IAPP

Summary

IAPP (islet amyloid polypeptide, HGNC:5329) is a protein-coding gene on chromosome 12p12.1, encoding Islet amyloid polypeptide (P10997). Amylin/IAPP is a glucoregulatory peptide hormone that plays an important role in the regulation of energy homeostasis.

This gene encodes a member of the calcitonin family of peptide hormones. This hormone is released from pancreatic beta cells following food intake to regulate blood glucose levels and act as a satiation signal. Human patients with type 1 and advanced type 2 diabetes exhibit reduced levels of the encoded hormone in blood and pancreas. This protein also exhibits a bactericidal, antimicrobial activity.

Source: NCBI Gene 3375 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 9 total
• GTEx eGene: eQTL in 1 tissue, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.35 (intermediate), LOEUF 1.50 (unconstrained)
• MANE Select transcript: NM_000415

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5329
Approved symbol	IAPP
Name	islet amyloid polypeptide
Location	12p12.1
Locus type	gene with protein product
Status	Approved
Aliases	AMYLIN, DAP, IAP
Ensembl gene	ENSG00000121351
Ensembl biotype	protein_coding
OMIM	147940
Entrez	3375

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

MANE Select: ENST00000240652

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 2, TSL 3: 2

ENST00000240652, ENST00000535428, ENST00000537593, ENST00000539393, ENST00000542023, ENST00000877981

RefSeq mRNA: 2 — MANE Select: NM_000415 NM_000415, NM_001329201

CCDS: CCDS8688

Canonical transcript exons

ENST00000240652 — 3 exons

Exon	Start	End
ENSE00000822246	21373337	21373431
ENSE00000994897	21372902	21373004
ENSE00004791583	21378237	21379980

Expression profiles

Bgee: expression breadth broad, 68 present calls, max score 99.74.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0391 / max 32.9224, expressed in 3 samples.

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

Genetic regulation across tissues (GTEx eQTL / sQTL)

IAPP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 1 tissue and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

1 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Liver	eqtl	1.3e-02	+0.38	12:21324903:G:T

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
124661	0.0391	3

Top tissues by expression

showing 100 of 244 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	99.74	gold quality
islet of Langerhans	UBERON:0000006	99.74	gold quality
pancreas	UBERON:0001264	91.03	gold quality
body of pancreas	UBERON:0001150	87.66	gold quality
epithelial cell of pancreas	CL:0000083	82.02	gold quality
hair follicle	UBERON:0002073	71.98	gold quality
right lobe of liver	UBERON:0001114	67.56	gold quality
olfactory bulb	UBERON:0002264	63.47	gold quality
diaphragm	UBERON:0001103	58.10	gold quality
epithelium of nasopharynx	UBERON:0001951	57.71	gold quality
thymus	UBERON:0002370	57.30	gold quality
decidua	UBERON:0002450	56.55	gold quality
superficial temporal artery	UBERON:0001614	56.36	gold quality
oocyte	CL:0000023	56.08	gold quality
liver	UBERON:0002107	56.02	gold quality
left testis	UBERON:0004533	55.37	gold quality
cerebellar vermis	UBERON:0004720	54.64	gold quality
trachea	UBERON:0003126	53.88	gold quality
testis	UBERON:0000473	53.40	gold quality
layer of synovial tissue	UBERON:0007616	53.31	gold quality
saphenous vein	UBERON:0007318	53.28	gold quality
nipple	UBERON:0002030	52.61	gold quality
urethra	UBERON:0000057	52.54	gold quality
dorsal plus ventral thalamus	UBERON:0001897	52.41	gold quality
nephron tubule	UBERON:0001231	52.28	gold quality
dorsal root ganglion	UBERON:0000044	52.27	gold quality
metanephric glomerulus	UBERON:0004736	52.21	gold quality
pericardium	UBERON:0002407	52.11	gold quality
trigeminal ganglion	UBERON:0001675	52.05	gold quality
synovial joint	UBERON:0002217	51.93	gold quality
penis	UBERON:0000989	51.87	gold quality
renal medulla	UBERON:0000362	51.84	gold quality
epithelium of mammary gland	UBERON:0003244	51.77	gold quality
inferior vagus X ganglion	UBERON:0005363	51.74	gold quality
pylorus	UBERON:0001166	51.72	gold quality
superior surface of tongue	UBERON:0007371	51.66	gold quality
quadriceps femoris	UBERON:0001377	51.64	gold quality
mammary duct	UBERON:0001765	51.51	gold quality
superior vestibular nucleus	UBERON:0007227	51.48	gold quality
medulla oblongata	UBERON:0001896	51.43	gold quality
pons	UBERON:0000988	51.41	gold quality
cardia of stomach	UBERON:0001162	51.41	gold quality
tongue	UBERON:0001723	51.33	gold quality
vastus lateralis	UBERON:0001379	51.31	gold quality
subthalamic nucleus	UBERON:0001906	51.25	gold quality
ventral tegmental area	UBERON:0002691	51.18	gold quality
substantia nigra pars compacta	UBERON:0001965	51.16	gold quality
renal glomerulus	UBERON:0000074	51.15	gold quality
pharyngeal mucosa	UBERON:0000355	51.04	gold quality
vena cava	UBERON:0004087	50.98	gold quality
substantia nigra pars reticulata	UBERON:0001966	50.91	gold quality
kidney epithelium	UBERON:0004819	50.91	gold quality
body of tongue	UBERON:0011876	50.88	gold quality
lateral nuclear group of thalamus	UBERON:0002736	50.62	gold quality
lateral globus pallidus	UBERON:0002476	50.54	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
right testis	UBERON:0004534	49.65	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
deltoid	UBERON:0001476	49.11	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
cervix epithelium	UBERON:0004801	48.51	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
oviduct epithelium	UBERON:0004804	48.45	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
nasal cavity epithelium	UBERON:0005384	48.11	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
periodontal ligament	UBERON:0008266	47.14	gold quality
gluteal muscle	UBERON:0002000	47.03	gold quality
triceps brachii	UBERON:0001509	47.01	gold quality
endometrium epithelium	UBERON:0004811	46.85	gold quality
lower lobe of lung	UBERON:0008949	46.78	silver quality
duodenum	UBERON:0002114	46.55	gold quality
embryo	UBERON:0000922	45.74	gold quality
jejunum	UBERON:0002115	45.57	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	45.35	gold quality
inferior olivary complex	UBERON:0002127	45.14	gold quality
skeletal muscle tissue	UBERON:0001134	44.73	gold quality
muscle tissue	UBERON:0002385	44.48	gold quality
palpebral conjunctiva	UBERON:0001812	44.31	gold quality
bronchus	UBERON:0002185	44.03	gold quality
globus pallidus	UBERON:0001875	43.84	gold quality
epithelium of bronchus	UBERON:0002031	43.77	gold quality
squamous epithelium	UBERON:0006914	43.42	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
epithelium of esophagus	UBERON:0001976	42.87	gold quality
amniotic fluid	UBERON:0000173	42.84	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
bone marrow	UBERON:0002371	42.29	gold quality
mammalian vulva	UBERON:0000997	42.20	gold quality
tibialis anterior	UBERON:0001385	42.16	silver quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-81608	yes	21484.31
E-HCAD-31	yes	20293.35
E-ENAD-27	yes	15955.23
E-GEOD-81547	yes	15193.96
E-GEOD-83139	yes	14637.92
E-MTAB-5061	yes	10939.21
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Tissue enriched

26 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Pancreas	tissue	157.0	high
Testis	tissue	2.9	not detected
Substantia nigra	tissue	2.2
Choroid plexus	tissue	1.5
Retrosplenial cortex	tissue	1.1
Bone marrow	tissue	1.0	not detected
Putamen	tissue	0.9
Medulla oblongata	tissue	0.9
Liver	tissue	0.9	not detected
Spinal cord	tissue	0.8
Hippocampus	tissue	0.8	not detected
Skin 1	tissue	0.7	not detected
Nucleus accumbens	tissue	0.7
Locus coeruleus	tissue	0.7
Postcentral gyrus	tissue	0.6
Adipose tissue	tissue	0.4	not detected
Stomach 1	tissue	0.3	not detected
Duodenum	tissue	0.3	not detected
Lymph node	tissue	0.2	not detected
Esophagus	tissue	0.1	not detected
Urinary bladder	tissue	0.1	not detected
Basal ganglia	tissue	0.1	not detected
Gallbladder	tissue	0.1	not detected
Kidney	tissue	0.1	not detected
Ventral forebrain	tissue	0.1
Ovary	tissue	0.0	low

Brain sub-regions (HPA Brain Atlas): detected in 183; highest nTPM — Subthalamic nucleus (2.5), Flocculonodular lobe (1.6), Ventral tegmental area (1.5), Reticular pontine nucleus, oral (1.4), Cerebellar cortex (1.3).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets:

Target	Regulation
FOS	Activation

Upstream regulators (CollecTRI, top): CDX1, CDX2, FEZF2, FOXA2, FOXO1, GATA4, HNF1A, HOXB7, ISL1, KLF4, LMX1A, MAZ, NEUROD1, NFAT5, NKX6-1, NRF1, PAX6, PDX1, SSRP1, TFAP2A, ZGLP1, ZNF148

miRNA regulators (miRDB)

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

showing 30 of 62 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-5584-5P	99.49	68.22	2814

Functional genomics

gnomAD constraint: pLI 0.349, LOEUF 1.5, missense Z -0.221 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000240652 — one region, missense o/e 1.08.

Literature-anchored findings (GeneRIF, showing 40)

• structure-based design and study of non-amyloidogenic, double N-methylated IAPP amyloid core sequences as inhibitors of IAPP amyloid formation and cytotoxicity (PMID:11786016)
• progressive intermittent exercise protocol of moderate to maximum exercise intensities stimulates increases in amylin levels (PMID:11979402)
• estrogen prevents or reverses obesity and diabetes in transgenic mice expressing the human gene (PMID:12086946)
• The presence of amylin-derived islet amyloid is felt to play a significant role in the remodeling of the endocrine pancreas as well as the natural progressive history of type 2 diabetes mellitus. (PMID:12221327)
• Inhibition of amyloid fibril formation of human amylin by N-alkylated amino acid and alpha-hydroxy acid residue containing peptides (PMID:12298020)
• Results describe a novel molecular recognition motif within the human islet amyloid polypeptide (hIAPP) molecule. (PMID:12367525)
• results suggest strongly that human amylin induces apoptosis in pancreatic islet beta-cells through stimulation of expression and activation of c-Jun (PMID:12441106)
• Increased dietary fat promotes islet cell formation and dysfunction in transgenic mice models. (PMID:12540610)
• polymorphism of IAPP gene in nondiabetic subjects and type 2 diabetes is associated with lower levels of LDL cholesterol; abnormalities of coding regions or 5’-UTR not associated with type 2 diabetes or gestational diabetes mellitus in Spanish population. (PMID:12588049)
• Data show that the three specific proline residues in human and rat amylin play a dominant negative role in fibril formation. (PMID:12589759)
• Human amylin, like beta-Amyloid, is capable of modulating ion channel function in rat cholinergic basal forebrain neurons. The hAmylin effects could be occluded by beta-amyloid and vice versa. (PMID:12611974)
• IAPP is found in 90% of patients with NIDDM at post-mortem. More extensive amyloidosis is associated with decreased islet function and requirement for insulin therapy. (PMID:12706318)
• The frequency of the S20G mutation in the amylin gene is 1.92% in unrelated Korean type 2 diabetic patients and this mutation is associated with a lower BMI and a higher HbA(1c) level. (PMID:12706321)
• DAP 12 gene of chromosome 19q13.1 is implicated in Nasu Hakola disease (PMID:12717671)
• conformational preferences of hIAPP(20-29) in membrane-mimicking environments (PMID:12717720)
• role played by the hydrophobic and aromatic residues in inter-sheet association and fibril formation (PMID:12767835)
• amylin has a role in evoking a JNK1-mediated apoptotic pathway, which is partially dependent and partially independent of caspase-8, and in which caspase-3 acts as a common downstream effector (PMID:14532296)
• Islet amyloid deposits were identified using Congo red staining in islets of patients with NIDDM. (PMID:14578294)
• Amylin is widely expressed in non-tumorous pancreatic islets and in one insulin producing beta cell tumor (PMID:14656003)
• the dominant effect of insulin is to act on the elongation portion of the fiber formation reaction (PMID:14659752)
• this study reports the expression, purification and characterization of the amyloidogenicity and cytotoxicity of recombinant human mature IAPP (PMID:15292167)
• Results describe the interactions of islet amyloid polypeptide (IAPP) with phospholipid bilayers and the morphological effects of membranes on IAPP fibers. (PMID:15321714)
• interaction between lipid bilayers and the 37 amino acid residue polypeptide amylin, which is the primary constituent of the pancreatic amyloid associated with type 2 diabetes (PMID:15342243)
• Data are consistent with a parallel arrangement of islet amyloid polypeptide (IAPP) peptides within the amyloid fibril. (PMID:15358791)
• process of hIAPP amyloid formation is accompanied by a loss of barrier function, whereby lipids are extracted from the membrane and taken up in the forming amyloid deposits (PMID:15527771)
• Structure of the amylin fibrils was studied using atomic force microscopy. (PMID:15638806)
• findings are consistent with the hypothesis that membrane-active pre-fibrillar hIAPP oligomers insert into beta cell membranes in NIDDM (PMID:15710403)
• Structural analysis of the clusters clearly suggested the formation of “flat” ellipsoid-shaped clusters through a preferred locally parallel alignment of the peptides in water. (PMID:15778964)
• protein structure of amylin (as a model for amyloid fibrils) (PMID:15811365)
• Genetic polymorphism of the islet amyloid polypeptide gene promoter region is not associated with type 2 diabetes or islet amyloidosis. (PMID:15878744)
• Oligomeric IAPP assemblies exert toxic effects on beta cells that die, leading to reduced beta-cell mass. (review) (PMID:15929864)
• Rosiglitazone and metformin protect beta-cells from the deleterious effects of islet amyloid, and this effect may contribute to the ability of these treatments to alleviate the progressive loss of beta-cell mass and function in type 2 diabetes. (PMID:15983227)
• conditions that promote weakly stable alpha-helical conformations may promote IAPP aggregation (PMID:16142909)
• In human islets, activation of PPAR-gamma inhibits h-IAPP-induced islet cell apoptosis, and this action is at least in part mediated through activation of the phosphatidylinositol 3’-kinase-Akt cascade. (PMID:16204373)
• The amino acid residues 20-29 region of IAPP was tested for amyloidogenic domain. (PMID:16303136)
• Results describe the role of Histidine-18 in amyloid formation by human islet amyloid polypeptide. (PMID:16331989)
• IAPP monomers might insert with high efficiency in biological membranes in vivo; this process could play an important role as a first step in IAPP-induced membrane damage in type 2 diabetes. (PMID:16403520)
• The HIP rat, a human IAPP transgenic rat model that develops islet pathology comparable to humans with type 2 diabetes. (PMID:16804082)
• The heparin binding site in the N-terminus of IAPP precursor is characterized in detail, and an important role for the IAPP Cys-13/Cys-18 disulfide bridge in heparin binding is demonstrated. (PMID:16866369)
• No mutation in IAPP was found in the Mexican Mestizo population. (PMID:16950544)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000105976
mus_musculus	Iapp	ENSMUSG00000041681
rattus_norvegicus	Iapp	ENSRNOG00000082704

Paralogs (2): CALCA (ENSG00000110680), CALCB (ENSG00000175868)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:96382) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 24 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal pancreatic islet morphology	2
decreased bone mineral density	1
osteoporosis	1
abnormal trabecular bone morphology	1
decreased compact bone thickness	1
increased body weight	1
hyperglycemia	1
abnormal homeostasis	1
increased circulating insulin level	1
abnormal pancreas physiology	1
increased circulating glucagon level	1
decreased circulating insulin level	1
decreased insulin secretion	1
decreased pancreatic beta cell number	1
abnormal pancreatic beta cell physiology	1
decreased bone mass	1
decreased susceptibility to autoimmune diabetes	1
increased osteoclast cell number	1
increased bone resorption	1
improved glucose tolerance	1
impaired glucose tolerance	1
decreased pancreatic beta cell mass	1
increased pancreatic beta cell apoptosis	1
increased amylin secretion	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
Cricetulus griseus	P19890	100.0%	Diamond
Mesocricetus auratus	P23442	100.0%	Diamond
Lepus europaeus	Q07333	100.0%	Diamond
Bos taurus	Q28207	100.0%	Diamond
Ovis aries	Q28605	100.0%	Diamond
Equus caballus	Q9N0T3	97.3%	Diamond
Oryctolagus cuniculus	Q07334	95.7%	Diamond
Gallus gallus	P10286	94.6%	Diamond
Pelophylax ridibundus	P31888	94.6%	Diamond
Canis lupus familiaris	Q9MYV1	94.6%	Diamond
Felis catus	P12967	86.5%	Diamond
Saguinus oedipus	Q28934	81.3%	Diamond
Cavia porcellus	P12966	80.4%	Diamond
Octodon degus	P22889	80.4%	Diamond
Sus scrofa	Q29119	78.1%	Diamond
Phyllomedusa bicolor	P81564	61.1%	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
SLCO1B1	protein-coding	10599
GOLT1B	protein-coding	51026
RECQL	protein-coding	5965
SLCO1A2	protein-coding	6579
PYROXD1	protein-coding	79912
SLCO1B3-SLCO1B7	protein-coding	115072896
SLCO1B3	protein-coding	28234
SLCO1C1	protein-coding	53919
GYS2	protein-coding	2998
SPX	protein-coding	80763

Protein

Protein identifiers

Islet amyloid polypeptide — P10997 (reviewed: P10997)

Alternative names: Amylin, Diabetes-associated peptide, Insulinoma amyloid peptide

All UniProt accessions (4): F5H0S1, F5H1F0, H0YF85, P10997

UniProt curated annotations — full annotation on UniProt →

Function. Amylin/IAPP is a glucoregulatory peptide hormone that plays an important role in the regulation of energy homeostasis. Selectively inhibits insulin-stimulated glucose utilization and glycogen deposition in muscle, while not affecting adipocyte glucose metabolism. IAPP function is mediated by the CALCR-RAMPs (AMYRs) receptor complexes. Amylin can also bind CALCR receptor in the absence of RAMPs, although it is more selective for AMYRs.

Subunit / interactions. Can form homodimers. Interacts with IDE and INS. Interaction with INS inhibits homodimerization and fibril formation.

Subcellular location. Secreted.

Post-translational modifications. Amyloid fibrils are degraded by insulin-degrading enzyme IDE.

Domain organisation. The mature protein is largely unstructured in the absence of a cognate ligand, and has a strong tendency to form fibrillar aggregates. Homodimerization may be the first step of amyloid formation.

Miscellaneous. IAPP is the peptide subunit of amyloid found in pancreatic islets of type 2 diabetic patients and in insulinomas.

Similarity. Belongs to the calcitonin family.

RefSeq proteins (2): NP_000406, NP_001316130 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000443	IAPP	Family
IPR001693	Calcitonin_peptide-like	Domain
IPR018360	Calcitonin_CS	Conserved_site
IPR021116	Calcitonin/adrenomedullin	Family
IPR021117	Calcitonin-like	Family

Pfam: PF00214

UniProt features (17 total): strand 4, helix 4, propeptide 2, signal peptide 1, peptide 1, modified residue 1, disulfide bond 1, sequence variant 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

showing 30 of 80 structures by resolution:

