IKBKG-related immunodeficiency with or without ectodermal dysplasia

Summary

IKBKG-related immunodeficiency with or without ectodermal dysplasia (MONDO:0100162) is a disease caused by IKBKG (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: IKBKG (GenCC Strong)
• Cohort genes: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	IKBKG-related immunodeficiency with or without ectodermal dysplasia
Mondo ID	MONDO:0100162
Is cancer (heuristic)	no

Also known as: NEMO related ID/EDA-ID

Data availability: 1 GenCC gene-disease record.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › immunodeficiency disease › IKBKG-related immunodeficiency with or without ectodermal dysplasia

Related subtypes (94): B cell deficiency, T-cell immunodeficiency, complement deficiency, myalgic encephalomeyelitis/chronic fatigue syndrome, hypoproteinemia, hypercatabolic, X-linked lymphoproliferative syndrome, Wiskott-Aldrich syndrome, autosomal dominant form, immunodeficiency due to CD25 deficiency, immunodeficiency 67, primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency, immunodeficiency 35, pyogenic bacterial infections due to MyD88 deficiency, lymphoproliferative syndrome 1, FADD-related immunodeficiency, immunodeficiency 31B, Wiskott-Aldrich syndrome 2, cryptosporidiosis-chronic cholangitis-liver disease syndrome, idiopathic CD4 lymphocytopenia, immunodeficiency 23, DOCK2 deficiency, immunodeficiency 45, TFRC-related combined immunodeficiency, combined immunodeficiency, autoimmune hemolytic anemia-autoimmune thrombocytopenia-primary immunodeficiency syndrome, immunodeficiency due to selective anti-polysaccharide antibody deficiency, immunodeficiency 57, immunodeficiency 14b, autosomal recessive, immunodeficiency 98 with autoinflammation, X-linked, immunodeficiency 102, immunodeficiency 74, COVID-19-related, X-linked, immunodeficiency 66, immunodeficiency 80 with or without congenital cardiomyopathy, immunodeficiency 81, immunodeficiency 82 with systemic inflammation, immunodeficiency 84, immunodeficiency 85 and autoimmunity, immunodeficiency 86, immunodeficiency 87 and autoimmunity, immunodeficiency 88, immunodeficiency 89 and autoimmunity, immunodeficiency 91 and hyperinflammation, immunodeficiency 92, immunodeficiency 93 and hypertrophic cardiomyopathy, immunodeficiency 95, immunodeficiency 96, immunodeficiency 97 with autoinflammation, immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias, immunodeficiency 101 (varicella zoster virus-specific), immunodeficiency 75, immunodeficiency 76, immunodeficiency 106, susceptibility to viral infections, immunodeficiency 78 with autoimmunity and developmental delay, immunodeficiency 77, immunodeficiency 107, susceptibility to invasive staphylococcus aureus infection, immunodeficiency 15a, immunodeficiency 60, immunodeficiency 62, immunodeficiency 63 with lymphoproliferation and autoimmunity, immunodeficiency 64, immunodeficiency 65, susceptibility to viral infections, immunodeficiency 69, immunodeficiency 70, immunodeficiency 72 with autoinflammation, GATA2 deficiency with susceptibility to MDS/AML, Shwachman-Diamond syndrome 1, immunodeficiency 53, immunodeficiency 11b with atopic dermatitis, FNIP1-associated syndrome, FASLG-related immunodeficiency, TNFRSF9-related immunodeficiency, DNAJC21-related Shwachman Diamond syndrome, IRF4-related immune disorder, PTEN harmartoma tumor syndrome with immune disorder, primary immunodeficiency due to calcium channel deficiency, chronic mucocutaneous candidiasis and connective tissue disease due to JNK1 haploinsufficiency, immune deficiency due to impaired neutrophil phagocytosis and migration, hatipoglu immunodeficiency syndrome, immunodeficiency 112, immunodeficiency 113 with autoimmunity and autoinflammation, immunodeficiency 114, folate-responsive, immunodeficiency 115 with autoinflammation, immunodeficiency 117, immunodeficiency 118, immunodeficiency 119, immunodeficiency 121 with autoinflammation, immunodeficiency 122, immunodeficiency 123 with HPV-related verrucosis, immunodeficiency 125, immunodeficiency 126, susceptibility to, immunodeficiency 127, immunodeficiency 128, immunodeficiency 132b, immunodeficiency 133 with ectodermal dysplasia with or without peripheral neuropathy, immunodeficiency 134 (Epstein-Barr virus-specific)

Subtypes (3): anhidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome, immunodeficiency 33, ectodermal dysplasia and immunodeficiency 1

