SST

Summary

SST (somatostatin, HGNC:11329) is a protein-coding gene on chromosome 3q27.3, encoding Somatostatin (P61278). Inhibits the secretion of pituitary hormones, including that of growth hormone/somatotropin (GH1), PRL, ACTH, luteinizing hormone (LH) and TSH.

The hormone somatostatin has active 14 aa and 28 aa forms that are produced by alternate cleavage of the single preproprotein encoded by this gene. Somatostatin is expressed throughout the body and inhibits the release of numerous secondary hormones by binding to high-affinity G-protein-coupled somatostatin receptors. This hormone is an important regulator of the endocrine system through its interactions with pituitary growth hormone, thyroid stimulating hormone, and most hormones of the gastrointestinal tract. Somatostatin also affects rates of neurotransmission in the central nervous system and proliferation of both normal and tumorigenic cells.

Source: NCBI Gene 6750 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 13 total
• GTEx eGene: eQTL in 2 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.01 (LoF-tolerant), LOEUF 1.53 (unconstrained)
• MANE Select transcript: NM_001048

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11329
Approved symbol	SST
Name	somatostatin
Location	3q27.3
Locus type	gene with protein product
Status	Approved
Aliases	SMST, SST1
Ensembl gene	ENSG00000157005
Ensembl biotype	protein_coding
OMIM	182450
Entrez	6750

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

MANE Select: ENST00000287641

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000287641, ENST00001143369

RefSeq mRNA: 1 — MANE Select: NM_001048 NM_001048

CCDS: CCDS3288

Canonical transcript exons

ENST00000287641 — 2 exons

Exon	Start	End
ENSE00001029669	187670154	187670394
ENSE00001029670	187668912	187669277

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 99.89.

FANTOM5 (CAGE): breadth broad, TPM avg 23.6973 / max 4534.5400, expressed in 321 samples.

Highest expression (Bgee): type B pancreatic cell, islet of Langerhans, body of pancreas, duodenum, cardia of stomach.

Genetic regulation across tissues (GTEx eQTL / sQTL)

SST is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 2 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

2 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Gastroesophageal Junction	eqtl	3.7e-04	-0.21	3:187575881:T:C
Artery Coronary	eqtl	3.5e-02	+0.91	3:187808367:C:T

