Telecanthus

Summary

Telecanthus (MONDO:0008537) is a disease with 3 cohort genes.

At a glance

• Cohort genes: 3
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	telecanthus
Mondo ID	MONDO:0008537
MeSH	C562941
OMIM	187350
Orphanet	98575
ICD-11	210416501
UMLS	C0423113
MedGen	140836
GARD	0019505
Is cancer (heuristic)	no

Also known as: telecanthus

Data availability: 7 ClinVar variants.

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 › telecanthus

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, cryptophthalmia, epiblepharon, congenital eyelid retraction, herpes zoster with dermatitis of eyelid, eyelid seborrheic keratosis, dermatosis of eyelid

Subtypes (2): blepharophimosis, ptosis, and epicanthus inversus syndrome, Opitz G/BBB 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

7 retrieved; paginated sample, class counts are floors:

4 likely pathogenic, 1 uncertain significance, 1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
523366	NM_000393.5(COL5A2):c.754G>T (p.Gly252Cys)	COL5A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
267825	46;XY;t(1;9;5)(compleX)dn		Likely pathogenic	criteria provided, single submitter
267867	46;XX;t(6;15)(q23;q22)dn		Likely pathogenic	criteria provided, single submitter
523552	NM_001854.4(COL11A1):c.4048_4065del (p.Ser1350_Pro1355del)	COL11A1	Likely pathogenic	criteria provided, single submitter
523499	NM_012330.4(KAT6B):c.3399_3402del (p.Arg1133fs)	KAT6B	Likely pathogenic	criteria provided, single submitter
333134	NM_000393.5(COL5A2):c.3614T>C (p.Val1205Ala)	COL5A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
268045	46;XX;t(5;7)(q12.2;q21.2)mat		Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KAT6B	Orphanet:3047	Blepharophimosis-intellectual disability syndrome, SBBYS type
KAT6B	Orphanet:85201	Genitopatellar syndrome
COL11A1	Orphanet:2021	Fibrochondrogenesis
COL11A1	Orphanet:440354	Autosomal dominant myopia-midfacial retrusion-sensorineural hearing loss-rhizomelic dysplasia syndrome
COL11A1	Orphanet:560	Marshall syndrome
COL11A1	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA
COL11A1	Orphanet:90654	Stickler syndrome type 2
COL5A2	Orphanet:287	Classical Ehlers-Danlos syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
KAT6B	HGNC:17582	ENSG00000156650	Q8WYB5	Histone acetyltransferase KAT6B	clinvar
COL11A1	HGNC:2186	ENSG00000060718	P12107	Collagen alpha-1(XI) chain	clinvar
COL5A2	HGNC:2210	ENSG00000204262	P05997	Collagen alpha-2(V) chain	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KAT6B	Histone acetyltransferase KAT6B	Histone acetyltransferase which may be involved in both positive and negative regulation of transcription.
COL11A1	Collagen alpha-1(XI) chain	May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.
COL5A2	Collagen alpha-2(V) chain	Type V collagen is a member of group I collagen (fibrillar forming collagen).

Protein-family classification

Druggable: 0 · Difficult: 1 · 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
Transcription factor	1	2.8×	0.587
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KAT6B	Transcription factor	no	2.3.1.48	Znf_PHD, HAT_MYST-type, Histone_H1/H5_H15
COL11A1	Other/Unknown	no		Fib_collagen_C, Laminin_G, Collagen
COL5A2	Other/Unknown	no		Fib_collagen_C, VWF_dom, Collagen

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
periodontal ligament	2
cortical plate	1
sural nerve	1
ventricular zone	1
cartilage tissue	1
tibia	1
stromal cell of endometrium	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KAT6B	140	ubiquitous	yes	cortical plate, ventricular zone, sural nerve
COL11A1	209	broad	marker	tibia, cartilage tissue, periodontal ligament
COL5A2	266	ubiquitous	marker	tendon of biceps brachii, periodontal ligament, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL11A1	2,433
COL5A2	2,286
KAT6B	2,214

