KCNV2

Summary

KCNV2 (potassium voltage-gated channel modifier subfamily V member 2, HGNC:19698) is a protein-coding gene on chromosome 9p24.2, encoding Potassium voltage-gated channel subfamily V member 2 (Q8TDN2). Potassium channel subunit.

Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium voltage-gated channel subfamily V. This member is identified as a ‘silent subunit’, and it does not form homomultimers, but forms heteromultimers with several other subfamily members. Through obligatory heteromerization, it exerts a function-altering effect on other potassium channel subunits. This protein is strongly expressed in pancreas and has a weaker expression in several other tissues.

Source: NCBI Gene 169522 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inherited retinal dystrophy (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 8
• Clinical variants (ClinVar): 849 total — 60 pathogenic, 24 likely-pathogenic
• Phenotypes (HPO): 11
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_133497

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19698
Approved symbol	KCNV2
Name	potassium voltage-gated channel modifier subfamily V member 2
Location	9p24.2
Locus type	gene with protein product
Status	Approved
Aliases	Kv8.2
Ensembl gene	ENSG00000168263
Ensembl biotype	protein_coding
OMIM	607604
Entrez	169522

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000382082

RefSeq mRNA: 1 — MANE Select: NM_133497 NM_133497

CCDS: CCDS6447

Canonical transcript exons

ENST00000382082 — 2 exons

Exon	Start	End
ENSE00001490861	2729446	2730037
ENSE00001490869	2717510	2719095

Expression profiles

Bgee: expression breadth broad, 61 present calls, max score 96.25.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4278 / max 444.1473, expressed in 6 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95873	0.2652	4
95874	0.0867	3
95876	0.0192	3
205412	0.0163	4
95872	0.0154	2
205411	0.0091	3
95875	0.0089	3
95871	0.0070	2

Top tissues by expression

220 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	96.25	gold quality
male germ cell	CL:0000015	92.23	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.94	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.62	gold quality
pigmented layer of retina	UBERON:0001782	67.81	gold quality
testis	UBERON:0000473	65.25	gold quality
right testis	UBERON:0004534	64.74	gold quality
left testis	UBERON:0004533	64.36	gold quality
Brodmann (1909) area 10	UBERON:0013541	63.15	gold quality
sural nerve	UBERON:0015488	62.81	silver quality
cerebellar vermis	UBERON:0004720	56.68	gold quality
quadriceps femoris	UBERON:0001377	51.48	gold quality
vastus lateralis	UBERON:0001379	50.56	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
pancreatic ductal cell	CL:0002079	50.03	silver quality
adult organism	UBERON:0007023	49.87	gold quality
metanephric glomerulus	UBERON:0004736	49.61	gold quality
oviduct epithelium	UBERON:0004804	49.37	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
bone marrow cell	CL:0002092	48.91	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
thymus	UBERON:0002370	48.43	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	1502.54
E-MTAB-7316	yes	47.26
E-GEOD-137537	yes	15.16
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CRX, FOXC1, NR1I2, NRL

miRNA regulators (miRDB)

21 targeting KCNV2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-496	98.66	69.80	931
HSA-MIR-7843-3P	98.31	67.94	803
HSA-MIR-493-3P	97.50	66.44	731
HSA-MIR-6773-5P	97.04	64.30	595
HSA-MIR-6724-5P	96.41	63.11	507

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 30)