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
45999	23.6973	321

Top tissues by expression

showing 100 of 287 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	99.89	gold quality
islet of Langerhans	UBERON:0000006	99.85	gold quality
body of pancreas	UBERON:0001150	99.05	gold quality
duodenum	UBERON:0002114	99.04	gold quality
cardia of stomach	UBERON:0001162	98.88	gold quality
pancreas	UBERON:0001264	98.54	gold quality
jejunal mucosa	UBERON:0000399	98.25	gold quality
pylorus	UBERON:0001166	98.25	gold quality
orbitofrontal cortex	UBERON:0004167	97.20	gold quality
prefrontal cortex	UBERON:0000451	97.06	gold quality
nucleus accumbens	UBERON:0001882	96.97	gold quality
putamen	UBERON:0001874	96.93	gold quality
caudate nucleus	UBERON:0001873	96.89	gold quality
Brodmann (1909) area 10	UBERON:0013541	96.29	gold quality
hypothalamus	UBERON:0001898	96.26	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.84	gold quality
lateral globus pallidus	UBERON:0002476	95.61	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.26	gold quality
amygdala	UBERON:0001876	95.14	gold quality
cingulate cortex	UBERON:0003027	94.06	gold quality
frontal pole	UBERON:0002795	93.97	gold quality
anterior cingulate cortex	UBERON:0009835	93.92	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	93.29	gold quality
frontal cortex	UBERON:0001870	93.05	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.97	gold quality
telencephalon	UBERON:0001893	92.86	gold quality
temporal lobe	UBERON:0001871	92.85	gold quality
neocortex	UBERON:0001950	92.50	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.47	gold quality
body of stomach	UBERON:0001161	92.17	gold quality
cerebral cortex	UBERON:0000956	92.14	gold quality
stomach	UBERON:0000945	92.03	gold quality
adult organism	UBERON:0007023	91.38	gold quality
superior vestibular nucleus	UBERON:0007227	91.35	gold quality
Ammon’s horn	UBERON:0001954	91.16	gold quality
middle frontal gyrus	UBERON:0002702	91.05	gold quality
small intestine	UBERON:0002108	90.69	gold quality
right frontal lobe	UBERON:0002810	90.49	gold quality
dorsal root ganglion	UBERON:0000044	90.34	gold quality
entorhinal cortex	UBERON:0002728	90.25	gold quality
medulla oblongata	UBERON:0001896	90.12	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.06	gold quality
forebrain	UBERON:0001890	89.91	gold quality
colonic mucosa	UBERON:0000317	89.86	gold quality
fundus of stomach	UBERON:0001160	89.59	gold quality
ileal mucosa	UBERON:0000331	89.07	gold quality
superior frontal gyrus	UBERON:0002661	88.60	gold quality
decidua	UBERON:0002450	87.61	gold quality
inferior olivary complex	UBERON:0002127	87.56	gold quality
CA1 field of hippocampus	UBERON:0003881	87.28	gold quality
cortical plate	UBERON:0005343	87.00	gold quality
ganglionic eminence	UBERON:0004023	86.78	gold quality
rectum	UBERON:0001052	86.61	gold quality
mucosa of transverse colon	UBERON:0004991	86.52	gold quality
parietal lobe	UBERON:0001872	86.25	gold quality
epithelial cell of pancreas	CL:0000083	86.05	gold quality
postcentral gyrus	UBERON:0002581	85.28	gold quality
trigeminal ganglion	UBERON:0001675	84.30	gold quality
brain	UBERON:0000955	83.64	gold quality
central nervous system	UBERON:0001017	83.62	gold quality
occipital lobe	UBERON:0002021	83.39	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.98	gold quality
spinal cord	UBERON:0002240	82.68	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	82.48	gold quality
intestine	UBERON:0000160	81.43	gold quality
jejunum	UBERON:0002115	81.16	gold quality
pancreatic ductal cell	CL:0002079	81.07	silver quality
transverse colon	UBERON:0001157	80.90	gold quality
stromal cell of endometrium	CL:0002255	80.67	gold quality
primary visual cortex	UBERON:0002436	80.58	gold quality
embryo	UBERON:0000922	79.67	gold quality
endothelial cell	CL:0000115	79.64	silver quality
middle temporal gyrus	UBERON:0002771	79.28	gold quality
substantia nigra	UBERON:0002038	78.92	gold quality
ventral tegmental area	UBERON:0002691	78.61	gold quality
amniotic fluid	UBERON:0000173	78.54	gold quality
large intestine	UBERON:0000059	78.49	gold quality
colon	UBERON:0001155	78.09	gold quality
midbrain	UBERON:0001891	77.47	gold quality
ventricular zone	UBERON:0003053	75.75	gold quality
globus pallidus	UBERON:0001875	75.14	gold quality
sigmoid colon	UBERON:0001159	74.60	gold quality
colonic epithelium	UBERON:0000397	73.03	gold quality
paraflocculus	UBERON:0005351	71.89	gold quality
caecum	UBERON:0001153	71.33	gold quality
medial globus pallidus	UBERON:0002477	71.24	gold quality
vermiform appendix	UBERON:0001154	70.70	gold quality
muscle layer of sigmoid colon	UBERON:0035805	69.85	gold quality
renal glomerulus	UBERON:0000074	69.32	gold quality
seminal vesicle	UBERON:0000998	68.96	gold quality
metanephric glomerulus	UBERON:0004736	67.83	gold quality
substantia nigra pars compacta	UBERON:0001965	66.01	gold quality
cortex of kidney	UBERON:0001225	65.87	gold quality
vena cava	UBERON:0004087	65.19	silver quality
dorsal plus ventral thalamus	UBERON:0001897	64.81	gold quality
kidney epithelium	UBERON:0004819	63.50	silver quality
corpus callosum	UBERON:0002336	62.97	gold quality
olfactory bulb	UBERON:0002264	62.41	gold quality
mucosa of stomach	UBERON:0001199	62.40	gold quality
right adrenal gland	UBERON:0001233	61.81	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	342935.31
E-HCAD-31	yes	231389.04
E-GEOD-81547	yes	128339.49
E-GEOD-81608	yes	96965.90
E-ENAD-27	yes	92159.39
E-GEOD-83139	yes	67542.42
E-GEOD-93593	yes	15706.58
E-MTAB-8894	yes	2814.34
E-HCAD-25	yes	2520.70
E-ANND-3	no	1.46

