Coloboma of iris

Summary

Coloboma of iris (MONDO:0020356) is a disease with 5 cohort genes.

At a glance

• Cohort genes: 5
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	coloboma of iris
Mondo ID	MONDO:0020356
Orphanet	98944
ICD-10-CM	Q13.0
ICD-11	1552972259
NCIT	C98879
SNOMED CT	9446007
UMLS	C0240063
MedGen	116097
GARD	0001434
MedDRA	10052642
Is cancer (heuristic)	no

Also known as: coloboma of iris · coloboma of iris (disease) · coloboma of the iris

Data availability: 8 ClinVar variants · 1 HPO phenotype.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › coloboma › coloboma, ocular, autosomal dominant › coloboma of iris

Related subtypes (1): coloboma of choroid and retina

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

8 retrieved; paginated sample, class counts are floors:

5 pathogenic, 1 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1710336	NM_017780.4(CHD7):c.6045_6046del (p.Phe2015fs)	CHD7	Pathogenic	criteria provided, single submitter
446254	NM_020719.3(PRR12):c.1918G>T (p.Glu640Ter)	PRR12	Pathogenic	criteria provided, multiple submitters, no conflicts
446255	NM_020719.3(PRR12):c.4502_4505del (p.Leu1501fs)	PRR12	Pathogenic	criteria provided, single submitter
446256	NM_020719.3(PRR12):c.903_909dup (p.Pro304fs)	PRR12	Pathogenic	criteria provided, multiple submitters, no conflicts
523459	NM_001372066.1(TFAP2A):c.1043_1044del (p.Lys348fs)	TFAP2A	Pathogenic	criteria provided, multiple submitters, no conflicts
506012	NM_153704.6(TMEM67):c.514C>T (p.Arg172Ter)	TMEM67	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
523562	NM_153704.6(TMEM67):c.2418_2423dup (p.805_806MN[3])	TMEM67	Likely pathogenic	criteria provided, single submitter
1710344	NM_001368894.2(PAX6):c.142-3T>C	PAX6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 24 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TFAP2A	Orphanet:1297	Branchio-oculo-facial syndrome
CHD7	Orphanet:138	CHARGE syndrome
CHD7	Orphanet:39041	Omenn syndrome
CHD7	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
CHD7	Orphanet:478	Kallmann syndrome
TMEM67	Orphanet:140976	RHYNS syndrome
TMEM67	Orphanet:1454	Joubert syndrome with hepatic defect
TMEM67	Orphanet:475	Isolated Joubert syndrome
TMEM67	Orphanet:564	Meckel syndrome
TMEM67	Orphanet:84081	Senior-Boichis syndrome
PRR12	Orphanet:659904	Multiple congenital anomalies-neurodevelopmental delay-ocular abnormalities syndrome
PAX6	Orphanet:1065	Aniridia-cerebellar ataxia-intellectual disability syndrome
PAX6	Orphanet:2253	Foveal hypoplasia-presenile cataract syndrome
PAX6	Orphanet:2334	Autosomal dominant keratitis
PAX6	Orphanet:250923	Isolated aniridia
PAX6	Orphanet:35737	Morning glory disc anomaly
PAX6	Orphanet:708	Peters anomaly
PAX6	Orphanet:893	WAGR syndrome
PAX6	Orphanet:98942	Coloboma of choroid and retina
PAX6	Orphanet:98943	Coloboma of eye lens
PAX6	Orphanet:98944	Coloboma of iris
PAX6	Orphanet:98945	Coloboma of macula
PAX6	Orphanet:98946	Coloboma of eyelid
PAX6	Orphanet:98947	Coloboma of optic disc

