Endocrine pancreas disorder

Summary

Endocrine pancreas disorder (MONDO:0001933) is a disease (an umbrella term covering 12 Mondo subtypes) with 1 cohort gene (1 GWAS associations across 1 studies) and 3 clinical trials.

At a glance

• Umbrella term: 12 Mondo subtypes
• Cohort genes: 1
• GWAS associations: 1
• ClinVar variants: 1
• Clinical trials: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	endocrine pancreas disorder
Mondo ID	MONDO:0001933
DOID	DOID:1428
NCIT	C27067
SNOMED CT	17346000
UMLS	C0271633
MedGen	124407
Anatomy (UBERON)	UBERON:0000016
Is cancer (heuristic)	no

Also known as: disease of endocrine pancreas · disease or disorder of endocrine pancreas · disorder of endocrine pancreas · endocrine pancreas disease · endocrine pancreas disease or disorder · endocrine pancreas disorder

Data availability: 1 ClinVar variant · 1 GWAS association (1 study).

Disease family

An umbrella term covering 12 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › digestive system disorder › pancreas disorder › endocrine pancreas disorder

Related subtypes (13): pancreatic steatorrhea, pancreatic mucinous ductal ectasia, exocrine pancreatic insufficiency, pancreatitis, annular pancreas, pancreatic triacylglycerol lipase deficiency, follicular cholangitis and pancreatitis, congenital pancreatic cyst, recurrent acute pancreatitis, accessory pancreas, pancreatic neoplasm, acinar cystic transformation of the pancreas, lymphoepithelial cyst of the pancreas

Subtypes (12): gastrin secretion abnormality, abnormality of glucagon secretion, hyperinsulinism, post-surgical hypoinsulinemia, pancreatic cholera, diabetes mellitus, aggressive insulitis, benign insulitis, pancreatic neuroendocrine neoplasm, islet cell adenomatosis, insulin-resistance syndrome type A, insulin-resistance syndrome type B

Genetics & variants

GWAS landscape

1 GWAS associations across 1 studies. Top hits map to 1 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs113993960	1e-16	CFTR	?	7.37

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90837496	Koyama S	2025	0	0	Genetics and context for precision health in Greater Boston.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	1
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	0

MAF distribution

Bucket	Variants
common (>=0.05)	1
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
inframe_insertion	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs113993960	7	117559591	ATCT>A,ATCTTCT	0.05	inframe_insertion	CFTR	1e-16	Tier 1: coding

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
4074953	NM_002734.5(PRKAR1A):c.561C>G (p.Asn187Lys)	PRKAR1A	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 6 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRKAR1A	Orphanet:1359	Carney complex
PRKAR1A	Orphanet:1501	Adrenocortical carcinoma
PRKAR1A	Orphanet:520	Acute promyelocytic leukemia
PRKAR1A	Orphanet:615	Familial atrial myxoma
PRKAR1A	Orphanet:647772	Isolated primary pigmented nodular adrenocortical disease
PRKAR1A	Orphanet:950	Acrodysostosis

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PRKAR1A	HGNC:9388	ENSG00000108946	P10644	cAMP-dependent protein kinase type I-alpha regulatory subunit	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PRKAR1A	cAMP-dependent protein kinase type I-alpha regulatory subunit	Regulatory subunit of the cAMP-dependent protein kinases involved in cAMP signaling in cells.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PRKAR1A	Other/Unknown	no		cNMP-bd_dom, cAMP_dep_PK_reg_su_I/II_a/b, cAMP_dep_PK_reg_su

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
germinal epithelium of ovary	1
lateral nuclear group of thalamus	1
mucosa of paranasal sinus	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PRKAR1A	295	ubiquitous	marker	mucosa of paranasal sinus, germinal epithelium of ovary, lateral nuclear group of thalamus

