Combined immunodeficiency due to moesin deficiency

Summary

Combined immunodeficiency due to moesin deficiency (MONDO:0010514) is a disease caused by MSN (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: MSN (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 8

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

Identifiers

Disease identifiers

Field	Value
Canonical name	combined immunodeficiency due to moesin deficiency
Mondo ID	MONDO:0010514
OMIM	300988
Orphanet	504530
DOID	DOID:0112001
UMLS	C5568123
MedGen	1799546
GARD	0017939
Is cancer (heuristic)	no

Also known as: CID due to Moesin deficiency · IMD50 · immunodeficiency 50 · immunodeficiency type 50 · MSN-related combined immunodeficiency · X-linked Moesin-associated immunodeficiency

Data availability: 8 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › combined immunodeficiency due to moesin deficiency

Related subtypes (40): B cell deficiency, complement deficiency, phagocyte bactericidal dysfunction, trichohepatoenteric syndrome, hepatic veno-occlusive disease-immunodeficiency syndrome, immunodeficiency with defective T-cell response to interleukin 1, Say-Barber-Miller syndrome, familial isolated congenital asplenia, X-linked immunoneurologic disorder, ectodermal dysplasia and immune deficiency, immunodeficiency 33, immunodeficiency 47, immunodeficiency, X-linked, with deficiency of 115,000 Dalton surface glycoprotein, properdin deficiency, X-linked, combined immunodeficiency with faciooculoskeletal anomalies, recurrent infections associated with rare immunoglobulin isotypes deficiency, immunodeficiency 28, autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity, immunodeficiency 37, immunodeficiency 39, BENTA disease, primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection, immunodeficiency 49, chronic mucocutaneous candidiasis, hereditary hemophagocytic lymphohistiocytosis, immunoglobulin heavy chain deficiency, immuno-osseous dysplasia, lymphoproliferative syndrome, IL10-related early-onset inflammatory bowel disease, T-cell immunodeficiency with epidermodysplasia verruciformis, Aicardi-Goutieres syndrome, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, inflammatory bowel disease-recurrent sinopulmonary infections syndrome, A20 haploinsufficiency, NK cell deficiency, T cell and NK cell immunodeficiency, dendritic cell deficiency, immunodysregulation with variable immunodeficiency and autoimmunity, immune dysregulation with immunodeficiency due to AIOLOS haploinsufficiency, STAT5 haploinsufficiency

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

8 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 2 pathogenic, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1252064	NM_002444.3(MSN):c.1056del (p.Lys352fs)	MSN	Pathogenic	no assertion criteria provided
372154	NM_002444.3(MSN):c.511C>T (p.Arg171Trp)	MSN	Pathogenic	criteria provided, multiple submitters, no conflicts
372155	NM_002444.3(MSN):c.1657C>T (p.Arg553Ter)	MSN	Likely pathogenic	criteria provided, single submitter
804017	NM_002444.3(MSN):c.1601A>C (p.Asp534Ala)	MSN	Likely pathogenic	criteria provided, single submitter
2433807	NM_002444.3(MSN):c.1099G>A (p.Glu367Lys)	MSN	Uncertain significance	criteria provided, multiple submitters, no conflicts
2584545	NM_002444.3(MSN):c.877C>T (p.Arg293Cys)	MSN	Uncertain significance	criteria provided, multiple submitters, no conflicts
4071546	NM_002444.3(MSN):c.1141C>T (p.Arg381Cys)	MSN	Uncertain significance	criteria provided, single submitter
982967	NM_002444.3(MSN):c.817C>T (p.Arg273Trp)	MSN	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
MSN	Strong	X-linked	combined immunodeficiency due to moesin deficiency	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MSN	Orphanet:504530	Combined immunodeficiency due to Moesin deficiency

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
MSN	HGNC:7373	ENSG00000147065	P26038	Moesin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MSN	Moesin	Ezrin-radixin-moesin (ERM) family protein that connects the actin cytoskeleton to the plasma membrane and thereby regulates the structure and function of specific domains of the cell cortex.

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)
MSN	Other/Unknown	no		FERM_domain, Ez/rad/moesin-like, Moesin_tail_sf

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
leukocyte	1
lower lobe of lung	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MSN	293	ubiquitous	marker	lower lobe of lung, monocyte, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MSN	3,443

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MSN	P26038	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. 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
Interleukin-12 family signaling	1	475.8×	0.013	MSN
Interleukin-12 signaling	1	407.9×	0.013	MSN
Sensory processing of sound	1	308.6×	0.013	MSN
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	300.5×	0.013	MSN
Signaling by ALK in cancer	1	271.9×	0.013	MSN
Recycling pathway of L1	1	223.9×	0.013	MSN
Sensory processing of sound by outer hair cells of the cochlea	1	203.9×	0.013	MSN
Sensory processing of sound by inner hair cells of the cochlea	1	163.1×	0.014	MSN
Signaling by ALK fusions and activated point mutants	1	150.3×	0.014	MSN
L1CAM interactions	1	120.2×	0.016	MSN
Sensory Perception	1	95.2×	0.018	MSN
Signaling by Interleukins	1	64.2×	0.025	MSN
Diseases of signal transduction by growth factor receptors and second messengers	1	56.8×	0.026	MSN
Axon guidance	1	45.1×	0.029	MSN
Nervous system development	1	42.9×	0.029	MSN
Cytokine Signaling in Immune system	1	40.8×	0.029	MSN
Developmental Biology	1	14.5×	0.077	MSN
Disease	1	13.1×	0.077	MSN
Immune System	1	13.0×	0.077	MSN

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
T cell aggregation	1	8426.0×	0.001	MSN
regulation of lymphocyte migration	1	5617.3×	0.001	MSN
regulation of organelle assembly	1	3370.4×	0.001	MSN
membrane to membrane docking	1	2808.7×	0.001	MSN
gland morphogenesis	1	2407.4×	0.001	MSN
positive regulation of podosome assembly	1	1872.4×	0.001	MSN
positive regulation of early endosome to late endosome transport	1	1872.4×	0.001	MSN
positive regulation of protein localization to early endosome	1	1685.2×	0.001	MSN
T cell migration	1	1404.3×	0.001	MSN
immunological synapse formation	1	1296.3×	0.001	MSN
establishment of epithelial cell apical/basal polarity	1	1053.2×	0.002	MSN
regulation of cell size	1	766.0×	0.002	MSN
establishment of endothelial barrier	1	766.0×	0.002	MSN
leukocyte migration	1	624.1×	0.002	MSN
leukocyte cell-cell adhesion	1	468.1×	0.003	MSN
T cell proliferation	1	383.0×	0.003	MSN
positive regulation of protein catabolic process	1	203.0×	0.006	MSN
regulation of cell shape	1	123.0×	0.009	MSN
positive regulation of gene expression	1	38.7×	0.026	MSN

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
MSN	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
MSN	4	Binding:4

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	MSN

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)
MSN	4	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.