pseudohypoaldosteronism, type IB3, autosomal recessive

Summary

pseudohypoaldosteronism, type IB3, autosomal recessive (MONDO:0859318) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 96

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pseudohypoaldosteronism, type IB3, autosomal recessive
Mondo ID	MONDO:0859318
OMIM	620126
UMLS	C5774256
MedGen	1824029
GARD	0026694
Is cancer (heuristic)	no

Data availability: 96 ClinVar variants.

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 IB3, 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 IB2, 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

96 retrieved; paginated sample, class counts are floors:

88 uncertain significance, 4 conflicting classifications of pathogenicity, 3 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
8825	NM_001039.4(SCNN1G):c.1570-1G>A	SCNN1G	Pathogenic	no assertion criteria provided
8826	NM_001039.4(SCNN1G):c.318-1G>A	SCNN1G	Pathogenic	no assertion criteria provided
8827	NM_001039.4(SCNN1G):c.1627del (p.Val543fs)	SCNN1G	Pathogenic	no assertion criteria provided
3579896	NM_001039.4(SCNN1G):c.416_417del (p.Glu139fs)	SCNN1G	Likely pathogenic	criteria provided, single submitter
2883968	NM_001039.4(SCNN1G):c.1550T>A (p.Met517Lys)	SCNN1G	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
318350	NM_001039.4(SCNN1G):c.538C>T (p.Arg180Trp)	SCNN1G	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
318359	NM_001039.4(SCNN1G):c.1589A>G (p.Asn530Ser)	SCNN1G	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
318360	NM_001039.4(SCNN1G):c.1827G>C (p.Leu609Phe)	SCNN1G	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1185021	NM_001039.4(SCNN1G):c.1532T>A (p.Leu511Gln)	SCNN1G	Uncertain significance	criteria provided, multiple submitters, no conflicts
1304028	NM_001039.4(SCNN1G):c.1874C>G (p.Pro625Arg)	SCNN1G	Uncertain significance	criteria provided, multiple submitters, no conflicts
1313539	NM_001039.4(SCNN1G):c.470G>A (p.Arg157Gln)	SCNN1G	Uncertain significance	criteria provided, multiple submitters, no conflicts
1331727	NM_001039.4(SCNN1G):c.564C>A (p.His188Gln)	SCNN1G	Uncertain significance	criteria provided, multiple submitters, no conflicts
2068785	NM_001039.4(SCNN1G):c.835A>T (p.Met279Leu)	SCNN1G	Uncertain significance	criteria provided, multiple submitters, no conflicts
2074030	NM_001039.4(SCNN1G):c.436G>A (p.Val146Ile)	SCNN1G	Uncertain significance	criteria provided, multiple submitters, no conflicts
2075492	NM_001039.4(SCNN1G):c.1779_1781dup (p.Pro594_Ala595insPro)	SCNN1G	Uncertain significance	criteria provided, multiple submitters, no conflicts
2184220	NM_001039.4(SCNN1G):c.1868C>T (p.Pro623Leu)	SCNN1G	Uncertain significance	criteria provided, multiple submitters, no conflicts
2435777	NM_001039.4(SCNN1G):c.1082A>T (p.Glu361Val)	SCNN1G	Uncertain significance	criteria provided, multiple submitters, no conflicts
2435778	NM_001039.4(SCNN1G):c.1808C>G (p.Pro603Arg)	SCNN1G	Uncertain significance	criteria provided, multiple submitters, no conflicts
2514019	NM_001039.4(SCNN1G):c.1465G>C (p.Gly489Arg)	SCNN1G	Uncertain significance	criteria provided, multiple submitters, no conflicts
2549831	NM_001039.4(SCNN1G):c.326C>G (p.Thr109Ser)	SCNN1G	Uncertain significance	criteria provided, multiple submitters, no conflicts
2556560	NM_001039.4(SCNN1G):c.1576A>T (p.Met526Leu)	SCNN1G	Uncertain significance	criteria provided, multiple submitters, no conflicts
2610511	NM_001039.4(SCNN1G):c.1131T>G (p.Ser377Arg)	SCNN1G	Uncertain significance	criteria provided, multiple submitters, no conflicts
2631991	NM_001039.4(SCNN1G):c.1072C>T (p.His358Tyr)	SCNN1G	Uncertain significance	criteria provided, single submitter
2633627	NM_001039.4(SCNN1G):c.1874C>T (p.Pro625Leu)	SCNN1G	Uncertain significance	criteria provided, multiple submitters, no conflicts
2731600	NM_001039.4(SCNN1G):c.551G>T (p.Gly184Val)	SCNN1G	Uncertain significance	criteria provided, multiple submitters, no conflicts
2732418	NM_001039.4(SCNN1G):c.410G>A (p.Arg137His)	SCNN1G	Uncertain significance	criteria provided, multiple submitters, no conflicts
2895778	NM_001039.4(SCNN1G):c.899G>C (p.Gly300Ala)	SCNN1G	Uncertain significance	criteria provided, multiple submitters, no conflicts
2897266	NM_001039.4(SCNN1G):c.1891C>T (p.Arg631Cys)	SCNN1G	Uncertain significance	criteria provided, multiple submitters, no conflicts
2972605	NM_001039.4(SCNN1G):c.896T>C (p.Met299Thr)	SCNN1G	Uncertain significance	criteria provided, multiple submitters, no conflicts
2978189	NM_001039.4(SCNN1G):c.1798G>A (p.Asp600Asn)	SCNN1G	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SCNN1G	Orphanet:171876	Generalized pseudohypoaldosteronism type 1
SCNN1G	Orphanet:526	Liddle syndrome
SCNN1G	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
SCNN1G	HGNC:10602	ENSG00000166828	P51170	Epithelial sodium channel subunit gamma	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SCNN1G	Epithelial sodium channel subunit gamma	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)
SCNN1G	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
bronchial epithelial cell	1
kidney epithelium	1
renal medulla	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SCNN1G	133	broad	marker	renal medulla, kidney epithelium, bronchial epithelial cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SCNN1G	1,037

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SCNN1G	P51170	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	SCNN1G
Sensory perception of taste	1	335.9×	0.009	SCNN1G
Stimuli-sensing channels	1	135.9×	0.013	SCNN1G
Ion channel transport	1	96.0×	0.013	SCNN1G
Sensory Perception	1	95.2×	0.013	SCNN1G
Transport of small molecules	1	25.1×	0.040	SCNN1G

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
sensory perception of salty taste	1	4213.0×	0.001	SCNN1G
cellular response to aldosterone	1	2407.4×	0.001	SCNN1G
cellular response to vasopressin	1	2106.5×	0.001	SCNN1G
multicellular organismal-level water homeostasis	1	1685.2×	0.001	SCNN1G
sensory perception of sour taste	1	1685.2×	0.001	SCNN1G
sodium ion homeostasis	1	936.2×	0.002	SCNN1G
intracellular sodium ion homeostasis	1	766.0×	0.002	SCNN1G
cellular response to acidic pH	1	732.7×	0.002	SCNN1G
sodium ion import across plasma membrane	1	624.1×	0.002	SCNN1G
regulation of blood pressure	1	221.7×	0.005	SCNN1G
sodium ion transmembrane transport	1	203.0×	0.005	SCNN1G

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
SCNN1G	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
SCNN1G	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	SCNN1G

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)
SCNN1G	5	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.