Familial isolated pituitary adenoma

Summary

Familial isolated pituitary adenoma (MONDO:0017824) is a cancer (an umbrella term covering 6 Mondo subtypes) with 3 cohort genes (2 CIViC-evidence somatic drivers; 25 ClinVar predisposition records) and 2 clinical trials.

At a glance

• Classification: Cancer
• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Umbrella term: 6 Mondo subtypes
• Cohort genes: 3
• ClinVar variants: 25
• Clinical trials: 2

Clinical features

Epidemiology

Prevalence records

1 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		150	Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	familial isolated pituitary adenoma
Mondo ID	MONDO:0017824
OMIM	102200
Orphanet	314777
SNOMED CT	702375004
UMLS	C2676191
MedGen	436629
GARD	0010959
Is cancer (heuristic)	yes

Also known as: FIPA

Data availability: 25 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 6 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › epithelial neoplasm › adenoma › pituitary gland adenoma › familial isolated pituitary adenoma

Related subtypes (8): functioning pituitary gland adenoma, pituitary gland mixed eosinophil-basophil adenoma, ACTH-producing pituitary gland adenoma, growth hormone-producing pituitary gland adenoma, pituitary gland acidophil adenoma, pituitary gland basophil adenoma, chromophobe adenoma, non-functioning pituitary adenoma

Subtypes (6): growth hormone secreting pituitary adenoma 1, Cushing disease due to pituitary adenoma, pituitary adenoma, growth hormone-secreting, 2, prolactin-producing pituitary gland adenoma, pituitary adenoma 5, multiple types, pituitary adenoma 3, multiple types

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

25 retrieved; paginated sample, class counts are floors:

14 conflicting classifications of pathogenicity, 7 uncertain significance, 1 benign/likely benign, 1 likely pathogenic, 1 likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
41210	NM_003977.4(AIP):c.811C>T (p.Arg271Trp)	AIP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
253315	NM_003977.4(AIP):c.3G>A (p.Met1Ile)	AIP	Likely pathogenic	criteria provided, single submitter
1104093	NM_003977.4(AIP):c.787+10G>A	AIP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
41184	NM_003977.4(AIP):c.47G>A (p.Arg16His)	AIP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
41214	NM_003977.4(AIP):c.896C>T (p.Ala299Val)	AIP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
485053	NM_003977.4(AIP):c.382C>T (p.Arg128Cys)	AIP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
485063	NM_003977.4(AIP):c.967C>T (p.Arg323Trp)	AIP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
759986	NM_003977.4(AIP):c.692C>T (p.Thr231Met)	AIP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
218628	NM_004304.5(ALK):c.3271G>A (p.Asp1091Asn)	ALK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
335707	NM_004304.5(ALK):c.1550A>G (p.His517Arg)	ALK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
404335	NM_004304.5(ALK):c.3160G>A (p.Gly1054Ser)	ALK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
404367	NM_004304.5(ALK):c.3115G>A (p.Val1039Met)	ALK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
470745	NM_004304.5(ALK):c.1283-5T>C	ALK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
576618	NM_004304.5(ALK):c.2194G>A (p.Asp732Asn)	ALK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
580080	NM_004304.5(ALK):c.1582G>A (p.Ala528Thr)	ALK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
620627	NM_004304.5(ALK):c.2633-3C>T	ALK	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1023999	NM_003977.4(AIP):c.662C>T (p.Pro221Leu)	AIP	Uncertain significance	criteria provided, multiple submitters, no conflicts
823287	NM_003977.4(AIP):c.949G>T (p.Asp317Tyr)	AIP	Uncertain significance	criteria provided, multiple submitters, no conflicts
470743	NM_004304.5(ALK):c.1193A>G (p.Asn398Ser)	ALK	Uncertain significance	criteria provided, multiple submitters, no conflicts
538198	NM_004304.5(ALK):c.1517T>C (p.Leu506Pro)	ALK	Uncertain significance	criteria provided, multiple submitters, no conflicts
620599	NM_004304.5(ALK):c.164C>A (p.Ala55Glu)	ALK	Uncertain significance	criteria provided, single submitter
869193	NM_002070.4(GNAI2):c.879G>A (p.Gly293=)	GNAI2	Uncertain significance	criteria provided, single submitter
1794793	NM_003977.4(AIP):c.268T>C (p.Cys90Arg)	LOC130006206	Uncertain significance	criteria provided, multiple submitters, no conflicts
253316	NM_003977.4(AIP):c.469-17T>C	AIP	Likely benign	criteria provided, single submitter
239829	NM_004304.5(ALK):c.3837-9_3837-7dup	ALK	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 14 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
ALK	Act	BRCA,HCC,NBL,NSCLC,PROSTATE,SCLC	CIViC #1
GNAI2	Act	NHL	CIViC #2312

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
ALK	Orphanet:146	Differentiated thyroid carcinoma
ALK	Orphanet:178342	Inflammatory myofibroblastic tumor
ALK	Orphanet:251877	Ganglioneuroblastoma
ALK	Orphanet:251992	Ganglioneuroma
ALK	Orphanet:300895	ALK-positive anaplastic large cell lymphoma
ALK	Orphanet:364043	ALK-positive large B-cell lymphoma
ALK	Orphanet:626	Large/giant congenital melanocytic nevus
ALK	Orphanet:635	Neuroblastoma

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
ALK	HGNC:427	ENSG00000171094	Q9UM73	ALK tyrosine kinase receptor	clinvar
GNAI2	HGNC:4385	ENSG00000114353	P04899	Guanine nucleotide-binding protein G(i) subunit alpha-2	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.
ALK	ALK tyrosine kinase receptor	Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system.
GNAI2	Guanine nucleotide-binding protein G(i) subunit alpha-2	Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Kinase	1	9.2×	0.209
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AIP	Other/Unknown	no		PPIase_FKBP_dom, TPR-like_helical_dom_sf, TPR_rpt
ALK	Kinase	yes	2.7.10.1	Prot_kinase_dom, MAM_dom, Ser-Thr/Tyr_kinase_cat_dom
GNAI2	Other/Unknown	no		Gprotein_alpha_su, Gprotein_alpha_I, GproteinA_insert

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
male germ cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
sperm	1
monocyte	1
right lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AIP	241	ubiquitous	marker	granulocyte, popliteal artery, tibial artery
ALK	181	broad	marker	sperm, male germ cell, male germ line stem cell (sensu Vertebrata) in testis
GNAI2	291	ubiquitous	marker	granulocyte, monocyte, right lung

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ALK	4,792
GNAI2	3,311
AIP	1,268

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ALK	Q9UM73	79
GNAI2	P04899	34
AIP	O00170	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 37. 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
Drug resistance of ALK mutants	1	3806.7×	0.001	ALK
ASP-3026-resistant ALK mutants	1	3806.7×	0.001	ALK
NVP-TAE684-resistant ALK mutants	1	3806.7×	0.001	ALK
alectinib-resistant ALK mutants	1	3806.7×	0.001	ALK
brigatinib-resistant ALK mutants	1	3806.7×	0.001	ALK
ceritinib-resistant ALK mutants	1	3806.7×	0.001	ALK
crizotinib-resistant ALK mutants	1	3806.7×	0.001	ALK
lorlatinib-resistant ALK mutants	1	3806.7×	0.001	ALK
MDK and PTN in ALK signaling	1	951.7×	0.004	ALK
Aryl hydrocarbon receptor signalling	1	634.4×	0.006	AIP
ALK mutants bind TKIs	1	317.2×	0.011	ALK
Adenylate cyclase inhibitory pathway	1	253.8×	0.012	GNAI2
Signaling by ALK	1	190.3×	0.015	ALK
ADP signalling through P2Y purinoceptor 12	1	165.5×	0.016	GNAI2
Interleukin-12 family signaling	1	158.6×	0.016	AIP
Interleukin-12 signaling	1	135.9×	0.017	AIP
Adrenaline,noradrenaline inhibits insulin secretion	1	131.3×	0.017	GNAI2
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	100.2×	0.020	AIP
Signaling by ALK in cancer	1	90.6×	0.021	ALK
ADORA2B mediated anti-inflammatory cytokines production	1	84.6×	0.021	GNAI2
GPER1 signaling	1	82.8×	0.021	GNAI2
G alpha (z) signalling events	1	77.7×	0.021	GNAI2
Phase I - Functionalization of compounds	1	73.2×	0.021	AIP
Regulation of insulin secretion	1	73.2×	0.021	GNAI2
Extra-nuclear estrogen signaling	1	56.8×	0.026	GNAI2
Signaling by ALK fusions and activated point mutants	1	50.1×	0.028	ALK
Biological oxidations	1	43.3×	0.031	AIP
G alpha (s) signalling events	1	24.4×	0.053	GNAI2
Signaling by Interleukins	1	21.4×	0.059	AIP
Diseases of signal transduction by growth factor receptors and second messengers	1	18.9×	0.064	ALK

