Nephrotic syndrome, type 20

Summary

Nephrotic syndrome, type 20 (MONDO:0026726) is a disease caused by TBC1D8B (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: TBC1D8B (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 25

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nephrotic syndrome, type 20
Mondo ID	MONDO:0026726
OMIM	301028
DOID	DOID:0070357
UMLS	C5193011
MedGen	1678854
GARD	0015285
Is cancer (heuristic)	no

Also known as: NPHS20

Data availability: 25 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › nephrotic syndrome › familial nephrotic syndrome › nephrotic syndrome, type 20

Related subtypes (17): congenital nephrotic syndrome, Finnish type, nephrotic syndrome, type 4, LAMB2-related infantile-onset nephrotic syndrome, immunoglobulin-mediated membranoproliferative glomerulonephritis, familial idiopathic steroid-resistant nephrotic syndrome, nephrotic syndrome, type 22, nephrotic syndrome, type 23, nephrotic syndrome, type 24, nephrotic syndrome, IIa 26, nephrotic syndrome, type 17, nephrotic syndrome, type 18, nephrotic syndrome, type 19, nephrotic syndrome, type 21, nephrotic syndrome 14, nephrotic syndrome 15, nephrotic syndrome 16, idiopathic multidrug-resistant nephrotic syndrome

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

25 retrieved; paginated sample, class counts are floors:

13 uncertain significance, 5 likely pathogenic, 4 pathogenic, 2 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1013501	NM_017752.3(TBC1D8B):c.2338A>T (p.Thr780Ser)	TBC1D8B	Pathogenic	no assertion criteria provided
1013502	NM_017752.3(TBC1D8B):c.190C>T (p.Arg64Cys)	TBC1D8B	Pathogenic	no assertion criteria provided
1013503	NM_017752.3(TBC1D8B):c.1383G>A (p.Trp461Ter)	TBC1D8B	Pathogenic	no assertion criteria provided
4819038	NM_017752.3(TBC1D8B):c.1463_1467del (p.Ile488fs)	TBC1D8B	Pathogenic	criteria provided, single submitter
3066339	NM_017752.3(TBC1D8B):c.421C>T (p.Arg141Ter)	TBC1D8B	Likely pathogenic	criteria provided, single submitter
3338671	NM_017752.3(TBC1D8B):c.2091del (p.Asp698fs)	TBC1D8B	Likely pathogenic	criteria provided, single submitter
3894571	NM_017752.3(TBC1D8B):c.607del (p.Asp203fs)	TBC1D8B	Likely pathogenic	criteria provided, single submitter
635779	NM_017752.3(TBC1D8B):c.738G>C (p.Gln246His)	TBC1D8B	Likely pathogenic	criteria provided, single submitter
635780	NM_017752.3(TBC1D8B):c.872T>C (p.Phe291Ser)	TBC1D8B	Likely pathogenic	criteria provided, single submitter
2200565	NM_017752.3(TBC1D8B):c.922T>C (p.Trp308Arg)	TBC1D8B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3068691	NM_017752.3(TBC1D8B):c.3062G>A (p.Ser1021Asn)	TBC1D8B	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1344699	NM_017752.3(TBC1D8B):c.1030C>T (p.Arg344Ter)	TBC1D8B	Uncertain significance	criteria provided, single submitter
2072366	NM_017752.3(TBC1D8B):c.104_106dup (p.Gly35_Glu36insGly)	TBC1D8B	Uncertain significance	criteria provided, multiple submitters, no conflicts
2436965	NM_017752.3(TBC1D8B):c.1165G>A (p.Gly389Arg)	TBC1D8B	Uncertain significance	criteria provided, multiple submitters, no conflicts
2436966	NM_017752.3(TBC1D8B):c.163G>A (p.Asp55Asn)	TBC1D8B	Uncertain significance	criteria provided, multiple submitters, no conflicts
2585132	NM_017752.3(TBC1D8B):c.2209C>T (p.His737Tyr)	TBC1D8B	Uncertain significance	criteria provided, single submitter
2585262	NM_017752.3(TBC1D8B):c.245C>A (p.Ala82Asp)	TBC1D8B	Uncertain significance	criteria provided, single submitter
3068408	NM_017752.3(TBC1D8B):c.20A>G (p.Glu7Gly)	TBC1D8B	Uncertain significance	criteria provided, single submitter
3377338	NM_017752.3(TBC1D8B):c.1732T>G (p.Leu578Val)	TBC1D8B	Uncertain significance	criteria provided, single submitter
3892601	NM_017752.3(TBC1D8B):c.2633T>C (p.Ile878Thr)	TBC1D8B	Uncertain significance	criteria provided, single submitter
3892602	NM_017752.3(TBC1D8B):c.3230T>C (p.Phe1077Ser)	TBC1D8B	Uncertain significance	criteria provided, single submitter
3897929	NM_017752.3(TBC1D8B):c.827+12T>C	TBC1D8B	Uncertain significance	criteria provided, single submitter
4291782	NM_017752.3(TBC1D8B):c.2414T>C (p.Ile805Thr)	TBC1D8B	Uncertain significance	criteria provided, single submitter
4819804	NM_017752.3(TBC1D8B):c.1838-607A>G	TBC1D8B	Uncertain significance	criteria provided, single submitter
1254057	NM_017752.3(TBC1D8B):c.2920C>T (p.Leu974Phe)	TBC1D8B	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
TBC1D8B	Strong	X-linked	nephrotic syndrome, type 20	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TBC1D8B	Orphanet:656	Hereditary steroid-resistant nephrotic syndrome

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
TBC1D8B	HGNC:24715	ENSG00000133138	Q0IIM8	TBC1 domain family member 8B	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TBC1D8B	TBC1 domain family member 8B	Involved in vesicular recycling, probably as a RAB11B GTPase-activating protein.

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)
TBC1D8B	Other/Unknown	no		Rab-GAP-TBC_dom, EF_hand_dom, GRAM

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
left adrenal gland cortex	1
right adrenal gland	1
right adrenal gland cortex	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TBC1D8B	237	ubiquitous	marker	right adrenal gland cortex, right adrenal gland, left adrenal gland cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TBC1D8B	809

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TBC1D8B	Q0IIM8	79.33

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
trans-Golgi Network Vesicle Budding	1	253.8×	0.010	TBC1D8B
Golgi Associated Vesicle Biogenesis	1	200.3×	0.010	TBC1D8B
Membrane Trafficking	1	37.1×	0.029	TBC1D8B
Vesicle-mediated transport	1	34.8×	0.029	TBC1D8B

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
glomerular filtration	1	936.2×	0.002	TBC1D8B
vesicle-mediated transport	1	96.3×	0.010	TBC1D8B

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
TBC1D8B	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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TBC1D8B

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)
TBC1D8B	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.