Pituitary gigantism

Summary

Pituitary gigantism (MONDO:0020479) is a disease with 2 cohort genes and 4 clinical trials.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Cohort genes: 2
• ClinVar variants: 1
• Phenotypes (HPO): 20
• Clinical trials: 4

Clinical features

Signs & symptoms

Clinical features (HPO)

20 HPO clinical features (Orphanet curated; top 20 by frequency):

HPO ID	Term	Frequency
HP:0000098	Tall stature	Very frequent (80-99%)
HP:0000280	Coarse facial features	Very frequent (80-99%)
HP:0000303	Mandibular prognathia	Very frequent (80-99%)
HP:0000845	Elevated circulating growth hormone concentration	Very frequent (80-99%)
HP:0000975	Hyperhidrosis	Very frequent (80-99%)
HP:0001176	Large hands	Very frequent (80-99%)
HP:0001639	Hypertrophic cardiomyopathy	Very frequent (80-99%)
HP:0001712	Left ventricular hypertrophy	Very frequent (80-99%)
HP:0001833	Long foot	Very frequent (80-99%)
HP:0002007	Frontal bossing	Very frequent (80-99%)
HP:0005616	Accelerated skeletal maturation	Very frequent (80-99%)
HP:0005978	Type II diabetes mellitus	Very frequent (80-99%)
HP:0011407	Proportionate tall stature	Very frequent (80-99%)
HP:0011760	Pituitary growth hormone cell adenoma	Very frequent (80-99%)
HP:0012411	Premature pubarche	Very frequent (80-99%)
HP:0030269	Increased circulating insulin-like growth factor 1 concentration	Very frequent (80-99%)
HP:0000141	Amenorrhea	Frequent (30-79%)
HP:0000870	Increased circulating prolactin concentration	Frequent (30-79%)
HP:0006767	Pituitary prolactin cell adenoma	Frequent (30-79%)
HP:0100829	Galactorrhea	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	pituitary gigantism
Mondo ID	MONDO:0020479
MeSH	D005877
Orphanet	99725
NCIT	C93046
SNOMED CT	86073008
UMLS	C0017547
MedGen	6602
GARD	0006506
MedDRA	10018265
Is cancer (heuristic)	no

Also known as: gigantism · hypophyseal gigantism · infantile and juvenile forms of acromegaly

Data availability: 1 ClinVar variant · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › reproductive system disorder › pituitary gland disorder › anterior pituitary gland disorder › hyperpituitarism › pituitary gigantism

Related subtypes (3): hyperprolactinemia, acromegaly, ACTH-dependent Cushing syndrome

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

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
570014	NM_001370259.2(MEN1):c.982C>A (p.His328Asn)	MEN1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 14 · Orphanet: 13 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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
MEN1	Supportive	Autosomal dominant	pituitary gigantism	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
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

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MEN1	HGNC:7010	ENSG00000133895	O00255	Menin	gencc,clinvar
AIP	HGNC:358	ENSG00000110711	O00170	AH receptor-interacting protein	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MEN1	Menin	Essential component of a MLL/SET1 histone methyltransferase (HMT) complex, a complex that specifically methylates ‘Lys-4’ of histone H3 (H3K4).
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.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

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

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	2
lower esophagus mucosa	1
right hemisphere of cerebellum	1
popliteal artery	1
tibial artery	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MEN1	271	ubiquitous	marker	granulocyte, lower esophagus mucosa, right hemisphere of cerebellum
AIP	241	ubiquitous	marker	granulocyte, popliteal artery, tibial artery

