Retinitis pigmentosa 77

Summary

Retinitis pigmentosa 77 (MONDO:0015013) is a disease caused by REEP6 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: REEP6 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 23

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	retinitis pigmentosa 77
Mondo ID	MONDO:0015013
OMIM	617304
DOID	DOID:0080350
UMLS	C4310626
MedGen	934593
GARD	0016221
Is cancer (heuristic)	no

Also known as: REEP6 retinitis pigmentosa · retinitis pigmentosa 77 · retinitis pigmentosa caused by mutation in REEP6 · retinitis pigmentosa type 77 · RP77

Data availability: 23 ClinVar variants · 2 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 77

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 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 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

23 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
1213893	NM_138393.4(REEP6):c.349-1G>A	REEP6	Pathogenic	criteria provided, single submitter
1397844	NM_138393.4(REEP6):c.127_128del (p.Leu43fs)	REEP6	Pathogenic	criteria provided, multiple submitters, no conflicts
374991	NM_001329556.3(REEP6):c.557dup (p.Val187fs)	REEP6	Pathogenic	no assertion criteria provided
374992	NM_138393.4(REEP6):c.383C>T (p.Pro128Leu)	REEP6	Pathogenic	no assertion criteria provided
375312	NM_138393.4(REEP6):c.448del (p.Ala150fs)	REEP6	Pathogenic	criteria provided, single submitter
3776019	NM_001329556.3(REEP6):c.518-2A>T	REEP6	Pathogenic	criteria provided, single submitter
4292703	NM_138393.4(REEP6):c.280_281del (p.Leu94fs)	REEP6	Pathogenic	criteria provided, single submitter
3338286	NM_138393.4(REEP6):c.276C>A (p.Tyr92Ter)	REEP6	Likely pathogenic	criteria provided, single submitter
374989	NM_138393.4(REEP6):c.404T>C (p.Leu135Pro)	REEP6	Likely pathogenic	criteria provided, single submitter
1037002	NM_001329556.3(REEP6):c.598+1G>A	REEP6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
860344	NM_138393.4(REEP6):c.223G>A (p.Glu75Lys)	REEP6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
866272	NM_138393.4(REEP6):c.268G>C (p.Val90Leu)	REEP6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1019378	NM_138393.4(REEP6):c.349-4G>T	REEP6	Uncertain significance	criteria provided, multiple submitters, no conflicts
2043925	NM_138393.4(REEP6):c.517+5G>T	REEP6	Uncertain significance	criteria provided, multiple submitters, no conflicts
4292193	NM_138393.4(REEP6):c.391G>C (p.Gly131Arg)	REEP6	Uncertain significance	criteria provided, single submitter
4819170	NM_138393.4(REEP6):c.209+5dup	REEP6	Uncertain significance	criteria provided, single submitter
1164954	NM_138393.4(REEP6):c.116-16C>T	REEP6	Benign	criteria provided, multiple submitters, no conflicts
1185478	NM_138393.4(REEP6):c.348+28G>A	REEP6	Benign	criteria provided, multiple submitters, no conflicts
1185479	NM_138393.4(REEP6):c.349-21A>G	REEP6	Benign	criteria provided, multiple submitters, no conflicts
1185480	NM_138393.4(REEP6):c.517+265GC[6]	REEP6	Benign	criteria provided, single submitter
1185481	NM_138393.4(REEP6):c.518-113C>T	REEP6	Benign	criteria provided, multiple submitters, no conflicts
1185482	NM_138393.4(REEP6):c.518-52G>T	REEP6	Benign	criteria provided, multiple submitters, no conflicts
1185531	NM_138393.4(REEP6):c.518-29C>T	REEP6	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
REEP6	Definitive	Autosomal recessive	retinitis pigmentosa	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
REEP6	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
REEP6	HGNC:30078	ENSG00000115255	Q96HR9	Receptor expression-enhancing protein 6	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
REEP6	Receptor expression-enhancing protein 6	Required for correct function and survival of retinal photoreceptors.

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)
REEP6	Other/Unknown	no		TB2_DP1_HVA22

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
left testis	1
right lobe of liver	1
right testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
REEP6	180	ubiquitous	marker	right testis, left testis, right lobe of liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
REEP6	1,573

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
REEP6	Q96HR9	73.80

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
detection of light stimulus involved in visual perception	1	648.1×	0.002	REEP6
endoplasmic reticulum organization	1	421.3×	0.002	REEP6

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
REEP6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	REEP6

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)
REEP6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.