Intra-cohort edges

A	B	Sources
COL11A1	COL5A2	string_interaction

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
KAT6B	Q8WYB5	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
COL5A2	P05997	53.15
COL11A1	P12107	53.06

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
MET activates PTK2 signaling	2	253.8×	3e-04	COL11A1, COL5A2
Collagen chain trimerization	2	173.0×	3e-04	COL11A1, COL5A2
Developmental Lineage of Pancreatic Ductal Cells	2	152.3×	3e-04	COL11A1, COL5A2
Assembly of collagen fibrils and other multimeric structures	2	133.6×	3e-04	COL11A1, COL5A2
Collagen degradation	2	117.1×	3e-04	COL11A1, COL5A2
Collagen biosynthesis and modifying enzymes	2	113.6×	3e-04	COL11A1, COL5A2
Non-integrin membrane-ECM interactions	2	102.9×	3e-04	COL11A1, COL5A2
Fibronectin matrix formation	1	190.3×	0.011	COL5A2
Attachment of bacteria to epithelial cells	1	165.5×	0.011	COL5A2
Syndecan interactions	1	141.0×	0.012	COL5A2
Signaling by PDGF	1	84.6×	0.017	COL5A2
NCAM1 interactions	1	82.8×	0.017	COL5A2
ECM proteoglycans	1	50.1×	0.026	COL5A2
Integrin cell surface interactions	1	44.8×	0.027	COL5A2
Chromatin organization	1	27.2×	0.040	KAT6B
HATs acetylate histones	1	26.4×	0.040	KAT6B
Chromatin modifying enzymes	1	24.1×	0.041	KAT6B

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
collagen fibril organization	2	149.8×	0.001	COL11A1, COL5A2
negative regulation of endodermal cell differentiation	1	2808.7×	0.004	COL5A2
tendon development	1	1404.3×	0.004	COL11A1
eye morphogenesis	1	1404.3×	0.004	COL5A2
regulation of developmental process	1	802.5×	0.006	KAT6B
proteoglycan metabolic process	1	624.1×	0.007	COL11A1
regulation of hemopoiesis	1	510.7×	0.007	KAT6B
chondrocyte development	1	312.1×	0.009	COL11A1
detection of mechanical stimulus involved in sensory perception of sound	1	312.1×	0.009	COL11A1
cartilage condensation	1	255.3×	0.010	COL11A1
ventricular cardiac muscle tissue morphogenesis	1	234.1×	0.010	COL11A1
endodermal cell differentiation	1	165.2×	0.013	COL11A1
skin development	1	147.8×	0.013	COL5A2
embryonic skeletal system morphogenesis	1	130.6×	0.014	COL11A1
cellular response to amino acid stimulus	1	102.1×	0.016	COL5A2
inner ear morphogenesis	1	100.3×	0.016	COL11A1
nucleosome assembly	1	46.8×	0.031	KAT6B
skeletal system development	1	41.9×	0.033	COL5A2
sensory perception of sound	1	33.6×	0.039	COL11A1
visual perception	1	26.5×	0.047	COL11A1
regulation of DNA-templated transcription	1	10.5×	0.105	KAT6B
negative regulation of DNA-templated transcription	1	10.5×	0.105	KAT6B
positive regulation of DNA-templated transcription	1	9.3×	0.113	KAT6B
positive regulation of transcription by RNA polymerase II	1	5.0×	0.196	KAT6B
regulation of transcription by RNA polymerase II	1	3.9×	0.236	KAT6B

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 3 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
KAT6B	0	0
COL11A1	0	0
COL5A2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
KAT6B	22	Binding:20, Functional:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
KAT6B	2.3.1.48	histone acetyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	KAT6B, COL11A1, COL5A2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
KAT6B	22	—
COL11A1	0	—
COL5A2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.