Cornea plana

Summary

Cornea plana (MONDO:0000733) is a disease caused by KERA (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: KERA (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cornea plana
Mondo ID	MONDO:0000733
OMIM	121400
Orphanet	53691
DOID	DOID:0060287
ICD-10-CM	Q13.4
ICD-11	262157734
SNOMED CT	204145006
UMLS	C0344529
MedGen	576329
GARD	0016657
Is cancer (heuristic)	no

Also known as: congenital cornea plana · flat cornea

Data availability: 1 ClinVar variant · 1 GenCC gene-disease record · 1 HPO phenotype.

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 disorder › corneal disorder › cornea plana

Related subtypes (23): pseudopterygium, corneal deposit, Bowman’s membrane folds or rupture, corneal degeneration, corneal staphyloma, corneal argyrosis, corneal ectasia, keratopathy, keratitis, corneal edema, brittle cornea syndrome, megalocornea, X-linked corneal dermoid, Peters anomaly, pellucid marginal degeneration, keratoconus, corneal dystrophy, sclerocornea, cornea neoplasm, Arnold stickler bourne syndrome, limbal stem cell deficiency, thygeson superficial punctate keratopathy, Terrien marginal degeneration

Subtypes (2): cornea plana 1, autosomal dominant, cornea plana 2

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
637953	NM_007374.3(SIX6):c.-227_572+235del	C14orf39	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
KERA	Definitive	Autosomal recessive	cornea plana	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KERA	Orphanet:53691	Congenital cornea plana
C14orf39	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation

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
KERA	HGNC:6309	ENSG00000139330	O60938	Keratocan	gencc
C14orf39	HGNC:19849	ENSG00000179008	Q8N1H7	Protein SIX6OS1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KERA	Keratocan	May be important in developing and maintaining corneal transparency and for the structure of the stromal matrix.
C14orf39	Protein SIX6OS1	Meiotic protein that localizes to the central element of the synaptonemal complex and is required for chromosome synapsis during meiotic recombination.

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)
KERA	Other/Unknown	no		LRRNT, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp
C14orf39	Other/Unknown	no		SIX6OS1

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
male germ line stem cell (sensu Vertebrata) in testis	2
calcaneal tendon	1
tendon	1
adenohypophysis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KERA	85	tissue_specific	yes	calcaneal tendon, male germ line stem cell (sensu Vertebrata) in testis, tendon
C14orf39	129	broad	marker	primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis, adenohypophysis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KERA	1,184
C14orf39	478

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KERA	O60938	87.42
C14orf39	Q8N1H7	58.97

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 2 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
Defective CHST6 causes MCDC1	1	1427.5×	0.003	KERA
Defective ST3GAL3 causes MCT12 and EIEE15	1	1427.5×	0.003	KERA
Defective B4GALT1 causes B4GALT1-CDG (CDG-2d)	1	1427.5×	0.003	KERA
Diseases associated with glycosaminoglycan metabolism	1	761.3×	0.004	KERA
Keratan sulfate degradation	1	713.8×	0.004	KERA
Keratan sulfate/keratin metabolism	1	496.5×	0.004	KERA
Keratan sulfate biosynthesis	1	380.7×	0.005	KERA
Glycosaminoglycan metabolism	1	219.6×	0.007	KERA
Diseases of glycosylation	1	131.3×	0.011	KERA
Metabolism of carbohydrates and carbohydrate derivatives	1	120.2×	0.011	KERA
Diseases of metabolism	1	80.4×	0.015	KERA
Disease	1	13.1×	0.083	KERA
Metabolism	1	11.6×	0.086	KERA

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
meiotic DNA double-strand break processing involved in reciprocal meiotic recombination	1	2808.7×	0.003	C14orf39
obsolete regulation of DNA-binding transcription factor activity	1	766.0×	0.004	C14orf39
cornea development in camera-type eye	1	648.1×	0.004	KERA
synaptonemal complex assembly	1	324.1×	0.005	C14orf39
homologous chromosome pairing at meiosis	1	300.9×	0.005	C14orf39
oogenesis	1	191.5×	0.007	C14orf39
visual perception	1	39.8×	0.029	KERA
spermatogenesis	1	17.6×	0.056	C14orf39

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
KERA	0	0
C14orf39	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	KERA, C14orf39

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)
KERA	0	—
C14orf39	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.