Bronchiectasis with or without elevated sweat chloride 1

Summary

Bronchiectasis with or without elevated sweat chloride 1 (MONDO:0008887) is a disease with 4 cohort genes.

At a glance

• Cohort genes: 4
• ClinVar variants: 811

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	bronchiectasis with or without elevated sweat chloride 1
Mondo ID	MONDO:0008887
MeSH	C567618
OMIM	211400
DOID	DOID:0080526
UMLS	C2749757
MedGen	440868
GARD	0018054
Is cancer (heuristic)	no

Also known as: BESC1 · bronchiectasis with or without elevated sweat chloride 1 · bronchiectasis with or without elevated sweat chloride 1, modifier of · bronchiectasis with or without elevated sweat chloride type 1

Data availability: 811 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › respiratory system disorder › lower respiratory tract disorder › bronchial disorder › bronchiectasis › idiopathic bronchiectasis › bronchiectasis with or without elevated sweat chloride 1

Related subtypes (2): bronchiectasis with or without elevated sweat chloride 2, bronchiectasis with or without elevated sweat chloride 3

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

600 retrieved; paginated sample, class counts are floors:

183 pathogenic, 151 uncertain significance, 95 conflicting classifications of pathogenicity, 83 pathogenic/likely pathogenic, 47 likely pathogenic, 12 benign/likely benign, 10 pathogenic; drug response, 9 drug response, 6 benign, 3 likely benign, 1 pathogenic/likely pathogenic; other

ClinVar	Variant (HGVS)	Gene	Classification	Review
1027585	NM_000492.4(CFTR):c.1585-2A>T	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070544	NM_000492.4(CFTR):c.4340del (p.Val1447fs)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1177286	NM_000492.4(CFTR):c.1132C>T (p.Gln378Ter)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1300164	NM_000492.4(CFTR):c.580G>A (p.Gly194Arg)	CFTR	Pathogenic	reviewed by expert panel
1330378	NM_000492.4(CFTR):c.3741_3745dup (p.Gly1249fs)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1438022	NM_000492.4(CFTR):c.1465_1469del (p.Ser489fs)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1449135	NM_000492.4(CFTR):c.1334del (p.Asn445fs)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1456282	NM_000492.4(CFTR):c.1261dup (p.Thr421fs)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1704258	NM_000492.4(CFTR):c.769G>T (p.Glu257Ter)	CFTR	Pathogenic	criteria provided, multiple submitters, no conflicts
1704259	NM_000492.4(CFTR):c.308del (p.Gly103fs)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1706001	NM_000492.4(CFTR):c.3140-16T>A	CFTR	Pathogenic	criteria provided, multiple submitters, no conflicts
1706049	NM_000492.4(CFTR):c.498del (p.Lys166fs)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1706055	NM_000492.4(CFTR):c.777del (p.Leu259_Val260insTer)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1706061	NM_000492.4(CFTR):c.3930G>A (p.Trp1310Ter)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1706062	NM_000492.4(CFTR):c.1068G>A (p.Trp356Ter)	CFTR	Pathogenic	criteria provided, multiple submitters, no conflicts
1731130	NM_000492.4(CFTR):c.3407_3422del (p.Ala1136fs)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1736923	NM_000492.4(CFTR):c.40_44del (p.Lys14fs)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
178713	NM_000492.4(CFTR):c.1210-11T>G	CFTR	Pathogenic/Likely pathogenic; other	criteria provided, multiple submitters, no conflicts
188783	NM_000492.4(CFTR):c.3368-2A>G	CFTR	Pathogenic	reviewed by expert panel
188958	NM_000492.4(CFTR):c.1327_1330dup (p.Ile444fs)	CFTR	Pathogenic	reviewed by expert panel
189095	NM_000492.4(CFTR):c.850dup (p.Met284fs)	CFTR	Pathogenic	reviewed by expert panel
2006304	NM_000492.4(CFTR):c.9del (p.Arg3fs)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2082996	NM_000492.4(CFTR):c.3622_3623delinsT (p.Gly1208fs)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2136607	NM_000492.4(CFTR):c.3743C>G (p.Ser1248Ter)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2443046	NM_000492.4(CFTR):c.3718-1G>C	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2503929	NM_000492.4(CFTR):c.4408G>T (p.Glu1470Ter)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2577712	NM_000492.4(CFTR):c.2819_2823del (p.Thr940fs)	CFTR	Pathogenic	criteria provided, multiple submitters, no conflicts
2584868	NM_000492.4(CFTR):c.1871_1878del (p.Ser624fs)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2680693	NM_000492.4(CFTR):c.3904A>T (p.Lys1302Ter)	CFTR	Pathogenic	criteria provided, single submitter
2680699	NM_000492.4(CFTR):c.850del (p.Lys283_Met284insTer)	CFTR	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 9 · 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
SCNN1B	Limited	Semidominant	bronchiectasis with or without elevated sweat chloride 1	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCNN1B	Orphanet:171876	Generalized pseudohypoaldosteronism type 1
SCNN1B	Orphanet:526	Liddle syndrome
SCNN1B	Orphanet:60033	Idiopathic bronchiectasis
CFTR	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
CFTR	Orphanet:48	Congenital bilateral absence of vas deferens
CFTR	Orphanet:498359	Aquagenic palmoplantar keratoderma
CFTR	Orphanet:586	Cystic fibrosis
CFTR	Orphanet:60033	Idiopathic bronchiectasis
CFTR	Orphanet:700124	Autosomal recessive hereditary chronic pancreatitis

