Benign neoplasm of eye

Summary

Benign neoplasm of eye (MONDO:0021454) is a cancer (an umbrella term covering 7 Mondo subtypes) with 1 cohort gene (48 GWAS associations across 11 studies).

At a glance

• Classification: Cancer
• Umbrella term: 7 Mondo subtypes
• Cohort genes: 1
• GWAS associations: 48
• ClinVar variants: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	benign neoplasm of eye
Mondo ID	MONDO:0021454
NCIT	C4780
SNOMED CT	92097004
UMLS	C1867616
MedGen	401267
Anatomy (UBERON)	UBERON:0010230
Is cancer (heuristic)	yes

Also known as: benign eye neoplasm · benign eye tumor · benign eye tumour · benign neoplasm of the eye · benign ocular neoplasm · benign ocular tumor · benign ocular tumour · benign tumor of eye · benign tumor of the eye · benign tumour of eye · benign tumour of the eye · eye benign neoplasm

Data availability: 1 ClinVar variant · 48 GWAS associations (11 studies).

Disease family

An umbrella term covering 7 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › benign neoplasm › nervous system benign neoplasm › sensory organ benign neoplasm › benign neoplasm of eye

Related subtypes (9): paranasal sinus Schneiderian papilloma, benign neoplasm of ear, benign neoplasm of nasal cavity, benign neoplasm of tongue, benign neoplasm of sphenoidal sinus, benign neoplasm of frontal sinus, benign neoplasm of maxillary sinus, benign neoplasm of ethmoidal sinus, auditory system benign neoplasm

Subtypes (7): benign conjunctival neoplasm, benign neoplasm of cornea, benign neoplasm of retina, benign neoplasm of iris, benign neoplasm of choroid, benign neoplasm of lacrimal gland, benign eyelid neoplasm

Genetics & variants

GWAS landscape

48 GWAS associations across 11 studies. Top hits map to 12 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs12203592	2e-79	IRF4	C	0.28
rs1800407	1e-57	OCA2	C	0.29
rs1426654	4e-49	SLC24A5	A	0.55
rs7503221	2e-38	NPLOC4	C	0.14
chr17:79526821	8e-38		C	0.15
rs12948708	1e-36	NPLOC4	G	0.13
chr12:20710145	9e-36		A	0.16
rs55679363	7e-31	LINC00964	A	0.13
rs76931114	2e-30	PDE3A	T	0.15
chr15:48433494	1e-24		A	0.6
rs10967906	4e-24	MOB3B	G	0.11
rs7048625	9e-23	MOB3B	G	0.1
rs1129038	1e-22	HERC2	C	0.65
rs2413887	4e-21	SLC12A1, CTXN2	T	0.52
rs1126809	8e-21	TYR	G	0.11
chr15:29145030	3e-15		T	0.45
chr15:34253831	3e-14		G	0.49
rs747571	2e-13	RAB38	T	0.08
chr15:26106487	3e-13		G	0.42
chr15:49200830	7e-13		A	0.39
chr15:47166145	8e-13		C	0.47
chr15:46811273	1e-12		G	0.4
rs12898729	2e-12	HERC2	G	0.38
chr15:45397566	2e-12		G	0.41
chr15:42725684	4e-12		C	0.43
chr15:27694075	1e-11		G	0.34
chr15:35753474	2e-11		G	0.55

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90475626	Verma A	2024	19,748	421,282	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90475629	Verma A	2024	18,840	423,317	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90475624	Verma A	2024	1,294	57,693	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90475625	Verma A	2024	1,240	119,408	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479850	Verma A	2024	1,240	119,408	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90475627	Verma A	2024	1,126	58,072	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90475628	Verma A	2024	858	120,332	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90479849	Verma A	2024	858	120,332	Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.
GCST90246043	Walters RG	2023	184	75,688	Genotyping and population characteristics of the China Kadoorie Biobank.
GCST90435672	Zhou W	2018	130	407,239	Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	3
Tier 2: splice/UTR	1
Tier 3: regulatory	0
Tier 4: intronic/intergenic	23

MAF distribution

Bucket	Variants
common (>=0.05)	27
low_freq (0.01-0.05)	0
rare (<0.01)	0
unknown	0

