SSTR5

protein-coding

somatostatin receptor 5, the group of Somatostatin receptors

Gene summary

Somatostatin and its related peptide cortistatin exert multiple biological actions on normal and tumoral tissue targets by interacting with somatostatin receptors (SSTRs). The protein encoded by this gene is one of the SSTRs, which is a multi-pass membrane protein and belongs to the G-protein coupled receptor 1 family. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase, and different regions of this receptor molecule are required for the activation of different signaling pathways. A mutation in this gene results in somatostatin analog resistance. Alternatively spliced transcript variants have been identified in this gene.[provided by RefSeq, Feb 2010]

MANE transcript

NM_001172560.3

Inheritance

ClinVar variants

U:82B:24

Top phenotype

Resistance to somatostatin treatment

gnomAD constraint

pLI —, LoF o/e 0.78

Max pathogenic AF

—

Genomic locus

chr16:1,063,867-1,081,454

External References & Databases

Ensembl (ENSG00000162009)

Transcript & Mutation Effects

hg38 • Region Span ~17.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Resistance to somatostatin treatmentAD

Manifestation: General

Intervention: Pharmacogenomic

Rationale: The presence of variants may impact the use of medications to treat conditions such as acromegaly

Refs: 11502816; 15914528; 21744088; 21810856

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SSTR5 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 89

not providedTotal: 14

SSTR5-related disorderTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001172560.3. 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				9 clinvar	9 clinvar	18
missense			82 clinvar	5 clinvar	1 clinvar	88
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	82	14	10	106

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001172560.3	RefSeq	NP_001166031.1	1	MANE Select
ENST00000689027.1	Ensembl	ENSP00000508487.1	1	MANE Select
NM_001053.4	RefSeq	NP_001044.1	1	Standard
ENST00000293897.7	Ensembl	ENSP00000293897.4	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

cAMP signaling pathway - Homo sapiens (human)
Neuroactive ligand-receptor interaction - Homo sapiens (human)
Peptide GPCRs
GPCRs, Class A Rhodopsin-like
Signaling by GPCR

Biological Process

G protein-coupled receptor signaling pathway
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger
neuropeptide signaling pathway
negative regulation of cell population proliferation
positive regulation of cytokinesis

Molecular Function

G protein-coupled receptor activity
somatostatin receptor activity
peptide binding
neuropeptide binding

Cellular Component

plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000293897
Coding exons: 1
Length: 8699
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.287	256	269	0.951	0.0000208	2275
Missense (PolyPhen)		106	121.14	0.87503		1120
Synonymous	-0.278	139	135	1.03	0.0000113	840
Loss of Function	0.506	5	6.38	0.784	2.74e-7	64

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	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for somatostatin 28 and to a lesser extent for somatostatin-14. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase. Increases cell growth inhibition activity of SSTR2 following heterodimerization. {ECO:0000269|PubMed:12072395, ECO:0000269|PubMed:7908405, ECO:0000269|PubMed:8078491, ECO:0000269|PubMed:8373420}.;

Intolerance Scores

LoFtool: 0.508
RVIS EVS: -0.39
RVIS percentile EVS: 27.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.924

Gene Damage Prediction

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