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
TFAP2A	HGNC:11742	ENSG00000137203	P05549	Transcription factor AP-2-alpha	clinvar
CHD7	HGNC:20626	ENSG00000171316	Q9P2D1	ATP-dependent chromatin remodeler CHD7	clinvar
TMEM67	HGNC:28396	ENSG00000164953	Q5HYA8	Meckelin	clinvar
PRR12	HGNC:29217	ENSG00000126464	Q9ULL5	Proline-rich protein 12	clinvar
PAX6	HGNC:8620	ENSG00000007372	P26367	Paired box protein Pax-6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TFAP2A	Transcription factor AP-2-alpha	Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes.
CHD7	ATP-dependent chromatin remodeler CHD7	ATP-dependent chromatin-remodeling factor, slides nucleosomes along DNA; nucleosome sliding requires ATP.
TMEM67	Meckelin	Required for ciliary structure and function.
PRR12	Proline-rich protein 12	May play a role in the regulation of cohesin complex loading onto chromatin, probably acting in coordination with NIPBL and MAU2.
PAX6	Paired box protein Pax-6	Transcription factor with important functions in the development of the eye, nose, central nervous system and pancreas.

Protein-family classification

Druggable: 0 · Difficult: 2 · Unknown: 3 · 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	2	3.3×	0.229
Other/Unknown	3	1.1×	0.608

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TFAP2A	Transcription factor	no		TF_AP2, TF_AP2_alpha_N, TF_AP2_C
CHD7	Other/Unknown	no		SNF2_N, Chromo/chromo_shadow_dom, Helicase_C-like
TMEM67	Other/Unknown	no		Growth_fac_rcpt_cys_sf, Meckelin
PRR12	Other/Unknown	no		DUF4211, DNA_MethProtect_Complex
PAX6	Transcription factor	no		HD, Paired_dom, Homeodomain-like_sf

Expression context

Cohort genes with no expression data: 0.

4 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)	5
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gingiva	1
gingival epithelium	1
upper leg skin	1
cerebellar vermis	1
secondary oocyte	1
sural nerve	1
buccal mucosa cell	1
calcaneal tendon	1
right uterine tube	1
cardia of stomach	1
kidney epithelium	1
nipple	1
palpebral conjunctiva	1
type B pancreatic cell	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TFAP2A	220	ubiquitous	marker	upper leg skin, gingival epithelium, gingiva
CHD7	269	ubiquitous	marker	secondary oocyte, cerebellar vermis, sural nerve
TMEM67	203	ubiquitous	marker	buccal mucosa cell, right uterine tube, calcaneal tendon
PRR12	210	ubiquitous	yes	kidney epithelium, cardia of stomach, nipple
PAX6	201	broad	marker	palpebral conjunctiva, type B pancreatic cell, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PAX6	4,971
CHD7	4,819
TFAP2A	2,734
TMEM67	1,194
PRR12	1,018

Structural data

PDB: 4 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TFAP2A	P05549	3
CHD7	Q9P2D1	3
PAX6	P26367	2
TMEM67	Q5HYA8	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PRR12	Q9ULL5	43.84

