Cone dystrophy with supernormal rod response

Summary

Cone dystrophy with supernormal rod response (MONDO:0012475) is a disease caused by KCNV2 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: KCNV2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 129

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		45	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	cone dystrophy with supernormal rod response
Mondo ID	MONDO:0012475
MeSH	C563678
OMIM	610356
Orphanet	209932
DOID	DOID:0081022
ICD-11	545671557
SNOMED CT	719455002
UMLS	C1835897
MedGen	332081
GARD	0010649
Is cancer (heuristic)	no

Also known as: cone dystrophy with night blindness and supernormal rod responses KCNV2 related · cone dystrophy with supernormal rod electroretinogram · cone dystrophy with supernormal rod ERG · cone dystrophy with supernormal rod response · cone dystrophy with supernormal scotopic electroretinogram · RCD3B · retinal cone dystrophy 3B · retinal cone dystrophy type 3B

Data availability: 129 ClinVar variants · 3 GenCC gene-disease records · 2 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › hereditary macular dystrophy › cone dystrophy › cone dystrophy with supernormal rod response

Related subtypes (5): retinal cone dystrophy type 1, cone dystrophy, X-linked, with tapetal-like sheen, cone dystrophy 3, retinal cone dystrophy 4, cone dystrophy 4

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

129 retrieved; paginated sample, class counts are floors:

43 uncertain significance, 26 conflicting classifications of pathogenicity, 18 benign, 11 pathogenic, 9 benign/likely benign, 6 likely pathogenic, 6 pathogenic/likely pathogenic, 5 likely benign, 4 drug response, 1 pathogenic; drug response

ClinVar	Variant (HGVS)	Gene	Classification	Review
1048137	NM_133497.4(KCNV2):c.1096del (p.Val366fs)	KCNV2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1184555	NM_133497.4(KCNV2):c.1199del (p.Phe400fs)	KCNV2	Pathogenic	criteria provided, single submitter
1452213	NM_133497.4(KCNV2):c.325C>T (p.Gln109Ter)	KCNV2	Pathogenic	criteria provided, multiple submitters, no conflicts
1936062	NM_133497.4(KCNV2):c.625G>T (p.Glu209Ter)	KCNV2	Pathogenic	criteria provided, multiple submitters, no conflicts
265419	NM_133497.4(KCNV2):c.778A>T (p.Lys260Ter)	KCNV2	Pathogenic	criteria provided, multiple submitters, no conflicts
3010	NM_133497.4(KCNV2):c.427G>T (p.Glu143Ter)	KCNV2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
37247	NM_133497.4(KCNV2):c.1381G>A (p.Gly461Arg)	KCNV2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
37249	NM_133497.4(KCNV2):c.226C>T (p.Gln76Ter)	KCNV2	Pathogenic	criteria provided, single submitter
39810	NM_133497.4(KCNV2):c.8_11del (p.Lys3fs)	KCNV2	Pathogenic	criteria provided, multiple submitters, no conflicts
39811	NM_133497.4(KCNV2):c.442G>T (p.Glu148Ter)	KCNV2	Pathogenic	criteria provided, multiple submitters, no conflicts
636178	NM_133497.4(KCNV2):c.357dup (p.Lys120fs)	KCNV2	Pathogenic; drug response	no assertion criteria provided
812343	NM_133497.4(KCNV2):c.958C>T (p.Arg320Cys)	KCNV2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
812344	NM_133497.4(KCNV2):c.995_996dup (p.Ser333fs)	KCNV2	Pathogenic	criteria provided, multiple submitters, no conflicts
835076	NM_133497.4(KCNV2):c.531T>A (p.Cys177Ter)	KCNV2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
849612	NM_133497.4(KCNV2):c.417C>A (p.Cys139Ter)	KCNV2	Pathogenic	criteria provided, multiple submitters, no conflicts
867070	NM_133497.4(KCNV2):c.339C>A (p.Cys113Ter)	KCNV2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
962719	NM_133497.4(KCNV2):c.866C>A (p.Ser289Ter)	KCNV2	Pathogenic	criteria provided, multiple submitters, no conflicts
978435	NM_133497.4:c.1357_1638del	KCNV2	Pathogenic	no assertion criteria provided
1027360	NM_133497.4(KCNV2):c.153T>G (p.Tyr51Ter)	KCNV2	Likely pathogenic	criteria provided, single submitter
1048135	NC_000009.11:g.2716981_2787016del	KCNV2	Likely pathogenic	criteria provided, single submitter
1324610	NM_133497.4(KCNV2):c.1A>G (p.Met1Val)	KCNV2	Likely pathogenic	criteria provided, single submitter
3062009	NM_133497.4(KCNV2):c.1408G>C (p.Gly470Arg)	KCNV2	Likely pathogenic	criteria provided, single submitter
3065781	NM_133497.4(KCNV2):c.238G>T (p.Glu80Ter)	KCNV2	Likely pathogenic	criteria provided, single submitter
4813465	NM_133497.4(KCNV2):c.39C>A (p.Tyr13Ter)	KCNV2	Likely pathogenic	criteria provided, single submitter
3011	NM_133497.4(KCNV2):c.916G>T (p.Glu306Ter)	KCNV2	drug response	no assertion criteria provided
3012	NM_133497.4(KCNV2):c.1376G>A (p.Gly459Asp)	KCNV2	drug response	no assertion criteria provided
3014	NM_133497.4(KCNV2):c.767C>G (p.Ser256Trp)	KCNV2	drug response	no assertion criteria provided
39813	NG_012181.1:g.5233_16321delinsCATTTG	KCNV2	drug response	no assertion criteria provided
1031606	NM_133497.4(KCNV2):c.1123G>A (p.Val375Met)	KCNV2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1080229	NM_133497.4(KCNV2):c.1196C>T (p.Ala399Val)	KCNV2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
KCNV2	Strong	Autosomal recessive	cone dystrophy with supernormal rod response	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
KCNV2	Orphanet:209932	Cone dystrophy with supernormal rod response

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
KCNV2	HGNC:19698	ENSG00000168263	Q8TDN2	Potassium voltage-gated channel subfamily V member 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
KCNV2	Potassium voltage-gated channel subfamily V member 2	Potassium channel subunit.

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
Ion channel	1	111.5×	0.009

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
KCNV2	Ion channel	yes		T1-type_BTB, K_chnl_volt-dep_Kv, K_chnl_volt-dep_Kv5/Kv9

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
male germ cell	1
primordial germ cell in gonad	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
KCNV2	61	tissue_specific	marker	sperm, male germ cell, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
KCNV2	1,908

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
KCNV2	Q8TDN2	75.55

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Voltage gated Potassium channels	1	243.0×	0.011	KCNV2
Potassium Channels	1	134.3×	0.011	KCNV2
Neuronal System	1	44.3×	0.023	KCNV2

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
action potential	1	358.6×	0.008	KCNV2
potassium ion transmembrane transport	1	135.9×	0.008	KCNV2
protein homooligomerization	1	122.1×	0.008	KCNV2

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
KCNV2	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
KCNV2	21	Binding:20, Toxicity: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	0
D	Druggable family + AlphaFold only, no drug	1	KCNV2
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)
KCNV2	21	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.