Deficiency in anterior pituitary function - variable immunodeficiency syndrome

Summary

Deficiency in anterior pituitary function - variable immunodeficiency syndrome (MONDO:0017407) is a disease with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• Phenotypes (HPO): 38

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		7	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

38 HPO clinical features (Orphanet curated; top 38 by frequency):

HPO ID	Term	Frequency
HP:0000403	Recurrent otitis media	Very frequent (80-99%)
HP:0001325	Hypoglycemic coma	Very frequent (80-99%)
HP:0001988	Recurrent hypoglycemia	Very frequent (80-99%)
HP:0002615	Hypotension	Very frequent (80-99%)
HP:0002788	Recurrent upper respiratory tract infections	Very frequent (80-99%)
HP:0002837	Recurrent bronchitis	Very frequent (80-99%)
HP:0002902	Hyponatremia	Very frequent (80-99%)
HP:0002920	Decreased circulating ACTH level	Very frequent (80-99%)
HP:0004313	Decreased circulating antibody level	Very frequent (80-99%)
HP:0004429	Recurrent viral infections	Very frequent (80-99%)
HP:0005365	Severe B lymphocytopenia	Very frequent (80-99%)
HP:0006532	Recurrent pneumonia	Very frequent (80-99%)
HP:0008163	Decreased circulating cortisol level	Very frequent (80-99%)
HP:0011108	Recurrent sinusitis	Very frequent (80-99%)
HP:0011735	Adrenocorticotropin deficient adrenal insufficiency	Very frequent (80-99%)
HP:0012378	Fatigue	Very frequent (80-99%)
HP:0100776	Recurrent pharyngitis	Very frequent (80-99%)
HP:0001596	Alopecia	Frequent (30-79%)
HP:0002110	Bronchiectasis	Frequent (30-79%)
HP:0004332	Abnormal lymphocyte morphology	Frequent (30-79%)
HP:0008404	Nail dystrophy	Frequent (30-79%)
HP:0012504	Abnormal size of pituitary gland	Frequent (30-79%)
HP:0100803	Abnormality of the periungual region	Frequent (30-79%)
HP:0000651	Diplopia	Occasional (5-29%)
HP:0000824	Decreased response to growth hormone stimulation test	Occasional (5-29%)
HP:0001263	Global developmental delay	Occasional (5-29%)
HP:0001508	Failure to thrive	Occasional (5-29%)
HP:0001973	Autoimmune thrombocytopenia	Occasional (5-29%)
HP:0002121	Generalized non-motor (absence) seizure	Occasional (5-29%)
HP:0003765	Psoriasiform dermatitis	Occasional (5-29%)
HP:0007418	Alopecia totalis	Occasional (5-29%)
HP:0030349	Decreased circulating androgen level	Occasional (5-29%)
HP:0030353	Decreased serum insulin-like growth factor 1	Occasional (5-29%)
HP:0100806	Sepsis	Occasional (5-29%)
HP:0001045	Vitiligo	Excluded (0%)
HP:0002153	Hyperkalemia	Excluded (0%)
HP:0030057	Autoimmune antibody positivity	Excluded (0%)
HP:0100646	Thyroiditis	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	deficiency in anterior pituitary function - variable immunodeficiency syndrome
Mondo ID	MONDO:0017407
Orphanet	293978
UMLS	C4751122
MedGen	1666981
GARD	0017353
Is cancer (heuristic)	no

Also known as: David syndrome

Data availability: 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic agammaglobulinemia › common variable immunodeficiency › immunodeficiency, common variable, 10 › 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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
NFKB2	Strong	Autosomal dominant	immunodeficiency, common variable, 10	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NFKB2	Orphanet:293978	Deficiency in anterior pituitary function-variable immunodeficiency syndrome

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
NFKB2	HGNC:7795	ENSG00000077150	Q00653	Nuclear factor NF-kappa-B p100 subunit	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NFKB2	Nuclear factor NF-kappa-B p100 subunit	NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as infl…

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)
NFKB2	Transcription factor	no		NFkB/Dor, Death_dom, Ankyrin_rpt

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
granulocyte	1
muscle layer of sigmoid colon	1
spleen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NFKB2	221	ubiquitous	marker	granulocyte, muscle layer of sigmoid colon, spleen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NFKB2	4,041

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NFKB2	Q00653	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. 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
DEx/H-box helicases activate type I IFN and inflammatory cytokines production	1	1631.4×	0.003	NFKB2
IkBA variant leads to EDA-ID	1	1631.4×	0.003	NFKB2
Interleukin-1 processing	1	1268.9×	0.003	NFKB2
SUMOylation of immune response proteins	1	951.7×	0.003	NFKB2
RIP-mediated NFkB activation via ZBP1	1	671.8×	0.003	NFKB2
The NLRP3 inflammasome	1	671.8×	0.003	NFKB2
TRAF6 mediated NF-kB activation	1	456.8×	0.004	NFKB2
Purinergic signaling in leishmaniasis infection	1	423.0×	0.004	NFKB2
TAK1-dependent IKK and NF-kappa-B activation	1	300.5×	0.005	NFKB2
NIK–>noncanonical NF-kB signaling	1	228.4×	0.005	NFKB2
Dectin-1 mediated noncanonical NF-kB signaling	1	215.5×	0.005	NFKB2
PKMTs methylate histone lysines	1	160.8×	0.007	NFKB2
Regulation of PD-L1(CD274) transcription	1	108.8×	0.009	NFKB2

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
follicular dendritic cell differentiation	1	8426.0×	0.001	NFKB2
germinal center formation	1	1685.2×	0.003	NFKB2
non-canonical NF-kappaB signal transduction	1	842.6×	0.004	NFKB2
spleen development	1	401.2×	0.005	NFKB2
response to cytokine	1	374.5×	0.005	NFKB2
canonical NF-kappaB signal transduction	1	366.4×	0.005	NFKB2
rhythmic process	1	251.5×	0.006	NFKB2
response to lipopolysaccharide	1	124.8×	0.010	NFKB2
extracellular matrix organization	1	122.1×	0.010	NFKB2
regulation of DNA-templated transcription	1	31.6×	0.035	NFKB2
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	NFKB2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
NFKB2	INDOPROFEN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NFKB2	15	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
INDOPROFEN	4	NFKB2
VAMOROLONE	4	NFKB2
BORTEZOMIB	4	NFKB2
DEXAMETHASONE	4	NFKB2
SULFASALAZINE	4	NFKB2
CURCUMIN	3	NFKB2
RESVERATROL	3	NFKB2
IXAZOMIB	3	NFKB2
WITHANOLIDE D	3	NFKB2
TRIPTOLIDE	3	NFKB2
FRENTIZOLE	2	NFKB2
LAPACHONE	2	NFKB2
SANGUINARIUM	2	NFKB2
AS-602868	1	NFKB2
WITHAFERIN A	1	NFKB2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
NFKB2	230	Binding:226, Functional:4

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
NFKB2	230

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

15 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)
INDOPROFEN	4	NFKB2
VAMOROLONE	4	NFKB2
BORTEZOMIB	4	NFKB2
DEXAMETHASONE	4	NFKB2
SULFASALAZINE	4	NFKB2
CURCUMIN	3	NFKB2
RESVERATROL	3	NFKB2
IXAZOMIB	3	NFKB2
WITHANOLIDE D	3	NFKB2
TRIPTOLIDE	3	NFKB2
FRENTIZOLE	2	NFKB2
LAPACHONE	2	NFKB2
SANGUINARIUM	2	NFKB2
AS-602868	1	NFKB2
WITHAFERIN A	1	NFKB2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	NFKB2
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	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: 0.