• Obligatory heterotetramerization of three previously uncharacterized Kv channel subunits identified in human genome (Kv6.3)(Kv10.1) (Kv11.1) (PMID:12060745)
• Mutations mapped to KCNV2 are responsible for cone dystrophy with supernormal rod electoretinogram. (PMID:16909397)
• KCNV2 mutations account for most if not all cases of cone dystrophy with a supernormal rod electroretinography. We found 1 frameshift, 2 nonsense, 1 non-stop, and 6 missense mutations. (PMID:17896311)
• The phenotype of cone dystrophy with supernormal rod response is tightly linked with mutations in KCNV2. (PMID:18235024)
• The three novel truncative mutations are likely to be null mutations leading to loss of function, with no difference in the phenotype presentation. (PMID:18400204)
• Kv11.1 (ERG1) K+ channels localize in cholesterol and sphingolipid enriched membranes and are modulated by membrane cholesterol. (PMID:18708743)
• Individuals with mutations in KCNV2 manifest a wide range of macular and autofluorescence abnormalities. (PMID:19952985)
• Results demonstrate that altered potassium subunit function influences epilepsy susceptibility and implicate Kcnv2 as an epilepsy gene. (PMID:21402906)
• In KCNV2 retinopathy foveal morphological changes are evident on SD-OCT even in the early stages of disease. (PMID:21558291)
• In this study, we found that KCNV2 mutations are present in a substantial fraction (2.2-4.3%) of a sample of 367 independent patients with a variety of initial clinical diagnoses of cone malfunctino. (PMID:21882291)
• For all patients, KCNV2 sequencing revealed one of three homozygous recessive mutations (PMID:21900228)
• Early ocular phenotype in siblings with a homozygous p.G461R mutation in the KCNV2 gene presented nystagmus, increased light sensitivity, reduced color discrimination, and relative central scotomas. (PMID:21911584)
• KCNV2 mutations cause a unique form of retinal disorder illustrating the importance of K(+)-channels for the resting potential, activation and deactivation of photoreceptors, while phototransduction remains unchanged (PMID:23077521)
• two pore mutations (W467G and G478R) led to the formation of nonconducting heteromeric Kv2.1/Kv8.2 channels (PMID:23115240)
• important finding leading to identification of KCNV2 as a candidate gene for causative mutations was the characteristic pattern of findings on full field ERGs. (PMID:23143909)
• Central vision parameters progressively worsen in KCNV2 cone dystrophy, structural retinal and lipofuscin accumulation abnormalities are commonly present and macular cone photoreceptor mosaic is markedly disrupted early in the disease. (PMID:23221069)
• This is the first report of genetic and clinical analysis of cone dystrophy with supernormal rod response in the Israeli population leading to the identification of 4 novel KCNV2 mutations. (PMID:23725738)
• Compound heterozygosity for the two alleles of KCNV2, p.C177R and p.G461R, in three patients, and homozygosity for complex alleles, p.R27H and p.R206P, in one patient from the consanguineous family, is reported. (PMID:23885164)
• The 2 mutations identified are novel and thus expand the current knowledge of Retinal Cone Dystrophy 3B genotype-phenotype descriptions in the literature. (PMID:24029832)
• Pharmacogenetic and case-control study evaluated the role of the variants of KCNA1, KCNA2, and KCNV2 in the susceptibility and drug resistance of genetic generalized epilepsies and revealed no significant association between 8 variants of KCNA1, KCNA2, and KCNV2 genes and risk or drug resistance of genetic generalized epilepsies after a Bonferroni correction for multiple comparisons. (PMID:28658141)
• Biallelic loss-of-function KCNV2 variants (p.W67X and p.D174GfsX198) were identified as the cause of cone dystrophy with supernormal rod responses (CDSRR). Long-term FF-ERG findings demonstrated there were no ERG changes during 15 years of observation, indicating that there was no evidence of progressive peripheral retinal dysfunction, in spite of worsening macular atrophy. (PMID:30877594)
• KCNV2 retinopathy: clinical features, molecular genetics and directions for future therapy. (PMID:32441199)
• KCNV2-Associated Retinopathy: Genetics, Electrophysiology, and Clinical Course-KCNV2 Study Group Report 1. (PMID:33309813)
• Cone dystrophy with supernormal rod responses: A rare KCNV2 gene variant. (PMID:33706576)
• KCNV2-Associated Retinopathy: Detailed Retinal Phenotype and Structural Endpoints-KCNV2 Study Group Report 2. (PMID:33737031)
• A novel KCNV2 mutation in a patient taking hydroxychloroquine associated with cone dystrophy with supernormal rod response. (PMID:33960280)
• Molecular, Cellular and Functional Changes in the Retinas of Young Adult Mice Lacking the Voltage-Gated K(+) Channel Subunits Kv8.2 and K2.1. (PMID:34063002)
• Compound heterozygous KCNV2 variants contribute to cone dystrophy with supernormal rod responses in a Chinese family. (PMID:34535971)
• Initial diagnoses of patients found to be homozygous for a KCNV2 founder mutation on the Arabian Peninsula (c.427G>T; p.Glu143*). (PMID:36278409)
• KCNV2-associated retinopathy: genotype-phenotype correlations - KCNV2 study group report 3. (PMID:37852740)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnv2b	ENSDARG00000062906
danio_rerio	kcnv2a	ENSDARG00000076644
mus_musculus	Kcnv2	ENSMUSG00000047298
rattus_norvegicus	Kcnv2	ENSRNOG00000012566

