity	3	ethanol	Alcohol abuse

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1500	CRHBP		0.00	0
rs10055255	CRHBP	3	1.75	1	ethanol
rs10062367	CRHBP		0.00	0

Binding affinities (BindingDB)

462 measured of 2314 human assays (2420 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
5-[[[1-(4-fluorophenyl)-4-keto-2H-pyrazolo[3,4-d]pyrimidin-6-yl]thio]methyl]furan-2-carboxylic acid methyl ester	EC50	0.00249 nM
1-(1,3-benzodioxol-5-yl)-5-[(2-fluorobenzyl)thio]-1H-tetrazole	EC50	0.00446 nM
3-(2-furanylmethyl)-2-propylthiochromeno[2,3-d]pyrimidine-4,5-dione	EC50	0.0148 nM
2-(2-methylallylthio)-1-pyrindan-3-carbonitrile	EC50	0.0335 nM
1-Pyrimidin-2-yl-piperidine-3-carboxylic acid (4-phenoxy-phenyl)-amide	IC50	54 nM
2-[(4-fluorobenzyl)thio]-N-[2-(2-fluorophenoxy)ethyl]benzamide	EC50	313 nM
MLS000114796	IC50	449 nM
(2E)-5-bromo-4-chloro-2-{[(3-methylphenyl)amino]methylene}-1,2-dihydro-3H-indol-3-one	EC50	460 nM
MLS000543555	EC50	544 nM
cid_2235475	EC50	709 nM
5-nitro-2-[[oxo-[4-[(3,3,5-trimethyl-7-azabicyclo[3.2.1]octan-7-yl)sulfonyl]phenyl]methyl]amino]-3-thiophenecarboxylic acid ethyl ester	EC50	793 nM
[1-(cyclohexylcarbamoylamino)-1-oxidanylidene-propan-2-yl] 2-(furan-2-ylcarbonylamino)-4-methylsulfanyl-butanoate	EC50	832 nM
4-chloranyl-N-[1-methyl-2-(piperidin-1-ylmethyl)benzimidazol-5-yl]benzenesulfonamide	IC50	1060 nM
cid_5864804	EC50	1110 nM
cid_760116	EC50	1120 nM
N-[1-[(2E)-2-[(1,2-dimethylindol-3-yl)methylidene]hydrazinyl]-3-methyl-1-oxidanylidene-butan-2-yl]-1,3-benzodioxole-5-carboxamide	EC50	1240 nM
2-furancarboxylic acid [5-amino-1-(4-fluorophenyl)sulfonyl-3-pyrazolyl] ester	IC50	1260 nM
N-[4-[(E)-[4-[4-(difluoromethoxy)phenyl]-4-methyl-2,5-dioxoimidazolidin-1-yl]iminomethyl]phenyl]acetamide	EC50	1370 nM
N-[4-[bis(fluoranyl)methylsulfanyl]phenyl]-9-oxidanylidene-2,3-dihydro-1H-pyrrolo[2,1-b]quinazoline-6-carboxamide	EC50	1400 nM
4-({2-[(E)-(3-isopropyl-2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]phenoxy}methyl)benzoic acid	EC50	1480 nM
4-[(2Z)-2-(3H-1,3-benzothiazol-2-ylidene)-2-cyano-1-oxoethyl]benzoic acid methyl ester	EC50	1610 nM
cid_1791279	EC50	1650 nM
MLS002608645	EC50	1690 nM
2-methyl-4-nitro-N-(phenylmethyl)aniline	EC50	1740 nM
2-[(4-fluorophenyl)sulfonylamino]-N-(2-hydroxy-5-piperidin-1-ylsulfonylphenyl)benzamide;hydrochloride	EC50	1830 nM
2-[[3-(1-ethyl-3-methyl-pyrazol-4-yl)-2-isoxazoline-5-carbonyl]amino]benzoic acid methyl ester	IC50	1890 nM
2-{[6-(acetylamino)-3-pyridinyl]sulfanyl}-N-(4-fluorophenyl)nicotinamide	EC50	1970 nM
6-hexyl-7-hydroxy-N-(2-methoxyphenyl)-2-oxo-1-benzopyran-3-carboxamide	EC50	1970 nM
cid_5025735	EC50	2050 nM
MLS002637146	EC50	2100 nM
cid_4252281	EC50	2260 nM
4-(2,5-Dimethoxy-benzylidene)-2-phenyl-4H-oxazol-5-one	EC50	2290 nM
MLS001197016	EC50	2380 nM
MLS000568786	EC50	2430 nM
1-[(4-methoxy-3-methyl-phenyl)methyl]-2-methyl-piperidine	EC50	2450 nM
3-bromo-N-[(2-methoxyphenoxy)-methylphosphoryl]aniline	EC50	2540 nM
2-[4-[[(E)-amino-[(4,6-dimethyl-2-pyrimidinyl)imino]methyl]amino]phenyl]acetic acid propan-2-yl ester	EC50	2560 nM
MLS003115217	EC50	2560 nM
4-[4-(4-methylphenyl)sulfonylpiperazin-1-yl]-5-phenylthieno[2,3-d]pyrimidine	EC50	2650 nM
cid_114429	EC50	2690 nM
SMR000710049	EC50	2730 nM
SMR000041898	EC50	2740 nM
3-amino-N-(2-thiazolyl)-6-thiophen-2-yl-4-(trifluoromethyl)-2-thieno[2,3-b]pyridinecarboxamide	EC50	2760 nM
MLS000051091	EC50	2770 nM
cid_1790620	EC50	2780 nM
SMR000305235	EC50	2800 nM
4,4-dimethyl-N-(phenylmethyl)-5H-thiazol-2-amine	EC50	2840 nM
cid_3138334	EC50	2890 nM
2-[(6-acetamido-3-pyridinyl)thio]-N-[4-(trifluoromethoxy)phenyl]-3-pyridinecarboxamide	EC50	2960 nM
2-cyano-2-[3-(4-o-phenetylpiperazino)quinoxalin-2-yl]acetic acid allyl ester	EC50	3050 nM