PDB	Title	Method	Resolution (Å)
8YG2	Crystal structure of amyloidogenic peptide Piv-NFGAIL-NH2 from Islet Amyloid Polypeptide	X-RAY DIFFRACTION	1.25
5KO0	Human Islet Amyloid Polypeptide Segment 15-FLVHSSNNFGA-25 Determined by MicroED	ELECTRON CRYSTALLOGRAPHY	1.4
3FPO	HSSNNF segment from Islet Amyloid Polypeptide (IAPP or Amylin)	X-RAY DIFFRACTION	1.5
3FTK	NVGSNTY segment from Islet Amyloid Polypeptide (IAPP or Amylin), hydrated crystal form	X-RAY DIFFRACTION	1.5
3FTL	NVGSNTY segment from Islet Amyloid Polypeptide (IAPP or Amylin), dehydrated crystal form	X-RAY DIFFRACTION	1.6
3FTR	Structure of an amyloid forming peptide SSTNVG from IAPP (alternate polymorph)	X-RAY DIFFRACTION	1.61
3DG1	Segment SSTNVG derived from IAPP	X-RAY DIFFRACTION	1.66
3G7W	Islet Amyloid Polypeptide (IAPP or Amylin) Residues 1 to 22 fused to Maltose Binding …	X-RAY DIFFRACTION	1.75
3FTH	NFLVHSS segment from Islet Amyloid Polypeptide (IAPP or Amylin)	X-RAY DIFFRACTION	1.84
3FR1	NFLVHS segment from Islet Amyloid Polypeptide (IAPP or Amylin)	X-RAY DIFFRACTION	1.85
3G7V	Islet Amyloid Polypeptide (IAPP or Amylin) fused to Maltose Binding Protein	X-RAY DIFFRACTION	1.86
9CC5	De novo design of high-affinity protein binders to bio active peptide Amylin	X-RAY DIFFRACTION	1.87
5KNZ	Human Islet Amyloid Polypeptide Segment 19-SGNNFGAILSS-29 with Early Onset S20G Mutation …	ELECTRON CRYSTALLOGRAPHY	1.9
8F0K	Human Amylin3 Receptor in complex with Gs and Pramlintide analogue peptide San385	ELECTRON MICROSCOPY	1.9
8F0J	Calcitonin Receptor in complex with Gs and Pramlintide analogue peptide San45	ELECTRON MICROSCOPY	2
8F2B	Amylin 3 Receptor in complex with Gs and Pramlintide analogue peptide San45	ELECTRON MICROSCOPY	2
9NZH	Crystal Structure of Amylin-NHO-18 binder complex	X-RAY DIFFRACTION	2.03
8AZ4	IAPP S20G plateau-phase fibril polymorph 2PF-L	ELECTRON MICROSCOPY	2.2
8F2A	Human Amylin3 Receptor in complex with Gs and Pramlintide analogue peptide San385 …	ELECTRON MICROSCOPY	2.2
9BP3	Human Amylin1 Receptor in complex with Gs and cagrilintide	ELECTRON MICROSCOPY	2.2
8AZ5	IAPP S20G plateau-phase fibril polymorph 4PF-CU	ELECTRON MICROSCOPY	2.3
9BUB	Human calcitonin Receptor in complex with Gs and cagrilintide in the bypass conformation	ELECTRON MICROSCOPY	2.3
9BUD	Human calcitonin Receptor in complex with Gs and cagrilintide in the CT-like conformation	ELECTRON MICROSCOPY	2.5
2G48	crystal structure of human insulin-degrading enzyme in complex with amylin	X-RAY DIFFRACTION	2.6
9BQ3	Human Amylin2 Receptor in Complex with Gs and Cagrilintide	ELECTRON MICROSCOPY	2.8
7BG0	Fusion of MBP and the backbone of the long-acting amylin analog AM833.	X-RAY DIFFRACTION	2.89
8AZ7	IAPP S20G plateau-phase fibril polymorph 4PF-LJ	ELECTRON MICROSCOPY	2.9
9GZP	WT-IAPP cryo-EM structure Type LL - control reaction	ELECTRON MICROSCOPY	2.9
9GZT	WT-IAPP cryo-EM structure Type LLUU - control reaction	ELECTRON MICROSCOPY	2.9
9GZW	WT-IAPP cryo-EM structure Type LL, doxazosin reaction	ELECTRON MICROSCOPY	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10997-F1	78.59	0.09

Antibody-complex structures (SAbDab)

9 antibodies co-crystallized with this protein: 8F0J, 8F0K, 8F2A, 8F2B, 9BLB, 9BLC, 9BLW, 9BTW, 9BUE

Human Protein Atlas

Protein class: Predicted secreted proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IH enhanced · IF approved

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
Tyrosine amide	70

Disulfide bonds (1)

Type	Positions
Disulfide bond	35–40

Mutagenesis-validated functional residues (1)

Position	Phenotype
48	promotes formation of fibrillar aggregates.