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 68 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Prefrontal cortex	tissue	539.2
Cerebral cortex	tissue	539.2	medium
Retrosplenial and cingulate cortex	tissue	473.0
Retrosplenial cortex	tissue	467.7
Occipital cortex	tissue	454.0
Insular cortex	tissue	448.9
Motor cortex	tissue	433.0
Frontal cortex	tissue	408.4
Hippocampal formation	tissue	406.5
Entorhinal cortex	tissue	406.5
Amygdala	tissue	383.3
Duodenum	tissue	363.7	high
Pancreas	tissue	356.6	medium
Somatosensory cortex	tissue	348.9
Temporal cortex	tissue	304.1
Stomach 1	tissue	297.3	medium
Caudate putamen	tissue	289.4
Hypothalamus	tissue	268.6	high
Putamen	tissue	179.2
Basal ganglia	tissue	151.3	not detected
Superior colliculi	tissue	142.7
Ventral forebrain	tissue	141.9
Periaqueductal gray	tissue	138.6
Septum	tissue	135.3
Spinal cord	tissue	131.1
Small intestine	tissue	125.4	high
Nucleus accumbens	tissue	109.9
Thalamus	tissue	107.6
Midbrain	tissue	85.9
Pons	tissue	80.7
Corpus callosum	tissue	71.9
Medulla oblongata	tissue	71.5
Adrenal gland	tissue	40.5	medium
Locus coeruleus	tissue	36.0
Postcentral gyrus	tissue	30.4
Colon	tissue	29.8	high
Hippocampus	tissue	27.0	not detected
Substantia nigra	tissue	23.5
Rectum	tissue	22.4	high
Seminal vesicle	tissue	20.4	not detected
Cerebellum	tissue	10.7	not detected
Olfactory bulb	tissue	10.6
Pituitary gland	tissue	8.7
Skin 1	tissue	8.4	not detected
Urinary bladder	tissue	6.9	not detected
Retina	tissue	5.8
Kidney	tissue	5.7	not detected
Adipose tissue	tissue	5.2	not detected
Appendix	tissue	4.4	high
Bone marrow	tissue	4.0	not detected
Choroid plexus	tissue	3.5
Smooth muscle	tissue	2.6	not detected
Esophagus	tissue	1.5	not detected
Lymph node	tissue	1.4	not detected
Heart muscle	tissue	1.2	not detected
Vagina	tissue	1.1	not detected
Gallbladder	tissue	1.1	not detected
Thymus	tissue	1.0
Endometrium 1	tissue	0.7	not detected
Thyroid gland	tissue	0.7	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Arcuate nucleus (999.9), Ventral hippocampus (367.7), Subiculum (332.7), Cervical spinal cord, dorsal horn (310.8), Supraoptic nucleus (297.8).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ALX3, AP1, ARX, ATF1, CEBPA, CEBPB, CEBPG, CREB1, ELK1, EWSR1, FOS, GATA3, IRF9, ISL1, JUN, LBX1, NEUROD1, NEUROG3, NKX2-2, NR3C1, PAX6, PDX1, PITX1, PTF1A, RAI1, SALL3, TOP2B, ZNF699

miRNA regulators (miRDB)

Targeting SST by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

28 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-3149	98.77	67.13	1639
HSA-MIR-6894-5P	98.70	63.78	809
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-10395-3P	98.10	66.70	1726
HSA-MIR-197-3P	98.09	69.23	1004
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-4257	97.86	68.05	1190
HSA-MIR-1182	96.41	64.89	336
HSA-MIR-1237-5P	95.38	62.21	451
HSA-MIR-4488	95.38	62.00	443
HSA-MIR-4697-5P	95.38	61.72	457
HSA-MIR-6822-5P	93.94	66.34	812
HSA-MIR-6750-5P	93.94	66.68	797

Functional genomics

gnomAD constraint: pLI 0.00511, LOEUF 1.53, missense Z -0.392 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000287641 — one region, missense o/e 1.03.

