Neuroocular syndrome 1

Summary

Neuroocular syndrome 1 (MONDO:0971007) is a disease caused by PRR12 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: PRR12 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 36

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		29	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	neuroocular syndrome 1
Mondo ID	MONDO:0971007
OMIM	619539
Orphanet	659904
UMLS	C5925133
MedGen	1863661
GARD	0027154
Is cancer (heuristic)	no

Also known as: multiple congenital anomalies-neurodevelopmental delay-ocular abnormalities syndrome

Data availability: 36 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › neuroocular syndrome › neuroocular syndrome 1

Related subtypes (1): benign paroxysmal tonic upgaze of childhood with ataxia

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

36 retrieved; paginated sample, class counts are floors:

12 uncertain significance, 11 pathogenic, 9 likely pathogenic, 3 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1013592	NM_020719.3(PRR12):c.3273del (p.Lys1092fs)	PRR12	Pathogenic	criteria provided, multiple submitters, no conflicts
1184838	NM_020719.3(PRR12):c.5624-2A>G	PRR12	Pathogenic/Likely pathogenic	no assertion criteria provided
1184840	NM_020719.3(PRR12):c.677dup (p.Tyr227fs)	PRR12	Pathogenic	criteria provided, single submitter
1699083	NM_020719.3(PRR12):c.4344del (p.Glu1449fs)	PRR12	Pathogenic	criteria provided, single submitter
3897600	NM_020719.3(PRR12):c.3073_3079del (p.Glu1025fs)	PRR12	Pathogenic	criteria provided, single submitter
4071987	NM_020719.3(PRR12):c.1167C>G (p.Tyr389Ter)	PRR12	Pathogenic	criteria provided, single submitter
4294534	NM_020719.3(PRR12):c.4723del (p.Arg1575fs)	PRR12	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
4531734	NM_020719.3(PRR12):c.3242dup (p.Arg1082fs)	PRR12	Pathogenic	criteria provided, single submitter
4813548	NM_020719.3(PRR12):c.2028dup (p.Ser677fs)	PRR12	Pathogenic	criteria provided, single submitter
4819169	NM_020719.3(PRR12):c.3012_3013del (p.Glu1004fs)	PRR12	Pathogenic	criteria provided, single submitter
1285639	NM_020719.3(PRR12):c.3505C>T (p.Arg1169Trp)	PRR12	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2432862	NM_020719.3(PRR12):c.3404C>A (p.Ser1135Ter)	PRR12	Likely pathogenic	criteria provided, single submitter
3256557	NM_020719.3(PRR12):c.3969_3984dup (p.Thr1329fs)	PRR12	Likely pathogenic	criteria provided, single submitter
3338095	NM_020719.3(PRR12):c.5587del (p.Asp1863fs)	PRR12	Likely pathogenic	no assertion criteria provided
3383033	NM_020719.3(PRR12):c.715_725del (p.Arg239fs)	PRR12	Likely pathogenic	criteria provided, single submitter
3777126	NM_020719.3(PRR12):c.2065_2071dup (p.Ala691fs)	PRR12	Likely pathogenic	criteria provided, single submitter
4071988	NM_020719.3(PRR12):c.2623_2630dup (p.Gly878fs)	PRR12	Likely pathogenic	criteria provided, single submitter
4076230	NM_020719.3(PRR12):c.4813C>T (p.Arg1605Ter)	PRR12	Likely pathogenic	criteria provided, single submitter
4531234	NM_020719.3(PRR12):c.2986_2999del (p.Gly996fs)	PRR12	Likely pathogenic	criteria provided, single submitter
1176714	NM_020719.3(PRR12):c.3508C>T (p.Pro1170Ser)	PRR12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1285640	NM_020719.3(PRR12):c.5909T>C (p.Leu1970Pro)	PRR12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
983349	NM_020719.3(PRR12):c.2123C>T (p.Ala708Val)	PRR12	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2435263	NM_020719.3(PRR12):c.577C>G (p.Pro193Ala)	PRR12	Uncertain significance	criteria provided, single submitter
2689832	NM_020719.3(PRR12):c.2405T>A (p.Leu802His)	PRR12	Uncertain significance	criteria provided, single submitter
3255046	NM_020719.3(PRR12):c.5083A>C (p.Lys1695Gln)	PRR12	Uncertain significance	criteria provided, single submitter
3366997	NM_020719.3(PRR12):c.3869A>G (p.Lys1290Arg)	PRR12	Uncertain significance	criteria provided, single submitter
3376328	NM_020719.3(PRR12):c.4741G>A (p.Val1581Ile)	PRR12	Uncertain significance	criteria provided, single submitter
3731455	NM_020719.3(PRR12):c.3497G>A (p.Gly1166Glu)	PRR12	Uncertain significance	criteria provided, single submitter

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.