Paralogs (31): KCNG1 (ENSG00000026559), KCNQ1 (ENSG00000053918), KCNQ2 (ENSG00000075043), KCND1 (ENSG00000102057), KCNA7 (ENSG00000104848), KCNA1 (ENSG00000111262), KCNC4 (ENSG00000116396), KCNQ4 (ENSG00000117013), KCNS1 (ENSG00000124134), KCNC1 (ENSG00000129159), KCNA5 (ENSG00000130037), KCNC3 (ENSG00000131398), KCNA10 (ENSG00000143105), KCNA6 (ENSG00000151079), KCNS2 (ENSG00000156486), KCNB1 (ENSG00000158445), KCNF1 (ENSG00000162975), KCNV1 (ENSG00000164794), KCNC2 (ENSG00000166006), KCNG4 (ENSG00000168418), KCNS3 (ENSG00000170745), KCNG3 (ENSG00000171126), KCND3 (ENSG00000171385), KCNA3 (ENSG00000177272), KCNA2 (ENSG00000177301), KCNG2 (ENSG00000178342), KCNA4 (ENSG00000182255), KCNB2 (ENSG00000182674), KCNQ3 (ENSG00000184156), KCND2 (ENSG00000184408), KCNQ5 (ENSG00000185760)

Protein

Protein identifiers

Potassium voltage-gated channel subfamily V member 2 — Q8TDN2 (reviewed: Q8TDN2)

Alternative names: Voltage-gated potassium channel subunit Kv8.2

All UniProt accessions (1): Q8TDN2

UniProt curated annotations — full annotation on UniProt →

Function. Potassium channel subunit. Modulates channel activity by shifting the threshold and the half-maximal activation to more negative values.

Subunit / interactions. Heteromultimer with KCNB1, KCNC1 and KCNF1. Does not form homomultimers.

Subcellular location. Cell membrane.

Tissue specificity. Detected in lung, liver, kidney, pancreas, spleen, thymus, prostate, testis, ovary and colon.

Disease relevance. Cone dystrophy with supernormal rod responses (CDSRR) [MIM:610356] An autosomal recessive ocular disorder characterized by macular dysfunction, reduced and delayed cone responses, and supernormal and delayed rod responses. The onset of symptoms is in the first and second decades of life, and patients have reduced central vision, marked photophobia, reduced color discrimination predominantly along the red-green axes while tritan color vision is relatively well preserved. Nyctalopia is a later feature of the disorder. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.

Similarity. Belongs to the potassium channel family. V (TC 1.A.1.2) subfamily. Kv8.2/KCNV2 sub-subfamily.

RefSeq proteins (1): NP_598004* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003131	T1-type_BTB	Domain
IPR003968	K_chnl_volt-dep_Kv	Family
IPR003971	K_chnl_volt-dep_Kv5/Kv9	Family
IPR005821	Ion_trans_dom	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR027359	Volt_channel_dom_sf	Homologous_superfamily
IPR028325	VG_K_chnl	Family

Pfam: PF00520, PF02214

UniProt features (27 total): topological domain 8, sequence variant 8, transmembrane region 6, chain 1, intramembrane region 1, region of interest 1, short sequence motif 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TDN2-F1	75.55	0.40

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 440

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1296072	Voltage gated Potassium channels
R-HSA-112316	Neuronal System
R-HSA-1296071	Potassium Channels

MSigDB gene sets: 98 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, REACTOME_VOLTAGE_GATED_POTASSIUM_CHANNELS, REACTOME_POTASSIUM_CHANNELS, TAKADA_GASTRIC_CANCER_COPY_NUMBER_DN, GOBP_MONOATOMIC_CATION_TRANSPORT, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, TGCTGAY_UNKNOWN, MODULE_99, GOBP_PROTEIN_HOMOOLIGOMERIZATION, KORKOLA_EMBRYONIC_CARCINOMA_VS_SEMINOMA_DN, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_POTASSIUM_CHANNEL_COMPLEX, SPZ1_01, GOBP_REGULATION_OF_MEMBRANE_POTENTIAL, GOCC_CATION_CHANNEL_COMPLEX

