Microphthalmia/coloboma 11

Summary

Microphthalmia/coloboma 11 (MONDO:0958239) is a disease caused by FZD5 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: FZD5 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	microphthalmia/coloboma 11
Mondo ID	MONDO:0958239
OMIM	620731
UMLS	C5935584
MedGen	1856733
GARD	0026984
Is cancer (heuristic)	no

Data availability: 9 ClinVar variants · 2 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/coloboma 11

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, isolated, with coloboma 10, microphthalmia with coloboma 1, microphthalmia, isolated, with coloboma 8, 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

9 retrieved; paginated sample, class counts are floors:

5 pathogenic, 2 uncertain significance, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
3024142	NM_003468.4(FZD5):c.656delinsAG (p.Ala219fs)	FZD5	Pathogenic	no assertion criteria provided
3024143	NM_003468.4(FZD5):c.830del (p.Cys277fs)	FZD5	Pathogenic	no assertion criteria provided
3024145	NM_003468.4(FZD5):c.1232A>G (p.Tyr411Cys)	FZD5	Pathogenic	no assertion criteria provided
3024146	NM_003468.4(FZD5):c.1428del (p.Ser477fs)	FZD5	Pathogenic	no assertion criteria provided
3024147	NM_003468.4(FZD5):c.1403_1406dup (p.Tyr470fs)	FZD5	Pathogenic	no assertion criteria provided
4531810	NM_003468.4(FZD5):c.986G>T (p.Ser329Ile)	FZD5	Likely pathogenic	criteria provided, single submitter
694331	NM_003468.4(FZD5):c.1181_1246del (p.Asn394_Gly415del)	FZD5	Likely pathogenic	criteria provided, single submitter
4070926	NM_003468.4(FZD5):c.395del (p.Ser132fs)	FZD5	Uncertain significance	criteria provided, single submitter
4814130	NM_003468.4(FZD5):c.1500C>G (p.Tyr500Ter)	FZD5	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 6 · 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
FZD5	Strong	Autosomal dominant	microphthalmia/coloboma 11	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FZD5	Orphanet:98942	Coloboma of choroid and retina
FZD5	Orphanet:98943	Coloboma of eye lens
FZD5	Orphanet:98944	Coloboma of iris
FZD5	Orphanet:98945	Coloboma of macula
FZD5	Orphanet:98946	Coloboma of eyelid
FZD5	Orphanet:98947	Coloboma of optic disc

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
FZD5	HGNC:4043	ENSG00000163251	Q13467	Frizzled-5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FZD5	Frizzled-5	Receptor for Wnt proteins.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
GPCR	1	23.9×	0.042

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FZD5	GPCR	yes		Frizzled/Smoothened_7TM, Frizzled/SFRP, GPCR_2-like_7TM

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
colonic mucosa	1
jejunal mucosa	1
mucosa of sigmoid colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FZD5	256	ubiquitous	marker	jejunal mucosa, mucosa of sigmoid colon, colonic mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FZD5	1,428

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FZD5	Q13467	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. 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
Signaling by RNF43 mutants	1	1268.9×	0.004	FZD5
WNT5A-dependent internalization of FZD2, FZD5 and ROR2	1	878.5×	0.004	FZD5
Regulation of FZD by ubiquitination	1	519.1×	0.004	FZD5
Disassembly of the destruction complex and recruitment of AXIN to the membrane	1	356.9×	0.005	FZD5
Asymmetric localization of PCP proteins	1	203.9×	0.006	FZD5
Class B/2 (Secretin family receptors)	1	190.3×	0.006	FZD5
Ca2+ pathway	1	178.4×	0.006	FZD5

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
regulation of chorionic trophoblast cell proliferation	1	8426.0×	0.001	FZD5
Spemann organizer formation	1	5617.3×	0.001	FZD5
syncytiotrophoblast cell differentiation involved in labyrinthine layer development	1	5617.3×	0.001	FZD5
post-embryonic camera-type eye development	1	4213.0×	0.001	FZD5
intestinal epithelial cell maturation	1	4213.0×	0.001	FZD5
apoptotic process involved in morphogenesis	1	2808.7×	0.001	FZD5
chorionic trophoblast cell differentiation	1	2808.7×	0.001	FZD5
embryonic axis specification	1	2407.4×	0.001	FZD5
glandular epithelial cell maturation	1	2407.4×	0.001	FZD5
anterior/posterior axis specification, embryo	1	2106.5×	0.001	FZD5
cellular response to molecule of bacterial origin	1	2106.5×	0.001	FZD5
regulation of bicellular tight junction assembly	1	1685.2×	0.001	FZD5
branching involved in labyrinthine layer morphogenesis	1	1532.0×	0.002	FZD5
positive regulation of T cell cytokine production	1	1296.3×	0.002	FZD5
regulation of mitophagy	1	1203.7×	0.002	FZD5
embryonic camera-type eye morphogenesis	1	1123.5×	0.002	FZD5
labyrinthine layer blood vessel development	1	802.5×	0.002	FZD5
non-canonical Wnt signaling pathway	1	581.1×	0.003	FZD5
obsolete positive regulation of protein targeting to mitochondrion	1	495.6×	0.003	FZD5
T cell differentiation in thymus	1	411.0×	0.004	FZD5
eye development	1	351.1×	0.004	FZD5
positive regulation of interleukin-1 beta production	1	259.3×	0.005	FZD5
synapse assembly	1	230.8×	0.006	FZD5
positive regulation of type II interferon production	1	224.7×	0.006	FZD5
positive regulation of tumor necrosis factor production	1	153.2×	0.008	FZD5
canonical Wnt signaling pathway	1	153.2×	0.008	FZD5
neuron differentiation	1	100.3×	0.011	FZD5
angiogenesis	1	62.4×	0.017	FZD5
negative regulation of cell population proliferation	1	42.1×	0.025	FZD5
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	FZD5

Therapeutics

Drug target analysis

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

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

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FZD5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
FZD5	8	Functional:6, Binding:2

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	1	FZD5
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
FZD5	8	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.