Liddle syndrome 1

Summary

Liddle syndrome 1 (MONDO:0020607) is a disease caused by SCNN1B (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: SCNN1B (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 195

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Liddle syndrome 1
Mondo ID	MONDO:0020607
OMIM	177200
GARD	0025186
Is cancer (heuristic)	no

Also known as: Liddle syndrome 1 · Liddle syndrome caused by mutation in SCNN1B · LIDLS1 · SCNN1B Liddle syndrome

Data availability: 195 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › Liddle syndrome › Liddle syndrome 1

Related subtypes (2): Liddle syndrome 2, Liddle syndrome 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

195 retrieved; paginated sample, class counts are floors:

109 uncertain significance, 40 conflicting classifications of pathogenicity, 13 likely pathogenic, 11 benign/likely benign, 6 benign, 6 pathogenic, 6 likely benign, 4 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323566	NM_000336.3(SCNN1B):c.648dup (p.Glu217fs)	SCNN1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1705177	NM_000336.3(SCNN1B):c.1850C>T (p.Pro617Leu)	SCNN1B	Pathogenic	criteria provided, single submitter
805492	NM_000336.3(SCNN1B):c.1852C>T (p.Pro618Ser)	SCNN1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8830	NM_000336.3(SCNN1B):c.1696C>T (p.Arg566Ter)	SCNN1B	Pathogenic	criteria provided, multiple submitters, no conflicts
8831	NM_000336.3(SCNN1B):c.1847C>T (p.Pro616Leu)	SCNN1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8833	NM_000336.3(SCNN1B):c.1858T>C (p.Tyr620His)	SCNN1B	Pathogenic	no assertion criteria provided
8834	SCNN1B, 1-BP INS, 592C	SCNN1B	Pathogenic	no assertion criteria provided
8835	NM_000336.3(SCNN1B):c.1735_1766del (p.Ala579Leufs*4)	SCNN1B	Pathogenic	no assertion criteria provided
8836	NM_000336.3(SCNN1B):c.1849C>T (p.Pro617Ser)	SCNN1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
8837	NM_000336.3(SCNN1B):c.1847C>G (p.Pro616Arg)	SCNN1B	Pathogenic	no assertion criteria provided
3579970	NM_000336.3(SCNN1B):c.653G>A (p.Trp218Ter)	SCNN1B	Likely pathogenic	criteria provided, single submitter
3579980	NM_000336.3(SCNN1B):c.964G>T (p.Glu322Ter)	SCNN1B	Likely pathogenic	criteria provided, single submitter
3579987	NM_000336.3(SCNN1B):c.1054C>T (p.Gln352Ter)	SCNN1B	Likely pathogenic	criteria provided, single submitter
3579989	NM_000336.3(SCNN1B):c.1074C>G (p.Tyr358Ter)	SCNN1B	Likely pathogenic	criteria provided, single submitter
3579991	NM_000336.3(SCNN1B):c.1212C>A (p.Tyr404Ter)	SCNN1B	Likely pathogenic	criteria provided, single submitter
3579992	NM_000336.3(SCNN1B):c.1228del (p.Arg410fs)	SCNN1B	Likely pathogenic	criteria provided, single submitter
3579997	NM_000336.3(SCNN1B):c.1314_1315del (p.Glu438fs)	SCNN1B	Likely pathogenic	criteria provided, single submitter
3579998	NM_000336.3(SCNN1B):c.1312_1315del (p.Glu438fs)	SCNN1B	Likely pathogenic	criteria provided, single submitter
3580021	NM_000336.3(SCNN1B):c.1849C>A (p.Pro617Thr)	SCNN1B	Likely pathogenic	criteria provided, single submitter
4278315	NM_000336.3(SCNN1B):c.1487A>G (p.Asn496Ser)	SCNN1B	Likely pathogenic	criteria provided, single submitter
4820202	NM_000336.3(SCNN1B):c.1853C>G (p.Pro618Arg)	SCNN1B	Likely pathogenic	criteria provided, single submitter
4845410	NM_000336.3(SCNN1B):c.1783_1784insT (p.Ala595fs)	SCNN1B	Likely pathogenic	criteria provided, single submitter
8838	NM_000336.3(SCNN1B):c.800C>T (p.Pro267Leu)	SCNN1B	Likely pathogenic	criteria provided, single submitter
178803	NM_000336.3(SCNN1B):c.1221A>G (p.Pro407=)	SCNN1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
229239	NM_000336.3(SCNN1B):c.1706C>T (p.Ala569Val)	SCNN1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2646319	NM_000336.3(SCNN1B):c.943G>A (p.Gly315Arg)	SCNN1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3022839	NM_000336.3(SCNN1B):c.1466+18C>T	SCNN1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3025040	NM_000336.3(SCNN1B):c.153G>A (p.Met51Ile)	SCNN1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
318419	NM_000336.3(SCNN1B):c.246C>T (p.Ser82=)	SCNN1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
318421	NM_000336.3(SCNN1B):c.428C>T (p.Ser143Phe)	SCNN1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 3 · 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	Definitive	Autosomal dominant	Liddle syndrome 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

