Microphthalmia, isolated, with coloboma 10

Summary

Microphthalmia, isolated, with coloboma 10 (MONDO:0014635) is a disease caused by RBP4 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: RBP4 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microphthalmia, isolated, with coloboma 10
Mondo ID	MONDO:0014635
OMIM	616428
UMLS	C4225330
MedGen	909133
GARD	0016110
Is cancer (heuristic)	no

Also known as: MCOPCB10 · microphthalmia, isolated, with coloboma 10 · microphthalmia, isolated, with coloboma caused by mutation in RBP4 · microphthalmia, isolated, with coloboma type 10 · RBP4 microphthalmia, isolated, with coloboma

Data availability: 7 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 › isolated microphthalmia › microphthalmia, isolated, with coloboma › microphthalmia, isolated, with coloboma 10

Related subtypes (11): microphthalmia, isolated, with coloboma 4, microphthalmia with coloboma 2, microphthalmia, isolated, with coloboma 3, microphthalmia, isolated, with coloboma 5, microphthalmia, isolated, with coloboma 6, microphthalmia, isolated, with coloboma 7, microphthalmia, isolated, with coloboma 9, microphthalmia with coloboma 1, microphthalmia, isolated, with coloboma 8, microphthalmia/coloboma 11, microphthalmia/coloboma 13

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

7 retrieved; paginated sample, class counts are floors:

2 likely pathogenic, 2 uncertain significance, 1 benign, 1 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
192377	NM_006744.4(RBP4):c.217G>A (p.Ala73Thr)	RBP4	Pathogenic	criteria provided, single submitter
192376	NM_006744.4(RBP4):c.223G>A (p.Ala75Thr)	RBP4	Likely pathogenic	criteria provided, single submitter
929566	NM_006744.4(RBP4):c.569-1G>A	RBP4	Likely pathogenic	criteria provided, single submitter
2430198	NM_006744.4(RBP4):c.271A>G (p.Met91Val)	RBP4	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
499650	NM_006744.4(RBP4):c.24G>T (p.Leu8Phe)	RBP4	Uncertain significance	criteria provided, multiple submitters, no conflicts
966812	NM_006744.4(RBP4):c.302C>A (p.Pro101His)	RBP4	Uncertain significance	criteria provided, multiple submitters, no conflicts
1277035	NM_006744.4(RBP4):c.356-25G>C	RBP4	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 2 · 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
RBP4	Strong	Autosomal dominant	microphthalmia, isolated, with coloboma 10	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RBP4	Orphanet:352718	Progressive retinal dystrophy due to retinol transport defect
RBP4	Orphanet:98938	Colobomatous microphthalmia

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
RBP4	HGNC:9922	ENSG00000138207	P02753	Retinol-binding protein 4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RBP4	Retinol-binding protein 4	Retinol-binding protein that mediates retinol transport in blood plasma.

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)
RBP4	Other/Unknown	no		Lipocln_cytosolic_FA-bd_dom, Retinol-bd/Purpurin, Calycin

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
liver	1
right lobe of liver	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RBP4	244	broad	marker	right lobe of liver, liver, type B pancreatic cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RBP4	1,143

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RBP4	P02753	23

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
Retinoid metabolism disease events	1	11420.0×	4e-04	RBP4
Defective visual phototransduction due to STRA6 loss of function	1	3806.7×	5e-04	RBP4
The canonical retinoid cycle in rods (twilight vision)	1	519.1×	0.003	RBP4
Retinoid metabolism and transport	1	248.3×	0.004	RBP4

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
retinol transport	1	8426.0×	0.001	RBP4
vitamin A import into cell	1	8426.0×	0.001	RBP4
female genitalia morphogenesis	1	5617.3×	0.001	RBP4
embryonic organ morphogenesis	1	4213.0×	0.001	RBP4
urinary bladder development	1	4213.0×	0.001	RBP4
embryonic retina morphogenesis in camera-type eye	1	2407.4×	0.002	RBP4
negative regulation of cardiac muscle cell proliferation	1	1872.4×	0.002	RBP4
vagina development	1	1532.0×	0.003	RBP4
phototransduction, visible light	1	1296.3×	0.003	RBP4
heart trabecula formation	1	1123.5×	0.003	RBP4
maintenance of gastrointestinal epithelium	1	1053.2×	0.003	RBP4
retinal metabolic process	1	936.2×	0.003	RBP4
cardiac muscle tissue development	1	887.0×	0.003	RBP4
uterus development	1	802.5×	0.003	RBP4
detection of light stimulus involved in visual perception	1	648.1×	0.003	RBP4
response to muscle activity	1	581.1×	0.003	RBP4
retinol metabolic process	1	495.6×	0.004	RBP4
positive regulation of immunoglobulin production	1	481.5×	0.004	RBP4
embryonic skeletal system development	1	391.9×	0.004	RBP4
response to retinoic acid	1	383.0×	0.004	RBP4
eye development	1	351.1×	0.004	RBP4
gluconeogenesis	1	324.1×	0.004	RBP4
positive regulation of insulin secretion	1	255.3×	0.005	RBP4
response to insulin	1	230.8×	0.006	RBP4
lung development	1	198.3×	0.006	RBP4
male gonad development	1	156.0×	0.008	RBP4
response to ethanol	1	146.5×	0.008	RBP4
glucose homeostasis	1	130.6×	0.008	RBP4
heart development	1	78.8×	0.014	RBP4
response to xenobiotic stimulus	1	69.1×	0.015	RBP4

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
RBP4	RETINOL

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RBP4	3	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RETINOL	4	RBP4
TINLAREBANT	3	RBP4
FENRETINIDE	3	RBP4

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
RBP4	32	Binding:29, Functional:3

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

3 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.

Compound	Max phase	Cohort target (bioactivity)
RETINOL	4	RBP4
TINLAREBANT	3	RBP4
FENRETINIDE	3	RBP4

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	RBP4
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	0

Undrugged target profiles

0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Clinical trials & evidence

Clinical trials

Clinical trials: 0.