Non-acquired combined pituitary hormone deficiency
diseaseOn this page
Also known as congenital combined pituitary hormone deficiencycongenital hypopituitarism
Summary
Non-acquired combined pituitary hormone deficiency (MONDO:0018762) is a disease (an umbrella term covering 7 Mondo subtypes) with 1 cohort gene and 1 clinical trial.
At a glance
- Prevalence: 1-5 / 10 000 (Europe) [Orphanet-validated]
- Umbrella term: 7 Mondo subtypes
- Cohort genes: 1
- ClinVar variants: 1
- Clinical trials: 1
Clinical features
Epidemiology
Prevalence records
2 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Point prevalence | 1-5 / 10 000 | Europe | Validated | |
| Prevalence at birth | 1-5 / 10 000 | 29 | Europe | Validated |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | non-acquired combined pituitary hormone deficiency |
| Mondo ID | MONDO:0018762 |
| Orphanet | 467 |
| UMLS | C5680091 |
| MedGen | 1842250 |
| GARD | 0002252 |
| Is cancer (heuristic) | no |
Also known as: congenital combined pituitary hormone deficiency · congenital hypopituitarism
Data availability: 1 ClinVar variant.
Disease family
An umbrella term covering 7 Mondo subtypes.
Classification path: disease › human disease › disease by body system or component › endocrine system disorder › pituitary deficiency › non-acquired pituitary hormone deficiency › non-acquired combined pituitary hormone deficiency
Related subtypes (4): isolated thyroid-stimulating hormone deficiency, short stature due to GHSR deficiency, congenital hypogonadotropic hypogonadism, pituitary stalk interruption syndrome
Subtypes (7): Pallister-Hall syndrome, non-acquired combined pituitary hormone deficiency with spine abnormalities, short stature-pituitary and cerebellar defects-small sella turcica syndrome, ANE syndrome, postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome, holoprosencephaly, deficiency in anterior pituitary function - variable immunodeficiency 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 likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 3544360 | NM_021784.5(FOXA2):c.619C>T (p.Gln207Ter) | FOXA2 | Likely pathogenic | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| FOXA2 | Orphanet:95494 | Combined pituitary hormone deficiencies, genetic forms |
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 |
|---|---|---|---|---|---|
| FOXA2 | HGNC:5022 | ENSG00000125798 | Q9Y261 | Hepatocyte nuclear factor 3-beta | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| FOXA2 | Hepatocyte nuclear factor 3-beta | Transcription factor that is involved in embryonic development, establishment of tissue-specific gene expression and regulation of gene expression in differentiated tissues. |
Protein-family classification
Druggable: 0 · Difficult: 1 · Unknown: 0 · 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 |
|---|---|---|---|
| Transcription factor | 1 | 8.3× | 0.121 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| FOXA2 | Transcription factor | no | Fork_head_dom, Fork-head_N, TF_fork_head_CS_1 |
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 |
|---|---|
| buccal mucosa cell | 1 |
| pancreatic ductal cell | 1 |
| pylorus | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| FOXA2 | 105 | broad | marker | pancreatic ductal cell, pylorus, buccal mucosa cell |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| FOXA2 | 2,789 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| FOXA2 | Q9Y261 | 3 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 7. 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 |
|---|---|---|---|---|
| Positive Regulation of CDH1 Gene Transcription | 1 | 951.7× | 0.003 | FOXA2 |
| Formation of axial mesoderm | 1 | 815.7× | 0.003 | FOXA2 |
| Formation of definitive endoderm | 1 | 713.8× | 0.003 | FOXA2 |
| Developmental Lineage of Multipotent Pancreatic Progenitor Cells | 1 | 601.0× | 0.003 | FOXA2 |
| Regulation of gene expression in beta cells | 1 | 519.1× | 0.003 | FOXA2 |
| Developmental Lineage of Pancreatic Acinar Cells | 1 | 300.5× | 0.004 | FOXA2 |
| Developmental Lineage of Pancreatic Ductal Cells | 1 | 228.4× | 0.004 | FOXA2 |
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 |
|---|---|---|---|---|
| response to interleukin-6 | 1 | 4213.0× | 0.003 | FOXA2 |
| positive regulation of gastrulation | 1 | 2407.4× | 0.003 | FOXA2 |
| regulation of blood coagulation | 1 | 1872.4× | 0.003 | FOXA2 |
| primitive streak formation | 1 | 1404.3× | 0.003 | FOXA2 |
| positive regulation of cell-cell adhesion mediated by cadherin | 1 | 1296.3× | 0.003 | FOXA2 |
| positive regulation of embryonic development | 1 | 1123.5× | 0.003 | FOXA2 |
| endocrine pancreas development | 1 | 936.2× | 0.003 | FOXA2 |
| regulation of insulin secretion involved in cellular response to glucose stimulus | 1 | 936.2× | 0.003 | FOXA2 |
| dopaminergic neuron differentiation | 1 | 624.1× | 0.003 | FOXA2 |
| cell fate specification | 1 | 526.6× | 0.004 | FOXA2 |
| negative regulation of epithelial to mesenchymal transition | 1 | 411.0× | 0.004 | FOXA2 |
| adult locomotory behavior | 1 | 300.9× | 0.005 | FOXA2 |
| anatomical structure morphogenesis | 1 | 139.3× | 0.010 | FOXA2 |
| chromatin organization | 1 | 99.1× | 0.014 | FOXA2 |
| cell differentiation | 1 | 29.1× | 0.042 | FOXA2 |
| positive regulation of DNA-templated transcription | 1 | 27.9× | 0.042 | FOXA2 |
| negative regulation of transcription by RNA polymerase II | 1 | 17.7× | 0.063 | FOXA2 |
| positive regulation of transcription by RNA polymerase II | 1 | 14.9× | 0.071 | FOXA2 |
| regulation of transcription by RNA polymerase II | 1 | 11.7× | 0.086 | FOXA2 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1
Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| FOXA2 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
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 | FOXA2 |
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) |
|---|---|---|
| FOXA2 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 1.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| Not specified | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT04463316 | Not specified | RECRUITING | GROWing Up With Rare GENEtic Syndromes |
Related Atlas pages
- Cohort genes: FOXA2