Cohort genes → proteins

4 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SCNN1B	HGNC:10600	ENSG00000168447	P51168	Epithelial sodium channel subunit beta	gencc,clinvar
CFTR	HGNC:1884	ENSG00000001626	P13569	Cystic fibrosis transmembrane conductance regulator	clinvar
CFTR-AS1	HGNC:40144	ENSG00000232661		CFTR antisense RNA 1	clinvar
CFTR-AS2	HGNC:40145	ENSG00000083622		CFTR antisense RNA 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCNN1B	Epithelial sodium channel subunit beta	This is one of the three pore-forming subunits of the heterotrimeric epithelial sodium channel (ENaC), a critical regulator of sodium balance and fluid homeostasis.
CFTR	Cystic fibrosis transmembrane conductance regulator	Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.25

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
Transporter	1	19.4×	0.101
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SCNN1B	Other/Unknown	no		ENaC, ENaC_chordates, ENaC_CS
CFTR	Transporter	yes	2.7.4.3	ABC_transporter-like_ATP-bd, AAA+_ATPase, CFTR/ABCC7
CFTR-AS1	Other/Unknown	no
CFTR-AS2	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
body of pancreas	3
pancreas	3
esophagus mucosa	1
lower esophagus mucosa	1
rectum	1
gall bladder	1
islet of Langerhans	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCNN1B	188	broad	marker	lower esophagus mucosa, esophagus mucosa, rectum
CFTR	193	broad	marker	body of pancreas, gall bladder, pancreas
CFTR-AS1	68		yes	body of pancreas, islet of Langerhans, pancreas
CFTR-AS2	94		marker	body of pancreas, pancreas, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CFTR	7,664
SCNN1B	1,013
CFTR-AS1	0
CFTR-AS2	0