Literature-anchored findings (GeneRIF, showing 40)

• A critical analysis is made of the structure and physiology of SST and its receptors, and the possible role it plays in cell proliferation in animal models and the treatment of human tumors. (PMID:11753230)
• The somatostatin-28 (S-28) NPAMAP peptide sequence constitutes an accurate alpha-helix nucleation motif allowing for the generation of equal amounts of S-28 and somatostatin-14 from their common precursor in cultured cells. (PMID:11814357)
• Somatostatin acts as a selective chemoattractant for immature hematopoietic cells (PMID:11823046)
• Structural motifs in the somatostatin precursor (PMID:11860030)
• Somatostatin modulates G-CSF-induced but not interleukin-3-induced proliferative responses in myeloid 32D cells via activation of somatostatin receptor subtype 2. (PMID:11920268)
• present in human colorectal adenocarcinomas and liver metastases (PMID:12174892)
• somatostatin receptor 2 mRNA was selectively expressed, somatostatin mRNA was not detectable, and cortistatin mRNA was expressed in all samples of monocytes monocyte-derived macrophages, and dendritic cells in basal and lipopolysaccharide-activated state (PMID:12684217)
• somatostatin has a role in inhibiting ERK 1/2 signaling and the PI3-K pathway via the inhibition of Rac in SHSY5Y cells (PMID:12902325)
• Fasting but not postprandial hypersomatostatinemia, mainly due to an increase in SS-14, characterizes acromegaly. Excess GH/IGF-I could be a causal factor in somatostatin hypersecretion. (PMID:12952361)
• Reduced ghrelin, impaired growth hormone(GH) response to GHRH by excess FFA, and increased somatostatin tone contribute to reduced GH secretion in patients with HIV-lipodystrophy. (PMID:14559725)
• High concentration of somatostatin (SST) in respiratory centers of fetal brainstems correlates with its involvement in the inhibition of intrauterine breathing. (PMID:15266779)
• SST acts both centrally and peripherally to control the GH-IGF-I axis. (PMID:15286801)
• certain bioactive peptides such as somatostatin and substance P directly interact with human P-glycoprotein as endogenous substrates for P-glycoprotein-mediated transport (PMID:15358539)
• human visceral adipose tissue secretes SRIF during inflammation and sepsis (PMID:15472172)
• The regulation and control of gastrin, somatostatin in cell apoptosis of large intestine carcinoma may be directly related to the abnormal expression of bcl-2, bax. (PMID:15655830)
• Cortistatin is abundant in the vitreous fluid and significantly contributes to somatostatin-like immunoreactivity. (PMID:16043736)
• results show that Neuropilin-1 is expressed in ovarian tumours and that VEGF and somatostatin are co-expressed in the same tissue compartments raising the intriguing possibility that somatostatin may be important in angiogenesis in ovarian cancer (PMID:16211223)
• immunostaining for somatostatin identifies a subgroup of pancreatic ductal adenocarcinomas with a neuroendocrine component. This pattern of expression in neoplasms recapitulates the normal pattern during the embryonal development of the organ. (PMID:16284732)
• Abeta and hyperphosphorylated tau formation in somatostatin cells are basically independent events Decreased somatostatin only partly goes together with cytoskeletal changes in somatostatin cells in nucleus tuberalis lateralis of Alzheimer’s disease. (PMID:16456666)
• From 7 weeks of gestation, pancreatic duct epithelial cells begin to differentiate into insulin, glucagon and somatostatin-positive cells. (PMID:16736556)
• The present study, provides evidence of pro-SST and SST receptor (SSTR1 and 2A) mRNA expression in ocular ciliary epithelium (CE). (PMID:16764985)
• To the best of our knowledge, the present report is the second case report of a neuroendocrine gastric carcinoma expressing diffusely somatostatin as the only neuroendocrine regulatory peptide. (PMID:16804989)
• SST and TAC1 are involved in colon carcinogenesis. (PMID:16952549)
• Whereas disruption of cytoskeletal genes has been noted in HIVE, dysregulation of somatostatin has not, indicating that dysregulation of somatostatin is part of the molecular pathologic process of MDD in the setting of HIV. (PMID:17130427)
• Data show an increasing tendency in the expressions of GAS and SS in children with chronic gastritis and duodenal ulcer. (PMID:17229384)
• In proliferative diabetic retionopaathy, intravitreal SST-28 levels are significantly decreased in patients with diabetic macular edema. (PMID:17327350)
• Possible role of the lower production of SST in the pathogenesis of diabetic retinopathy. (PMID:17704349)
• This study provide the genetic association study between somatostatin and AD indicates that genetic variations in the somatostatin gene may modify the risk for AD among Finnish AD subjects. (PMID:17987251)
• Developmentally regulated expression of galanin and somatostatin may play a role in liver morphogenesis. (PMID:18196269)
• data show that somatostatin expression is not only seen in sporadic neuroendocrine tumors (NETs) but may also occur in gangliocytic paragangliomas, poorly differentiated NECs, and hereditary NETs (PMID:18310290)
• Gastrin and somatostatin play important roles in the regulation and control of cell apoptosis in large intestinal carcinoma, and the mechanism may be directly related to the aberrant expression of Fas and Fas ligand. (PMID:18473402)
• TGF beta induces the production of SST and potentially activates the negative growth autocrine loop of SST, which leads to the downstream induction of multiple growth inhibitory effectors. (PMID:18567806)
• Somatostatin regulates early trophoblast functions mainly through an interaction with SSTR2. (PMID:18617261)
• demonstrate diverse neuronal, neuroendocrine, and cardiovascular actions of a somatostatin gene-encoded hormone (PMID:18753129)
• An autocrine and paracrine role of SST in the lacrimal system and at the ocular surface and a role of SST in corneal immunology. (PMID:19106227)
• No clear association between prostate cancer risk and genetic variation of the SST gene was identified. (PMID:19423539)
• somatostatin decreases in Alzheimer’s disease and its expression may be linked with Abeta deposition (PMID:19559700)
• EPHB3, MASP1 and SST map to 3q26.2-q29 and may have roles in squamous cell carcinoma of the lung (PMID:19607727)
• Our results supported the notion that the C allele of the rs4988514 polymorphism may increase the risk for AD in the Chinese population and possibly have additive effect with the APOE epsilon4 allele. (PMID:19733630)
• down-regulated KLF4, CHGA, GPX3, SST and LIPF, together with up-regulated SERPINH1, THY1 and INHBA is an 8-gene signature for gastric cancer (PMID:20043075)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	sst2	ENSDARG00000014190
danio_rerio	sst1.2	ENSDARG00000033161
danio_rerio	sst1.1	ENSDARG00000040799
mus_musculus	Sst	ENSMUSG00000004366
rattus_norvegicus	Sst	ENSRNOG00000001837

