Nanophthalmos 2

Summary

Nanophthalmos 2 (MONDO:0012299) is a disease caused by MFRP (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: MFRP (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 18

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nanophthalmos 2
Mondo ID	MONDO:0012299
MeSH	C563700
OMIM	609549
UMLS	C1836006
MedGen	372177
GARD	0018626
Is cancer (heuristic)	no

Also known as: MFRP nanophthalmia · nanophthalmia caused by mutation in MFRP · nanophthalmos 2 · nanophthalmos type 2 · NNO2

Data availability: 18 ClinVar variants · 2 GenCC gene-disease records · 1 cell line.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › nanophthalmia › nanophthalmos 2

Related subtypes (3): nanophthalmos 1, nanophthalmos 3, nanophthalmos 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

18 retrieved; paginated sample, class counts are floors:

9 pathogenic, 3 pathogenic/likely pathogenic, 3 likely pathogenic, 2 uncertain significance, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1069330	NM_031433.4(MFRP):c.666del (p.Thr223fs)	C1QTNF5	Pathogenic	criteria provided, multiple submitters, no conflicts
1071727	NM_031433.4(MFRP):c.1090_1091del (p.Thr364fs)	C1QTNF5	Pathogenic	criteria provided, multiple submitters, no conflicts
183046	NM_031433.4(MFRP):c.491_492insT (p.Asn167fs)	C1QTNF5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4474	NM_031433.4(MFRP):c.1150dup (p.His384fs)	C1QTNF5	Pathogenic	criteria provided, multiple submitters, no conflicts
4475	NM_031433.4(MFRP):c.523C>T (p.Gln175Ter)	C1QTNF5	Pathogenic	criteria provided, multiple submitters, no conflicts
4476	NM_031433.4(MFRP):c.498del (p.Asn167fs)	C1QTNF5	Pathogenic	criteria provided, multiple submitters, no conflicts
4477	NM_031433.4(MFRP):c.545T>C (p.Ile182Thr)	C1QTNF5	Pathogenic	no assertion criteria provided
497208	NM_031433.4(MFRP):c.642-2A>G	C1QTNF5	Pathogenic	criteria provided, multiple submitters, no conflicts
560469	NM_031433.4(MFRP):c.1615C>T (p.Arg539Cys)	C1QTNF5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
631652	NM_031433.4(MFRP):c.1124+1G>T	C1QTNF5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
915449	NM_031433.4(MFRP):c.1180G>A (p.Val394Met)	C1QTNF5	Pathogenic	no assertion criteria provided
915451	NM_031433.4(MFRP):c.899-3C>A	C1QTNF5	Pathogenic	no assertion criteria provided
3779848	NM_031433.4(MFRP):c.47C>A (p.Ser16Ter)	C1QTNF5	Likely pathogenic	criteria provided, single submitter
4849410	NM_031433.4(MFRP):c.47del (p.Glu15_Ser16insTer)	C1QTNF5	Likely pathogenic	criteria provided, single submitter
915447	NM_031433.4(MFRP):c.497C>T (p.Pro166Leu)	C1QTNF5	Likely pathogenic	criteria provided, single submitter
861498	NM_031433.4(MFRP):c.1345G>A (p.Gly449Ser)	C1QTNF5	Uncertain significance	criteria provided, multiple submitters, no conflicts
3780862	NM_031433.4(MFRP):c.*853+1dup	MFRP	Uncertain significance	criteria provided, single submitter
197357	NM_031433.4(MFRP):c.355A>G (p.Ile119Val)	C1QTNF5	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 3 · 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
MFRP	Definitive	Autosomal recessive	nanophthalmos 2	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MFRP	Orphanet:251279	Microphthalmia-retinitis pigmentosa-foveoschisis-optic disc drusen syndrome
MFRP	Orphanet:35612	Nanophthalmos
C1QTNF5	Orphanet:67042	Late-onset retinal degeneration

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MFRP	HGNC:18121	ENSG00000235718	Q9BY79	Membrane frizzled-related protein	gencc,clinvar
C1QTNF5	HGNC:14344	ENSG00000223953	Q9BXJ0	Complement C1q tumor necrosis factor-related protein 5	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MFRP	Membrane frizzled-related protein	May play a role in eye development.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MFRP	Other/Unknown	no		CUB_dom, LDrepeatLR_classA_rpt, Frizzled_dom
C1QTNF5	Other/Unknown	no		C1q_dom, Collagen, Tumour_necrosis_fac-like_dom

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
primordial germ cell in gonad	1
stromal cell of endometrium	1
sural nerve	1
apex of heart	1
ascending aorta	1
gall bladder	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MFRP	29	tissue_specific	marker	primordial germ cell in gonad, stromal cell of endometrium, sural nerve
C1QTNF5	128	ubiquitous	yes	apex of heart, gall bladder, ascending aorta

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MFRP	858
C1QTNF5	369

Intra-cohort edges

A	B	Sources
C1QTNF5	MFRP	intact, string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
C1QTNF5	Q9BXJ0	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MFRP	Q9BY79	73.09

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
eye photoreceptor cell development	1	421.3×	0.008	MFRP
embryo development ending in birth or egg hatching	1	366.4×	0.008	MFRP
inner ear development	1	187.2×	0.009	C1QTNF5
protein secretion	1	131.7×	0.009	C1QTNF5
retina development in camera-type eye	1	127.7×	0.009	MFRP
visual perception	1	39.8×	0.025	MFRP

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
MFRP	0	0
C1QTNF5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	MFRP, C1QTNF5

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MFRP	0	—
C1QTNF5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.