Growth hormone secreting pituitary adenoma 1

Summary

Growth hormone secreting pituitary adenoma 1 (MONDO:0007052) is a cancer caused by AIP (GenCC Definitive), with 3 cohort genes (2 CIViC-evidence somatic drivers; 173 ClinVar predisposition records).

At a glance

• Classification: Cancer
• Causal gene: AIP (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 173

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	growth hormone secreting pituitary adenoma 1
Mondo ID	MONDO:0007052
OMIM	102200
DOID	DOID:0112009
UMLS	C4538355
MedGen	1618709
GARD	0024520
Is cancer (heuristic)	yes

Also known as: familial isolated pituitary adenoma syndrome · PAGH1 · PITA1 · pituitary adenoma 1, multiple types, autosomal dominant, somatic mutation · pituitary adenoma predisposition, autosomal dominant, somatic mutation · pituitary adenoma, growth hormone-secreting, 1 · pituitary adenoma, growth hormone-secreting, type 1

Data availability: 173 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › epithelial neoplasm › adenoma › pituitary gland adenoma › growth hormone-producing pituitary gland adenoma › growth hormone secreting pituitary adenoma 1

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

173 retrieved; paginated sample, class counts are floors:

67 uncertain significance, 35 conflicting classifications of pathogenicity, 22 not provided, 15 pathogenic, 10 likely pathogenic, 9 benign, 7 benign/likely benign, 6 likely benign, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2582409	NM_003977.4(AIP):c.504_510del (p.Pro167_Trp168insTer)	AIP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
41167	NM_003977.4(AIP):c.241C>T (p.Arg81Ter)	AIP	Pathogenic	criteria provided, multiple submitters, no conflicts
41179	NM_003977.4(AIP):c.424C>T (p.Gln142Ter)	AIP	Pathogenic	criteria provided, single submitter
41185	NM_003977.4(AIP):c.490C>T (p.Gln164Ter)	AIP	Pathogenic	criteria provided, single submitter
41188	NM_003977.4(AIP):c.550C>T (p.Gln184Ter)	AIP	Pathogenic	criteria provided, single submitter
41194	NM_003977.4(AIP):c.649C>T (p.Gln217Ter)	AIP	Pathogenic	criteria provided, multiple submitters, no conflicts
41196	NM_003977.4(AIP):c.70G>T (p.Glu24Ter)	AIP	Pathogenic	criteria provided, single submitter
41208	NM_003977.4(AIP):c.805_825dup (p.Phe269_His275dup)	AIP	Pathogenic	criteria provided, multiple submitters, no conflicts
41210	NM_003977.4(AIP):c.811C>T (p.Arg271Trp)	AIP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4886	NM_003977.4(AIP):c.40C>T (p.Gln14Ter)	AIP	Pathogenic	criteria provided, multiple submitters, no conflicts
4888	NM_003977.4(AIP):c.910C>T (p.Arg304Ter)	AIP	Pathogenic	criteria provided, multiple submitters, no conflicts
4889	NM_003977.4(AIP):c.66_71del (p.Gly23_Glu24del)	AIP	Pathogenic	no assertion criteria provided
4890	NM_003977.4(AIP):c.824dup (p.His275fs)	AIP	Pathogenic	no assertion criteria provided
4891	NM_003977.4(AIP):c.543del (p.Ile182fs)	AIP	Pathogenic	no assertion criteria provided
4892	NM_003977.4(AIP):c.804C>A (p.Tyr268Ter)	AIP	Pathogenic	criteria provided, multiple submitters, no conflicts
4894	NM_003977.4(AIP):c.64C>T (p.Arg22Ter)	AIP	Pathogenic	no assertion criteria provided
446502	NM_001370259.2(MEN1):c.1831T>A (p.Ter611Arg)	MEN1	Pathogenic	criteria provided, single submitter
424704	NM_003977.3(AIP):c.[-125-145_-125-144delCGinsAA];[-125-95G>A]		Likely pathogenic	no assertion criteria provided
424705	NM_003977.3(AIP):c.[878_879delAGinsGT];[880_891delCTGGACCCAGCC]		Likely pathogenic	no assertion criteria provided
2675412	NM_003977.4(AIP):c.301_423del (p.Val101_Leu141del)	AIP	Likely pathogenic	criteria provided, single submitter
2675420	NM_003977.4(AIP):c.844dup (p.Gln282fs)	AIP	Likely pathogenic	criteria provided, single submitter
41160	NM_003977.2(AIP):c.(?1)(*_?)del	AIP	Likely pathogenic	no assertion criteria provided
41161	NM_003977.4(AIP):c.100-1025_279+357del	AIP	Likely pathogenic	no assertion criteria provided
41197	NM_003977.4(AIP):c.713G>A (p.Cys238Tyr)	AIP	Likely pathogenic	criteria provided, multiple submitters, no conflicts
41203	NM_003977.3(AIP):c.74_81delTCCCGGACins7	AIP	Likely pathogenic	no assertion criteria provided
41158	NC_000011.10:g.67481947_67487763del	LOC130006204	Likely pathogenic	no assertion criteria provided
446503	NM_001370259.2(MEN1):c.*412G>A	MEN1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1022659	NM_003977.4(AIP):c.164C>T (p.Ala55Val)	AIP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1692753	NM_003977.4(AIP):c.476G>A (p.Ser159Asn)	AIP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
305724	NM_003977.4(AIP):c.68G>A (p.Gly23Glu)	AIP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 23 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
GNAS	Act	BRCA,COADREAD,ESCA,HCC,LUAD,MBL,PAAD,PANCREAS	CIViC #2319
MEN1	LoF	ACC,BLCA,BRCA,HCC,LUNG,PANCREAS,PANET,WDTC	CIViC #3485