Function

Pathways and Gene Ontology

Reactome pathways

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

12 pathways:

ID	Pathway	Evidence
R-HSA-977225	Amyloid fiber formation	curated
R-HSA-419812	Calcitonin-like ligand receptors	curated
R-HSA-418555	G alpha (s) signalling events	curated
R-HSA-373080	Class B/2 (Secretin family receptors)	—
R-HSA-1266738	Developmental Biology	—
R-HSA-388396	GPCR downstream signalling	—
R-HSA-500792	GPCR ligand binding	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-186712	Regulation of beta-cell development	—
R-HSA-210745	Regulation of gene expression in beta cells	electronic
R-HSA-162582	Signal Transduction	—
R-HSA-372790	Signaling by GPCR	—

MSigDB gene sets: 158 (showing top): GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_DN, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CELL_CELL_SIGNALING, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_TISSUE_REMODELING, MARTINEZ_RB1_TARGETS_UP, GOBP_SENSORY_PERCEPTION_OF_PAIN

GO Biological Process (15): apoptotic process (GO:0006915), signal transduction (GO:0007165), cell-cell signaling (GO:0007267), negative regulation of protein-containing complex assembly (GO:0031333), eating behavior (GO:0042755), positive regulation of apoptotic process (GO:0043065), positive regulation of MAPK cascade (GO:0043410), positive regulation of calcium-mediated signaling (GO:0050850), amylin receptor signaling pathway (GO:0097647), positive regulation of cAMP/PKA signal transduction (GO:0141163), amylin receptor 1 signaling pathway (GO:0150059), amylin receptor 2 signaling pathway (GO:0150060), amylin receptor 3 signaling pathway (GO:0150061), negative regulation of amyloid fibril formation (GO:1905907), calcitonin family receptor signaling pathway (GO:0097646)

GO Molecular Function (7): amyloid-beta binding (GO:0001540), signaling receptor binding (GO:0005102), hormone activity (GO:0005179), lipid binding (GO:0008289), identical protein binding (GO:0042802), receptor ligand activity (GO:0048018), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), neuronal cell body (GO:0043025)

Reactome top-level categories

8 top-level categories:

Category	Pathways
Signaling by GPCR	2
Regulation of beta-cell development	1
GPCR downstream signalling	1
Class B/2 (Secretin family receptors)	1
Metabolism of proteins	1
Developmental Biology	1
Signal Transduction	1
GPCR ligand binding	1

GO top-level categories

39 GO namespaces:

Category	Terms
positive regulation of intracellular signal transduction	3
amylin receptor signaling pathway	3
cell communication	2
signaling	2
protein binding	2
binding	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of protein-containing complex assembly	1
negative regulation of cellular component organization	1
protein-containing complex assembly	1
feeding behavior	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
MAPK cascade	1
regulation of MAPK cascade	1
calcium-mediated signaling	1
regulation of calcium-mediated signaling	1
calcitonin family receptor signaling pathway	1
cAMP/PKA signal transduction	1
regulation of cAMP/PKA signal transduction	1
negative regulation of protein metabolic process	1
negative regulation of supramolecular fiber organization	1
regulation of amyloid fibril formation	1
amyloid fibril formation	1
G protein-coupled receptor signaling pathway	1
peptide binding	1
receptor ligand activity	1
signaling receptor binding	1
signal transduction	1
signaling receptor activator activity	1
cellular anatomical structure	1
somatodendritic compartment	1
cell body	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 10 of 25 annotations. The rest are phylogenetic / computational / electronic (IEA).

10 experimentally-supported GO terms:

GO term	NS	Evidence
amylin receptor 1 signaling pathway	BP	direct assay
amylin receptor 2 signaling pathway	BP	direct assay
amylin receptor 3 signaling pathway	BP	direct assay
amylin receptor signaling pathway	BP	direct assay
positive regulation of cAMP/PKA signal transduction	BP	genetic interaction
positive regulation of calcium-mediated signaling	BP	genetic interaction
identical protein binding	MF	physical interaction
lipid binding	MF	experiment
receptor ligand activity	MF	direct assay
signaling receptor binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,512 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IAPP	RAMP1	O60894	956
IAPP	RAMP3	O60896	950
IAPP	CALCB	P10092	949
IAPP	RAMP2	O60895	947
IAPP	CALCR	P30988	937
IAPP	INS	P01308	928
IAPP	ADM	P35318	925
IAPP	GCG	P01275	904
IAPP	CALCRL	Q16602	902
IAPP	CALCA	P01258	867
IAPP	PPY	P01298	771
IAPP	SNCA	P37840	757
IAPP	PYY	P10082	746
IAPP	GHRL	Q9UBU3	724
IAPP	LEP	P41159	720

IntAct

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

4 partners by confidence:

Partner	Interaction type	MIscore	Records
IDE	direct interaction	0.620	3
BACE1	protein cleavage	0.560	2
BACE2	protein cleavage	0.560	2
TRIP6	physical association	0.400	1

BioGRID (5 interactions; top human partners by supporting records): CSK (Synthetic Lethality), P4HB (Affinity Capture-Western), POLI (Reconstituted Complex), SNCA (Co-localization), TRIP6 (Affinity Capture-MS)

SIGNOR signaling

5 signaling interactions:

A	Effect	B	Mechanism
IAPP	“up-regulates activity”	“Amylin receptor 1 complex”	binding
IAPP	“up-regulates activity”	“Amylin receptor 2 complex”	binding
IAPP	“up-regulates activity”	“Amylin receptor 3 complex”	binding
PCSK1	“up-regulates activity”	IAPP	cleavage
PCSK2	“up-regulates activity”	IAPP	cleavage

Ligand–receptor pairs (CellPhoneDB) (4)

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

4 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
CALCR;RAMP2	ligand	Signaling by Amylin
CALCR;RAMP1	ligand	Signaling by Amylin
CALCR;RAMP3	ligand	Signaling by Amylin
CALCR	ligand	Signaling by Amylin