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MEN1	5,226
AIP	1,268

Intra-cohort edges

A	B	Sources
AIP	MEN1	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MEN1	O00255	69
AIP	O00170	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 34. Enrichment computed across 2 evidence-associated genes (2 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 2 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	951.7×	0.031	AIP
Interleukin-12 family signaling	1	237.9×	0.031	AIP
Interleukin-12 signaling	1	203.9×	0.031	AIP
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1	184.2×	0.031	MEN1
RHO GTPases activate IQGAPs	1	173.0×	0.031	MEN1
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription	1	154.3×	0.031	MEN1
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	150.3×	0.031	AIP
Formation of WDR5-containing histone-modifying complexes	1	132.8×	0.031	MEN1
Deactivation of the beta-catenin transactivating complex	1	116.5×	0.031	MEN1
Phase I - Functionalization of compounds	1	109.8×	0.031	AIP
Signaling by TGF-beta Receptor Complex	1	100.2×	0.031	MEN1
Epigenetic regulation by WDR5-containing histone modifying complexes	1	77.2×	0.034	MEN1
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	1	73.2×	0.034	MEN1
Biological oxidations	1	64.9×	0.034	AIP
Formation of the beta-catenin:TCF transactivating complex	1	60.1×	0.034	MEN1
TCF dependent signaling in response to WNT	1	58.9×	0.034	MEN1
Signaling by TGFB family members	1	57.7×	0.034	MEN1
Signaling by WNT	1	56.0×	0.034	MEN1
Post-translational protein phosphorylation	1	50.1×	0.036	MEN1
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	1	43.3×	0.039	MEN1
Epigenetic regulation of gene expression	1	35.7×	0.045	MEN1
RHO GTPase Effectors	1	34.0×	0.045	MEN1
Signaling by Interleukins	1	32.1×	0.046	AIP
Cytokine Signaling in Immune system	1	20.4×	0.069	AIP
Signaling by Rho GTPases	1	17.1×	0.077	MEN1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	16.7×	0.077	MEN1
RNA Polymerase II Transcription	1	11.3×	0.109	MEN1
Post-translational protein modification	1	9.6×	0.123	MEN1
Gene expression (Transcription)	1	8.9×	0.128	MEN1
Generic Transcription Pathway	1	7.5×	0.145	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 2 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 cyclin-dependent protein serine/threonine kinase activity	1	1053.2×	0.010	MEN1
T-helper 2 cell differentiation	1	936.2×	0.010	MEN1
osteoblast development	1	495.6×	0.010	MEN1
obsolete negative regulation of DNA-binding transcription factor activity	1	366.4×	0.010	MEN1
negative regulation of protein phosphorylation	1	290.6×	0.010	MEN1
obsolete protein targeting to mitochondrion	1	290.6×	0.010	AIP
response to gamma radiation	1	290.6×	0.010	MEN1
negative regulation of JNK cascade	1	280.9×	0.010	MEN1
positive regulation of transforming growth factor beta receptor signaling pathway	1	263.3×	0.010	MEN1
transcription initiation-coupled chromatin remodeling	1	191.5×	0.011	MEN1
response to UV	1	183.2×	0.011	MEN1
negative regulation of osteoblast differentiation	1	147.8×	0.012	MEN1
negative regulation of cell cycle	1	145.3×	0.012	MEN1
protein maturation	1	81.8×	0.019	AIP
MAPK cascade	1	76.6×	0.019	MEN1
xenobiotic metabolic process	1	74.6×	0.019	AIP
DNA repair	1	31.9×	0.042	MEN1
DNA damage response	1	26.8×	0.047	MEN1
negative regulation of cell population proliferation	1	21.1×	0.057	MEN1
negative regulation of DNA-templated transcription	1	15.8×	0.072	MEN1
negative regulation of transcription by RNA polymerase II	1	8.9×	0.120	MEN1
positive regulation of transcription by RNA polymerase II	1	7.4×	0.136	MEN1
regulation of transcription by RNA polymerase II	1	5.8×	0.164	MEN1

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 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

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: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

30 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.

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	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: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	3
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01673646	PHASE2	COMPLETED	Efficacy and Safety of Pasireotide LAR (Long-acting Release) in Japanese Patients With Acromegaly or Pituitary Gigantism
NCT00001595	Not specified	RECRUITING	An Investigation of Pituitary Tumors and Related Hypothalmic Disorders
NCT00461188	Not specified	RECRUITING	Genetics of Endocrine Tumours - Familial Isolated Pituitary Adenoma - FIPA
NCT01775332	Not specified	UNKNOWN	Interdisciplinary Pituitary Disorders Centre of Excellence: Assessment of Patient Education Tools