CRH

corticotropin releasing hormone, the group of Neuropeptides

Basic information

Region (hg38): 8:66176376-66178464

Links

ENSG00000147571 ∙ NCBI:1392 ∙ OMIM:122560 ∙ HGNC:2355 ∙ Uniprot:P06850 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nocturnal frontal lobe epilepsy (Supportive), mode of inheritance: AD
• frontal lobe epilepsy (Limited), mode of inheritance: AD
• epilepsy (Refuted Evidence), mode of inheritance: AD

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CRH 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				7	2	9
missense			14	1		15
nonsense						0
start loss						0
frameshift						0
inframe indel			1		1	2
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	15	8	3

Variants in CRH

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

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

Position	Type	Phenotype	Significance	ClinVar
8-66176899-A-G		not specified	Likely benign (Mar 28, 2017)
8-66176949-C-T		not specified	Uncertain significance (Jul 15, 2021)
8-66176956-C-G		not specified	Uncertain significance (Feb 27, 2024)
8-66177010-C-T		not specified	Likely benign (Mar 26, 2020)
8-66177022-C-T		CRH-related disorder • not specified	Benign/Likely benign (Dec 31, 2019)
8-66177040-C-T		not specified	Likely benign (Jul 05, 2016)
8-66177054-C-T		not specified	Uncertain significance (May 08, 2023)
8-66177057-G-C		not specified	Uncertain significance (Sep 14, 2022)
8-66177059-G-C		not specified	Uncertain significance (Mar 30, 2024)
8-66177084-G-C		not specified	Uncertain significance (Aug 12, 2021)
8-66177100-G-C			Likely benign (Jul 03, 2018)
8-66177111-G-C		not specified	Uncertain significance (May 01, 2022)
8-66177138-C-G		not specified	Uncertain significance (Jan 11, 2023)
8-66177149-T-C		not specified	Uncertain significance (Jan 31, 2024)
8-66177190-T-G		not specified	Benign (Apr 20, 2017)
8-66177239-T-C		not specified	Uncertain significance (May 17, 2016)
8-66177276-T-A		not specified	Uncertain significance (May 13, 2019)
8-66177297-C-CCTGCGGCTGCTGGGGCTGCTCGGA		not specified	Uncertain significance (May 17, 2018)
8-66177323-T-TGCG		not specified	Benign (Dec 18, 2019)
8-66177355-A-C		not specified	Likely benign (Apr 23, 2021)
8-66177368-G-A		not specified	Uncertain significance (Mar 21, 2017)
8-66177389-G-C		Autosomal dominant nocturnal frontal lobe epilepsy • not specified	Likely benign (Sep 07, 2017)
8-66177393-C-T		not specified	Uncertain significance (May 24, 2019)
8-66177406-C-T		not specified	Likely benign (Jun 13, 2016)
8-66177408-C-T		not specified	Uncertain significance (Jul 06, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CRH	protein_coding	protein_coding	ENST00000276571	1	2341

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.716	0.271	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.10	73	105	0.697	0.00000476	1205
Missense in Polyphen		11	29.891	0.36801		369
Synonymous	0.0138	49	49.1	0.998	0.00000233	428
Loss of Function	1.89	0	4.15	0.00	1.78e-7	45

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hormone regulating the release of corticotropin from pituitary gland (By similarity). Induces NLRP6 in intestinal epithelial cells, hence may influence gut microbiota profile (By similarity). {ECO:0000250|UniProtKB:P06296, ECO:0000250|UniProtKB:Q8CIT0}.
• Pathway: Cushing,s syndrome - Homo sapiens (human);Long-term depression - Homo sapiens (human);Alcoholism - Homo sapiens (human);Glucocorticoid Pathway (HPA Axis), Pharmacodynamics;Corticotropin-releasing hormone signaling pathway;Serotonin and anxiety;Myometrial Relaxation and Contraction Pathways;Serotonin and anxiety-related events;Signaling by GPCR;Signal Transduction;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;G alpha (s) signalling events;CRH;Class B/2 (Secretin family receptors);GPCR ligand binding;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;GPCR signaling-G alpha i;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.487

Haploinsufficiency Scores

• pHI: 1.00
• hipred: Y
• hipred_score: 0.514
• ghis: 0.542

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.902

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Crh
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; renal/urinary system phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; normal phenotype; hematopoietic 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); limbs/digits/tail phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: crhb
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: aggregated

Gene ontology

• Biological process: positive regulation of protein phosphorylation;synaptic transmission, dopaminergic;negative regulation of systemic arterial blood pressure;glucocorticoid biosynthetic process;inflammatory response;signal transduction;G protein-coupled receptor signaling pathway;chemical synaptic transmission;female pregnancy;parturition;learning or memory;positive regulation of cell population proliferation;associative learning;hormone-mediated apoptotic signaling pathway;positive regulation of gene expression;negative regulation of gene expression;negative regulation of norepinephrine secretion;positive regulation of circadian sleep/wake cycle, wakefulness;positive regulation of cell death;regulation of serotonin secretion;diterpenoid metabolic process;hypothalamus development;lung development;adrenal gland development;negative regulation of epinephrine secretion;negative regulation of luteinizing hormone secretion;locomotory exploration behavior;positive regulation of insulin secretion involved in cellular response to glucose stimulus;response to immobilization stress;negative regulation of circadian sleep/wake cycle, REM sleep;response to estrogen;positive regulation of cAMP-mediated signaling;response to ethanol;response to ether;response to pain;ion homeostasis;response to corticosterone;positive regulation of corticotropin secretion;positive regulation of cortisol secretion;long-term synaptic potentiation;positive regulation of digestive system process;negative regulation of cell death;negative regulation of glucagon secretion;cellular response to cocaine;cellular response to dexamethasone stimulus;positive regulation of calcium ion import;regulation of NMDA receptor activity;positive regulation of corticosterone secretion;positive regulation of behavioral fear response
• Cellular component: extracellular region;extracellular space;cytoplasm;varicosity;perikaryon
• Molecular function: signaling receptor binding;hormone activity;neuropeptide hormone activity;protein binding;corticotropin-releasing hormone activity;corticotropin-releasing hormone receptor 1 binding;corticotropin-releasing hormone receptor 2 binding