Retinitis pigmentosa 37

Summary

Retinitis pigmentosa 37 (MONDO:0012625) is a disease caused by NR2E3 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: NR2E3 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 87

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 37
Mondo ID	MONDO:0012625
MeSH	C567005
OMIM	611131
DOID	DOID:0110399
UMLS	C1970163
MedGen	410004
GARD	0015508
Is cancer (heuristic)	no

Also known as: NR2E3 retinitis pigmentosa · retinitis pigmentosa 37 · retinitis pigmentosa caused by mutation in NR2E3 · retinitis pigmentosa type 37 · RP37

Data availability: 87 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › retinitis pigmentosa › retinitis pigmentosa 37

Related subtypes (101): retinitis pigmentosa 6, cone-rod dystrophy 2, retinitis pigmentosa 1, retinitis pigmentosa 9, retinitis pigmentosa 10, dominant pericentral pigmentary retinopathy, late-adult onset retinitis pigmentosa, autosomal recessive pericentral pigmentary retinopathy, retinitis pigmentosa 3, retinitis pigmentosa 24, retinitis pigmentosa 23, retinitis pigmentosa 34, retinitis pigmentosa 2, retinitis pigmentosa Y-linked, retinitis pigmentosa 13, retinitis pigmentosa 12, retinitis pigmentosa 14, retinitis pigmentosa 11, retinitis pigmentosa 17, retinitis pigmentosa 18, retinitis pigmentosa 19, retinitis pigmentosa 22, retinitis pigmentosa 25, retinitis pigmentosa 28, retinitis pigmentosa 30, retinitis pigmentosa 7, retinitis pigmentosa 26, retinitis pigmentosa 32, retinitis pigmentosa 31, retinitis pigmentosa 35, retinitis pigmentosa 33, retinitis pigmentosa 36, retinitis pigmentosa 41, retinitis pigmentosa 29, retinitis pigmentosa 46, retinitis pigmentosa 42, retinitis pigmentosa 50, retinitis pigmentosa 54, retinitis pigmentosa 51, retinitis pigmentosa 55, retinitis pigmentosa 56, retinitis pigmentosa 57, retinitis pigmentosa 58, cone-rod dystrophy 15, retinitis pigmentosa 4, retinitis pigmentosa 27, retinitis pigmentosa 49, retinitis pigmentosa 47, retinitis pigmentosa 45, retinitis pigmentosa 44, retinitis pigmentosa 20, retinitis pigmentosa 40, retinitis pigmentosa 39, retinitis pigmentosa 43, retinitis pigmentosa 48, retinitis pigmentosa 59, retinitis pigmentosa 38, retinitis pigmentosa 60, retinitis pigmentosa 61, retinitis pigmentosa 62, retinitis pigmentosa 63, cone-rod dystrophy 16, retinitis pigmentosa 66, retinitis pigmentosa with or without situs inversus, retinitis pigmentosa 67, retinitis pigmentosa 68, retinitis pigmentosa 69, retinitis pigmentosa 70, retinal dystrophy and obesity, retinitis pigmentosa 71, retinitis pigmentosa 72, retinitis pigmentosa 73, retinitis pigmentosa 74, retinitis pigmentosa 75, retinitis pigmentosa 76, retinitis pigmentosa 77, retinitis pigmentosa 92, retinitis pigmentosa 93, retinitis pigmentosa 83, retinitis pigmentosa 84, retinitis pigmentosa 85, retinitis pigmentosa 86, retinitis pigmentosa 87 with choroidal involvement, retinitis pigmentosa 88, retinitis pigmentosa 90, retinitis pigmentosa 81, retinitis pigmentosa 78, retinitis pigmentosa 79, retinitis pigmentosa 80, retinitis pigmentosa 94, variable age at onset, retinitis pigmentosa 53, retinitis pigmentosa 65, retinitis pigmentosa 64, retinitis pigmentosa 95, retinitis pigmentosa 96, retinitis pigmentosa 97, retinitis pigmentosa 98, retinitis pigmentosa 99, retinitis pigmentosa 100, retinitis pigmentosa 101, retinitis pigmentosa 7, digenic

