Pituitary adenoma 5, multiple types

Summary

Pituitary adenoma 5, multiple types (MONDO:0054601) is a cancer with 5 cohort genes (1 CIViC-evidence somatic driver; 422 ClinVar predisposition records).

At a glance

• Classification: Cancer
• Cohort genes: 5
• ClinVar variants: 422

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pituitary adenoma 5, multiple types
Mondo ID	MONDO:0054601
OMIM	617540
DOID	DOID:0112008
UMLS	C4539685
MedGen	1615593
GARD	0025954
Is cancer (heuristic)	yes

Also known as: PITA5 · pituitary adenoma 5, multiple types

Data availability: 422 ClinVar variants.

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 › familial isolated pituitary adenoma › pituitary adenoma 5, multiple types

Related subtypes (5): 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 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

422 retrieved; paginated sample, class counts are floors:

125 likely pathogenic, 108 uncertain significance, 78 pathogenic/likely pathogenic, 43 conflicting classifications of pathogenicity, 39 pathogenic, 12 benign/likely benign, 11 benign, 6 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1073637	NM_022124.6(CDH23):c.3655C>T (p.Arg1219Ter)	C10orf105	Pathogenic	criteria provided, multiple submitters, no conflicts
1458365	NM_022124.6(CDH23):c.3579+2T>C	C10orf105	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2136882	NM_022124.6(CDH23):c.3862C>T (p.Gln1288Ter)	C10orf105	Pathogenic	criteria provided, multiple submitters, no conflicts
2680507	NM_022124.6(CDH23):c.3769G>T (p.Glu1257Ter)	C10orf105	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
45920	NM_022124.6(CDH23):c.3481C>T (p.Arg1161Ter)	C10orf105	Pathogenic	criteria provided, multiple submitters, no conflicts
4923	NM_022124.6(CDH23):c.4021G>A (p.Asp1341Asn)	C10orf105	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
521399	NM_022124.6(CDH23):c.3241C>T (p.Arg1081Ter)	C10orf105	Pathogenic	criteria provided, multiple submitters, no conflicts
644005	NM_022124.6(CDH23):c.4105-4_4105-2delinsTCT	C10orf105	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1065907	NM_022124.6(CDH23):c.871G>A (p.Gly291Arg)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068626	NM_022124.6(CDH23):c.2349C>G (p.Tyr783Ter)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068921	NM_022124.6(CDH23):c.8383C>T (p.Arg2795Ter)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069075	NM_022124.6(CDH23):c.9254del (p.Leu3085fs)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070502	NM_022124.6(CDH23):c.5300_5303dup (p.His1769fs)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071895	NM_022124.6(CDH23):c.8432G>A (p.Trp2811Ter)	CDH23	Pathogenic	criteria provided, multiple submitters, no conflicts
1072295	NM_022124.6(CDH23):c.871G>T (p.Gly291Ter)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1180612	NM_022124.6(CDH23):c.4562A>G (p.Asn1521Ser)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1357019	NM_022124.6(CDH23):c.1143_1176del	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1393120	NM_022124.6(CDH23):c.9280_9286del	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1406663	NM_022124.6(CDH23):c.7274_7275del (p.Thr2425fs)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1450996	NM_022124.6(CDH23):c.8054_8055del (p.Ala2685fs)	CDH23	Pathogenic	criteria provided, multiple submitters, no conflicts
1453264	NM_022124.6(CDH23):c.856del (p.Leu286fs)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454111	NM_022124.6(CDH23):c.7210C>T (p.Gln2404Ter)	CDH23	Pathogenic	criteria provided, multiple submitters, no conflicts
1457546	NM_022124.6(CDH23):c.5125del (p.Thr1708_Leu1709insTer)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1457569	NM_022124.6(CDH23):c.6307G>T (p.Glu2103Ter)	CDH23	Pathogenic	criteria provided, multiple submitters, no conflicts
1460205	NM_022124.6(CDH23):c.1735C>T (p.Gln579Ter)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
162876	NM_022124.6(CDH23):c.945+1G>T	CDH23	Pathogenic	criteria provided, multiple submitters, no conflicts
1687042	NM_022124.6(CDH23):c.805C>T (p.Arg269Trp)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
178309	NM_022124.6(CDH23):c.6050-15G>A	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2014525	NM_022124.6(CDH23):c.2476del (p.Leu826fs)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2017022	NM_022124.6(CDH23):c.1891C>T (p.Gln631Ter)	CDH23	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 19 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
MEN1	LoF	ACC,BLCA,BRCA,HCC,LUNG,PANCREAS,PANET,WDTC	CIViC #3485