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
AIP	Definitive	Autosomal dominant	growth hormone secreting pituitary adenoma 1	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
AIP	Orphanet:2965	Prolactinoma
AIP	Orphanet:314777	Familial isolated pituitary adenoma
AIP	Orphanet:314786	Silent pituitary adenoma
AIP	Orphanet:314790	Null pituitary adenoma
AIP	Orphanet:963	Acromegaly
AIP	Orphanet:99725	Pituitary gigantism
GNAS	Orphanet:189427	Cushing syndrome due to bilateral macronodular adrenocortical disease
GNAS	Orphanet:2762	Progressive osseous heteroplasia
GNAS	Orphanet:562	McCune-Albright syndrome
GNAS	Orphanet:57782	Mazabraud syndrome
GNAS	Orphanet:79443	Pseudohypoparathyroidism type 1A
GNAS	Orphanet:79444	Pseudohypoparathyroidism type 1C
GNAS	Orphanet:79445	Pseudopseudohypoparathyroidism
GNAS	Orphanet:93276	Polyostotic fibrous dysplasia
GNAS	Orphanet:93277	Monostotic fibrous dysplasia
GNAS	Orphanet:94089	Pseudohypoparathyroidism type 1B
MEN1	Orphanet:2965	Prolactinoma
MEN1	Orphanet:314786	Silent pituitary adenoma
MEN1	Orphanet:314790	Null pituitary adenoma
MEN1	Orphanet:652	Multiple endocrine neoplasia type 1
MEN1	Orphanet:97279	Insulinoma
MEN1	Orphanet:99725	Pituitary gigantism
MEN1	Orphanet:99879	Familial isolated hyperparathyroidism

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
AIP	HGNC:358	ENSG00000110711	O00170	AH receptor-interacting protein	gencc,clinvar
GNAS	HGNC:4392	ENSG00000087460	O95467	Neuroendocrine secretory protein 55	clinvar
MEN1	HGNC:7010	ENSG00000133895	O00255	Menin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AIP	AH receptor-interacting protein	May play a positive role in AHR-mediated (aromatic hydrocarbon receptor) signaling, possibly by influencing its receptivity for ligand and/or its nuclear targeting.
MEN1	Menin	Essential component of a MLL/SET1 histone methyltransferase (HMT) complex, a complex that specifically methylates ‘Lys-4’ of histone H3 (H3K4).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AIP	Other/Unknown	no		PPIase_FKBP_dom, TPR-like_helical_dom_sf, TPR_rpt
GNAS	Other/Unknown	no		NESP55, Gprotein_alpha_S, Gprotein_alpha_su
MEN1	Other/Unknown	no		Menin

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	2
popliteal artery	1
tibial artery	1
Brodmann (1909) area 46	1
postcentral gyrus	1
type B pancreatic cell	1
lower esophagus mucosa	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AIP	241	ubiquitous	marker	granulocyte, popliteal artery, tibial artery
GNAS	312	ubiquitous	marker	type B pancreatic cell, postcentral gyrus, Brodmann (1909) area 46
MEN1	271	ubiquitous	marker	granulocyte, lower esophagus mucosa, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MEN1	5,226
AIP	1,268
GNAS	410

Intra-cohort edges

A	B	Sources
AIP	MEN1	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GNAS	O95467	490
MEN1	O00255	69
AIP	O00170	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 47. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Aryl hydrocarbon receptor signalling	1	634.4×	0.033	AIP
PKA activation in glucagon signalling	1	223.9×	0.033	GNAS
Prostacyclin signalling through prostacyclin receptor	1	200.3×	0.033	GNAS
Interleukin-12 family signaling	1	158.6×	0.033	AIP
Interleukin-12 signaling	1	135.9×	0.033	AIP
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1	122.8×	0.033	MEN1
Glucagon signaling in metabolic regulation	1	115.3×	0.033	GNAS
Glucagon-type ligand receptors	1	115.3×	0.033	GNAS
RHO GTPases activate IQGAPs	1	115.3×	0.033	MEN1
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	1	102.9×	0.033	MEN1
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	100.2×	0.033	AIP
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	1	88.5×	0.033	GNAS
Vasopressin regulates renal water homeostasis via Aquaporins	1	88.5×	0.033	GNAS
Formation of WDR5-containing histone-modifying complexes	1	88.5×	0.033	MEN1
ADORA2B mediated anti-inflammatory cytokines production	1	84.6×	0.033	GNAS
GPER1 signaling	1	82.8×	0.033	GNAS
Deactivation of the beta-catenin transactivating complex	1	77.7×	0.033	MEN1
G alpha (z) signalling events	1	77.7×	0.033	GNAS
Phase I - Functionalization of compounds	1	73.2×	0.034	AIP
Signaling by TGF-beta Receptor Complex	1	66.8×	0.035	MEN1
Hedgehog ‘off’ state	1	59.5×	0.037	GNAS
High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells	1	53.6×	0.039	GNAS
Epigenetic regulation by WDR5-containing histone modifying complexes	1	51.4×	0.039	MEN1
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	48.8×	0.040	MEN1
Biological oxidations	1	43.3×	0.043	AIP
Formation of the beta-catenin:TCF transactivating complex	1	40.1×	0.043	MEN1
TCF dependent signaling in response to WNT	1	39.2×	0.043	MEN1
Signaling by TGFB family members	1	38.5×	0.043	MEN1
Signaling by WNT	1	37.3×	0.043	MEN1
Post-translational protein phosphorylation	1	33.4×	0.046	MEN1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway	1	1872.4×	0.010	GNAS
response to parathyroid hormone	1	1404.3×	0.010	GNAS
adenylate cyclase-activating serotonin receptor signaling pathway	1	1123.5×	0.010	GNAS
hair follicle placode formation	1	1123.5×	0.010	GNAS
regulation of skeletal muscle contraction	1	936.2×	0.010	GNAS
cellular response to catecholamine stimulus	1	802.5×	0.010	GNAS
negative regulation of cyclin-dependent protein serine/threonine kinase activity	1	702.2×	0.010	MEN1
T-helper 2 cell differentiation	1	624.1×	0.010	MEN1
adenylate cyclase-activating dopamine receptor signaling pathway	1	510.7×	0.010	GNAS
intracellular transport	1	510.7×	0.010	GNAS
response to prostaglandin E	1	468.1×	0.010	GNAS
adenylate cyclase-activating adrenergic receptor signaling pathway	1	401.2×	0.010	GNAS
activation of adenylate cyclase activity	1	374.5×	0.010	GNAS
sensory perception of chemical stimulus	1	374.5×	0.010	GNAS
negative regulation of multicellular organism growth	1	374.5×	0.010	GNAS
osteoblast development	1	330.4×	0.010	MEN1
cellular response to glucagon stimulus	1	280.9×	0.010	GNAS
cellular response to prostaglandin E stimulus	1	280.9×	0.010	GNAS
obsolete negative regulation of DNA-binding transcription factor activity	1	244.2×	0.010	MEN1
developmental growth	1	244.2×	0.010	GNAS
cellular response to acidic pH	1	244.2×	0.010	GNAS
vascular endothelial cell response to laminar fluid shear stress	1	244.2×	0.010	GNAS
negative regulation of inflammatory response to antigenic stimulus	1	200.6×	0.011	GNAS
intracellular glucose homeostasis	1	193.7×	0.011	GNAS
negative regulation of protein phosphorylation	1	193.7×	0.011	MEN1
obsolete protein targeting to mitochondrion	1	193.7×	0.011	AIP
response to gamma radiation	1	193.7×	0.011	MEN1
negative regulation of JNK cascade	1	187.2×	0.011	MEN1
positive regulation of transforming growth factor beta receptor signaling pathway	1	175.5×	0.011	MEN1
renal water homeostasis	1	170.2×	0.011	GNAS