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

87 retrieved; paginated sample, class counts are floors:

27 uncertain significance, 14 conflicting classifications of pathogenicity, 13 pathogenic/likely pathogenic, 13 likely benign, 8 likely pathogenic, 5 benign/likely benign, 5 pathogenic, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
143147	NM_014249.4(NR2E3):c.364C>T (p.Arg122Cys)	NR2E3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
183143	NM_014249.4(NR2E3):c.143_144delinsAGTGTGCCTCCAGTGCCTCGCTCCA (p.Arg48fs)	NR2E3	Pathogenic	criteria provided, multiple submitters, no conflicts
191059	NM_014249.4(NR2E3):c.119-2A>C	NR2E3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
191060	NM_014249.4(NR2E3):c.373C>T (p.Arg125Ter)	NR2E3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2155106	NM_014249.4(NR2E3):c.302_325del (p.Gln101_Cys108del)	NR2E3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2677371	NM_014249.4(NR2E3):c.119-2A>T	NR2E3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
438227	NM_014249.4(NR2E3):c.305C>A (p.Ala102Asp)	NR2E3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
438228	NM_014249.4(NR2E3):c.311G>A (p.Arg104Gln)	NR2E3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
438229	NM_014249.4(NR2E3):c.767C>A (p.Ala256Glu)	NR2E3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
551852	NM_014249.4(NR2E3):c.194_202del (p.Asn65_Cys67del)	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
5533	NM_014249.4(NR2E3):c.166G>A (p.Gly56Arg)	NR2E3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
5534	NM_014249.4(NR2E3):c.1034_1038del (p.Ala344_Leu345insTer)	NR2E3	Pathogenic	criteria provided, single submitter
560471	NM_014249.4(NR2E3):c.724_725del (p.Ser242fs)	NR2E3	Pathogenic	criteria provided, multiple submitters, no conflicts
636047	NM_014249.4(NR2E3):c.481del (p.Thr161fs)	NR2E3	Pathogenic	criteria provided, multiple submitters, no conflicts
867206	NM_014249.4(NR2E3):c.309C>A (p.Cys103Ter)	NR2E3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
871412	NM_014249.4(NR2E3):c.328C>T (p.Gln110Ter)	NR2E3	Pathogenic	criteria provided, multiple submitters, no conflicts
191061	NM_014249.4(NR2E3):c.646G>A (p.Gly216Ser)	NR2E3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
191062	NM_014249.4(NR2E3):c.926G>T (p.Arg309Leu)	NR2E3	Likely pathogenic	criteria provided, single submitter
2585341	NM_014249.4(NR2E3):c.532dup (p.Ile178fs)	NR2E3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2736233	NM_014249.4(NR2E3):c.242A>G (p.Tyr81Cys)	NR2E3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3577620	NM_014249.4(NR2E3):c.16_47del (p.Thr6fs)	NR2E3	Likely pathogenic	criteria provided, single submitter
3577622	NM_014249.4(NR2E3):c.1112T>G (p.Leu371Trp)	NR2E3	Likely pathogenic	criteria provided, single submitter
4537474	NM_014249.4(NR2E3):c.1039G>C (p.Asp347His)	NR2E3	Likely pathogenic	criteria provided, single submitter
4755397	NM_014249.4(NR2E3):c.449del (p.Pro150fs)	NR2E3	Likely pathogenic	criteria provided, single submitter
1001884	NM_014249.4(NR2E3):c.142C>T (p.Arg48Cys)	NR2E3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1060772	NM_014249.4(NR2E3):c.349G>A (p.Ala117Thr)	NR2E3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1065725	NM_014249.4(NR2E3):c.151G>A (p.Gly51Arg)	NR2E3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1687199	NM_014249.4(NR2E3):c.352G>C (p.Val118Leu)	NR2E3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

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	Definitive	Autosomal dominant	retinitis pigmentosa 37	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: 0.