Disease & clinical

Genetic variants

Variant evidence for IAPP: 9 ClinVar records (0 pathogenic / likely pathogenic); 1 PharmGKB clinical annotation; 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	2
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 22 predictions of 297):

Position(s)	Effect	Δscore	Sites
12:21373005–21373006	donor_loss	1.0000	3
12:21373005	donor_loss	0.9900	2
12:21373432–21373433	donor_loss	0.9900	5
12:21378228	acceptor_gain	0.9800
12:21376320	acceptor_gain	0.9700
12:21373335–21373336	acceptor_loss	0.9600	6
12:21373334	acceptor_loss	0.9500
12:21376320	acceptor_gain	0.9500
12:21373334	acceptor_loss	0.9300
12:21373440	donor_gain	0.9300

AlphaMissense

29 missense substitutions predicted likely pathogenic (of 571 scored), across 12 residues. Top 12 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
F48	5	0.696	0.779
C35	5	0.645	0.726
C40	4	0.663	0.684
G71	3	0.672	0.713
L45	3	0.664	0.729
R73	2	0.722	0.722
K72	2	0.721	0.721
R44	1	0.741	0.741
R33	1	0.654	0.654
L49	1	0.654	0.654
A46	1	0.591	0.591
A38	1	0.568	0.568

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Pancreatic Adenocarcinoma)

Disease associations

OMIM: gene MIM:147940 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST002875_60	Diisocyanate-induced asthma	7e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0006995	response to diisocyanate

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1914266 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

1 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs11045995	Dosage	3	rocuronium

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11045995	IAPP, SLCO1A2	3	0.00	1	rocuronium

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs11045995	rocuronium	Dosage	Genotype CC is associated with decreased dose of rocuronium in women as compared to genotypes CT + TT.	PMID:33676726

Binding affinities (BindingDB)

17 measured of 18 human assays (19 total across all organisms); most potent 17 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4866117	IC50	700 nM
CHEMBL439677	IC50	800 nM
CHEMBL4877746	IC50	800 nM
CHEMBL4853313	IC50	800 nM
CHEMBL4876955	IC50	1200 nM
CHEMBL4867746	IC50	3200 nM
CHEMBL4861462	IC50	3300 nM
CHEMBL4861649	IC50	3400 nM
CHEMBL4862006	IC50	3500 nM
CHEMBL4867456	IC50	3500 nM
CHEMBL4871404	IC50	3500 nM
CHEMBL75390	IC50	3700 nM
CHEMBL4876866	IC50	3900 nM
CHEMBL4877898	IC50	4400 nM
CHEMBL5272189	IC50	8000 nM
CHEMBL4878532	IC50	8500 nM
CHEMBL4856745	IC50	9500 nM

ChEMBL bioactivities

18 potent at pChembl≥5 of 18 total, top 18 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.16	IC50	700	nM	CHEMBL4866117
6.10	IC50	800	nM	CHEMBL439677
6.10	IC50	800	nM	CHEMBL4877746
6.10	IC50	800	nM	CHEMBL4853313
5.92	IC50	1200	nM	CHEMBL4876955
5.50	IC50	3200	nM	CHEMBL4867746
5.48	IC50	3300	nM	CHEMBL4861462
5.47	IC50	3400	nM	CHEMBL4861649
5.46	IC50	3500	nM	CHEMBL4862006
5.46	IC50	3500	nM	CHEMBL4867456
5.46	IC50	3500	nM	CHEMBL4871404
5.43	IC50	3700	nM	CHEMBL75390
5.41	IC50	3900	nM	CHEMBL4876866
5.36	IC50	4400	nM	CHEMBL4877898
5.11	IC50	7800	nM	MORIN
5.10	IC50	8000	nM	CHEMBL5272189
5.07	IC50	8500	nM	CHEMBL4878532
5.02	IC50	9500	nM	CHEMBL4856745