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 2 · Undrugged: 1

Druggability breadth: 3 of 3 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
MEN1	LOPERAMIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MEN1	475	4
AIP	1	2
GNAS	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
LOPERAMIDE	4	MEN1
CANDESARTAN CILEXETIL	4	MEN1
EVANS BLUE FREE ACID	4	MEN1
DIENESTROL	4	MEN1
BEXAROTENE	4	MEN1
IFOSFAMIDE	4	MEN1
PROGESTERONE	4	MEN1
CLOTRIMAZOLE	4	MEN1
AMINOCAPROIC ACID	4	MEN1
LATANOPROST	4	MEN1
FLUORESCEIN	4	MEN1
OXCARBAZEPINE	4	MEN1
SALMETEROL XINAFOATE	4	MEN1
AMIODARONE HYDROCHLORIDE	4	MEN1
TRICLABENDAZOLE	4	MEN1
TRYPAN BLUE FREE ACID	4	MEN1
MIGALASTAT	4	MEN1
DROPERIDOL	4	MEN1
ARIPIPRAZOLE	4	MEN1
AMOXAPINE	4	MEN1
RALOXIFENE HYDROCHLORIDE	4	MEN1
IDARUBICIN	4	MEN1
ACETAMINOPHEN	4	MEN1
OXYBUTYNIN CHLORIDE	4	MEN1
DECAMETHONIUM BROMIDE	4	MEN1
DESLORATADINE	4	MEN1
DITHIAZANINE	4	MEN1
TRIMETREXATE	4	MEN1
NICARDIPINE HYDROCHLORIDE	4	MEN1
PROTRIPTYLINE HYDROCHLORIDE	4	MEN1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
MEN1	93	Binding:86, Functional:7
AIP	10	Binding:10

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

30 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
LOPERAMIDE	4	MEN1
CANDESARTAN CILEXETIL	4	MEN1
EVANS BLUE FREE ACID	4	MEN1
DIENESTROL	4	MEN1
BEXAROTENE	4	MEN1
IFOSFAMIDE	4	MEN1
PROGESTERONE	4	MEN1
CLOTRIMAZOLE	4	MEN1
AMINOCAPROIC ACID	4	MEN1
LATANOPROST	4	MEN1
FLUORESCEIN	4	MEN1
OXCARBAZEPINE	4	MEN1
SALMETEROL XINAFOATE	4	MEN1
AMIODARONE HYDROCHLORIDE	4	MEN1
TRICLABENDAZOLE	4	MEN1
TRYPAN BLUE FREE ACID	4	MEN1
MIGALASTAT	4	MEN1
DROPERIDOL	4	MEN1
ARIPIPRAZOLE	4	MEN1
AMOXAPINE	4	MEN1
RALOXIFENE HYDROCHLORIDE	4	MEN1
IDARUBICIN	4	MEN1
ACETAMINOPHEN	4	MEN1
OXYBUTYNIN CHLORIDE	4	MEN1
DECAMETHONIUM BROMIDE	4	MEN1
DESLORATADINE	4	MEN1
DITHIAZANINE	4	MEN1
TRIMETREXATE	4	MEN1
NICARDIPINE HYDROCHLORIDE	4	MEN1
PROTRIPTYLINE HYDROCHLORIDE	4	MEN1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	MEN1
B	Phased (≥1) drug, not yet approved	1	AIP
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	GNAS

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)
GNAS	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.