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:98326) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 25 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased circulating corticosterone level	1
increased circulating insulin level	1
abnormal nervous system electrophysiology	1
abnormal motor learning	1
abnormal inhibitory postsynaptic potential	1
abnormal excitatory postsynaptic potential	1
increased circulating serum albumin level	1
decreased circulating alkaline phosphatase level	1
increased susceptibility to age related obesity	1
abnormal bone structure	1
enlarged stomach	1
abnormal gastric gland morphology	1
decreased lean body mass	1
abnormal gastric parietal cell morphology	1
increased circulating gastrin level	1
abnormal circulating pituitary hormone level	1
decreased circulating prolactin level	1
increased circulating growth hormone level	1
decreased growth hormone level	1
hyperchlorhydria	1
increased circulating iron level	1
increased total body fat amount	1
decreased bone mineral content	1
abnormal stomach fundus morphology	1
increased circulating ghrelin level	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Ovis aries	O46688	100.0%	Diamond
Sus scrofa	P01168	100.0%	Diamond
Lophius americanus	P01169	100.0%	Diamond
Ictalurus punctatus	P01171	100.0%	Diamond
Myxine glutinosa	P19209	100.0%	Diamond
Bos taurus	P26917	100.0%	Diamond
Gallus gallus	P33094	100.0%	Diamond
Canis lupus familiaris	P49670	100.0%	Diamond
Macaca fascicularis	P61279	100.0%	Diamond
Alligator mississippiensis	P61298	100.0%	Diamond
Trachemys scripta	P61299	100.0%	Diamond
Myoxocephalus scorpius	P69132	100.0%	Diamond
Oncorhynchus kisutch	P69133	100.0%	Diamond
Anguilla anguilla	P69134	100.0%	Diamond
Pelophylax ridibundus	P87384	100.0%	Diamond
Amia calva	Q9PRZ6	100.0%	Diamond
Protopterus annectens	Q9W7F0	100.0%	Diamond
Carassius auratus	Q9YGH5	100.0%	Diamond
Lampetra fluviatilis	Q9PRR0	95.7%	Diamond
Petromyzon marinus	P21779	94.4%	Diamond
Platichthys flesus	P21780	85.7%	Diamond
Oncorhynchus mykiss	Q91194	85.7%	Diamond
Oreochromis niloticus	P81029	82.1%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
BCL6-AS1	ncRNA	122526776
RTP2	protein-coding	344892
BCL6	protein-coding	604
LINC02041	ncRNA	105374261