PubChem BioAssay actives

18 with measured affinity, of 45 total; 18 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(E)-1-(2,3-dihydroxyphenyl)hept-1-en-3-one	1775270: Inhibition of islet amyloid polypeptide (unknown origin) aggregation after 24 hrs by thioflavin T based fluorescence assay	ic50	0.7000	uM
(E)-4-(2,3-dihydroxyphenyl)but-3-en-2-one	1775270: Inhibition of islet amyloid polypeptide (unknown origin) aggregation after 24 hrs by thioflavin T based fluorescence assay	ic50	0.8000	uM
(E)-1-(2,3-dihydroxyphenyl)pent-1-en-3-one	1775270: Inhibition of islet amyloid polypeptide (unknown origin) aggregation after 24 hrs by thioflavin T based fluorescence assay	ic50	0.8000	uM
(E)-1-(2,3-dihydroxyphenyl)hex-1-en-3-one	1775270: Inhibition of islet amyloid polypeptide (unknown origin) aggregation after 24 hrs by thioflavin T based fluorescence assay	ic50	0.8000	uM
(E)-1-(3,4-dihydroxyphenyl)-7-(2-hydroxyphenyl)hept-1-en-3-one	1775270: Inhibition of islet amyloid polypeptide (unknown origin) aggregation after 24 hrs by thioflavin T based fluorescence assay	ic50	1.2000	uM
(E)-1-(3,4-dihydroxyphenyl)hept-1-en-3-one	1775270: Inhibition of islet amyloid polypeptide (unknown origin) aggregation after 24 hrs by thioflavin T based fluorescence assay	ic50	3.2000	uM
1-(2,3-dihydroxyphenyl)hexan-3-one	1775270: Inhibition of islet amyloid polypeptide (unknown origin) aggregation after 24 hrs by thioflavin T based fluorescence assay	ic50	3.3000	uM
1-(2,3-dihydroxyphenyl)heptan-3-one	1775270: Inhibition of islet amyloid polypeptide (unknown origin) aggregation after 24 hrs by thioflavin T based fluorescence assay	ic50	3.4000	uM
(E)-1-(3,4-dihydroxyphenyl)hex-1-en-3-one	1775270: Inhibition of islet amyloid polypeptide (unknown origin) aggregation after 24 hrs by thioflavin T based fluorescence assay	ic50	3.5000	uM
4-(2,3-dihydroxyphenyl)butan-2-one	1775270: Inhibition of islet amyloid polypeptide (unknown origin) aggregation after 24 hrs by thioflavin T based fluorescence assay	ic50	3.5000	uM
1-(3,4-dihydroxyphenyl)heptan-3-one	1775270: Inhibition of islet amyloid polypeptide (unknown origin) aggregation after 24 hrs by thioflavin T based fluorescence assay	ic50	3.5000	uM
(E)-4-(3,4-dihydroxyphenyl)but-3-en-2-one	1775270: Inhibition of islet amyloid polypeptide (unknown origin) aggregation after 24 hrs by thioflavin T based fluorescence assay	ic50	3.7000	uM
1-(2,3-dihydroxyphenyl)pentan-3-one	1775270: Inhibition of islet amyloid polypeptide (unknown origin) aggregation after 24 hrs by thioflavin T based fluorescence assay	ic50	3.9000	uM
(E)-1-(3,4-dihydroxyphenyl)pent-1-en-3-one	1775270: Inhibition of islet amyloid polypeptide (unknown origin) aggregation after 24 hrs by thioflavin T based fluorescence assay	ic50	4.4000	uM
2-(2,4-dihydroxyphenyl)-3,5,7-trihydroxychromen-4-one	1775270: Inhibition of islet amyloid polypeptide (unknown origin) aggregation after 24 hrs by thioflavin T based fluorescence assay	ic50	7.8000	uM
2-[[3-acetamido-6-[[2-(carboxymethoxy)-6-[[2-(carboxymethoxy)-6-[[2-(carboxymethoxy)-6-[[2-(carboxymethoxy)-6-methoxycarbonyl-3-pyridinyl]carbamoyl]-3-pyridinyl]carbamoyl]-3-pyridinyl]carbamoyl]-3-pyridinyl]carbamoyl]-2-pyridinyl]oxy]acetic acid	1937856: Inhibition of islet amyloid polypeptide (unknown origin) aggregation	ic50	8.0000	uM
1-(3,4-dihydroxyphenyl)hexan-3-one	1775270: Inhibition of islet amyloid polypeptide (unknown origin) aggregation after 24 hrs by thioflavin T based fluorescence assay	ic50	8.5000	uM
1-(3,4-dihydroxyphenyl)pentan-3-one	1775270: Inhibition of islet amyloid polypeptide (unknown origin) aggregation after 24 hrs by thioflavin T based fluorescence assay	ic50	9.5000	uM

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Copper	increases abundance, affects binding, decreases reaction, increases expression, increases chemical synthesis (+6 more)	2
propionaldehyde	decreases expression	1
bisphenol A	increases methylation	1
trichostatin A	increases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases phosphorylation, increases expression, increases reaction, affects cotreatment	1
N,N’-bis(salicylideneamino)ethane-manganese(II)	decreases metabolic processing	1
kukoamine A	affects binding, decreases reaction	1
2-palmitoylglycerol	increases expression	1
EUK-134	decreases metabolic processing	1
kukoamine B	affects binding, decreases reaction	1
Rosiglitazone	increases reaction, increases secretion, affects cotreatment, decreases reaction, increases phosphorylation (+1 more)	1
Glucose	decreases reaction, increases secretion	1
Glutathione	affects cotreatment, decreases reaction, increases abundance	1
Hydrogen Peroxide	decreases abundance, increases chemical synthesis, increases reaction, affects cotreatment, decreases reaction (+1 more)	1
Tretinoin	affects expression	1
Valproic Acid	decreases expression	1
Zinc	affects degradation, affects reaction	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

21 unique, capped per target: 21 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1918760	Binding	Inhibition of IAPP fibril formation assessed as fold increase in lag time for aggregate formation at 1:10 protein to compound ratio by thioflavin T fluorescence assay relative to untreated control	Sugar-based peptidomimetics inhibit amyloid β-peptide aggregation. — *Eur J Med Chem*

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for IAPP across ~30M SureChEMBL compounds — explore on Sugi Predict.