Cone-rod dystrophy 7

Summary

Cone-rod dystrophy 7 (MONDO:0011355) is a disease caused by RIMS1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: RIMS1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 144

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	cone-rod dystrophy 7
Mondo ID	MONDO:0011355
MeSH	C566350
OMIM	603649
DOID	DOID:0111012
UMLS	C1863634
MedGen	355026
GARD	0015356
Is cancer (heuristic)	no

Also known as: cone-rod dystrophy 7 · cone-rod dystrophy type 7 · CORD7

Data availability: 144 ClinVar variants · 4 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 › cone-rod dystrophy › cone-rod dystrophy 7

Related subtypes (27): cone-rod dystrophy 2, macular degeneration, X-linked atrophic, cone-rod dystrophy 1, cone-rod dystrophy 5, cone-rod dystrophy 6, cone dystrophy 3, cone-rod dystrophy 3, Leber congenital amaurosis 4, cone-rod dystrophy 8, Newfoundland cone-rod dystrophy, cone-rod dystrophy 13, cone-rod dystrophy 10, cone-rod dystrophy 11, retinal cone dystrophy 4, cone-rod dystrophy 12, cone-rod dystrophy 9, cone-rod dystrophy 15, cone-rod dystrophy 16, cone-rod dystrophy 17, cone-rod dystrophy 18, cone-rod dystrophy 19, cone-rod dystrophy 20, cone-rod dystrophy 21, X-linked cone-rod dystrophy, cone-rod dystrophy 22, cone-rod dystrophy 14, cone-rod dystrophy 24

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

144 retrieved; paginated sample, class counts are floors:

59 uncertain significance, 44 benign, 25 conflicting classifications of pathogenicity, 8 benign/likely benign, 7 likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
828152	NM_014989.7(RIMS1):c.2770+2T>C	RIMS1	Likely pathogenic	no assertion criteria provided
156391	NM_014989.7(RIMS1):c.3139del (p.Thr1047fs)	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
194658	NM_014989.7(RIMS1):c.2699-8T>C	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
287848	NM_014989.7(RIMS1):c.2894C>T (p.Pro965Leu)	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
357828	NM_014989.7(RIMS1):c.28C>T (p.Pro10Ser)	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
357832	NM_014989.7(RIMS1):c.672A>G (p.Thr224=)	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
357837	NM_014989.7(RIMS1):c.1311G>A (p.Arg437=)	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
357839	NM_014989.7(RIMS1):c.1384C>A (p.Pro462Thr)	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
357842	NM_014989.7(RIMS1):c.1704T>C (p.Asp568=)	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
357844	NM_014989.7(RIMS1):c.2294A>G (p.Gln765Arg)	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
357851	NM_014989.7(RIMS1):c.3399-4A>G	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
357855	NM_014989.7(RIMS1):c.3941T>C (p.Leu1314Pro)	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
357857	NM_014989.7(RIMS1):c.4159C>T (p.Arg1387Trp)	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
4168	NM_014989.7(RIMS1):c.2459G>A (p.Arg820His)	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
497703	NM_014989.7(RIMS1):c.169G>C (p.Val57Leu)	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
746942	NM_014989.7(RIMS1):c.3588C>T (p.His1196=)	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
840239	NM_014989.7(RIMS1):c.3703G>A (p.Gly1235Arg)	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
862711	NM_014989.7(RIMS1):c.826G>A (p.Gly276Arg)	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
872603	NM_014989.7(RIMS1):c.3430C>T (p.Arg1144Ter)	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
908313	NM_014989.7(RIMS1):c.1957+10C>A	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
908316	NM_014989.7(RIMS1):c.2545-4T>C	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
909234	NM_014989.7(RIMS1):c.4945T>A (p.Ser1649Thr)	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
911157	NM_014989.7(RIMS1):c.3249C>T (p.Ser1083=)	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
911298	NM_014989.7(RIMS1):c.1386G>A (p.Pro462=)	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
911362	NM_014989.7(RIMS1):c.3758C>T (p.Pro1253Leu)	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
958710	NM_014989.7(RIMS1):c.2890A>G (p.Lys964Glu)	RIMS1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
357827	NM_014989.7(RIMS1):c.-13G>T	LOC129996708	Uncertain significance	criteria provided, single submitter
1449441	NM_014989.7(RIMS1):c.2024T>C (p.Ile675Thr)	RIMS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1805699	NM_014989.7(RIMS1):c.1679-20589C>T	RIMS1	Uncertain significance	criteria provided, single submitter
2441928	NM_014989.7(RIMS1):c.797A>G (p.Glu266Gly)	RIMS1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · 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
RIMS1	Strong	Autosomal dominant	cone-rod dystrophy 7	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RIMS1	Orphanet:1872	Cone rod dystrophy

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
RIMS1	HGNC:17282	ENSG00000079841	Q86UR5	Regulating synaptic membrane exocytosis protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RIMS1	Regulating synaptic membrane exocytosis protein 1	Rab effector involved in exocytosis.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RIMS1	Transcription factor	no		C2_dom, PDZ, Rab_BD

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
cerebellar cortex	1
cerebellar hemisphere	1
cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RIMS1	175	broad	marker	cerebellar cortex, cerebellar hemisphere, cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RIMS1	1,987

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RIMS1	Q86UR5	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Acetylcholine Neurotransmitter Release Cycle	1	671.8×	0.002	RIMS1
Serotonin Neurotransmitter Release Cycle	1	634.4×	0.002	RIMS1
Norepinephrine Neurotransmitter Release Cycle	1	634.4×	0.002	RIMS1
GABA synthesis, release, reuptake and degradation	1	634.4×	0.002	RIMS1
Dopamine Neurotransmitter Release Cycle	1	496.5×	0.002	RIMS1
Glutamate Neurotransmitter Release Cycle	1	456.8×	0.002	RIMS1

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
acrosomal vesicle exocytosis	1	2808.7×	0.002	RIMS1
positive regulation of inhibitory postsynaptic potential	1	2808.7×	0.002	RIMS1
secretion	1	2106.5×	0.002	RIMS1
obsolete synaptic vesicle docking	1	1296.3×	0.002	RIMS1
calcium-ion regulated exocytosis	1	991.3×	0.002	RIMS1
regulated exocytosis	1	887.0×	0.002	RIMS1
synaptic vesicle priming	1	802.5×	0.002	RIMS1
synaptic vesicle exocytosis	1	766.0×	0.002	RIMS1
regulation of neurotransmitter secretion	1	766.0×	0.002	RIMS1
positive regulation of dendrite extension	1	732.7×	0.002	RIMS1
membrane fusion	1	624.1×	0.003	RIMS1
positive regulation of excitatory postsynaptic potential	1	526.6×	0.003	RIMS1
regulation of synaptic vesicle exocytosis	1	455.5×	0.003	RIMS1
protein-containing complex assembly	1	113.9×	0.011	RIMS1
visual perception	1	79.5×	0.015	RIMS1
intracellular protein transport	1	64.8×	0.017	RIMS1
positive regulation of gene expression	1	38.7×	0.027	RIMS1
cell differentiation	1	29.1×	0.034	RIMS1

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
RIMS1	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	RIMS1

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)
RIMS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.