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRKAR1A	3,586

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PRKAR1A	P10644	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 52. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
ALK mutants bind TKIs	1	951.7×	0.008	PRKAR1A
CREB1 phosphorylation through the activation of Adenylate Cyclase	1	878.5×	0.008	PRKAR1A
PKA activation in glucagon signalling	1	671.8×	0.008	PRKAR1A
PKA activation	1	634.4×	0.008	PRKAR1A
PKA-mediated phosphorylation of CREB	1	571.0×	0.008	PRKAR1A
DARPP-32 events	1	475.8×	0.008	PRKAR1A
Anti-inflammatory response favouring Leishmania parasite infection	1	393.8×	0.008	PRKAR1A
Leishmania parasite growth and survival	1	393.8×	0.008	PRKAR1A
Calmodulin induced events	1	380.7×	0.008	PRKAR1A
CaM pathway	1	380.7×	0.008	PRKAR1A
Ca-dependent events	1	368.4×	0.008	PRKAR1A
Aquaporin-mediated transport	1	368.4×	0.008	PRKAR1A
Glucagon signaling in metabolic regulation	1	346.1×	0.008	PRKAR1A
G-protein mediated events	1	326.3×	0.008	PRKAR1A
DAG and IP3 signaling	1	317.2×	0.008	PRKAR1A
Response of endothelial cells to shear stress	1	300.5×	0.008	PRKAR1A
FCGR3A-mediated IL10 synthesis	1	292.8×	0.008	PRKAR1A
Signaling by ALK in cancer	1	271.9×	0.008	PRKAR1A
Opioid Signalling	1	265.6×	0.008	PRKAR1A
PLC beta mediated events	1	265.6×	0.008	PRKAR1A
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	1	265.6×	0.008	PRKAR1A
Vasopressin regulates renal water homeostasis via Aquaporins	1	265.6×	0.008	PRKAR1A
Cellular responses to mechanical stimuli	1	259.6×	0.008	PRKAR1A
ADORA2B mediated anti-inflammatory cytokines production	1	253.8×	0.008	PRKAR1A
GPER1 signaling	1	248.3×	0.008	PRKAR1A
Regulation of insulin secretion	1	219.6×	0.009	PRKAR1A
Post NMDA receptor activation events	1	203.9×	0.009	PRKAR1A
Activation of NMDA receptors and postsynaptic events	1	184.2×	0.010	PRKAR1A
Signaling by Hedgehog	1	184.2×	0.010	PRKAR1A
Hedgehog ‘off’ state	1	178.4×	0.010	PRKAR1A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
negative regulation of activated T cell proliferation	1	1053.2×	0.004	PRKAR1A
cellular response to glucagon stimulus	1	842.6×	0.004	PRKAR1A
vascular endothelial cell response to laminar fluid shear stress	1	732.7×	0.004	PRKAR1A
negative regulation of inflammatory response to antigenic stimulus	1	601.9×	0.004	PRKAR1A
negative regulation of cAMP/PKA signal transduction	1	601.9×	0.004	PRKAR1A
cardiac muscle cell proliferation	1	581.1×	0.004	PRKAR1A
renal water homeostasis	1	510.7×	0.004	PRKAR1A
mesoderm formation	1	495.6×	0.004	PRKAR1A
sarcomere organization	1	383.0×	0.004	PRKAR1A
positive regulation of insulin secretion	1	255.3×	0.006	PRKAR1A
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1	113.1×	0.012	PRKAR1A
chemical synaptic transmission	1	77.3×	0.016	PRKAR1A
negative regulation of gene expression	1	69.1×	0.017	PRKAR1A
intracellular signal transduction	1	38.1×	0.028	PRKAR1A
regulation of transcription by RNA polymerase II	1	11.7×	0.086	PRKAR1A

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PRKAR1A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PRKAR1A	2	Binding:2

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	PRKAR1A

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PRKAR1A	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 3.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02872571	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Evaluation of the Efficacy of Intramuscular Islet Autograft After Extensive Pancreatectomy
NCT02175459	Not specified	RECRUITING	Investigating Predictive Factors of Diabetes Occurence After Duodenalpancreatectomy
NCT03775681	Not specified	COMPLETED	Feasibility of Laryngeal Mask Airway Gastro on Patients Undergoing Endoscopic Retrograde Cholangiopancreatography for Pancreas and Bile Duct Disorders