pseudohypoaldosteronism, type IB2, autosomal recessive

Summary

pseudohypoaldosteronism, type IB2, autosomal recessive (MONDO:0859317) 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: 128

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pseudohypoaldosteronism, type IB2, autosomal recessive
Mondo ID	MONDO:0859317
OMIM	620125
UMLS	C5774255
MedGen	1824028
GARD	0026693
Is cancer (heuristic)	no

Data availability: 128 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › pseudohypoaldosteronism, type IB2, autosomal recessive

Related subtypes (218): immunodeficiency-centromeric instability-facial anomalies syndrome, hypercalcemia, infantile, Ochoa syndrome, autosomal recessive Ehlers-Danlos syndrome, vascular type, hydrolethalus syndrome, 3-M syndrome, isolated hyperchlorhidrosis, dacryocystitis-osteopoikilosis syndrome, Hutchinson-Gilford progeria syndrome, achalasia microcephaly syndrome, acrorenal syndrome, autosomal recessive, beta-ketothiolase deficiency, autosomal recessive Alport syndrome, Alstrom syndrome, microphthalmia with limb anomalies, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, Behr syndrome, bifid nose, autosomal recessive, Bloom syndrome, Bowen-Conradi syndrome, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, heart defects-limb shortening syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, COFS syndrome, craniometaphyseal dysplasia, autosomal recessive, Fraser syndrome, cystic fibrosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, persistent hyperplastic primary vitreous, autosomal recessive, Donnai-Barrow syndrome, Schöpf-Schulz-Passarge syndrome, cleft lip/palate-ectodermal dysplasia syndrome, Ellis-van Creveld syndrome, Wolcott-Rallison syndrome, autosomal recessive faciodigitogenital syndrome, acromesomelic dysplasia 2B, brittle cornea syndrome, triple-A syndrome, autosomal recessive humeroradial synostosis, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, hydrocephalus, nonsyndromic, autosomal recessive 1, autosomal recessive hydrocephalus due to congenital stenosis of aqueduct of Sylvius, hypertelorism, microtia, facial clefting syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, Vici syndrome, Johanson-Blizzard syndrome, autosomal recessive Kenny-Caffey syndrome, Papillon-Lefevre disease, Haim-Munk syndrome, Laurence-Moon syndrome, Donohue syndrome, lipase deficiency, combined, autosomal recessive familial Mediterranean fever, thiamine-responsive megaloblastic anemia syndrome, cartilage-hair hypoplasia, Nijmegen breakage syndrome, pseudo-TORCH syndrome, Galloway-Mowat syndrome, mulibrey nanism, myotonia congenita, autosomal recessive, Schwartz-Jampel syndrome, proteosome-associated autoinflammatory syndrome, Netherton syndrome, Niemann-Pick disease type A, oculodentodigital dysplasia, autosomal recessive, odonto-onycho-dermal dysplasia, autosomal recessive omodysplasia, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, phenylketonuria, Bjornstad syndrome, Laron syndrome, autosomal recessive polycystic kidney disease, autosomal recessive inherited pseudoxanthoma elasticum, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, short-rib thoracic dysplasia 9 with or without polydactyly, autosomal recessive Robinow syndrome, Sjogren-Larsson syndrome, scapuloperoneal spinal muscular atrophy, autosomal recessive, spondyloepiphyseal dysplasia tarda, autosomal recessive, inherited threoninemia, Pendred syndrome, autosomal recessive spondylocostal dysostosis, Werner syndrome, ABCD syndrome, Naxos disease, autosomal recessive amelia, human HOXA1 syndromes, sickle cell disease, autosomal recessive proximal renal tubular acidosis, hyper-IgM syndrome type 2, temtamy preaxial brachydactyly syndrome, TH-deficient dopa-responsive dystonia, craniosynostosis syndrome, autosomal recessive, Niemann-Pick disease type B, skin fragility-woolly hair-palmoplantar keratoderma syndrome, CoQ-responsive OXPHOS deficiency, familial adenomatous polyposis 2, Pierson syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, cardiomyopathy-hypotonia-lactic acidosis syndrome, PHARC syndrome, Kahrizi syndrome, cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies, congenital prothrombin deficiency, immunodeficiency 31B, dyskeratosis congenita, autosomal recessive 2, dyskeratosis congenita, autosomal recessive 3, Nestor-Guillermo progeria syndrome, leukoencephalopathy with calcifications and cysts, mitochondrial pyruvate carrier deficiency, branched-chain keto acid dehydrogenase kinase deficiency, dyskeratosis congenita, autosomal recessive 5, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, alacrima, achalasia, and intellectual disability syndrome, hyperlipoproteinemia, type 1D, microcephaly and chorioretinopathy 2, congenital stationary night blindness 1G, combined oxidative phosphorylation deficiency 29, hypermanganesemia with dystonia 2, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, gnb5-related intellectual disability-cardiac arrhythmia syndrome, autosomal recessive spastic paraplegia type 78, autosomal recessive limb-girdle muscular dystrophy, Bardet-Biedl syndrome, autosomal recessive cerebellar ataxia, neuronopathy, distal hereditary motor, autosomal recessive, UV-sensitive syndrome, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Cockayne syndrome, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, leukoencephalopathy-palmoplantar keratoderma syndrome, autosomal recessive hypohidrotic ectodermal dysplasia, Warburg micro syndrome, autosomal recessive primary microcephaly, autosomal recessive progressive external ophthalmoplegia, Meier-Gorlin syndrome, autosomal recessive sideroblastic anemia, autosomal recessive intermediate Charcot-Marie-Tooth disease, Perrault syndrome, autosomal recessive hypophosphatemic rickets, de Barsy syndrome, leukocyte adhesion deficiency, Senior-Loken syndrome, autosomal recessive spastic ataxia, childhood-onset autosomal recessive myopathy with external ophthalmoplegia, autosomal recessive cerebral atrophy, GM3 synthase deficiency, autosomal recessive distal renal tubular acidosis, pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome, autosomal recessive brachyolmia, Aicardi-Goutieres syndrome, homocystinuria without methylmalonic aciduria, Niemann-Pick disease type C, nephronophthisis, autosomal recessive osteopetrosis, peroxisome biogenesis disorder, congenital non-bullous ichthyosiform erythroderma, Seckel syndrome, Usher syndrome, autosomal recessive cutis laxa type 1, autosomal recessive cutis laxa type 2, hearing loss, autosomal recessive, microcephaly, growth restriction, and increased sister chromatid exchange 2, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1, congenital vertebral-cardiac-renal anomalies syndrome, hair defect with photosensitivity and intellectual disability syndrome, autosomal recessive severe congenital neutropenia, severe combined immunodeficiency due to CARMIL2 deficiency, extraoral halitosis due to methanethiol oxidase deficiency, neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, mitochondrial complex 2 deficiency, nuclear type 3, mitochondrial complex 2 deficiency, nuclear type 4, mismatch repair cancer syndrome, spondyloepimetaphyseal dysplasia with joint laxity, type 3, Kilquist syndrome, Duane anomaly-myopathy-scoliosis syndrome, autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome, congenital myopathy with reduced type 2 muscle fibers, NAD(P)HX dehydratase deficiency, autosomal recessive ocular albinism, ichthyosis linearis circumflexa, eosinophil peroxidase deficiency, hyperphenylalaninemia due to DNAJC12 deficiency, autosomal recessive epidermolytic ichthyosis, Ehlers-Danlos syndrome, classic-like, 2, joint laxity, short stature, and myopia, HELIX syndrome, auditory neuropathy-optic atrophy syndrome, glycosylphosphatidylinositol biosynthesis defect 15, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, SCN4A-related myopathy, autosomal recessive, Uner Tan Syndrome, nephropathic cystinosis, Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome type 2, permanent neonatal diabetes mellitus 1, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, Rajab interstitial lung disease with brain calcifications 1, Roberts-SC phocomelia syndrome, neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, RPE65-related recessive retinopathy, GUCY2D-related recessive retinopathy, autosomal recessive titinopathy, intellectual disability, autosomal recessive, ALPL-related autosomal recessive hypophosphatasia, spastic paraplegia 18b, autosomal recessive, CEP164-related ciliopathy, RP1-related recessive retinopathy, pseudohypoaldosteronism, type IB3, autosomal recessive, spastic paraplegia 30B, autosomal recessive, cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, brain small vessel disease 2B, autosomal recessive, IMPG1-related recessive retinopathy, PROM1-related recessive retinopathy