Functional consequences

Consequence	Count
unknown	13
intron_variant	10
missense_variant	3
3_prime_UTR_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs12203592	6	396321	C>G,T	0.128	intron_variant	IRF4	2e-79	Tier 4: intronic/intergenic
rs1800407	15	27985172	C>T	0.059	missense_variant	OCA2	1e-57	Tier 1: coding
rs1426654	15	48134287	A>C,G,T	0.192	missense_variant	SLC24A5	4e-49	Tier 1: coding
rs7503221	17	81616345	C>A,G	0.313	intron_variant	NPLOC4	2e-38	Tier 4: intronic/intergenic
chr17:79526821				0.368			8e-38	Tier 4: intronic/intergenic
rs12948708	17	81591715	G>A	0.299	intron_variant	NPLOC4	1e-36	Tier 4: intronic/intergenic
chr12:20710145				0.235			9e-36	Tier 4: intronic/intergenic
rs55679363	8	124855592	A>G,T	0.268	intron_variant	LINC00964	7e-31	Tier 4: intronic/intergenic
rs76931114	12	20558200	T>A,C	0.219	intron_variant	PDE3A	2e-30	Tier 4: intronic/intergenic
chr15:48433494				0.214			1e-24	Tier 4: intronic/intergenic
rs10967906	9	27351751	G>A	0.394	intron_variant	MOB3B	4e-24	Tier 4: intronic/intergenic
rs7048625	9	27355007	G>A,T	0.413	intron_variant	MOB3B	9e-23	Tier 4: intronic/intergenic
rs1129038	15	28111713	C>A,G,T	0.126	3_prime_UTR_variant	HERC2	1e-22	Tier 2: splice/UTR
rs2413887	15	48193729	T>C	0.351	intron_variant	SLC12A1, CTXN2	4e-21	Tier 4: intronic/intergenic
rs1126809	11	89284793	G>A	0.284	missense_variant	TYR	8e-21	Tier 1: coding
chr15:29145030				0.24			3e-15	Tier 4: intronic/intergenic
chr15:34253831				0.184			3e-14	Tier 4: intronic/intergenic
rs747571	11	88151580	T>C	0.362	intron_variant	RAB38	2e-13	Tier 4: intronic/intergenic
chr15:26106487				0.197			3e-13	Tier 4: intronic/intergenic
chr15:49200830				0.344			7e-13	Tier 4: intronic/intergenic
chr15:47166145				0.14			8e-13	Tier 4: intronic/intergenic
chr15:46811273				0.428			1e-12	Tier 4: intronic/intergenic
rs12898729	15	28147115	G>A,C	0.264	intron_variant	HERC2	2e-12	Tier 4: intronic/intergenic
chr15:45397566				0.214			2e-12	Tier 4: intronic/intergenic
chr15:42725684				0.21			4e-12	Tier 4: intronic/intergenic
chr15:27694075				0.185			1e-11	Tier 4: intronic/intergenic
chr15:35753474				0.099			2e-11	Tier 4: intronic/intergenic

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1065336	NM_001374353.1(GLI2):c.3784C>T (p.His1262Tyr)	GLI2	Uncertain significance	criteria provided, multiple submitters, no conflicts

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
GLI2	Orphanet:220386	Semilobar holoprosencephaly
GLI2	Orphanet:280195	Septopreoptic holoprosencephaly
GLI2	Orphanet:280200	Microform holoprosencephaly
GLI2	Orphanet:420584	Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome
GLI2	Orphanet:93924	Lobar holoprosencephaly
GLI2	Orphanet:93925	Alobar holoprosencephaly
GLI2	Orphanet:93926	Midline interhemispheric variant of holoprosencephaly
GLI2	Orphanet:95494	Combined pituitary hormone deficiencies, genetic forms

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
GLI2	HGNC:4318	ENSG00000074047	P10070	Zinc finger protein GLI2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GLI2	Zinc finger protein GLI2	Functions as a transcription regulator in the hedgehog (Hh) pathway.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GLI2	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, GLI-like

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
germinal epithelium of ovary	1
tibia	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GLI2	211	ubiquitous	marker	tibia, germinal epithelium of ovary, ventricular zone

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GLI2	3,112

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GLI2	P10070	42.68

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 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
RUNX2 regulates chondrocyte maturation	1	2284.0×	0.002	GLI2
GLI proteins bind promoters of Hh responsive genes to promote transcription	1	1631.4×	0.002	GLI2
Degradation of GLI2 by the proteasome	1	223.9×	0.006	GLI2
Hedgehog ‘off’ state	1	178.4×	0.006	GLI2
Hedgehog ‘on’ state	1	158.6×	0.006	GLI2

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
ventral midline development	1	5617.3×	0.002	GLI2
floor plate formation	1	5617.3×	0.002	GLI2
spinal cord ventral commissure morphogenesis	1	5617.3×	0.002	GLI2
hindgut morphogenesis	1	4213.0×	0.002	GLI2
tube development	1	4213.0×	0.002	GLI2
cerebellar cortex morphogenesis	1	2808.7×	0.002	GLI2
spinal cord dorsal/ventral patterning	1	2106.5×	0.002	GLI2
ventral spinal cord development	1	1872.4×	0.002	GLI2
epidermal cell differentiation	1	1685.2×	0.002	GLI2
positive regulation of T cell differentiation in thymus	1	1532.0×	0.002	GLI2
hindbrain development	1	1123.5×	0.003	GLI2
osteoblast development	1	991.3×	0.003	GLI2
embryonic digestive tract development	1	991.3×	0.003	GLI2
developmental growth	1	732.7×	0.003	GLI2
branching morphogenesis of an epithelial tube	1	732.7×	0.003	GLI2
proximal/distal pattern formation	1	648.1×	0.003	GLI2
pituitary gland development	1	648.1×	0.003	GLI2
mammary gland development	1	648.1×	0.003	GLI2
positive regulation of DNA replication	1	581.1×	0.003	GLI2
hair follicle morphogenesis	1	495.6×	0.004	GLI2
pattern specification process	1	468.1×	0.004	GLI2
odontogenesis of dentin-containing tooth	1	300.9×	0.005	GLI2
neuron development	1	255.3×	0.006	GLI2
cellular response to virus	1	200.6×	0.007	GLI2
lung development	1	198.3×	0.007	GLI2
smoothened signaling pathway	1	181.2×	0.008	GLI2
kidney development	1	140.4×	0.009	GLI2
skeletal system development	1	125.8×	0.010	GLI2
osteoblast differentiation	1	121.2×	0.010	GLI2
axon guidance	1	90.6×	0.013	GLI2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
GLI2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GLI2	6	Binding:6

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).

Drug repurposing candidates

0 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

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	GLI2

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)
GLI2	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.