Martsolf syndrome 2

Summary

Martsolf syndrome 2 (MONDO:0030376) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 14

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Martsolf syndrome 2
Mondo ID	MONDO:0030376
OMIM	619420
UMLS	C5543626
MedGen	1779703
GARD	0025555
Is cancer (heuristic)	no

Also known as: MARTS2

Data availability: 14 ClinVar variants.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › syndromic microphthalmia › RAB18 deficiency › Martsolf syndrome › Martsolf syndrome 2

Related subtypes (1): Martsolf syndrome 1

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

14 retrieved; paginated sample, class counts are floors:

5 pathogenic, 5 uncertain significance, 2 benign, 1 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1177055	NM_012233.3(RAB3GAP1):c.2607-1G>C	RAB3GAP1	Pathogenic	criteria provided, single submitter
1698016	NM_012233.3(RAB3GAP1):c.519G>A (p.Trp173Ter)	RAB3GAP1	Pathogenic	criteria provided, multiple submitters, no conflicts
3242259	NM_012233.3(RAB3GAP1):c.2709+1G>T	RAB3GAP1	Pathogenic	no assertion criteria provided
545408	NM_012233.3(RAB3GAP1):c.9del (p.Asp4fs)	RAB3GAP1	Pathogenic	no assertion criteria provided
545410	NM_012233.3(RAB3GAP1):c.1039C>T (p.Arg347Ter)	RAB3GAP1	Pathogenic	criteria provided, multiple submitters, no conflicts
4845893	NM_012233.3(RAB3GAP1):c.2389del (p.Ser797fs)	RAB3GAP1	Likely pathogenic	criteria provided, single submitter
1253981	NM_012233.3(RAB3GAP1):c.2917G>A (p.Ala973Thr)	RAB3GAP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
130062	NM_012233.3(RAB3GAP1):c.1226C>T (p.Thr409Ile)	RAB3GAP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1705651	NM_012233.3(RAB3GAP1):c.536G>C (p.Gly179Ala)	RAB3GAP1	Uncertain significance	criteria provided, single submitter
3892243	NM_012233.3(RAB3GAP1):c.235C>T (p.Leu79Phe)	RAB3GAP1	Uncertain significance	criteria provided, single submitter
436467	NM_012233.3(RAB3GAP1):c.2946A>G (p.Ter982Trp)	RAB3GAP1	Uncertain significance	criteria provided, multiple submitters, no conflicts
130064	NM_012233.3(RAB3GAP1):c.1793A>G (p.Asn598Ser)	RAB3GAP1	Benign	criteria provided, multiple submitters, no conflicts
130067	NM_012233.3(RAB3GAP1):c.2265T>C (p.Phe755=)	RAB3GAP1	Benign	criteria provided, multiple submitters, no conflicts
772447	NM_012233.3(RAB3GAP1):c.2800C>G (p.Pro934Ala)	RAB3GAP1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RAB3GAP1	Orphanet:1387	Cataract-intellectual disability-hypogonadism syndrome
RAB3GAP1	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
RAB3GAP1	HGNC:17063	ENSG00000115839	Q15042	Rab3 GTPase-activating protein catalytic subunit	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RAB3GAP1	Rab3 GTPase-activating protein catalytic subunit	Catalytic subunit of the Rab3 GTPase-activating (Rab3GAP) complex composed of RAB3GAP1 and RAB3GAP2, which accelerates the otherwise slow GTP hydrolysis catalyzed by Rab proteins.

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)
RAB3GAP1	Other/Unknown	no		Rab3GAP1_conserved, Rab3GAP1_C, Rab3GAP1

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
Brodmann (1909) area 23	1
hair follicle	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RAB3GAP1	300	ubiquitous	marker	hair follicle, Brodmann (1909) area 23, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RAB3GAP1	2,039

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RAB3GAP1	Q15042	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 2. 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×	0.008	RAB3GAP1
RAB GEFs exchange GTP for GDP on RABs	1	124.1×	0.008	RAB3GAP1

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 of glutamate neurotransmitter secretion in response to membrane depolarization	1	8426.0×	7e-04	RAB3GAP1
regulation of calcium ion-dependent exocytosis of neurotransmitter	1	8426.0×	7e-04	RAB3GAP1
establishment of protein localization to endoplasmic reticulum membrane	1	5617.3×	7e-04	RAB3GAP1
positive regulation of protein lipidation	1	4213.0×	7e-04	RAB3GAP1
positive regulation of endoplasmic reticulum tubular network organization	1	4213.0×	7e-04	RAB3GAP1
regulation of short-term neuronal synaptic plasticity	1	1123.5×	0.002	RAB3GAP1
hypothalamus development	1	1053.2×	0.002	RAB3GAP1
Rab protein signal transduction	1	991.3×	0.002	RAB3GAP1
lipid droplet organization	1	936.2×	0.002	RAB3GAP1
positive regulation of autophagosome assembly	1	802.5×	0.002	RAB3GAP1
face morphogenesis	1	495.6×	0.003	RAB3GAP1
excitatory postsynaptic potential	1	443.5×	0.003	RAB3GAP1
camera-type eye development	1	358.6×	0.003	RAB3GAP1
brain development	1	79.5×	0.013	RAB3GAP1

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
RAB3GAP1	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	RAB3GAP1

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)
RAB3GAP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.