Goldmann-Favre syndrome

Summary

Goldmann-Favre syndrome (MONDO:0100289) is a disease caused by NR2E3 (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: NR2E3 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 52
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		50	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	Goldmann-Favre syndrome
Mondo ID	MONDO:0100289
OMIM	268100
Orphanet	53540
DOID	DOID:0061231
ICD-11	890235941
SNOMED CT	232065000
UMLS	C0339541
MedGen	87387
GARD	0010781
Is cancer (heuristic)	no

Also known as: enhanced S-cone syndrome 1 · retinoschisis with early nyctalopia

Data availability: 52 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › disorder of orbital region › eye disorder › vitreous body disorder › vitreous disorder › vitreous syneresis › vitreoretinal degeneration › enhanced S-cone syndrome › Goldmann-Favre syndrome

Related subtypes (1): enhanced S-cone syndrome 2

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

52 retrieved; paginated sample, class counts are floors:

21 uncertain significance, 11 likely benign, 7 conflicting classifications of pathogenicity, 4 benign/likely benign, 4 benign, 3 pathogenic/likely pathogenic, 2 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
183143	NM_014249.4(NR2E3):c.143_144delinsAGTGTGCCTCCAGTGCCTCGCTCCA (p.Arg48fs)	NR2E3	Pathogenic	criteria provided, multiple submitters, no conflicts
3544433	NM_014249.4(NR2E3):c.146dup (p.Cys50fs)	NR2E3	Pathogenic	criteria provided, single submitter
438229	NM_014249.4(NR2E3):c.767C>A (p.Ala256Glu)	NR2E3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5530	NM_014249.4(NR2E3):c.227G>A (p.Arg76Gln)	NR2E3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5532	NM_014249.4(NR2E3):c.932G>A (p.Arg311Gln)	NR2E3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
317006	NM_014249.4(NR2E3):c.245+9G>A	NR2E3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
740115	NM_014249.4(NR2E3):c.843C>T (p.Pro281=)	NR2E3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
846003	NM_014249.4(NR2E3):c.50C>T (p.Ala17Val)	NR2E3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
846374	NM_014249.4(NR2E3):c.123G>A (p.Val41=)	NR2E3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
991922	NM_014249.4(NR2E3):c.229C>T (p.Arg77Trp)	NR2E3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
991927	NM_014249.4(NR2E3):c.456G>A (p.Pro152=)	NR2E3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
991929	NM_014249.4(NR2E3):c.489G>A (p.Met163Ile)	NR2E3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
286837	NM_014249.4(NR2E3):c.230G>A (p.Arg77Gln)	NR2E3	Uncertain significance	criteria provided, multiple submitters, no conflicts
317018	NM_014249.4(NR2E3):c.666G>C (p.Glu222Asp)	NR2E3	Uncertain significance	criteria provided, multiple submitters, no conflicts
426441	NM_014249.4(NR2E3):c.131C>T (p.Ser44Leu)	NR2E3	Uncertain significance	criteria provided, multiple submitters, no conflicts
558411	NM_014249.4(NR2E3):c.170A>G (p.Lys57Arg)	NR2E3	Uncertain significance	criteria provided, multiple submitters, no conflicts
807279	NM_014249.4(NR2E3):c.1127C>A (p.Pro376Gln)	NR2E3	Uncertain significance	criteria provided, multiple submitters, no conflicts
856848	NM_014249.4(NR2E3):c.67G>C (p.Ala23Pro)	NR2E3	Uncertain significance	criteria provided, multiple submitters, no conflicts
887280	NM_014249.4(NR2E3):c.844G>A (p.Glu282Lys)	NR2E3	Uncertain significance	criteria provided, multiple submitters, no conflicts
888478	NM_014249.4(NR2E3):c.428C>T (p.Pro143Leu)	NR2E3	Uncertain significance	criteria provided, multiple submitters, no conflicts
966185	NM_014249.4(NR2E3):c.463C>T (p.Arg155Cys)	NR2E3	Uncertain significance	criteria provided, single submitter
967411	NM_014249.4(NR2E3):c.640C>T (p.Pro214Ser)	NR2E3	Uncertain significance	criteria provided, multiple submitters, no conflicts
970775	NM_014249.4(NR2E3):c.1096G>A (p.Val366Met)	NR2E3	Uncertain significance	criteria provided, multiple submitters, no conflicts
989839	NM_014249.4(NR2E3):c.1175G>A (p.Arg392His)	NR2E3	Uncertain significance	criteria provided, single submitter
989840	NM_014249.4(NR2E3):c.*2G>A	NR2E3	Uncertain significance	no assertion criteria provided
990921	NM_014249.4(NR2E3):c.47C>T (p.Ala16Val)	NR2E3	Uncertain significance	no assertion criteria provided
990922	NM_014249.4(NR2E3):c.90C>A (p.Gly30=)	NR2E3	Uncertain significance	no assertion criteria provided
990923	NM_014249.4(NR2E3):c.119-10T>A	NR2E3	Uncertain significance	no assertion criteria provided
990924	NM_014249.4(NR2E3):c.121G>A (p.Val41Met)	NR2E3	Uncertain significance	criteria provided, single submitter
991928	NM_014249.4(NR2E3):c.479C>G (p.Pro160Arg)	NR2E3	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 2 · 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
NR2E3	Strong	Autosomal dominant	Goldmann-Favre syndrome	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NR2E3	Orphanet:53540	Goldmann-Favre syndrome
NR2E3	Orphanet:791	Retinitis pigmentosa

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
NR2E3	HGNC:7974	ENSG00000278570	Q9Y5X4	Photoreceptor-specific nuclear receptor	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NR2E3	Photoreceptor-specific nuclear receptor	Orphan nuclear receptor of retinal photoreceptor cells.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Nuclear receptor	1	385.9×	0.003

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NR2E3	Nuclear receptor	yes		Retinoid-X_rcpt/HNF4, Nucl_hrmn_rcpt_lig-bd, Znf_hrmn_rcpt

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
buccal mucosa cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NR2E3	156	tissue_specific	marker	buccal mucosa cell, male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NR2E3	1,319

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NR2E3	Q9Y5X4	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. 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
Nuclear Receptor transcription pathway	1	200.3×	0.005	NR2E3

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
eye photoreceptor cell development	1	842.6×	0.011	NR2E3
phototransduction	1	495.6×	0.011	NR2E3
retina development in camera-type eye	1	255.3×	0.014	NR2E3
cell population proliferation	1	102.8×	0.022	NR2E3
neuron differentiation	1	100.3×	0.022	NR2E3
visual perception	1	79.5×	0.023	NR2E3
negative regulation of cell population proliferation	1	42.1×	0.035	NR2E3
positive regulation of gene expression	1	38.7×	0.035	NR2E3
negative regulation of transcription by RNA polymerase II	1	17.7×	0.067	NR2E3
signal transduction	1	16.1×	0.067	NR2E3
positive regulation of transcription by RNA polymerase II	1	14.9×	0.067	NR2E3

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
NR2E3	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
NR2E3	6	Functional:5, Binding:1

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

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	1	NR2E3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
NR2E3	6	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry