SCT

Summary

SCT (secretin, HGNC:10607) is a protein-coding gene on chromosome 11p15.5, encoding Secretin (P09683). Hormone involved in different processes, such as regulation of the pH of the duodenal content, food intake and water homeostasis.

This gene encodes a member of the glucagon family of peptides. The encoded preproprotein is secreted by endocrine S cells in the proximal small intestinal mucosa as a prohormone, then proteolytically processed to generate the mature peptide hormone. The release of this active peptide hormone is stimulated by either fatty acids or acidic pH in the duodenum. This hormone stimulates the secretion of bile and bicarbonate in the duodenum, pancreatic and biliary ducts.

Source: NCBI Gene 6343 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_021920

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10607
Approved symbol	SCT
Name	secretin
Location	11p15.5
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000070031
Ensembl biotype	protein_coding
OMIM	182099
Entrez	6343

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000176195

RefSeq mRNA: 1 — MANE Select: NM_021920 NM_021920

CCDS: CCDS7709

Canonical transcript exons

ENST00000176195 — 4 exons

Exon	Start	End
ENSE00000655856	626888	626989
ENSE00000655858	626697	626789
ENSE00001291007	627073	627181
ENSE00001324300	626309	626530

Expression profiles

Bgee: expression breadth ubiquitous, 126 present calls, max score 92.96.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.8793 / max 182.8037, expressed in 122 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117801	0.7338	95
117802	0.1080	42
117800	0.0375	16

Top tissues by expression

133 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
duodenum	UBERON:0002114	92.96	gold quality
granulocyte	CL:0000094	74.55	gold quality
gastrocnemius	UBERON:0001388	73.91	gold quality
mucosa of transverse colon	UBERON:0004991	73.55	gold quality
muscle of leg	UBERON:0001383	73.06	gold quality
hindlimb stylopod muscle	UBERON:0004252	72.60	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.84	gold quality
sural nerve	UBERON:0015488	70.05	gold quality
lower esophagus mucosa	UBERON:0035834	69.33	gold quality
monocyte	CL:0000576	69.32	gold quality
leukocyte	CL:0000738	68.98	gold quality
skeletal muscle tissue	UBERON:0001134	68.87	gold quality
spleen	UBERON:0002106	67.11	gold quality
small intestine	UBERON:0002108	65.51	gold quality
right atrium auricular region	UBERON:0006631	64.80	gold quality
adenohypophysis	UBERON:0002196	63.69	gold quality
small intestine Peyer’s patch	UBERON:0003454	63.61	gold quality
pituitary gland	UBERON:0000007	63.34	gold quality
placenta	UBERON:0001987	62.49	gold quality
left testis	UBERON:0004533	62.21	gold quality
right testis	UBERON:0004534	62.17	gold quality
right uterine tube	UBERON:0001302	61.71	gold quality
testis	UBERON:0000473	61.51	gold quality
muscle tissue	UBERON:0002385	61.44	gold quality
intestine	UBERON:0000160	59.88	gold quality
apex of heart	UBERON:0002098	59.76	gold quality
colon	UBERON:0001155	58.24	gold quality
right lung	UBERON:0002167	58.23	gold quality
muscle layer of sigmoid colon	UBERON:0035805	58.21	gold quality
lower esophagus muscularis layer	UBERON:0035833	57.73	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	2275.48
E-HCAD-32	yes	368.41
E-HCAD-4	yes	65.19
E-HCAD-1	yes	19.24
E-MTAB-9467	yes	16.04
E-MTAB-6701	yes	15.93
E-CURD-112	yes	15.22
E-MTAB-10042	yes	12.96
E-CURD-122	yes	11.78
E-CURD-46	yes	9.17
E-HCAD-10	yes	7.20
E-ANND-3	no	3.10

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ARX, BHLHA15, ESRRA, NEUROD1, NEUROG3, NFIC, NR0B2, SP1, SP3, SP4, TCF3, ZGLP1

miRNA regulators (miRDB)

1 targeting SCT, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6781-5P	94.61	59.49	155

Literature-anchored findings (GeneRIF, showing 21)

• The purpose of this study was to investigate whether secretin exhibits similar properties in vitro by forming micelles in aqueous solution and interacting with phospholipids (PMID:11814635)
• Human VPAC1 receptor selectivity filter; Identification of a critical domain for restricting binding (PMID:12133828)
• fine structure in 11p15.5 and sequence variation in patients with autism (PMID:12160732)
• human secretin gene is controlled by the Sp1/Sp3 transcription factors ratio and the methylation status of the promoter (PMID:15118068)
• Transgenic mouse study suggests a trophic role for secretin on neurons known to be involved in multiple superior functions in the normal brain, and lost in neurodegenerative disorders. (PMID:15610158)
• Secretin mRNAs are found in Purkinje cells and secretin-immunoreactivities are localized in both the soma and dendrites of Purkinje cells of human cerebellum. (PMID:15706223)
• small heterodimer partner and secretin are potentially co-expressed and lead us to propose a novel regulatory pathway (PMID:16888194)
• first pathway is by changing the expression levels of nuclear factor-I C(NFI-C) and secretin proteins while the second pathway is by modifying the phosphorylation status of both NFI-C and secretin proteins via cyclin-dependent kinase 1 (PMID:16888198)
• Peptic ulceration may be a hormonal (secfretin) deficiency disease. (PMID:18280672)
• These results collectively suggest that variable of tandem repeats could potentially be a functional regulator to control the expression of the human secretin gene in different individuals. (PMID:18566919)
• secretin acts through stimulation of presynaptic cholinergic neurons in a vagally mediated pathway. (PMID:19239625)
• Bile acids inhibit duodenal secretin expression via orphan nuclear receptor small heterodimer partner (SHP). (PMID:19372104)
• secretin significantly inhibited the tumor size and more than doubled tumor latency, which was associated with a decrease in proliferating cell nuclear antigen and an increase in cleaved-caspase 3 expression levels (PMID:19904746)
• Secretin effect on increase in transcription of the tyrosine hydroxylase (Th) gene and modulate catecholamine secretion, was tested. (PMID:21597914)
• binding and activity of a series of 11 truncated and lactam-constrained secretin(5-27) analogues at the prototypic member of this family, the secretin receptor (PMID:21851058)
• Data suggest that the interaction between secretin peptide residue H1 and secretin receptor residue W274 is most compatible with a hydrophobic interaction. (PMID:22964305)
• a lineage of mature enteroendocrine cells have the ability to coexpress members of a group of functionally related peptides: CCK, secretin, GIP, GLP-1, PYY, and neurotensin (PMID:23064014)
• CD36 is a major mediator of FA-induced release of CCK and secretin. These peptides contribute to the role of CD36 in fat absorption and to its pleiotropic metabolic effects. (PMID:23233532)
• Inhibition of Secretin/Secretin Receptor Axis Ameliorates NAFLD Phenotypes. (PMID:33928675)
• Secretin modulates appetite via brown adipose tissue-brain axis. (PMID:36764966)
• Expression of Secretin and its Receptor Along the Intestinal Tract in Type 2 Diabetes Patients and Healthy Controls. (PMID:37335970)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sct	ENSMUSG00000038580
rattus_norvegicus	Sct	ENSRNOG00000017873

Protein

Protein identifiers

Secretin — P09683 (reviewed: P09683)

All UniProt accessions (1): P09683

UniProt curated annotations — full annotation on UniProt →

Function. Hormone involved in different processes, such as regulation of the pH of the duodenal content, food intake and water homeostasis. Exerts its biological effects by binding to secretin receptor (SCTR), a G-protein coupled receptor expressed in the basolateral domain of several cells. Acts as a key gastrointestinal hormone by regulating the pH of the duodenal content. Secreted by S cells of the duodenum in the crypts of Lieberkuehn and regulates the pH of the duodenum by (1) inhibiting the secretion of gastric acid from the parietal cells of the stomach and (2) stimulating the production of bicarbonate (NaHCO(3)) from the ductal cells of the pancreas. Production of bicarbonate is essential to neutralize the pH and ensure no damage is done to the small intestine by the gastric acid. In addition to regulating the pH of the duodenal content, plays a central role in diet induced thermogenesis: acts as a non-sympathetic brown fat (BAT) activator mediating prandial thermogenesis, which consequentially induces satiation. Mechanistically, secretin released by the gut after a meal binds to secretin receptor (SCTR) in brown adipocytes, activating brown fat thermogenesis by stimulating lipolysis, which is sensed in the brain and promotes satiation. Also able to stimulate lipolysis in white adipocytes. Also plays an important role in cellular osmoregulation: released into the systemic circulation in response to hyperosmolality and acts at different levels in the hypothalamus, pituitary and kidney to regulate water homeostasis. Also plays a role in the central nervous system, possibly by acting as a neuropeptide hormone: required for hippocampal synaptic function and neural progenitor cells maintenance.

Subcellular location. Secreted.

Induction. Serum secretin levels are increased after single-meal ingestion.

Similarity. Belongs to the glucagon family.

RefSeq proteins (1): NP_068739* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000532	Glucagon_GIP_secretin_VIP	Domain
IPR015675	Prosecretin	Family

Pfam: PF00123

UniProt features (7 total): propeptide 2, modified residue 2, signal peptide 1, peptide 1, helix 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6WZG	ELECTRON MICROSCOPY	2.3
7D3S	ELECTRON MICROSCOPY	2.9
6WI9	ELECTRON MICROSCOPY	4.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09683-F1	66.35	0.10

Antibody-complex structures (SAbDab): 3 — 6WI9, 6WZG, 7D3S

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 (2): 54, 58

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-418555	G alpha (s) signalling events
R-HSA-420092	Glucagon-type ligand receptors
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373080	Class B/2 (Secretin family receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 149 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_DIGESTION, REACTOME_GLUCAGON_TYPE_LIGAND_RECEPTORS, GOBP_ACID_SECRETION, GOBP_RESPONSE_TO_DIETARY_EXCESS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, TGACCTY_ERR1_Q2, GOBP_POSITIVE_REGULATION_OF_DIGESTIVE_SYSTEM_PROCESS, CAGCTG_AP4_Q5, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_CELL_CELL_SIGNALING, GOBP_DIGESTIVE_SYSTEM_DEVELOPMENT, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE

GO Biological Process (15): diet induced thermogenesis (GO:0002024), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), brain development (GO:0007420), intracellular water homeostasis (GO:0009992), hippocampus development (GO:0021766), pancreatic juice secretion (GO:0030157), response to nutrient levels (GO:0031667), regulation of appetite (GO:0032098), regulation of synaptic plasticity (GO:0048167), embryonic digestive tract development (GO:0048566), positive regulation of lipid catabolic process (GO:0050996), positive regulation of pancreatic juice secretion (GO:0090187), positive regulation of somatostatin secretion (GO:0090274), positive regulation of cAMP/PKA signal transduction (GO:0141163), negative regulation of gastrin-induced gastric acid secretion (GO:1903640)

