Retinitis pigmentosa 7

Summary

Retinitis pigmentosa 7 (MONDO:0011974) is a disease caused by variants in PRPH2 and ROM1, with 3 cohort genes.

At a glance

• Causal genes: PRPH2 (GenCC Definitive), ROM1 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 50

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 7
Mondo ID	MONDO:0011974
OMIM	608133
DOID	DOID:0110383
UMLS	C1842475
MedGen	334168
GARD	0010386
Is cancer (heuristic)	no

Also known as: retinitis pigmentosa 7 · retinitis pigmentosa type 7 · RP 7 · RP7

Data availability: 50 ClinVar variants · 6 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 7

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 26, retinitis pigmentosa 32, retinitis pigmentosa 31, retinitis pigmentosa 35, retinitis pigmentosa 33, retinitis pigmentosa 36, retinitis pigmentosa 37, 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

50 retrieved; paginated sample, class counts are floors:

12 pathogenic/likely pathogenic, 9 conflicting classifications of pathogenicity, 8 uncertain significance, 7 likely pathogenic, 7 pathogenic, 5 benign, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
4278403	NM_005570.4(LMAN1):c.604C>T (p.Arg202Ter)	LMAN1	Pathogenic	criteria provided, single submitter
1076073	NM_000322.5(PRPH2):c.692C>G (p.Ser231Ter)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1175271	NM_000322.5(PRPH2):c.738G>C (p.Trp246Cys)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1175277	NM_000322.5(PRPH2):c.914del (p.Gly305fs)	PRPH2	Pathogenic	criteria provided, multiple submitters, no conflicts
13162	NM_000322.5(PRPH2):c.353GCT[1] (p.Cys119del)	PRPH2	Pathogenic/Likely pathogenic	no assertion criteria provided
13164	NM_000322.5(PRPH2):c.647C>T (p.Pro216Leu)	PRPH2	Pathogenic	criteria provided, multiple submitters, no conflicts
13167	NM_000322.5(PRPH2):c.515G>A (p.Arg172Gln)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13170	NM_000322.5(PRPH2):c.514C>T (p.Arg172Trp)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13172	NM_000322.5(PRPH2):c.732C>A (p.Asn244Lys)	PRPH2	Pathogenic	criteria provided, multiple submitters, no conflicts
13178	NM_000322.5(PRPH2):c.458AGA[1] (p.Lys154del)	PRPH2	Pathogenic	criteria provided, multiple submitters, no conflicts
13179	NM_000322.5(PRPH2):c.136C>T (p.Arg46Ter)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
13181	NM_000322.5(PRPH2):c.518A>T (p.Asp173Val)	PRPH2	Pathogenic	criteria provided, single submitter
143069	NM_000322.5(PRPH2):c.410G>A (p.Gly137Asp)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
624247	NM_000322.5(PRPH2):c.331del (p.Ile111fs)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812387	NM_000322.5(PRPH2):c.518A>C (p.Asp173Ala)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
98666	NM_000322.5(PRPH2):c.422A>G (p.Tyr141Cys)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
98677	NM_000322.5(PRPH2):c.535T>C (p.Trp179Arg)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
98709	NM_000322.5(PRPH2):c.797G>A (p.Gly266Asp)	PRPH2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
98720	NM_000322.5(PRPH2):c.920del (p.Leu307fs)	PRPH2	Pathogenic	criteria provided, multiple submitters, no conflicts
1048139	NM_000322.5(PRPH2):c.512T>G (p.Phe171Cys)	PRPH2	Likely pathogenic	criteria provided, single submitter
1067264	NM_000322.5(PRPH2):c.625G>A (p.Val209Ile)	PRPH2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1685416	NM_000322.5(PRPH2):c.535T>G (p.Trp179Gly)	PRPH2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3767356	NM_000322.5(PRPH2):c.910_911insG (p.Gln304fs)	PRPH2	Likely pathogenic	criteria provided, single submitter
3899360	NM_000322.5(PRPH2):c.920_921insCTTGAGGAATCTGAGAGCGAGAGCCAGGGCTGGCT (p.Glu309fs)	PRPH2	Likely pathogenic	criteria provided, single submitter
4292765	NM_000322.5(PRPH2):c.594C>A (p.Ser198Arg)	PRPH2	Likely pathogenic	criteria provided, single submitter
98697	NM_000322.5(PRPH2):c.656_658del (p.Pro219del)	PRPH2	Likely pathogenic	criteria provided, single submitter
1175273	NM_000322.5(PRPH2):c.745G>A (p.Gly249Ser)	PRPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
285861	NM_000322.5(PRPH2):c.367C>T (p.Arg123Trp)	PRPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
812383	NM_000322.5(PRPH2):c.927G>T (p.Glu309Asp)	PRPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
908040	NM_000322.5(PRPH2):c.346G>T (p.Ala116Ser)	PRPH2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 24 · Orphanet: 11 · 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
PRPH2	Definitive	Semidominant	retinitis pigmentosa 7	21
ROM1	Strong	Autosomal dominant	retinitis pigmentosa 7	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ROM1	Orphanet:791	Retinitis pigmentosa
PRPH2	Orphanet:1872	Cone rod dystrophy
PRPH2	Orphanet:227796	Fundus albipunctatus
PRPH2	Orphanet:52427	Retinitis punctata albescens
PRPH2	Orphanet:75377	Central areolar choroidal dystrophy
PRPH2	Orphanet:791	Retinitis pigmentosa
PRPH2	Orphanet:827	Stargardt disease
PRPH2	Orphanet:99000	Adult-onset foveomacular vitelliform dystrophy
PRPH2	Orphanet:99001	Butterfly-shaped pigment dystrophy
PRPH2	Orphanet:99003	Multifocal pattern dystrophy simulating fundus flavimaculatus
LMAN1	Orphanet:35909	Combined deficiency of factor V and factor VIII