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
response to environmental enrichment	1	2808.7×	0.008	ALK
regulation of dopamine receptor signaling pathway	1	1404.3×	0.008	ALK
swimming behavior	1	1123.5×	0.008	ALK
G protein-coupled adenosine receptor signaling pathway	1	802.5×	0.008	GNAI2
response to stress	1	802.5×	0.008	ALK
negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway	1	802.5×	0.008	GNAI2
peptidyl-tyrosine autophosphorylation	1	624.1×	0.008	ALK
negative regulation of calcium ion-dependent exocytosis	1	624.1×	0.008	GNAI2
negative regulation of synaptic transmission	1	561.7×	0.008	GNAI2
negative regulation of adenylate cyclase activity	1	468.1×	0.008	GNAI2
phosphorylation	1	432.1×	0.008	ALK
positive regulation of urine volume	1	432.1×	0.008	GNAI2
G protein-coupled acetylcholine receptor signaling pathway	1	351.1×	0.009	GNAI2
positive regulation of dendrite development	1	330.4×	0.009	ALK
positive regulation of superoxide anion generation	1	295.6×	0.009	GNAI2
negative regulation of lipid catabolic process	1	280.9×	0.009	ALK
regulation of calcium ion transport	1	267.5×	0.009	GNAI2
positive regulation of neural precursor cell proliferation	1	255.3×	0.009	GNAI2
regulation of neuron differentiation	1	244.2×	0.009	ALK
obsolete protein targeting to mitochondrion	1	193.7×	0.011	AIP
negative regulation of apoptotic signaling pathway	1	187.2×	0.011	GNAI2
gamma-aminobutyric acid signaling pathway	1	181.2×	0.011	GNAI2
adult behavior	1	156.0×	0.012	ALK
positive regulation of vascular associated smooth muscle cell proliferation	1	144.0×	0.013	GNAI2
response to nutrient	1	98.5×	0.018	GNAI2
energy homeostasis	1	90.6×	0.018	ALK
signal transduction	2	10.7×	0.018	ALK, GNAI2
neuron development	1	85.1×	0.018	ALK
hippocampus development	1	77.0×	0.020	ALK
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	1	73.0×	0.020	GNAI2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 2 · Phased (≥1): 3 · Undrugged: 0

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
ALK	CERITINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ALK	61	4
GNAI2	2	3
AIP	1	2

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CERITINIB	4	ALK
BOSUTINIB	4	ALK
CRIZOTINIB	4	ALK
ALECTINIB	4	ALK
ENTRECTINIB	4	ALK
LORLATINIB	4	ALK
GILTERITINIB	4	ALK
OSIMERTINIB	4	ALK
BRIGATINIB	4	ALK
REPOTRECTINIB	4	ALK
FEDRATINIB	4	ALK
RUXOLITINIB	4	ALK
INFIGRATINIB PHOSPHATE	4	ALK
INFIGRATINIB	4	ALK
PALBOCICLIB	4	ALK
VANDETANIB	4	ALK
UPADACITINIB	4	ALK
PAZOPANIB	4	ALK
NINTEDANIB	4	ALK
SUNITINIB	4	ALK
ERLOTINIB	4	ALK
MIDOSTAURIN	4	ALK
DACTOLISIB	3	ALK
LINIFANIB	3	ALK
SEMAXANIB	3	ALK
CANERTINIB	3	ALK
ROCILETINIB	3	ALK
ALVOCIDIB	3	ALK
CEDIRANIB	3	ALK
QUERCETIN	3	ALK

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ALK	1,815	Binding:1801, Functional:13, ADMET:1
AIP	10	Binding:10
GNAI2	9	Binding:9

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ALK	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
ALK	1,815

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)
CERITINIB	4	ALK
BOSUTINIB	4	ALK
CRIZOTINIB	4	ALK
ALECTINIB	4	ALK
ENTRECTINIB	4	ALK
LORLATINIB	4	ALK
GILTERITINIB	4	ALK
OSIMERTINIB	4	ALK
BRIGATINIB	4	ALK
REPOTRECTINIB	4	ALK
FEDRATINIB	4	ALK
RUXOLITINIB	4	ALK
INFIGRATINIB PHOSPHATE	4	ALK
INFIGRATINIB	4	ALK
PALBOCICLIB	4	ALK
VANDETANIB	4	ALK
UPADACITINIB	4	ALK
PAZOPANIB	4	ALK
NINTEDANIB	4	ALK
SUNITINIB	4	ALK
ERLOTINIB	4	ALK
MIDOSTAURIN	4	ALK
DACTOLISIB	3	ALK
LINIFANIB	3	ALK
SEMAXANIB	3	ALK
CANERTINIB	3	ALK
ROCILETINIB	3	ALK
ALVOCIDIB	3	ALK
CEDIRANIB	3	ALK
QUERCETIN	3	ALK

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ALK
B	Phased (≥1) drug, not yet approved	2	AIP, GNAI2
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 2.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00461188	Not specified	RECRUITING	Genetics of Endocrine Tumours - Familial Isolated Pituitary Adenoma - FIPA
NCT06523582	Not specified	RECRUITING	Genetic Bases of Neuroendocrine Neoplasms in Mexican Patients