ChEMBL bioactivities

516 potent at pChembl≥5 of 805 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.34	EC50	460	nM	CHEMBL1995565
6.30	IC50	506	nM	CHEMBL1400385
6.26	IC50	545	nM	CHEMBL1375451
6.26	EC50	544	nM	CHEMBL1500274
6.21	IC50	610	nM	CHEMBL1489517
6.15	EC50	709	nM	CHEMBL1464584
6.14	IC50	727	nM	CHEMBL1974381
6.14	IC50	723	nM	CHEMBL1371902
6.12	IC50	754	nM	CHEMBL1734544
6.10	EC50	793	nM	CHEMBL1526609
6.08	EC50	832	nM	CHEMBL1519346
6.07	IC50	858	nM	CHEMBL1559259
6.06	EC50	870	nM	CHEMBL1731330
6.01	IC50	980	nM	CHEMBL579621
6.00	IC50	988	nM	CHEMBL1371510
6.00	IC50	1000	nM	CHEMBL1313479
5.96	EC50	1110	nM	CHEMBL1720673
5.95	EC50	1120	nM	CHEMBL1585011
5.94	IC50	1140	nM	CHEMBL1576123
5.92	IC50	1190	nM	CHEMBL1709644
5.91	EC50	1240	nM	CHEMBL2001226
5.86	EC50	1370	nM	CHEMBL1979183
5.85	EC50	1400	nM	CHEMBL1530418
5.80	IC50	1590	nM	CHEMBL1458284
5.78	IC50	1680	nM	CHEMBL1320148
5.78	EC50	1650	nM	CHEMBL1520994
5.77	EC50	1690	nM	CHEMBL1707960
5.76	IC50	1750	nM	CHEMBL1327923
5.74	IC50	1840	nM	CHEMBL1317248
5.74	EC50	1830	nM	CHEMBL1597458
5.73	IC50	1850	nM	CHEMBL1340114
5.73	IC50	1850	nM	CHEMBL1509034
5.72	IC50	1910	nM	CHEMBL1302523
5.71	EC50	1970	nM	CHEMBL1415013
5.71	EC50	1970	nM	CHEMBL1334503
5.70	IC50	2000	nM	CHEMBL1388565
5.70	IC50	2020	nM	CHEMBL1873436
5.69	EC50	2050	nM	CHEMBL1730038
5.68	IC50	2090	nM	CHEMBL1533222
5.68	EC50	2100	nM	CHEMBL1732456
5.67	IC50	2160	nM	CHEMBL1559196
5.67	IC50	2160	nM	CHEMBL1506533
5.67	IC50	2160	nM	CHEMBL1448881
5.65	EC50	2260	nM	CHEMBL1347204
5.64	EC50	2290	nM	CHEMBL1466606
5.63	IC50	2340	nM	CHEMBL1322948
5.62	IC50	2410	nM	CHEMBL1569153
5.62	EC50	2380	nM	CHEMBL1590944
5.61	EC50	2450	nM	CHEMBL1511951
5.61	EC50	2430	nM	CHEMBL1502602

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Doxorubicin	affects expression, decreases expression	2
arsenite	increases methylation	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
bisphenol S	increases methylation	1
Benzo(a)pyrene	increases methylation	1
Fluorouracil	affects expression	1
Silicon Dioxide	increases expression	1
Triclosan	decreases expression	1
Valproic Acid	affects expression	1
8-Bromo Cyclic Adenosine Monophosphate	decreases expression	1

ChEMBL screening assays

5 unique, capped per target: 3 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1963888	Functional	PUBCHEM_BIOASSAY: Dose Response confirmation of uHTS hits for small molecule antagonists of the CRF-binding protein and CRF-R2 receptor complex. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL3539310	Binding	Binding affinity to CRF-binding protein (unknown origin)	In vitro and in vivo metabolism and pharmacokinetics of BMS-562086, a potent and orally bioavailable corticotropin-releasing factor-1 receptor antagonist. — Drug Metab Dispos

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.