UCN

protein-coding

urocortin, the group of Neuropeptides

Gene summary

This gene encodes a member of the sauvagine/corticotropin-releasing factor/urotensin I family. The encoded preproprotein is proteolytically processed to generate the mature peptide, an endogenous ligand for both corticotropin-releasing factor receptor 1 and corticotropin-releasing factor receptor 2. In the brain this peptide may be responsible for the effects of stress on appetite. This peptide may also play a role in mood disorders, neurodegeneration, and skeletal system disorders. In spite of the gene family name similarity, the product of this gene has no sequence similarity to urotensin-2. [provided by RefSeq, Feb 2016]

MANE transcript

NM_003353.4

Inheritance

—

ClinVar variants

U:25B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr2:27,307,400-27,308,445

External References & Databases

Ensembl (ENSG00000163794)

Transcript & Mutation Effects

hg38 • Region Span ~1.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to UCN variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 26

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003353.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			25 clinvar	1 clinvar		26
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	25	1	0	26

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003353.4	RefSeq	NP_003344.1	1	MANE Select
ENST00000296099.2	Ensembl	ENSP00000296099.2	1	MANE Select

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glucocorticoid Pathway (HPA Axis), Pharmacodynamics
Signaling by GPCR
Signal Transduction
Class B/2 (Secretin family receptors)
GPCR ligand binding

Biological Process

startle response
inflammatory response
response to oxidative stress
G protein-coupled receptor signaling pathway
neuropeptide signaling pathway

Molecular Function

neuropeptide hormone activity
protein binding
corticotropin-releasing hormone activity
histone deacetylase inhibitor activity
corticotropin-releasing hormone receptor 1 binding

Cellular Component

extracellular region
extracellular space
dendrite
varicosity
perikaryon

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000296099
Coding exons: 1
Length: 1046
Individuals with no LoFs: 122701
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 122713
p: 0.0000489

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.151	52	55.1	0.943	0.00000251	739
Missense (PolyPhen)		20	22.274	0.89793		296
Synonymous	0.603	25	29.1	0.858	0.00000134	300
Loss of Function	1.13	0	1.49	0.00	6.79e-8	18

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000020	0.000018	rare
South Asian	0.000033	0.000033	rare
Other	0.00017	0.00017	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts in vitro to stimulate the secretion of adrenocorticotropic hormone (ACTH) (PubMed:8612563). Binds with high affinity to CRF receptor types 1, 2-alpha, and 2-beta (PubMed:8612563). Plays a role in the establishment of normal hearing thresholds (By similarity). Reduces food intake and regulates ghrelin levels in gastric body and plasma (By similarity). {ECO:0000250|UniProtKB:P55090, ECO:0000250|UniProtKB:P81615, ECO:0000269|PubMed:8612563}.;

Recessive Scores

pRec: 0.209

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.847

Gene Damage Prediction

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