Warburg micro syndrome 4

Summary

Warburg micro syndrome 4 (MONDO:0014296) is a disease caused by TBC1D20 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: TBC1D20 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 12

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Warburg micro syndrome 4
Mondo ID	MONDO:0014296
OMIM	615663
DOID	DOID:0110719
UMLS	C3810265
MedGen	816595
GARD	0015998
Is cancer (heuristic)	no

Also known as: TBC1D20 Warburg micro syndrome · WARBM4 · Warburg micro syndrome 4 · Warburg micro syndrome caused by mutation in TBC1D20 · Warburg micro syndrome type 4

Data availability: 12 ClinVar variants · 4 GenCC gene-disease records.

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 › Warburg micro syndrome › Warburg micro syndrome 4

Related subtypes (3): Warburg micro syndrome 1, Warburg micro syndrome 3, Warburg micro syndrome 2

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

12 retrieved; paginated sample, class counts are floors:

6 pathogenic, 3 uncertain significance, 3 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
100774	NM_144628.4(TBC1D20):c.199C>T (p.Arg67Ter)	TBC1D20	Pathogenic	no assertion criteria provided
100775	NM_144628.4(TBC1D20):c.292C>T (p.Gln98Ter)	TBC1D20	Pathogenic	no assertion criteria provided
100776	NM_144628.4(TBC1D20):c.352_353del (p.Gln118fs)	TBC1D20	Pathogenic	no assertion criteria provided
100777	NM_144628.4(TBC1D20):c.672G>A (p.Trp224Ter)	TBC1D20	Pathogenic	no assertion criteria provided
100778	NM_144628.4(TBC1D20):c.(70+1_71-1)(*3107+1?)del	TBC1D20	Pathogenic	no assertion criteria provided
3906950	NM_144628.4(TBC1D20):c.474C>T (p.Gly158=)	TBC1D20	Pathogenic	criteria provided, single submitter
1029160	NM_144628.4(TBC1D20):c.874A>G (p.Ile292Val)	TBC1D20	Uncertain significance	criteria provided, single submitter
2366105	NM_144628.4(TBC1D20):c.407G>A (p.Arg136His)	TBC1D20	Uncertain significance	criteria provided, multiple submitters, no conflicts
976405	NM_144628.4(TBC1D20):c.932C>A (p.Ala311Asp)	TBC1D20	Uncertain significance	criteria provided, single submitter
1185299	NM_144628.4(TBC1D20):c.71-210G>A	TBC1D20	Benign	criteria provided, multiple submitters, no conflicts
670224	NM_144628.4(TBC1D20):c.71-49T>G	TBC1D20	Benign	criteria provided, multiple submitters, no conflicts
670225	NM_144628.4(TBC1D20):c.337+88G>T	TBC1D20	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
TBC1D20	Definitive	Autosomal recessive	Warburg micro syndrome 4	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TBC1D20	Orphanet:2510	Micro 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
TBC1D20	HGNC:16133	ENSG00000125875	Q96BZ9	TBC1 domain family member 20	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TBC1D20	TBC1 domain family member 20	GTPase-activating protein (GAP) specific for Rab1 and Rab2 small GTPase families for which it can accelerate the intrinsic GTP hydrolysis rate by more than five orders of magnitude.

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)
TBC1D20	Other/Unknown	no		Rab-GAP-TBC_dom, Rab-GAP_TBC_sf, TBC20/Gyp8-like

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
medial globus pallidus	1
parotid gland	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TBC1D20	252	ubiquitous	marker	tendon of biceps brachii, medial globus pallidus, parotid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TBC1D20	1,105

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TBC1D20	Q96BZ9	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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
Rab regulation of trafficking	1	368.4×	0.019	TBC1D20
TBC/RABGAPs	1	259.6×	0.019	TBC1D20
COPII-mediated vesicle transport	1	163.1×	0.019	TBC1D20
ER to Golgi Anterograde Transport	1	132.8×	0.019	TBC1D20
Transport to the Golgi and subsequent modification	1	102.9×	0.019	TBC1D20
Asparagine N-linked glycosylation	1	60.1×	0.028	TBC1D20
Membrane Trafficking	1	37.1×	0.036	TBC1D20
Vesicle-mediated transport	1	34.8×	0.036	TBC1D20
Post-translational protein modification	1	19.2×	0.058	TBC1D20
Metabolism of proteins	1	12.4×	0.081	TBC1D20

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
positive regulation by virus of viral protein levels in host cell	1	4213.0×	0.002	TBC1D20
positive regulation of ER to Golgi vesicle-mediated transport	1	3370.4×	0.002	TBC1D20
lens fiber cell morphogenesis	1	2106.5×	0.002	TBC1D20
host-mediated activation of viral genome replication	1	1685.2×	0.002	TBC1D20
virion assembly	1	1532.0×	0.002	TBC1D20
COPII-coated vesicle cargo loading	1	991.3×	0.002	TBC1D20
lipid droplet organization	1	936.2×	0.002	TBC1D20
seminiferous tubule development	1	766.0×	0.002	TBC1D20
acrosome assembly	1	455.5×	0.003	TBC1D20
positive regulation of GTPase activity	1	276.3×	0.004	TBC1D20
endoplasmic reticulum to Golgi vesicle-mediated transport	1	135.9×	0.007	TBC1D20
Golgi organization	1	133.8×	0.007	TBC1D20

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
TBC1D20	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	TBC1D20

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)
TBC1D20	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.