Protein

Protein identifiers

Somatostatin — P61278 (reviewed: P61278)

Alternative names: Growth hormone release-inhibiting factor

All UniProt accessions (1): P61278

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits the secretion of pituitary hormones, including that of growth hormone/somatotropin (GH1), PRL, ACTH, luteinizing hormone (LH) and TSH. Also impairs ghrelin- and GnRH-stimulated secretion of GH1 and LH; the inhibition of ghrelin-stimulated secretion of GH1 can be further increased by neuronostatin. May enhance low-glucose-induced glucagon release by pancreatic alpha cells. This effect may be mediated by binding to GPR107 and PKA activation. May regulate cardiac contractile function. May compromise cardiomyocyte viability. In the central nervous system, may impair memory retention and may affect hippocampal excitability. May also have anxiolytic and anorexigenic effects. May play a role in arterial pressure regulation. May inhibit basal, but not ghrelin- or GnRH-stimulated secretion of GH1 or LH, but does not affect the release of other pituitary hormones, including PRL, ACTH, FSH or TSH. Potentiates inhibitory action of somatostatin on ghrelin-stimulated secretion of GH1, but not that on GnRH-stimulated secretion of LH.

Subcellular location. Secreted.

Post-translational modifications. C-terminal amidation of the neuronostatin peptide is required for its biological activity, including for the regulation of mean arterial pressure.

Similarity. Belongs to the somatostatin family.

RefSeq proteins (1): NP_001039* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004250	Somatostatin	Family
IPR018142	Somatostatin/Cortistatin_C	Domain

Pfam: PF03002

UniProt features (12 total): peptide 3, strand 2, sequence variant 2, signal peptide 1, propeptide 1, region of interest 1, modified residue 1, disulfide bond 1

Structure

Experimental structures (PDB)

10 structures by resolution:

PDB	Title	Method	Resolution (Å)
7T10	CryoEM structure of somatostatin receptor 2 in complex with somatostatin-14 and Gi3	ELECTRON MICROSCOPY	2.5
8ZBI	Cryo-EM structure of Somatostatin receptor 3 (SSTR3) with Gi1 complex	ELECTRON MICROSCOPY	2.79
7WIC	Cryo-EM structure of the SS-14-bound human SSTR2-Gi1 complex	ELECTRON MICROSCOPY	2.8
7XAT	Structure of somatostatin receptor 2 bound with SST14.	ELECTRON MICROSCOPY	2.85
7XMS	CryoEM structure of somatostatin receptor 4 (SSTR4) in complex with Gi1 and its …	ELECTRON MICROSCOPY	2.9
8ZBJ	Cryo-EM structure of Somatostatin receptor 5 (SSTR5) with Gi1 complex	ELECTRON MICROSCOPY	2.94
7XMR	CryoEM structure of the somatostatin receptor 2 (SSTR2) in complex with Gi1 and its …	ELECTRON MICROSCOPY	3.1
7Y27	Cryo-EM structure of the SST-14-bound SSTR2-miniGq-scFv16 complex	ELECTRON MICROSCOPY	3.48
7WJ5	Cryo-EM structure of human somatostatin receptor 2 complex with its agonist somatostatin …	ELECTRON MICROSCOPY	3.72
2MI1	Somatostatin-14 solution structure in 5% D-mannitol	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P61278-F1	65.76	0.05

Antibody-complex structures (SAbDab)

8 antibodies co-crystallized with this protein: 7T10, 7WIC, 7WJ5, 7XAT, 7XMS, 7Y27, 8ZBI, 8ZBJ

Human Protein Atlas

Protein class: Predicted secreted proteins, Plasma proteins, Cancer-related genes, Candidate cancer biomarkers

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

Functional residue map

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

Post-translational modifications (1)

Type	Positions
Alanine amide	43

Disulfide bonds (1)

Type	Positions
Disulfide bond	105–116

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 12; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

12 pathways:

ID	Pathway	Evidence
R-HSA-418594	G alpha (i) signalling events	curated
R-HSA-375276	Peptide ligand-binding receptors	curated
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-500792	GPCR ligand binding	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-9022702	MECP2 regulates transcription of neuronal ligands	electronic
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—
R-HSA-8986944	Transcriptional Regulation by MECP2	—

MSigDB gene sets: 186 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD8_TCELL_DN, GSE45365_NK_CELL_VS_CD8_TCELL_UP, ATF_B, GOBP_DIGESTION, MODULE_92, MODULE_274, GOBP_RESPONSE_TO_ACID_CHEMICAL, GOCC_SECRETORY_GRANULE, GOBP_HYPEROSMOTIC_RESPONSE, HANN_RESISTANCE_TO_BCL2_INHIBITOR_UP, GOBP_CELL_CELL_SIGNALING, CREB_Q4, MODULE_66, IRF7_01

GO Biological Process (16): hyperosmotic response (GO:0006972), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), cell-cell signaling (GO:0007267), chemical synaptic transmission (GO:0007268), response to nutrient (GO:0007584), digestion (GO:0007586), negative regulation of cell population proliferation (GO:0008285), hormone-mediated apoptotic signaling pathway (GO:0008628), response to xenobiotic stimulus (GO:0009410), response to acidic pH (GO:0010447), regulation of cell migration (GO:0030334), somatostatin signaling pathway (GO:0038170), response to amino acid (GO:0043200), response to steroid hormone (GO:0048545), regulation of postsynaptic membrane neurotransmitter receptor levels (GO:0099072)

GO Molecular Function (3): hormone activity (GO:0005179), protein binding (GO:0005515), receptor ligand activity (GO:0048018)

GO Cellular Component (5): extracellular region (GO:0005576), cytosol (GO:0005829), neuronal cell body (GO:0043025), GABA-ergic synapse (GO:0098982), neuronal dense core vesicle (GO:0098992)

Reactome top-level categories

9 top-level categories:

Category	Pathways
Signaling by GPCR	2
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1
Transcriptional Regulation by MECP2	1
RNA Polymerase II Transcription	1
Signal Transduction	1
GPCR ligand binding	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1

GO top-level categories

32 GO namespaces:

Category	Terms
signal transduction	3
response to chemical	2
hormone-mediated signaling pathway	2
cellular anatomical structure	2
response to osmotic stress	1
G protein-coupled receptor activity	1
cell communication	1
signaling	1
anterograde trans-synaptic signaling	1
response to nutrient levels	1
multicellular organismal process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
apoptotic signaling pathway	1
response to pH	1
cell migration	1
regulation of cell motility	1
somatostatin receptor signaling pathway	1
response to acid chemical	1
response to hormone	1
response to lipid	1
regulation of biological quality	1
receptor ligand activity	1
binding	1
signaling receptor binding	1
signaling receptor activator activity	1
cytoplasm	1
somatodendritic compartment	1
cell body	1
synapse	1
dense core granule	1