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: 12 · Orphanet: 4 · 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
IKBKG	Definitive	X-linked	ectodermal dysplasia and immunodeficiency 1	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
IKBKG	Orphanet:464	Incontinentia pigmenti
IKBKG	Orphanet:69088	Hypohidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome
IKBKG	Orphanet:699605	NEMO deleted exon 5 autoinflammatory syndrome
IKBKG	Orphanet:98813	Hypohidrotic ectodermal dysplasia with immunodeficiency

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
IKBKG	HGNC:5961	ENSG00000269335	Q9Y6K9	NF-kappa-B essential modulator	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
IKBKG	NF-kappa-B essential modulator	Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
IKBKG	Other/Unknown	no		NEMO_N, CC2-LZ_dom, NEMO_ZF

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
blood	1
granulocyte	1
spleen	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
IKBKG	134	ubiquitous	marker	granulocyte, blood, spleen

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
IKBKG	4,981

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
IKBKG	Q9Y6K9	17

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 88. 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
IKBKB deficiency causes SCID	1	3806.7×	0.008	IKBKG
IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR)	1	3806.7×	0.008	IKBKG
SLC15A4:TASL-dependent IRF5 activation	1	1903.3×	0.008	IKBKG
IkBA variant leads to EDA-ID	1	1631.4×	0.008	IKBKG
ZBP1(DAI) mediated induction of type I IFNs	1	1038.2×	0.008	IKBKG
SUMOylation of immune response proteins	1	951.7×	0.008	IKBKG
Diseases of Immune System	1	878.5×	0.008	IKBKG
Diseases associated with the TLR signaling cascade	1	878.5×	0.008	IKBKG
NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10	1	878.5×	0.008	IKBKG
Downstream signaling events of B Cell Receptor (BCR)	1	815.7×	0.008	IKBKG
IRAK1 recruits IKK complex	1	815.7×	0.008	IKBKG
IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation	1	815.7×	0.008	IKBKG
MAP3K8 (TPL2)-dependent MAPK1/3 activation	1	713.8×	0.008	IKBKG
RIP-mediated NFkB activation via ZBP1	1	671.8×	0.008	IKBKG
Regulation of NF-kappa B signaling	1	634.4×	0.008	IKBKG
TICAM1, RIP1-mediated IKK complex recruitment	1	601.0×	0.008	IKBKG
Modulation of host responses by IFN-stimulated genes	1	601.0×	0.008	IKBKG
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1	1	519.1×	0.008	IKBKG
TCR signaling	1	496.5×	0.008	IKBKG
activated TAK1 mediates p38 MAPK activation	1	496.5×	0.008	IKBKG
IKK complex recruitment mediated by RIP1	1	496.5×	0.008	IKBKG
TRAF6 mediated NF-kB activation	1	456.8×	0.009	IKBKG
TNF signaling	1	423.0×	0.009	IKBKG
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1	356.9×	0.009	IKBKG
Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells	1	356.9×	0.009	IKBKG
Signaling by the B Cell Receptor (BCR)	1	346.1×	0.009	IKBKG
TNFR1-induced NF-kappa-B signaling pathway	1	335.9×	0.009	IKBKG
Antigen processing-Cross presentation	1	317.2×	0.009	IKBKG
NOD1/2 Signaling Pathway	1	317.2×	0.009	IKBKG
MAP kinase activation	1	308.6×	0.009	IKBKG

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
establishment of vesicle localization	1	2407.4×	0.006	IKBKG
anoikis	1	1296.3×	0.006	IKBKG
negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway	1	842.6×	0.006	IKBKG
positive regulation of T cell receptor signaling pathway	1	766.0×	0.006	IKBKG
B cell homeostasis	1	561.7×	0.006	IKBKG
positive regulation of ubiquitin-dependent protein catabolic process	1	561.7×	0.006	IKBKG
positive regulation of macroautophagy	1	526.6×	0.006	IKBKG
canonical NF-kappaB signal transduction	1	366.4×	0.008	IKBKG
obsolete positive regulation of NF-kappaB transcription factor activity	1	205.5×	0.012	IKBKG
negative regulation of canonical NF-kappaB signal transduction	1	172.0×	0.013	IKBKG
T cell receptor signaling pathway	1	151.8×	0.013	IKBKG
response to virus	1	144.0×	0.013	IKBKG
protein-containing complex assembly	1	113.9×	0.015	IKBKG
defense response to bacterium	1	108.0×	0.015	IKBKG
positive regulation of canonical NF-kappaB signal transduction	1	72.6×	0.020	IKBKG
DNA damage response	1	53.5×	0.026	IKBKG
immune response	1	47.1×	0.027	IKBKG
positive regulation of gene expression	1	38.7×	0.031	IKBKG
inflammatory response	1	37.7×	0.031	IKBKG
innate immune response	1	33.6×	0.033	IKBKG
apoptotic process	1	28.7×	0.036	IKBKG
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	IKBKG

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
IKBKG	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
IKBKG	38	Binding:30, Functional:8

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	IKBKG

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)
IKBKG	38	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.