Neuroocular syndrome

Summary

Neuroocular syndrome (MONDO:0859193) is a disease caused by PRR12 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: PRR12 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 26

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	neuroocular syndrome
Mondo ID	MONDO:0859193
OMIM	619539
UMLS	C5551362
MedGen	1790414
Is cancer (heuristic)	no

Data availability: 26 ClinVar variants · 2 GenCC gene-disease records.

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 › neuroocular syndrome

Related subtypes (119): ptosis, eye accommodation disease, corneal disorder, asthenopia, lens disorder, keratomalacia, scleral disorder, ocular siderosis, coloboma, luxation of globe, mucopolysaccharidosis type 1, lacrimal apparatus disorder, Foster-Kennedy syndrome, anterior dislocation of lens, uveal disorder, eyelid disorder, ocular hypotension, scotoma, exophthalmos, ophthalmia nodosa, eye degenerative disorder, refractive error, glaucoma, retinal disorder, eye allergy, ocular vascular disorder, optic neuritis, conjunctival disorder, ocular hypertension, Tietz syndrome, Alagille syndrome, glaucoma-sleep apnea syndrome, Marshall syndrome, microcornea-glaucoma-absent frontal sinuses syndrome, nail-patella syndrome, oculodentodigital dysplasia, piebaldism, Sturge-Weber syndrome, cerebrotendinous xanthomatosis, ocular cystinosis, alpha-mannosidosis, megalocornea-intellectual disability syndrome, mucolipidosis type IV, mucopolysaccharidosis type 6, Netherton syndrome, galactosialidosis, Niemann-Pick disease type A, ocular motor apraxia, Cogan type, Peters plus syndrome, isolated Pierre-Robin syndrome, ectodermal dysplasia-blindness syndrome, Sandhoff disease, SHORT syndrome, Sjogren-Larsson syndrome, Smith-Lemli-Opitz syndrome, Tay-Sachs disease, tyrosinemia type II, Ito hypomelanosis, X-linked cone dysfunction syndrome with myopia, red color blindness, oculocerebrorenal syndrome, Lowry-MacLean syndrome, pigment dispersion syndrome, hereditary hyperferritinemia with congenital cataracts, dyssegmental dysplasia-glaucoma syndrome, mevalonic aciduria, familial cavitary optic disk anomaly, blindness - scoliosis - arachnodactyly syndrome, fatty acyl-CoA reductase 1 deficiency, microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome, neurotrophic keratopathy, Cogan syndrome, atopic keratoconjunctivitis, rhizomelic chondrodysplasia punctata, Ehlers-Danlos syndrome, kyphoscoliotic type 1, IRVAN syndrome, Rothmund-Thomson syndrome type 2, microcornea-corectopia-macular hypoplasia syndrome, isolated anophthalmia-microphthalmia syndrome, Spasmus nutans, toxic maculopathy due to antimalarial drugs, syndromic recessive X-linked ichthyosis, acute zonal occult outer retinopathy, acute annular outer retinopathy, phakomatosis pigmentovascularis, lamellar ichthyosis, idiopathic linear interstitial keratitis, chondroectodermal dysplasia with night blindness, galactosemia, GM1 gangliosidosis, Gaucher disease, visual snow syndrome, extensive peripapillary myelinated nerve fibers, IgG4-related ophthalmic disorder, global developmental delay-visual anomalies-progressive cerebellar atrophy-truncal hypotonia syndrome, vernal keratoconjunctivitis, Gardner syndrome, anterior segment dysgenesis, isolated ankyloblepharon filiforme adnatum, hereditary optic neuropathy, essential strabismus, Axenfeld anomaly, eye neoplasm, isolated blepharochalasis, punctate inner choroidopathy, eye infectious disorder, vitreous body disorder, 9q33.3q34.11 microdeletion syndrome, autoimmune/inflammatory optic neuropathy, LTBP2-related ocular dysgenesis, ocular growth disorder, ocular dysgenesis caused by defects in PAX6 regulation, choroidal neovascularization, anterior segment developmental abnormality with extraocular manifestations, congenital optic disk excavation, isolated angioid streaks, multiple evanescent white dot syndrome, stellate multiform amelanotic choroidopathy, macular telangiectasia

Subtypes (2): benign paroxysmal tonic upgaze of childhood with ataxia, neuroocular syndrome 1

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

26 retrieved; paginated sample, class counts are floors:

11 pathogenic, 11 likely pathogenic, 2 conflicting classifications of pathogenicity, 2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1013592	NM_020719.3(PRR12):c.3273del (p.Lys1092fs)	PRR12	Pathogenic	criteria provided, multiple submitters, no conflicts
1013594	NM_020719.3(PRR12):c.2755C>T (p.Gln919Ter)	PRR12	Pathogenic	criteria provided, multiple submitters, no conflicts
1013597	NM_020719.3(PRR12):c.790C>T (p.Gln264Ter)	PRR12	Pathogenic	criteria provided, multiple submitters, no conflicts
1676830	NM_020719.3(PRR12):c.1521T>G (p.Tyr507Ter)	PRR12	Pathogenic	criteria provided, single submitter
1676831	NM_020719.3(PRR12):c.3958C>T (p.Arg1320Ter)	PRR12	Pathogenic	criteria provided, multiple submitters, no conflicts
1701759	NM_020719.3(PRR12):c.2680_2695dup (p.Val899fs)	PRR12	Pathogenic	criteria provided, single submitter
2687488	NM_020719.3(PRR12):c.1549_1568del (p.Pro517fs)	PRR12	Pathogenic	criteria provided, single submitter
3061967	NM_020719.3(PRR12):c.521del (p.Pro174fs)	PRR12	Pathogenic	criteria provided, single submitter
3065991	NM_020719.3(PRR12):c.1205del (p.Gly402fs)	PRR12	Pathogenic	no assertion criteria provided
446254	NM_020719.3(PRR12):c.1918G>T (p.Glu640Ter)	PRR12	Pathogenic	criteria provided, multiple submitters, no conflicts
446256	NM_020719.3(PRR12):c.903_909dup (p.Pro304fs)	PRR12	Pathogenic	criteria provided, multiple submitters, no conflicts
1285639	NM_020719.3(PRR12):c.3505C>T (p.Arg1169Trp)	PRR12	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1333589	NM_020719.3(PRR12):c.2247C>G (p.Tyr749Ter)	PRR12	Likely pathogenic	criteria provided, single submitter
1526075	NM_020719.3(PRR12):c.2831_2832dup (p.Ser945fs)	PRR12	Likely pathogenic	criteria provided, single submitter
1676829	NM_020719.3(PRR12):c.1232C>A (p.Ser411Ter)	PRR12	Likely pathogenic	criteria provided, single submitter
1705305	NM_020719.3(PRR12):c.3959_3978del (p.Arg1320fs)	PRR12	Likely pathogenic	criteria provided, single submitter
1707516	NM_020719.3(PRR12):c.656_657del (p.Leu219fs)	PRR12	Likely pathogenic	criteria provided, single submitter
1727056	NM_020719.3(PRR12):c.1146del (p.Ile383fs)	PRR12	Likely pathogenic	criteria provided, single submitter
2429082	NM_020719.3(PRR12):c.2218G>T (p.Glu740Ter)	PRR12	Likely pathogenic	criteria provided, single submitter
2442383	NM_020719.3(PRR12):c.1345C>T (p.Gln449Ter)	PRR12	Likely pathogenic	criteria provided, single submitter
2505234	NM_020719.3(PRR12):c.3950_3951del (p.Val1317fs)	PRR12	Likely pathogenic	criteria provided, single submitter
2571626	NM_020719.3(PRR12):c.922_923del (p.His308fs)	PRR12	Likely pathogenic	criteria provided, single submitter
1285640	NM_020719.3(PRR12):c.5909T>C (p.Leu1970Pro)	PRR12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1687383	NM_020719.3(PRR12):c.3625C>T (p.Arg1209Ter)	PRR12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1328159	NM_020719.3(PRR12):c.4787C>T (p.Thr1596Met)	PRR12	Uncertain significance	criteria provided, single submitter
3066032	NM_020719.3(PRR12):c.3355C>T (p.Arg1119Trp)	PRR12	Uncertain significance	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · 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
PRR12	Definitive	Autosomal dominant	neuroocular syndrome	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PRR12	Orphanet:659904	Multiple congenital anomalies-neurodevelopmental delay-ocular abnormalities syndrome

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
PRR12	HGNC:29217	ENSG00000126464	Q9ULL5	Proline-rich protein 12	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.

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)
PRR12	Other/Unknown	no		DUF4211, DNA_MethProtect_Complex

Expression context

Cohort genes with no expression data: 0.

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
cardia of stomach	1
kidney epithelium	1
nipple	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PRR12	210	ubiquitous	yes	kidney epithelium, cardia of stomach, nipple

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PRR12	1,018

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PRR12	Q9ULL5	43.84

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
intracellular protein localization	1	104.7×	0.010	PRR12

Therapeutics

Drug target analysis

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

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
PRR12	1	2

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: 1; 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	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.