Isolated microphthalmia 7

Summary

Isolated microphthalmia 7 (MONDO:0013377) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	isolated microphthalmia 7
Mondo ID	MONDO:0013377
OMIM	613704
DOID	DOID:0060838
UMLS	C3150969
MedGen	462319
GARD	0024917
Is cancer (heuristic)	no

Also known as: GDF3 isolated microphthalmia · isolated microphthalmia caused by mutation in GDF3 · isolated microphthalmia type 7 · MCOP7 · microphthalmia, isolated 7 · microphthalmia, isolated type 7

Data availability: 6 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › isolated microphthalmia › isolated microphthalmia 7

Related subtypes (9): microphthalmia, isolated, with coloboma, microphthalmia, isolated, with cataract 1, isolated microphthalmia 1, isolated microphthalmia 2, isolated microphthalmia 3, isolated microphthalmia 5, isolated microphthalmia 4, isolated microphthalmia 6, isolated microphthalmia 8

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

6 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 1 benign, 1 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
30593	NM_020634.3(GDF3):c.584G>A (p.Arg195Gln)	GDF3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
30594	NM_020634.3(GDF3):c.820C>T (p.Arg274Trp)	GDF3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3893109	NM_020634.3(GDF3):c.236G>T (p.Arg79Leu)	GDF3	Uncertain significance	criteria provided, single submitter
3893110	NM_020634.3(GDF3):c.890G>T (p.Cys297Phe)	GDF3	Uncertain significance	criteria provided, single submitter
30592	NM_020634.3(GDF3):c.914T>C (p.Leu305Pro)	GDF3	Benign	criteria provided, multiple submitters, no conflicts
767184	NM_020634.3(GDF3):c.583C>T (p.Arg195Trp)	GDF3	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
GDF3	Supportive	Autosomal dominant	isolated Klippel-Feil syndrome	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GDF3	Orphanet:2345	Isolated Klippel-Feil syndrome
GDF3	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
GDF3	HGNC:4218	ENSG00000184344	Q9NR23	Growth/differentiation factor 3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GDF3	Growth/differentiation factor 3	Growth factor involved in early embryonic development and adipose-tissue homeostasis.

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)
GDF3	Other/Unknown	no		TGF-b_C, TGF-beta-like, TGFb_CS

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
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GDF3	82	tissue_specific	marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, type B pancreatic cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GDF3	1,113

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GDF3	Q9NR23	82.72

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
negative regulation of epidermal cell differentiation	1	8426.0×	0.001	GDF3
regulation of cell fate commitment	1	5617.3×	0.001	GDF3
formation of anatomical boundary	1	4213.0×	0.001	GDF3
notochord development	1	1685.2×	0.002	GDF3
somite rostral/caudal axis specification	1	1532.0×	0.002	GDF3
primitive streak formation	1	1404.3×	0.002	GDF3
response to dietary excess	1	1123.5×	0.002	GDF3
endoderm development	1	624.1×	0.003	GDF3
negative regulation of myoblast differentiation	1	624.1×	0.003	GDF3
mesoderm development	1	526.6×	0.003	GDF3
eye development	1	351.1×	0.004	GDF3
positive regulation of fat cell differentiation	1	300.9×	0.004	GDF3
negative regulation of BMP signaling pathway	1	290.6×	0.004	GDF3
BMP signaling pathway	1	200.6×	0.006	GDF3
skeletal system development	1	125.8×	0.008	GDF3
in utero embryonic development	1	72.0×	0.014	GDF3

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
GDF3	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	GDF3

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)
GDF3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.