Intra-cohort edges

A	B	Sources
CFTR	SCNN1B	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CFTR	P13569	58
SCNN1B	P51168	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. Enrichment computed across 4 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RHO GTPases regulate CFTR trafficking	1	1903.3×	0.009	CFTR
Sensory perception of salty taste	1	951.7×	0.009	SCNN1B
Chaperone Mediated Autophagy	1	248.3×	0.019	CFTR
Sensory perception of taste	1	167.9×	0.019	SCNN1B
Late endosomal microautophagy	1	163.1×	0.019	CFTR
Aggrephagy	1	124.1×	0.019	CFTR
Developmental Lineage of Pancreatic Ductal Cells	1	114.2×	0.019	CFTR
Defective CFTR causes cystic fibrosis	1	109.8×	0.019	CFTR
RHOQ GTPase cycle	1	90.6×	0.021	CFTR
Stimuli-sensing channels	1	68.0×	0.025	SCNN1B
ABC-family protein mediated transport	1	60.7×	0.025	CFTR
Cargo recognition for clathrin-mediated endocytosis	1	52.4×	0.025	CFTR
Ion channel transport	1	48.0×	0.025	SCNN1B
Sensory Perception	1	47.6×	0.025	SCNN1B
Clathrin-mediated endocytosis	1	42.6×	0.026	CFTR
Ub-specific processing proteases	1	26.6×	0.040	CFTR
Transport of small molecules	1	12.6×	0.078	SCNN1B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
multicellular organismal-level water homeostasis	2	1685.2×	1e-05	SCNN1B, CFTR
aldosterone metabolic process	1	4213.0×	0.003	SCNN1B
leukocyte activation involved in inflammatory response	1	2808.7×	0.003	SCNN1B
intracellular pH elevation	1	2808.7×	0.003	CFTR
sensory perception of salty taste	1	2106.5×	0.003	SCNN1B
neutrophil-mediated killing of bacterium	1	2106.5×	0.003	SCNN1B
transepithelial water transport	1	1685.2×	0.003	CFTR
positive regulation of enamel mineralization	1	1685.2×	0.003	CFTR
cellular response to aldosterone	1	1203.7×	0.003	SCNN1B
epithelial fluid transport	1	1053.2×	0.003	SCNN1B
cellular response to vasopressin	1	1053.2×	0.003	SCNN1B
neutrophil activation involved in immune response	1	936.2×	0.003	SCNN1B
artery smooth muscle contraction	1	936.2×	0.003	SCNN1B
membrane hyperpolarization	1	936.2×	0.003	CFTR
sensory perception of sour taste	1	842.6×	0.003	SCNN1B
amelogenesis	1	702.2×	0.004	CFTR
erythrocyte homeostasis	1	648.1×	0.004	SCNN1B
mucus secretion	1	648.1×	0.004	SCNN1B
renal system process	1	561.7×	0.004	SCNN1B
cellular response to forskolin	1	561.7×	0.004	CFTR
water transport	1	495.6×	0.004	CFTR
sodium ion homeostasis	1	468.1×	0.004	SCNN1B
bicarbonate transport	1	401.2×	0.004	CFTR
intracellular sodium ion homeostasis	1	383.0×	0.004	SCNN1B
potassium ion homeostasis	1	383.0×	0.004	SCNN1B
cholesterol transport	1	366.4×	0.004	CFTR
cellular response to acidic pH	1	366.4×	0.004	SCNN1B
sperm capacitation	1	337.0×	0.004	CFTR
sodium ion import across plasma membrane	1	312.1×	0.005	SCNN1B
response to food	1	247.8×	0.006	SCNN1B

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 4 evidence-associated genes (50%) 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
CFTR	IVACAFTOR

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CFTR	14	4
SCNN1B	0	0
CFTR-AS1	0	0
CFTR-AS2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
IVACAFTOR	4	CFTR
LUMACAFTOR	4	CFTR
TEZACAFTOR	4	CFTR
ELEXACAFTOR	4	CFTR
GLYBURIDE	4	CFTR
RUTIN	3	CFTR
BAMOCAFTOR	3	CFTR
QUERCETIN	3	CFTR
GALICAFTOR	2	CFTR
GENISTEIN	2	CFTR
ICENTICAFTOR	2	CFTR
NAVOCAFTOR	2	CFTR
RISELCAFTOR	2	CFTR
GLPG-2737	2	CFTR

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CFTR	520	Binding:497, Functional:17, ADMET:5, Toxicity:1
SCNN1B	5	Binding:3, ADMET:1, Functional:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CFTR	2.7.4.3, 5.6.1.6	adenylate kinase, channel-conductance-controlling ATPase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
CFTR	520

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 1.

Cohort genes with a CPIC/DPWG dosing guideline

Symbol	CPIC guidelines
CFTR	1

Chemical tractability of cohort targets

14 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)
IVACAFTOR	4	CFTR
LUMACAFTOR	4	CFTR
TEZACAFTOR	4	CFTR
ELEXACAFTOR	4	CFTR
GLYBURIDE	4	CFTR
RUTIN	3	CFTR
BAMOCAFTOR	3	CFTR
QUERCETIN	3	CFTR
GALICAFTOR	2	CFTR
GENISTEIN	2	CFTR
ICENTICAFTOR	2	CFTR
NAVOCAFTOR	2	CFTR
RISELCAFTOR	2	CFTR
GLPG-2737	2	CFTR

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CFTR
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	3	SCNN1B, CFTR-AS1, CFTR-AS2

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SCNN1B	5	CFTR
CFTR-AS1	0	—
CFTR-AS2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.