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 28. Enrichment computed across 5 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
TFAP2 (AP-2) family regulates transcription of other transcription factors	1	713.8×	0.014	TFAP2A
TFAP2 (AP-2) family regulates transcription of cell cycle factors	1	571.0×	0.014	TFAP2A
TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation	1	571.0×	0.014	TFAP2A
Negative regulation of activity of TFAP2 (AP-2) family transcription factors	1	285.5×	0.014	TFAP2A
Formation of the anterior neural plate	1	259.6×	0.014	PAX6
Activation of the TFAP2 (AP-2) family of transcription factors	1	237.9×	0.014	TFAP2A
Positive Regulation of CDH1 Gene Transcription	1	237.9×	0.014	TFAP2A
Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)	1	219.6×	0.014	PAX6
TFAP2 (AP-2) family regulates transcription of growth factors and their receptors	1	190.3×	0.014	TFAP2A
Developmental Lineage of Mammary Stem Cells	1	190.3×	0.014	TFAP2A
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1	158.6×	0.014	TFAP2A
Specification of the neural plate border	1	158.6×	0.014	TFAP2A
SUMOylation of transcription factors	1	142.8×	0.014	TFAP2A
Regulation of gene expression in beta cells	1	129.8×	0.014	PAX6
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)	1	129.8×	0.014	PAX6
Regulation of MITF-M-dependent genes involved in pigmentation	1	66.4×	0.025	TFAP2A
Gastrulation	1	64.9×	0.025	TFAP2A
MITF-M-dependent gene expression	1	45.3×	0.034	TFAP2A
CHD6, CHD7, CHD8, CHD9 subfamily	1	37.1×	0.039	CHD7
MITF-M-regulated melanocyte development	1	28.6×	0.046	TFAP2A
Anchoring of the basal body to the plasma membrane	1	28.3×	0.046	TMEM67
Cilium Assembly	1	27.2×	0.046	TMEM67
Activation of anterior HOX genes in hindbrain development during early embryogenesis	1	22.8×	0.052	PAX6
Organelle biogenesis and maintenance	1	16.5×	0.069	TMEM67
RNA Polymerase II Transcription	1	5.6×	0.186	TFAP2A
Gene expression (Transcription)	1	4.5×	0.222	TFAP2A
Generic Transcription Pathway	1	3.8×	0.249	TFAP2A
Developmental Biology	1	3.6×	0.249	TFAP2A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 5 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
right ventricular compact myocardium morphogenesis	1	3370.4×	0.005	CHD7
pancreatic A cell development	1	3370.4×	0.005	PAX6
optic cup structural organization	1	3370.4×	0.005	TFAP2A
oligodendrocyte cell fate specification	1	3370.4×	0.005	PAX6
forebrain-midbrain boundary formation	1	3370.4×	0.005	PAX6
somatic motor neuron fate commitment	1	3370.4×	0.005	PAX6
inner ear morphogenesis	2	120.4×	0.005	TFAP2A, CHD7
retina development in camera-type eye	2	102.1×	0.005	CHD7, PAX6
optic vesicle morphogenesis	1	1685.2×	0.007	TFAP2A
oculomotor nerve formation	1	1685.2×	0.007	TFAP2A
cranial nerve development	1	1123.5×	0.007	CHD7
olfactory nerve development	1	1123.5×	0.007	CHD7
habenula development	1	1123.5×	0.007	PAX6
regulation of growth hormone secretion	1	1123.5×	0.007	CHD7
positive regulation of tooth mineralization	1	1123.5×	0.007	TFAP2A
skeletal system development	2	50.3×	0.007	TFAP2A, CHD7
central nervous system development	2	46.2×	0.007	CHD7, PAX6
sensory perception of sound	2	40.4×	0.007	TFAP2A, CHD7
regulation of asymmetric cell division	1	842.6×	0.008	PAX6
regulation of timing of cell differentiation	1	842.6×	0.008	PAX6
negative regulation of centrosome duplication	1	674.1×	0.008	TMEM67
ventral spinal cord interneuron specification	1	561.7×	0.008	PAX6
commitment of neuronal cell to specific neuron type in forebrain	1	561.7×	0.008	PAX6
chordate embryonic development	1	561.7×	0.008	CHD7
salivary gland morphogenesis	1	481.5×	0.008	PAX6
trigeminal nerve development	1	481.5×	0.008	TFAP2A
cerebral cortex regionalization	1	481.5×	0.008	PAX6
female genitalia development	1	481.5×	0.008	CHD7
nose development	1	481.5×	0.008	CHD7
semicircular canal morphogenesis	1	481.5×	0.008	CHD7

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 5 evidence-associated genes (20%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PRR12	1	2
TFAP2A	0	0
CHD7	0	0
TMEM67	0	0
PAX6	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
MOLIBRESIB	2	PRR12

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
PRR12	6	Binding:6

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

1 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.

Compound	Max phase	Cohort target (bioactivity)
MOLIBRESIB	2	PRR12

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	1	PRR12
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	4	TFAP2A, CHD7, TMEM67, PAX6

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
TFAP2A	0	—
CHD7	0	—
TMEM67	0	—
PAX6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.