GO Molecular Function (5): G protein-coupled receptor binding (GO:0001664), signaling receptor binding (GO:0005102), hormone activity (GO:0005179), digestive hormone activity (GO:0046659), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by GPCR	2
GPCR downstream signalling	1
Class B/2 (Secretin family receptors)	1
Signal Transduction	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of biological quality	2
response to dietary excess	1
adaptive thermogenesis	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
central nervous system development	1
animal organ development	1
head development	1
cell volume homeostasis	1
intracellular chemical homeostasis	1
pallium development	1
limbic system development	1
anatomical structure development	1
body fluid secretion	1
digestive system process	1
secretion by tissue	1
response to stimulus	1
response to nutrient levels	1
modulation of chemical synaptic transmission	1
digestive tract development	1
embryonic organ development	1
positive regulation of catabolic process	1
lipid catabolic process	1
positive regulation of lipid metabolic process	1
regulation of lipid catabolic process	1
pancreatic juice secretion	1
positive regulation of secretion	1
positive regulation of digestive system process	1
regulation of pancreatic juice secretion	1
somatostatin secretion	1
regulation of somatostatin secretion	1
positive regulation of peptide hormone secretion	1
cAMP/PKA signal transduction	1
regulation of cAMP/PKA signal transduction	1
positive regulation of intracellular signal transduction	1
gastrin-induced gastric acid secretion	1
negative regulation of gastric acid secretion	1
regulation of gastrin-induced gastric acid secretion	1
signaling receptor binding	1
protein binding	1

Protein interactions and networks

STRING

976 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SCT	SCTR	P47872	998
SCT	VIP	P01282	987
SCT	GCG	P01275	970
SCT	GAST	P01350	952
SCT	ADCYAP1	P18509	932
SCT	GIP	P09681	914
SCT	SST	P01166	912
SCT	CCK	P06307	876
SCT	GHRH	P01286	871
SCT	GLP1R	P43220	861
SCT	PPY	P01298	855
SCT	CALCR	P30988	824
SCT	MLN	P12872	821
SCT	VIPR2	P41587	788
SCT	INS	P01308	775

IntAct

13 interactions, top by confidence:

A	B	Type	Score
SCT	USHBP1	psi-mi:“MI:0915”(physical association)	0.560
HGS	SCT	psi-mi:“MI:0915”(physical association)	0.560
MEIS2	SCT	psi-mi:“MI:0915”(physical association)	0.560
SCT	HOXA1	psi-mi:“MI:0915”(physical association)	0.560
HGS	SCT	psi-mi:“MI:0915”(physical association)	0.000
USHBP1	SCT	psi-mi:“MI:0915”(physical association)	0.000
MEIS2	SCT	psi-mi:“MI:0915”(physical association)	0.000
HOXA1	SCT	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): HOXA1 (Two-hybrid), USHBP1 (Two-hybrid), MEIS2 (Two-hybrid), HGS (Two-hybrid), SCT (Reconstituted Complex), SCT (Reconstituted Complex)

ESM2 similar proteins: O02686, O43555, O97655, O97686, P01142, P01143, P01297, P01351, P01352, P01353, P01354, P06296, P06850, P07492, P08949, P08989, P09683, P11384, P13083, P24393, P47851, P55089, P61312, P63152, P63153, P63298, P68248, P81264, P81277, P81278, P83859, P83860, P83862, Q08535, Q15726, Q2T9U8, Q6Y4S4, Q7TNK8, Q7TSB7, Q7Z4H4

Diamond homologs: P09683, P09910, P11384, P31299, P32647, P63296, P63297, P63298, Q08535, P01280

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

242 predictions. Top by Δscore:

Variant	Effect	Δscore
11:626883:CTCAC:C	donor_loss	1.0000
11:626884:TCAC:T	donor_loss	1.0000
11:626886:A:C	donor_loss	1.0000
11:626895:T:TA	donor_gain	1.0000
11:626896:C:A	donor_gain	0.9900
11:627067:GCTCA:G	donor_loss	0.9800
11:627068:CTCA:C	donor_loss	0.9800
11:627069:TCA:T	donor_loss	0.9800
11:627070:CA:C	donor_loss	0.9800
11:627071:A:C	donor_loss	0.9800
11:627072:C:A	donor_loss	0.9800
11:626788:CG:C	acceptor_gain	0.9700
11:626798:C:T	acceptor_gain	0.9700
11:627066:GGCTC:G	donor_loss	0.9700
11:626906:C:CA	donor_gain	0.9600
11:627065:CGGCT:C	donor_loss	0.9600
11:626790:C:CC	acceptor_gain	0.9500
11:626895:TCCCC:T	donor_gain	0.9500
11:626529:TC:T	acceptor_gain	0.9400
11:626530:CC:C	acceptor_gain	0.9400
11:626786:CTCG:C	acceptor_gain	0.9400
11:626530:CCTG:C	acceptor_loss	0.9300
11:626531:C:CA	acceptor_loss	0.9300
11:626531:C:CC	acceptor_gain	0.9300
11:626532:T:C	acceptor_loss	0.9300
11:626787:TCGC:T	acceptor_loss	0.9300
11:626789:GC:G	acceptor_loss	0.9300
11:626803:C:T	acceptor_gain	0.9300
11:626986:GGCCC:G	acceptor_loss	0.9300
11:626987:GCCCT:G	acceptor_loss	0.9300