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
SCNN1B	HGNC:10600	ENSG00000168447	P51168	Epithelial sodium channel subunit beta	gencc,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.

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)
SCNN1B	Other/Unknown	no		ENaC, ENaC_chordates, ENaC_CS

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
esophagus mucosa	1
lower esophagus mucosa	1
rectum	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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCNN1B	1,013

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCNN1B	P51168	5

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
Sensory perception of salty taste	1	1903.3×	0.003	SCNN1B
Sensory perception of taste	1	335.9×	0.009	SCNN1B
Stimuli-sensing channels	1	135.9×	0.013	SCNN1B
Ion channel transport	1	96.0×	0.013	SCNN1B
Sensory Perception	1	95.2×	0.013	SCNN1B
Transport of small molecules	1	25.1×	0.040	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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
aldosterone metabolic process	1	8426.0×	0.001	SCNN1B
leukocyte activation involved in inflammatory response	1	5617.3×	0.001	SCNN1B
sensory perception of salty taste	1	4213.0×	0.001	SCNN1B
neutrophil-mediated killing of bacterium	1	4213.0×	0.001	SCNN1B
cellular response to aldosterone	1	2407.4×	0.001	SCNN1B
epithelial fluid transport	1	2106.5×	0.001	SCNN1B
cellular response to vasopressin	1	2106.5×	0.001	SCNN1B
neutrophil activation involved in immune response	1	1872.4×	0.001	SCNN1B
artery smooth muscle contraction	1	1872.4×	0.001	SCNN1B
multicellular organismal-level water homeostasis	1	1685.2×	0.001	SCNN1B
sensory perception of sour taste	1	1685.2×	0.001	SCNN1B
erythrocyte homeostasis	1	1296.3×	0.002	SCNN1B
mucus secretion	1	1296.3×	0.002	SCNN1B
renal system process	1	1123.5×	0.002	SCNN1B
sodium ion homeostasis	1	936.2×	0.002	SCNN1B
intracellular sodium ion homeostasis	1	766.0×	0.002	SCNN1B
potassium ion homeostasis	1	766.0×	0.002	SCNN1B
cellular response to acidic pH	1	732.7×	0.002	SCNN1B
sodium ion import across plasma membrane	1	624.1×	0.002	SCNN1B
response to food	1	495.6×	0.003	SCNN1B
lung alveolus development	1	351.1×	0.004	SCNN1B
regulation of blood pressure	1	221.7×	0.005	SCNN1B
sodium ion transmembrane transport	1	203.0×	0.006	SCNN1B
multicellular organism growth	1	137.0×	0.008	SCNN1B
gene expression	1	79.9×	0.013	SCNN1B
response to xenobiotic stimulus	1	69.1×	0.014	SCNN1B

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
SCNN1B	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
SCNN1B	5	Binding:3, ADMET:1, Functional:1

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	SCNN1B

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)
SCNN1B	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.