Protein interactions and networks

IntAct

Human interaction partners of SST in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
APP	physical association	0.560	3

BioGRID (3 interactions; top human partners by supporting records): PDIA2 (Reconstituted Complex), SSTR3 (Protein-peptide), TP53 (Negative Genetic)

SIGNOR signaling

3 signaling interactions:

A	Effect	B	Mechanism
TOP2B	“up-regulates quantity by expression”	SST	“transcriptional regulation”
SST	up-regulates	SSTR4	binding
MECP2	“up-regulates quantity by expression”	SST	“post transcriptional regulation”

Ligand–receptor pairs (CellPhoneDB) (5)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

5 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
SSTR3	ligand	Signaling by Somatostatin
SSTR4	ligand	Signaling by Somatostatin
SSTR1	ligand	Signaling by Somatostatin
SSTR5	ligand	Signaling by Somatostatin
SSTR2	ligand	Signaling by Somatostatin

Disease & clinical

Genetic variants

Variant evidence for SST: 13 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	1
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 18 predictions of 54):

Position(s)	Effect	Δscore	Sites
3:187669278–187669279	acceptor_loss	1.0000	5
3:187669289	acceptor_gain	1.0000
3:187669296	acceptor_gain	1.0000
3:187670152–187670153	donor_loss	1.0000	4
3:187669278	acceptor_loss	0.9900
3:187669280–187669282	acceptor_gain	0.9900	2
3:187670153	donor_loss	0.9900
3:187670160	donor_gain	0.7200
3:187669955	acceptor_gain	0.6800
3:187669707	donor_gain	0.6400

AlphaMissense

254 missense substitutions predicted likely pathogenic (of 738 scored), across 67 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
N107	8	0.993	0.999
F108	8	0.975	1.000
F113	8	0.940	0.997
C105	7	0.999	1.000
F109	7	0.999	1.000
W110	7	0.999	1.000
C116	7	0.996	0.999
K111	7	0.991	1.000
K102	7	0.957	0.999
R101	6	0.995	1.000
K106	6	0.993	0.999
T114	6	0.991	0.999
G104	6	0.976	0.995
T112	6	0.952	0.999
F52	6	0.815	0.912
D28	6	0.733	0.784
S115	5	0.954	0.994
R88	5	0.932	0.957
K45	5	0.855	0.960
F34	5	0.850	0.924

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Pancreatic Adenocarcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000156
Kidney Chromophobe (TCGA)	favorable	0.000222
Uterine Corpus Endometrial Carcinoma (TCGA)	unfavorable	0.000331

Disease associations

OMIM: gene MIM:182450 | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST004219_1	Skin pigmentation	4e-7
GCST005024_16	Pursuit maintenance gain	4e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0008433	pursuit maintenance gain measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 2 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
SR 147778	KI	1000 nM

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	decreases expression, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Tretinoin	increases expression	2
Valproic Acid	decreases expression, affects expression	2
terbufos	increases methylation	1
trichostatin A	increases expression	1
arsenite	increases methylation	1
tetrabromobisphenol A	increases expression	1
tryptanthrine	increases expression	1
lafutidine	increases expression	1
CGP 52608	affects binding, increases reaction	1
Edotreotide	affects binding, decreases reaction	1
deguelin	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
belinostat	increases expression	1
thifluzamide	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
picoxystrobin	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Decitabine	affects methylation	1
Cyclic AMP	affects cotreatment, decreases reaction, increases chemical synthesis	1
Benzo(a)pyrene	affects methylation	1
Carbamazepine	affects expression	1
Dexamethasone	decreases expression	1
Fonofos	increases methylation	1
Colforsin	increases chemical synthesis, affects cotreatment, decreases reaction	1
Hydrogen Peroxide	decreases expression	1
Malathion	decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.