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDH23	Orphanet:231169	Usher syndrome type 1
CDH23	Orphanet:2965	Prolactinoma
CDH23	Orphanet:314777	Familial isolated pituitary adenoma
CDH23	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB
CDH23	Orphanet:91347	TSH-secreting pituitary adenoma
CDH23	Orphanet:96253	Cushing 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
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

5 cohort genes, 4 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CDH23	HGNC:13733	ENSG00000107736	Q9H251	Cadherin-23	clinvar
C10orf105	HGNC:20304	ENSG00000214688	Q8TEF2	Uncharacterized protein C10orf105	clinvar
CDH23-AS1	HGNC:31433	ENSG00000223817		CDH23 antisense RNA 1	clinvar
AIP	HGNC:358	ENSG00000110711	O00170	AH receptor-interacting protein	clinvar
MEN1	HGNC:7010	ENSG00000133895	O00255	Menin	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDH23	Cadherin-23	Cadherins are calcium-dependent cell adhesion proteins.
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: 5 · 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	5	1.8×	0.054

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CDH23	Other/Unknown	no		Cadherin-like_dom, Cadherin-like_sf, Cadherin_CS
C10orf105	Other/Unknown	no		DUF5527
CDH23-AS1	Other/Unknown	no
AIP	Other/Unknown	no		PPIase_FKBP_dom, TPR-like_helical_dom_sf, TPR_rpt
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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
blood	2
granulocyte	2
left ovary	1
right ovary	1
ventricular zone	1
cerebellar vermis	1
quadriceps femoris	1
monocyte	1
thoracic mammary gland	1
popliteal artery	1
tibial artery	1
lower esophagus mucosa	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDH23	161	broad	marker	ventricular zone, left ovary, right ovary
C10orf105	107	tissue_specific	yes	quadriceps femoris, blood, cerebellar vermis
CDH23-AS1	51		yes	blood, monocyte, thoracic mammary gland
AIP	241	ubiquitous	marker	granulocyte, popliteal artery, tibial artery
MEN1	271	ubiquitous	marker	granulocyte, lower esophagus mucosa, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MEN1	5,226
CDH23	1,575
AIP	1,268
C10orf105	53
CDH23-AS1	0

Intra-cohort edges

A	B	Sources
AIP	MEN1	string_interaction
C10orf105	CDH23	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 1 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MEN1	O00255	69
CDH23	Q9H251	6
AIP	O00170	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
C10orf105	Q8TEF2	63.46

