IAPP

protein-coding

islet amyloid polypeptide, the group of Neuropeptides

Gene summary

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. [provided by RefSeq, Jul 2016]

MANE transcript

NM_000415.3

Inheritance

—

ClinVar variants

U:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.55

Max pathogenic AF

—

Genomic locus

chr12:21,354,959-21,379,980

External References & Databases

Ensembl (ENSG00000121351)

Transcript & Mutation Effects

hg38 • Region Span ~25.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to IAPP variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 4

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000415.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			5 clinvar			5
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	5	0	0	5

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_000415.3	RefSeq	NP_000406.1	2	MANE Select
ENST00000240652.8	Ensembl	ENSP00000240652.3	2	MANE Select
NM_001329201.2	RefSeq	NP_001316130.1	2	Standard
ENST00000535428.1	Ensembl	ENSP00000437559.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Maturity onset diabetes of the young - Homo sapiens (human)
Signaling by GPCR
Signal Transduction
G alpha (s) signalling events
Calcitonin-like ligand receptors

Biological Process

apoptotic process
signal transduction
G protein-coupled receptor signaling pathway
adenylate cyclase-activating G protein-coupled receptor signaling pathway
positive regulation of cytosolic calcium ion concentration

Molecular Function

amyloid-beta binding
signaling receptor binding
hormone activity
protein binding
identical protein binding

Cellular Component

extracellular region
extracellular space
neuronal cell body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000240652
Coding exons: 2
Length: 25020
Individuals with no LoFs: 125586
Homozygous LoFs: 0
Heterozygous LoFs: 40
Defined: 125626
p: 0.000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.197	45	48.9	0.921	0.00000258	571
Missense (PolyPhen)		12	12.38	0.9693		135
Synonymous	0.0836	19	19.5	0.976	9.22e-7	189
Loss of Function	-0.712	3	1.93	1.55	8.13e-8	24

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00025	0.00025	rare
South Asian	0.000033	0.000033	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Selectively inhibits insulin-stimulated glucose utilization and glycogen deposition in muscle, while not affecting adipocyte glucose metabolism.;

Recessive Scores

pRec: 0.256

Intolerance Scores

LoFtool: 0.416
RVIS EVS: -0.14
RVIS percentile EVS: 42.88

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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