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

128 retrieved; paginated sample, class counts are floors:

87 uncertain significance, 16 conflicting classifications of pathogenicity, 10 likely pathogenic, 6 pathogenic, 5 pathogenic/likely pathogenic, 2 likely benign, 1 benign/likely benign, 1 benign

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
2577438	NM_000336.3(SCNN1B):c.84G>A (p.Trp28Ter)	SCNN1B	Pathogenic	no assertion criteria provided
2664487	NM_000336.3(SCNN1B):c.1271-1G>C	SCNN1B	Pathogenic	no assertion criteria provided
2664488	NM_000336.3(SCNN1B):c.87C>A (p.Tyr29Ter)	SCNN1B	Pathogenic	no assertion criteria provided
2664489	NM_000336.3(SCNN1B):c.1346+1G>A	SCNN1B	Pathogenic	no assertion criteria provided
3338256	NM_000336.3(SCNN1B):c.1404+1G>T	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
870735	NM_000336.3(SCNN1B):c.1542+1G>A	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
8836	NM_000336.3(SCNN1B):c.1849C>T (p.Pro617Ser)	SCNN1B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
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
3767335	NM_000336.3(SCNN1B):c.655T>G (p.Tyr219Asp)	SCNN1B	Likely pathogenic	criteria provided, single submitter
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
318421	NM_000336.3(SCNN1B):c.428C>T (p.Ser143Phe)	SCNN1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
318447	NM_000336.3(SCNN1B):c.1900G>C (p.Asp634His)	SCNN1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3380378	NM_000336.3(SCNN1B):c.1032C>T (p.Ile344=)	SCNN1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3579955	NM_000336.3(SCNN1B):c.178G>A (p.Ala60Thr)	SCNN1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3580020	NM_000336.3(SCNN1B):c.1847dup (p.Pro617fs)	SCNN1B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
561264	NM_000336.3(SCNN1B):c.1688G>A (p.Arg563Gln)	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 recessive	pseudohypoaldosteronism, type IB2, autosomal recessive	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.