Cryptophthalmia

Summary

Cryptophthalmia (MONDO:0020153) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cryptophthalmia
Mondo ID	MONDO:0020153
Orphanet	98562
DOID	DOID:0111716
ICD-11	740223582
NCIT	C124520
SNOMED CT	400951005
UMLS	C0311249
MedGen	81386
GARD	0010505
Is cancer (heuristic)	no

Also known as: cryptophthalmos

Data availability: 1 ClinVar variant.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye adnexa disorder › eyelid disorder › cryptophthalmia

Related subtypes (19): eyelid degenerative disorder, blepharophimosis, hypertrichosis of eyelid, hypotrichosis of eyelid, entropion, lagophthalmos, stenosis of lacrimal punctum, stenosis of lacrimal passage, ectropion, eyelid neoplasm, blepharochalasis, blepharitis, eyelid hypopigmentation, telecanthus, epiblepharon, congenital eyelid retraction, herpes zoster with dermatitis of eyelid, eyelid seborrheic keratosis, dermatosis of eyelid

Subtypes (2): isolated cryptophthalmia, Fraser syndrome

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

1 retrieved; paginated sample, class counts are floors:

1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
523570	NM_207361.6(FREM2):c.6727C>T (p.Arg2243Ter)	FREM2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 3 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FREM2	Orphanet:2052	Fraser syndrome
FREM2	Orphanet:93100	Renal agenesis, unilateral
FREM2	Orphanet:98949	Complete cryptophthalmia

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
FREM2	HGNC:25396	ENSG00000150893	Q5SZK8	FRAS1-related extracellular matrix protein 2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FREM2	FRAS1-related extracellular matrix protein 2	Extracellular matrix protein required for maintenance of the integrity of the skin epithelium and for maintenance of renal epithelia.

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)
FREM2	Other/Unknown	no		Calx_beta, CalX-like_sf, CSPG_rpt

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
adrenal tissue	1
kidney epithelium	1
renal medulla	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FREM2	160	broad	marker	adrenal tissue, kidney epithelium, renal medulla

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FREM2	1,652

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FREM2	Q5SZK8

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
cell communication	1	842.6×	0.006	FREM2
inner ear development	1	374.5×	0.006	FREM2
eye development	1	351.1×	0.006	FREM2
morphogenesis of an epithelium	1	343.9×	0.006	FREM2
embryonic digit morphogenesis	1	300.9×	0.006	FREM2
kidney development	1	140.4×	0.009	FREM2
anatomical structure morphogenesis	1	139.3×	0.009	FREM2
heart development	1	78.8×	0.014	FREM2
cell adhesion	1	37.5×	0.027	FREM2

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
FREM2	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	FREM2

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)
FREM2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.