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ROM1	HGNC:10254	ENSG00000149489	Q03395	Rod outer segment membrane protein 1	gencc,clinvar
PRPH2	HGNC:9942	ENSG00000112619	P23942	Peripherin-2	gencc,clinvar
LMAN1	HGNC:6631	ENSG00000074695	P49257	Protein ERGIC-53	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ROM1	Rod outer segment membrane protein 1	Plays a role in rod outer segment (ROS) morphogenesis.
PRPH2	Peripherin-2	Essential for retina photoreceptor outer segment disk morphogenesis, may also play a role with ROM1 in the maintenance of outer segment disk structure.
LMAN1	Protein ERGIC-53	Mannose-specific lectin.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 3 · 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	3	1.8×	0.174

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ROM1	Other/Unknown	no		Peripherin/rom-1, Tetraspanin_EC2_sf, Peripherin/rom-1_CS
PRPH2	Other/Unknown	no		Peripherin/rom-1, Tetraspanin_EC2_sf, Peripherin/rom-1_CS
LMAN1	Other/Unknown	no		Lectin_leg, ConA-like_dom_sf, Intracellular_Lectin-GPT

Expression context

Cohort genes with no expression data: 0.

3 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
C1 segment of cervical spinal cord	1
primordial germ cell in gonad	1
spinal cord	1
hindlimb stylopod muscle	1
quadriceps femoris	1
vastus lateralis	1
germinal epithelium of ovary	1
gingival epithelium	1
jejunal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ROM1	201	broad	marker	primordial germ cell in gonad, C1 segment of cervical spinal cord, spinal cord
PRPH2	176	tissue_specific	marker	quadriceps femoris, vastus lateralis, hindlimb stylopod muscle
LMAN1	280	ubiquitous	marker	germinal epithelium of ovary, jejunal mucosa, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LMAN1	2,474
PRPH2	1,234
ROM1	1,138

Intra-cohort edges

A	B	Sources
PRPH2	ROM1	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LMAN1	P49257	18
ROM1	Q03395	1
PRPH2	P23942	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 19. Enrichment computed across 3 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
Cargo concentration in the ER	1	335.9×	0.020	LMAN1
RHOD GTPase cycle	1	203.9×	0.020	LMAN1
COPII-mediated vesicle transport	1	163.1×	0.020	LMAN1
RHOG GTPase cycle	1	148.3×	0.020	LMAN1
RHOC GTPase cycle	1	146.4×	0.020	LMAN1
ER to Golgi Anterograde Transport	1	132.8×	0.020	LMAN1
RAC2 GTPase cycle	1	126.9×	0.020	LMAN1
RAC3 GTPase cycle	1	119.0×	0.020	LMAN1
Transport to the Golgi and subsequent modification	1	102.9×	0.021	LMAN1
RHOA GTPase cycle	1	74.6×	0.025	LMAN1
Asparagine N-linked glycosylation	1	60.1×	0.026	LMAN1
RHO GTPase cycle	1	60.1×	0.026	LMAN1
Membrane Trafficking	1	37.1×	0.035	LMAN1
Vesicle-mediated transport	1	34.8×	0.035	LMAN1
Signaling by Rho GTPases	1	34.2×	0.035	LMAN1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.035	LMAN1
Post-translational protein modification	1	19.2×	0.058	LMAN1
Metabolism of proteins	1	12.4×	0.085	LMAN1
Signal Transduction	1	10.2×	0.098	LMAN1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
photoreceptor cell outer segment organization	2	702.2×	3e-05	ROM1, PRPH2
protein heterooligomerization	2	702.2×	3e-05	ROM1, PRPH2
detection of light stimulus involved in visual perception	2	432.1×	5e-05	ROM1, PRPH2
response to low light intensity stimulus	1	5617.3×	9e-04	PRPH2
protein homooligomerization	2	81.4×	9e-04	ROM1, PRPH2
positive regulation of organelle organization	1	1872.4×	0.002	LMAN1
visual perception	2	53.0×	0.002	ROM1, PRPH2
camera-type eye photoreceptor cell differentiation	1	1123.5×	0.003	ROM1
obsolete negative regulation of protein targeting to mitochondrion	1	936.2×	0.003	LMAN1
protein localization to photoreceptor outer segment	1	802.5×	0.003	ROM1
retina vasculature development in camera-type eye	1	561.7×	0.004	ROM1
cell adhesion	2	25.0×	0.004	ROM1, PRPH2
endoplasmic reticulum organization	1	140.4×	0.013	LMAN1
retina development in camera-type eye	1	85.1×	0.019	PRPH2
blood coagulation	1	57.9×	0.026	LMAN1
protein maturation	1	54.5×	0.026	PRPH2
endoplasmic reticulum to Golgi vesicle-mediated transport	1	45.3×	0.028	LMAN1
Golgi organization	1	44.6×	0.028	LMAN1
protein localization to plasma membrane	1	36.2×	0.033	PRPH2
protein folding	1	34.5×	0.033	LMAN1
regulation of gene expression	1	27.8×	0.039	ROM1
in utero embryonic development	1	24.0×	0.043	LMAN1
protein transport	1	14.6×	0.067	LMAN1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ROM1	0	0
PRPH2	0	0
LMAN1	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
LMAN1	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	ROM1, PRPH2, LMAN1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
ROM1	0	—
PRPH2	0	—
LMAN1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.