Surfactant metabolism dysfunction, pulmonary, 5

Summary

Surfactant metabolism dysfunction, pulmonary, 5 (MONDO:0013712) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 17

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	surfactant metabolism dysfunction, pulmonary, 5
Mondo ID	MONDO:0013712
OMIM	614370
UMLS	C3280574
MedGen	482204
GARD	0015793
Is cancer (heuristic)	no

Also known as: CSF2RB hereditary pulmonary alveolar proteinosis · hereditary pulmonary alveolar proteinosis caused by mutation in CSF2RB · SMDP5 · surfactant metabolism dysfunction, pulmonary, 5 · surfactant metabolism dysfunction, pulmonary, type 5

Data availability: 17 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › respiratory system disorder › lower respiratory tract disorder › lung disorder › pulmonary alveolar proteinosis › hereditary pulmonary alveolar proteinosis › surfactant metabolism dysfunction, pulmonary, 5

Related subtypes (7): surfactant metabolism dysfunction, pulmonary, 1, surfactant metabolism dysfunction, pulmonary, 4, interstitial lung disease due to ABCA3 deficiency, severe early-onset pulmonary alveolar proteinosis due to MARS deficiency, chronic respiratory distress with surfactant metabolism deficiency, SFTPC-related interstitial lung disease, surfactant metabolism dysfunction, pulmonary, 2

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

17 retrieved; paginated sample, class counts are floors:

12 uncertain significance, 3 conflicting classifications of pathogenicity, 1 benign/likely benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
29744	NM_000395.3(CSF2RB):c.631del (p.Arg211fs)	CSF2RB	Pathogenic	no assertion criteria provided
1569485	NM_000395.3(CSF2RB):c.2491G>A (p.Gly831Ser)	CSF2RB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1638210	NM_000395.3(CSF2RB):c.313G>A (p.Val105Ile)	CSF2RB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
796279	NM_000395.3(CSF2RB):c.1874C>T (p.Ser625Phe)	CSF2RB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1002560	NM_000395.3(CSF2RB):c.1943_1944inv (p.Pro648Leu)	CSF2RB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1048656	NM_000395.3(CSF2RB):c.2533G>A (p.Gly845Ser)	CSF2RB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1048657	NM_000395.3(CSF2RB):c.632G>A (p.Arg211Gln)	CSF2RB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1390682	NM_000395.3(CSF2RB):c.1381C>T (p.Arg461Cys)	CSF2RB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1435738	NM_000395.3(CSF2RB):c.149C>T (p.Thr50Ile)	CSF2RB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1482263	NM_000395.3(CSF2RB):c.587C>A (p.Thr196Asn)	CSF2RB	Uncertain significance	criteria provided, multiple submitters, no conflicts
161978	NM_000395.3(CSF2RB):c.812C>T (p.Ser271Leu)	CSF2RB	Uncertain significance	criteria provided, single submitter
2440578	NM_000395.3(CSF2RB):c.2245G>C (p.Ala749Pro)	CSF2RB	Uncertain significance	criteria provided, single submitter
2440580	NM_000395.3(CSF2RB):c.1943C>T (p.Pro648Leu)	CSF2RB	Uncertain significance	criteria provided, multiple submitters, no conflicts
619290	NM_000395.3(CSF2RB):c.1267G>A (p.Gly423Arg)	CSF2RB	Uncertain significance	criteria provided, single submitter
689449	NM_000395.3(CSF2RB):c.2119G>A (p.Val707Met)	CSF2RB	Uncertain significance	criteria provided, single submitter
694631	NM_000395.3(CSF2RB):c.1597G>A (p.Glu533Lys)	CSF2RB	Uncertain significance	criteria provided, multiple submitters, no conflicts
1625320	NM_000395.3(CSF2RB):c.644G>A (p.Arg215His)	CSF2RB	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
CSF2RB	Moderate	Autosomal recessive	surfactant metabolism dysfunction, pulmonary, 5	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CSF2RB	Orphanet:264675	Hereditary pulmonary alveolar proteinosis

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
CSF2RB	HGNC:2436	ENSG00000100368	P32927	Cytokine receptor common subunit beta	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CSF2RB	Cytokine receptor common subunit beta	Cell surface receptor that plays a role in immune response and controls the production and differentiation of hematopoietic progenitor cells into lineage-restricted cells.

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CSF2RB	Antibody/Immunoglobulin	yes		Hempt_rcpt_S_F1_CS, FN3_dom, IL3_rcpt_beta

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
decidua	1
periodontal ligament	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CSF2RB	230	broad	marker	blood, periodontal ligament, decidua

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CSF2RB	1,948

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CSF2RB	P32927	10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Defective CSF2RB causes SMDP5	1	1631.4×	0.002	CSF2RB
Defective CSF2RA causes SMDP4	1	1631.4×	0.002	CSF2RB
Interleukin receptor SHC signaling	1	407.9×	0.004	CSF2RB
Surfactant metabolism	1	368.4×	0.004	CSF2RB
Interleukin-3, Interleukin-5 and GM-CSF signaling	1	317.2×	0.004	CSF2RB
RAF/MAP kinase cascade	1	61.1×	0.016	CSF2RB

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
granulocyte-macrophage colony-stimulating factor signaling pathway	1	4213.0×	8e-04	CSF2RB
cellular response to interleukin-3	1	2808.7×	8e-04	CSF2RB
interleukin-5-mediated signaling pathway	1	2808.7×	8e-04	CSF2RB
positive regulation of leukocyte proliferation	1	2808.7×	8e-04	CSF2RB
interleukin-3-mediated signaling pathway	1	2407.4×	8e-04	CSF2RB
immunoglobulin mediated immune response	1	702.2×	0.002	CSF2RB
respiratory gaseous exchange by respiratory system	1	624.1×	0.002	CSF2RB
cell surface receptor signaling pathway via JAK-STAT	1	290.6×	0.004	CSF2RB
response to lipopolysaccharide	1	124.8×	0.009	CSF2RB
signal transduction	1	16.1×	0.062	CSF2RB

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
CSF2RB	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	1	CSF2RB
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)
CSF2RB	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.