Immunodeficiency 133 with ectodermal dysplasia with or without peripheral neuropathy

Summary

Immunodeficiency 133 with ectodermal dysplasia with or without peripheral neuropathy (MONDO:0979570) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	immunodeficiency 133 with ectodermal dysplasia with or without peripheral neuropathy
Mondo ID	MONDO:0979570
OMIM	621254
DOID	DOID:0061096
UMLS	C6012744
MedGen	1876476
Is cancer (heuristic)	no

Data availability: 6 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › immunodeficiency disease › immunodeficiency 133 with ectodermal dysplasia with or without peripheral neuropathy

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, IKBKG-related immunodeficiency with or without ectodermal dysplasia, 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 134 (Epstein-Barr virus-specific)

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

6 retrieved; paginated sample, class counts are floors:

2 conflicting classifications of pathogenicity, 2 pathogenic, 1 benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4057194	NM_002224.4(ITPR3):c.586G>A (p.Ala196Thr)	ITPR3	Pathogenic	no assertion criteria provided
4057195	NM_002224.4(ITPR3):c.7517T>A (p.Ile2506Asn)	ITPR3	Pathogenic	no assertion criteria provided
3664150	NM_002224.4(ITPR3):c.7571G>A (p.Arg2524His)	ITPR3	Likely pathogenic	criteria provided, single submitter
1722509	NM_002224.4(ITPR3):c.7570C>T (p.Arg2524Cys)	ITPR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
739556	NM_002224.4(ITPR3):c.1148+10C>T	ITPR3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1293577	NM_002224.4(ITPR3):c.5549G>A (p.Arg1850Gln)	ITPR3	Benign	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

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

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
ITPR3	HGNC:6182	ENSG00000096433	Q14573	Inositol 1,4,5-trisphosphate-gated calcium channel ITPR3	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ITPR3	Inositol 1,4,5-trisphosphate-gated calcium channel ITPR3	Inositol 1,4,5-trisphosphate-gated calcium channel that, upon 1D-myo-inositol 1,4,5-trisphosphate binding, transports calcium from the endoplasmic reticulum lumen to cytoplasm, thus releasing the intracellular calcium and therefore partici…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Ion channel	1	111.5×	0.009

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ITPR3	Ion channel	yes		InsP3_rcpt, RIH_dom, Ion_trans_dom

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
cartilage tissue	1
pylorus	1
upper arm skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ITPR3	262	ubiquitous	marker	cartilage tissue, pylorus, upper arm skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ITPR3	3,135

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ITPR3	Q14573	24

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 52. 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
CLEC7A (Dectin-1) induces NFAT activation	1	1038.2×	0.009	ITPR3
Elevation of cytosolic Ca2+ levels	1	713.8×	0.009	ITPR3
Platelet calcium homeostasis	1	713.8×	0.009	ITPR3
VEGFR2 mediated cell proliferation	1	571.0×	0.009	ITPR3
Effects of PIP2 hydrolysis	1	456.8×	0.009	ITPR3
Role of phospholipids in phagocytosis	1	456.8×	0.009	ITPR3
Anti-inflammatory response favouring Leishmania parasite infection	1	393.8×	0.009	ITPR3
Leishmania parasite growth and survival	1	393.8×	0.009	ITPR3
FCERI mediated Ca+2 mobilization	1	356.9×	0.009	ITPR3
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	1	356.9×	0.009	ITPR3
Signaling by the B Cell Receptor (BCR)	1	346.1×	0.009	ITPR3
Sensory perception of taste	1	335.9×	0.009	ITPR3
G-protein mediated events	1	326.3×	0.009	ITPR3
DAG and IP3 signaling	1	317.2×	0.009	ITPR3
Beta-catenin independent WNT signaling	1	292.8×	0.009	ITPR3
FCGR3A-mediated IL10 synthesis	1	292.8×	0.009	ITPR3
Fcgamma receptor (FCGR) dependent phagocytosis	1	278.5×	0.009	ITPR3
Platelet homeostasis	1	278.5×	0.009	ITPR3
Sensory perception of sweet, bitter, and umami (glutamate) taste	1	278.5×	0.009	ITPR3
Fc epsilon receptor (FCERI) signaling	1	271.9×	0.009	ITPR3
Opioid Signalling	1	265.6×	0.009	ITPR3
PLC beta mediated events	1	265.6×	0.009	ITPR3
Glucagon-like Peptide-1 (GLP1) regulates insulin secretion	1	265.6×	0.009	ITPR3
C-type lectin receptors (CLRs)	1	237.9×	0.009	ITPR3
Signaling by VEGF	1	219.6×	0.009	ITPR3
Regulation of insulin secretion	1	219.6×	0.009	ITPR3
Ion homeostasis	1	203.9×	0.009	ITPR3
Ca2+ pathway	1	178.4×	0.010	ITPR3
Integration of energy metabolism	1	175.7×	0.010	ITPR3
Leishmania infection	1	163.1×	0.010	ITPR3

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
sensory perception of bitter taste	1	2808.7×	0.002	ITPR3
sensory perception of sweet taste	1	2407.4×	0.002	ITPR3
sensory perception of umami taste	1	2407.4×	0.002	ITPR3
sensory perception of taste	1	1123.5×	0.003	ITPR3
calcium ion homeostasis	1	443.5×	0.005	ITPR3
release of sequestered calcium ion into cytosol	1	343.9×	0.005	ITPR3
response to calcium ion	1	318.0×	0.005	ITPR3
long-term synaptic potentiation	1	280.9×	0.005	ITPR3
platelet activation	1	267.5×	0.005	ITPR3
protein homotetramerization	1	237.3×	0.005	ITPR3
memory	1	183.2×	0.006	ITPR3
positive regulation of cytosolic calcium ion concentration	1	117.0×	0.009	ITPR3
G protein-coupled receptor signaling pathway	1	36.2×	0.028	ITPR3

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
ITPR3	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
ITPR3	11	Binding:9, Functional:2

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	1	ITPR3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
ITPR3	11	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.