AlphaMissense

747 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:626962:G:C	F33L	0.994
11:626962:G:T	F33L	0.994
11:626964:A:G	F33L	0.994
11:626963:A:C	F33C	0.989
11:626963:A:G	F33S	0.985
11:626956:G:C	S35R	0.984
11:626956:G:T	S35R	0.984
11:626958:T:G	S35R	0.984
11:626947:G:C	S38R	0.980
11:626947:G:T	S38R	0.980
11:626949:T:G	S38R	0.980
11:626957:C:A	S35I	0.980
11:626893:C:A	K56N	0.975
11:626893:C:G	K56N	0.975
11:626960:G:A	T34I	0.970
11:626970:C:A	G31W	0.968
11:626977:G:C	H28Q	0.967
11:626977:G:T	H28Q	0.967
11:626972:T:A	D30V	0.965
11:626948:C:A	S38I	0.964
11:626964:A:T	F33I	0.963
11:626954:T:A	E36V	0.961
11:626970:C:G	G31R	0.960
11:626970:C:T	G31R	0.960
11:626969:C:T	G31E	0.958
11:626973:C:G	D30H	0.954
11:626969:C:A	G31V	0.952
11:626955:C:T	E36K	0.949
11:626912:A:G	L50P	0.948
11:626897:C:A	G55V	0.940

dbSNP variants (sampled 300 via entrez): RS1000226608 (11:627628 T>G), RS1000541351 (11:626871 A>C), RS1000660706 (11:627853 C>T), RS1000789412 (11:627041 C>G,T), RS1001696040 (11:627333 C>T), RS1001725451 (11:627461 G>A,T), RS1003300999 (11:626119 G>A), RS1003415802 (11:626261 A>G), RS1003779493 (11:628076 A>G), RS1003926744 (11:627974 C>T), RS1004211830 (11:626087 A>G), RS1004686684 (11:629036 CCTTTCTTTCTTTT>C), RS1004765889 (11:625914 G>A), RS1005378620 (11:628030 C>T), RS1005414542 (11:628161 T>A)

Disease associations

OMIM: gene MIM:182099 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
sapropterin	increases abundance	1
pirinixic acid	affects binding, increases activity, increases expression	1
benzamil	decreases activity	1
perfluorooctanoic acid	affects cotreatment, decreases expression	1
5-nitro-2-(3-phenylpropylamino)benzoic acid	decreases activity	1
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide	decreases activity	1
di-n-butylphosphoric acid	affects expression	1
1,2-bis(2-aminophenoxy)ethane N,N,N’,N’-tetraacetic acid acetoxymethyl ester	decreases activity	1
perfluorooctane sulfonic acid	decreases expression, affects cotreatment	1
perfluorohexanesulfonic acid	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Calcium	increases abundance	1
Chlorides	decreases transport	1
Cisplatin	affects cotreatment, decreases expression	1
Dopamine	increases metabolic processing	1
Homovanillic Acid	increases abundance	1
Pentagastrin	decreases activity	1
Plant Extracts	affects cotreatment, decreases expression	1
Potassium	decreases transport	1
Smoke	increases reaction, increases secretion	1
Sodium	decreases transport	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	affects reaction, increases expression	1
Triclosan	decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.