Warburg micro syndrome 3

Summary

Warburg micro syndrome 3 (MONDO:0013638) is a disease caused by RAB18 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: RAB18 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 118

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Warburg micro syndrome 3
Mondo ID	MONDO:0013638
OMIM	614222
DOID	DOID:0110718
UMLS	C3280203
MedGen	481833
GARD	0015778
Is cancer (heuristic)	no

Also known as: micro syndrome 3 · RAB18 Warburg micro syndrome · WARBM3 · Warburg micro syndrome 3 · Warburg micro syndrome caused by mutation in RAB18 · Warburg micro syndrome type 3

Data availability: 118 ClinVar variants · 3 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 3

Related subtypes (3): Warburg micro syndrome 1, Warburg micro syndrome 2, Warburg micro syndrome 4

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

118 retrieved; paginated sample, class counts are floors:

74 uncertain significance, 26 benign, 5 pathogenic, 5 likely benign, 3 benign/likely benign, 3 likely pathogenic, 2 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
100768	NM_021252.5(RAB18):c.284C>G (p.Thr95Arg)	RAB18	Pathogenic	no assertion criteria provided
30247	NM_021252.5(RAB18):c.71T>A (p.Leu24Gln)	RAB18	Pathogenic	no assertion criteria provided
30248	NG_032035.1:g.(5265_10701)_(10758_27654)del	RAB18	Pathogenic	no assertion criteria provided
30249	NM_021252.5(RAB18):c.274AGA[1] (p.Arg93del)	RAB18	Pathogenic	no assertion criteria provided
30250	NM_021252.5(RAB18):c.619T>C (p.Ter207Gln)	RAB18	Pathogenic	criteria provided, single submitter
3777096	NM_021252.5(RAB18):c.460del (p.Thr154fs)	RAB18	Likely pathogenic	criteria provided, single submitter
3777097	NM_021252.5(RAB18):c.272C>T (p.Thr91Ile)	RAB18	Likely pathogenic	criteria provided, single submitter
4077456	NM_021252.5(RAB18):c.125-23A>G	RAB18	Likely pathogenic	criteria provided, single submitter
299814	NM_021252.5(RAB18):c.36C>A (p.Leu12=)	LOC130003565	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
878561	NM_021252.5(RAB18):c.*419G>A	RAB18	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
299808	NM_021252.4(RAB18):c.-182G>A	LOC130003564	Uncertain significance	criteria provided, single submitter
299809	NM_021252.4(RAB18):c.-144T>A	LOC130003564	Uncertain significance	criteria provided, single submitter
1416085	NM_021252.5(RAB18):c.183A>G (p.Ile61Met)	RAB18	Uncertain significance	criteria provided, multiple submitters, no conflicts
2435348	NM_021252.5(RAB18):c.103C>T (p.Pro35Ser)	RAB18	Uncertain significance	criteria provided, single submitter
2689853	NM_021252.5(RAB18):c.199C>G (p.Gln67Glu)	RAB18	Uncertain significance	criteria provided, single submitter
299811	NM_021252.4(RAB18):c.-79T>A	RAB18	Uncertain significance	criteria provided, single submitter
299812	NM_021252.5(RAB18):c.-41A>G	RAB18	Uncertain significance	criteria provided, single submitter
299815	NM_021252.5(RAB18):c.68+10A>G	RAB18	Uncertain significance	criteria provided, single submitter
299817	NM_021252.5(RAB18):c.270C>A (p.Val90=)	RAB18	Uncertain significance	criteria provided, single submitter
299818	NM_021252.5(RAB18):c.298G>C (p.Asp100His)	RAB18	Uncertain significance	criteria provided, single submitter
299819	NM_021252.5(RAB18):c.394G>T (p.Asp132Tyr)	RAB18	Uncertain significance	criteria provided, multiple submitters, no conflicts
299820	NM_021252.5(RAB18):c.454G>A (p.Ala152Thr)	RAB18	Uncertain significance	criteria provided, single submitter
299822	NM_021252.5(RAB18):c.*62C>T	RAB18	Uncertain significance	criteria provided, single submitter
299823	NM_021252.5(RAB18):c.*99C>T	RAB18	Uncertain significance	criteria provided, single submitter
299827	NM_021252.5(RAB18):c.*325C>G	RAB18	Uncertain significance	criteria provided, single submitter
299828	NM_021252.5(RAB18):c.*382C>T	RAB18	Uncertain significance	criteria provided, single submitter
299830	NM_021252.5(RAB18):c.*402T>C	RAB18	Uncertain significance	criteria provided, multiple submitters, no conflicts
299832	NM_021252.5(RAB18):c.*557G>A	RAB18	Uncertain significance	criteria provided, single submitter
299833	NM_021252.5(RAB18):c.*741A>G	RAB18	Uncertain significance	criteria provided, single submitter
299836	NM_021252.5(RAB18):c.*764A>G	RAB18	Uncertain significance	criteria provided, single submitter

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
RAB18	Definitive	Autosomal recessive	Warburg micro syndrome 3	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RAB18	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
RAB18	HGNC:14244	ENSG00000099246	Q9NP72	Ras-related protein Rab-18	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RAB18	Ras-related protein Rab-18	The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes.

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)
RAB18	Other/Unknown	no		Small_GTPase, Small_GTP-bd, Sigma_54_int_dom_ATP-bd_1

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
adrenal tissue	1
cardiac muscle of right atrium	1
upper arm skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RAB18	256	ubiquitous	marker	adrenal tissue, cardiac muscle of right atrium, upper arm skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RAB18	2,122

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RAB18	Q9NP72	1

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
COPI-independent Golgi-to-ER retrograde traffic	1	207.6×	0.011	RAB18
RAB geranylgeranylation	1	173.0×	0.011	RAB18
RAB GEFs exchange GTP for GDP on RABs	1	124.1×	0.011	RAB18
Neutrophil degranulation	1	23.1×	0.043	RAB18

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
endoplasmic reticulum tubular network organization	1	1123.5×	0.003	RAB18
lipid droplet organization	1	936.2×	0.003	RAB18
eye development	1	351.1×	0.006	RAB18
small GTPase-mediated signal transduction	1	183.2×	0.008	RAB18
brain development	1	79.5×	0.015	RAB18
intracellular protein transport	1	64.8×	0.015	RAB18

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
RAB18	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	RAB18

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)
RAB18	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.