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 38. Enrichment computed across 5 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×	0.044	AIP
Interleukin-12 family signaling	1	158.6×	0.044	AIP
Interleukin-12 signaling	1	135.9×	0.044	AIP
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1	122.8×	0.044	MEN1
RHO GTPases activate IQGAPs	1	115.3×	0.044	MEN1
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	1	102.9×	0.044	MEN1
Sensory processing of sound	1	102.9×	0.044	CDH23
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	100.2×	0.044	AIP
Formation of WDR5-containing histone-modifying complexes	1	88.5×	0.044	MEN1
Deactivation of the beta-catenin transactivating complex	1	77.7×	0.044	MEN1
Phase I - Functionalization of compounds	1	73.2×	0.044	AIP
Sensory processing of sound by outer hair cells of the cochlea	1	68.0×	0.044	CDH23
Signaling by TGF-beta Receptor Complex	1	66.8×	0.044	MEN1
Sensory processing of sound by inner hair cells of the cochlea	1	54.4×	0.048	CDH23
Epigenetic regulation by WDR5-containing histone modifying complexes	1	51.4×	0.048	MEN1
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	48.8×	0.048	MEN1
Biological oxidations	1	43.3×	0.048	AIP
Formation of the beta-catenin:TCF transactivating complex	1	40.1×	0.048	MEN1
TCF dependent signaling in response to WNT	1	39.2×	0.048	MEN1
Signaling by TGFB family members	1	38.5×	0.048	MEN1
Signaling by WNT	1	37.3×	0.048	MEN1
Post-translational protein phosphorylation	1	33.4×	0.051	MEN1
Sensory Perception	1	31.7×	0.052	CDH23
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	28.8×	0.054	MEN1
Epigenetic regulation of gene expression	1	23.8×	0.063	MEN1
RHO GTPase Effectors	1	22.7×	0.064	MEN1
Signaling by Interleukins	1	21.4×	0.065	AIP
Cytokine Signaling in Immune system	1	13.6×	0.097	AIP
Signaling by Rho GTPases	1	11.4×	0.110	MEN1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	11.2×	0.110	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
equilibrioception	1	802.5×	0.015	CDH23
negative regulation of cyclin-dependent protein serine/threonine kinase activity	1	702.2×	0.015	MEN1
T-helper 2 cell differentiation	1	624.1×	0.015	MEN1
sensory perception of light stimulus	1	624.1×	0.015	CDH23
obsolete cell-cell adhesion via plasma-membrane adhesion molecules	1	374.5×	0.016	CDH23
osteoblast development	1	330.4×	0.016	MEN1
auditory receptor cell stereocilium organization	1	280.9×	0.016	CDH23
obsolete negative regulation of DNA-binding transcription factor activity	1	244.2×	0.016	MEN1
negative regulation of protein phosphorylation	1	193.7×	0.016	MEN1
obsolete protein targeting to mitochondrion	1	193.7×	0.016	AIP
response to gamma radiation	1	193.7×	0.016	MEN1
negative regulation of JNK cascade	1	187.2×	0.016	MEN1
positive regulation of transforming growth factor beta receptor signaling pathway	1	175.5×	0.016	MEN1
calcium-dependent cell-cell adhesion	1	160.5×	0.016	CDH23
cochlea development	1	156.0×	0.016	CDH23
transcription initiation-coupled chromatin remodeling	1	127.7×	0.017	MEN1
regulation of cytosolic calcium ion concentration	1	127.7×	0.017	CDH23
response to UV	1	122.1×	0.017	MEN1
photoreceptor cell maintenance	1	119.5×	0.017	CDH23
negative regulation of osteoblast differentiation	1	98.5×	0.019	MEN1
negative regulation of cell cycle	1	96.8×	0.019	MEN1
calcium ion transport	1	60.4×	0.027	CDH23
locomotory behavior	1	59.8×	0.027	CDH23
protein maturation	1	54.5×	0.029	AIP
MAPK cascade	1	51.1×	0.029	MEN1
xenobiotic metabolic process	1	49.7×	0.029	AIP
homophilic cell-cell adhesion	1	46.8×	0.030	CDH23
neuron projection development	1	40.7×	0.033	CDH23
sensory perception of sound	1	33.6×	0.039	CDH23
visual perception	1	26.5×	0.047	CDH23

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 5 evidence-associated genes (40%) 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
CDH23	0	0
C10orf105	0	0
CDH23-AS1	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: 5; 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	3	CDH23, C10orf105, CDH23-AS1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CDH23	0	—
C10orf105	0	—
CDH23-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.