CORT

protein-coding

cortistatin, the group of Receptor ligands

Gene summary

This gene encodes a neuropeptide that is structurally similar to somatostatin. It binds to all known somatostatin receptors, and shares many pharmacological and functional properties with somatostatin, including the depression of neuronal activity. However, it also has many properties distinct from somatostatin, such as induction of slow-wave sleep, apparently by antagonism of the excitatory effects of acetylcholine on the cortex, reduction of locomotor activity, and activation of cation selective currents not responsive to somatostatin. The preproprotein undergoes further processing into multiple mature products. Read-through transcripts exist between this gene and the upstream APITD1 (apoptosis-inducing, TAF9-like domain 1) gene, as represented in GeneID:100526739. [provided by RefSeq, Nov 2010]

MANE transcript

NM_001302.5

Inheritance

—

ClinVar variants

U:9B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 2.09

Max pathogenic AF

—

Genomic locus

chr1:10,450,031-10,451,998

External References & Databases

Ensembl (ENSG00000241563)

Transcript & Mutation Effects

hg38 • Region Span ~2.0 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 CORT variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001302.5. 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			9 clinvar	2 clinvar		11
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	9	2	0	11

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001302.5	RefSeq	NP_001293.3	2	MANE Select
ENST00000377049.4	Ensembl	ENSP00000366248.4	2	MANE Select
ENST00001091727.1	Ensembl	ENSP00000761533.1	2	Standard
ENST00001141203.1	Ensembl	ENSP00000810739.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling by GPCR
Signal Transduction
Peptide ligand-binding receptors
Class A/1 (Rhodopsin-like receptors)
GPCR ligand binding

Biological Process

G protein-coupled receptor signaling pathway
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
chemical synaptic transmission
regulation of signaling receptor activity

Molecular Function

G protein-coupled receptor binding
neuropeptide hormone activity

Cellular Component

extracellular region
extracellular space
Fanconi anaemia nuclear complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377049
Coding exons: 2
Length: 2184
Individuals with no LoFs: 124932
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 124938
p: 0.0000240

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.55	92	58.5	1.57	0.00000311	665
Missense (PolyPhen)		12	7.8696	1.5248		82
Synonymous	0.158	27	28.1	0.962	0.00000174	231
Loss of Function	-0.985	2	0.959	2.09	4.04e-8	14

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000028	0.000026	rare
South Asian	0.000034	0.000033	rare
Other	0.00017	0.00017	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds to all human somatostatin receptor (SSTR) subtypes. It also inhibits cAMP production induced by forskolin through SSTRs.;

Recessive Scores

pRec: 0.266

Intolerance Scores

LoFtool: 0.315
RVIS EVS: -0.14
RVIS percentile EVS: 42.88

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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