GO Biological Process (7): action potential (GO:0001508), protein homooligomerization (GO:0051260), potassium ion transmembrane transport (GO:0071805), monoatomic ion transport (GO:0006811), potassium ion transport (GO:0006813), monoatomic ion transmembrane transport (GO:0034220), transmembrane transport (GO:0055085)

GO Molecular Function (5): voltage-gated potassium channel activity (GO:0005249), potassium channel regulator activity (GO:0015459), monoatomic ion channel activity (GO:0005216), potassium channel activity (GO:0005267), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), voltage-gated potassium channel complex (GO:0008076), membrane (GO:0016020), monoatomic ion channel complex (GO:0034702)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Potassium Channels	1
Neuronal System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
potassium channel activity	2
regulation of membrane potential	1
protein complex oligomerization	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
metal ion transport	1
monoatomic ion transport	1
transmembrane transport	1
cellular process	1
voltage-gated monoatomic cation channel activity	1
ion channel regulator activity	1
monoatomic ion transmembrane transporter activity	1
channel activity	1
monoatomic cation channel activity	1
potassium ion transmembrane transporter activity	1
binding	1
membrane	1
cell periphery	1
potassium channel complex	1
plasma membrane protein complex	1
cellular anatomical structure	1
transmembrane transporter complex	1

Protein interactions and networks

STRING

1886 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNV2	PDE6H	Q13956	977
KCNV2	MPDZ	O75970	784
KCNV2	LNX1	Q8TBB1	777
KCNV2	CNGB3	Q9NQW8	608
KCNV2	GUCY2D	Q02846	601
KCNV2	SLC1A1	P43005	592
KCNV2	CDHR1	Q96JP9	584
KCNV2	PDE6C	P51160	583
KCNV2	ABCA4	P78363	581
KCNV2	CNGA3	Q16281	577
KCNV2	LINC03040	Q8N319	575
KCNV2	CFAP418	Q96NL8	571
KCNV2	RPGRIP1	Q96KN7	559
KCNV2	CACNA2D4	Q7Z3S7	556
KCNV2	ALDH7A1	P49419	552

IntAct

7 interactions, top by confidence:

A	B	Type	Score
ANKRD28	KCNV2	psi-mi:“MI:0915”(physical association)	0.560
KCNV2	HSPA8	psi-mi:“MI:0914”(association)	0.530
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
KCNV2	ANKRD28	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): MTHFR (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), AMZ2 (Affinity Capture-MS), KCNV2 (Affinity Capture-RNA), ANKRD28 (Two-hybrid), KCNV2 (Two-hybrid), KCNV2 (Two-hybrid), KCNV2 (Two-hybrid), KCNV2 (Affinity Capture-Western), MTHFR (Affinity Capture-MS), HSPA8 (Affinity Capture-MS), KCNV2 (Affinity Capture-MS), KCNV2 (Affinity Capture-Western), KCNV2 (Cross-Linking-MS (XL-MS)), KCNV2 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2BDX4, A4K2T1, A4K2Y2, D4AD53, O15554, O73606, O88454, O89109, P15388, P17971, P17972, P35739, P48547, P59053, P59994, P59995, P97557, Q03719, Q0P583, Q17ST2, Q52PG9, Q5RC10, Q60565, Q63881, Q6IVV8, Q6PIU1, Q7TN37, Q80XM3, Q8BZN2, Q8CFS6, Q8HYZ1, Q8IV77, Q8R1P5, Q8R523, Q8TAE7, Q8TD43, Q8TDN1, Q8TDN2, Q96RP8, Q9ERS0

Diamond homologs: A2BDX4, A4K2M4, A4K2N8, A4K2P6, A4K2Q6, A4K2R3, A4K2S2, A4K2T1, A4K2V2, A4K2W6, A4K2X4, A4K2Y2, A6H8H5, D4AD53, D4ADX7, G5EFC3, O18868, O35173, O35174, O73606, O88758, O88759, P10499, P15384, P15385, P15387, P15388, P16388, P16390, P17970, P17971, P17972, P22001, P22459, P22739, P25122, P48547, P59053, P59994, P59995

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

849 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	60
Likely pathogenic	24
Uncertain significance	463
Likely benign	207
Benign	23

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1060876	NM_133497.4(KCNV2):c.596G>A (p.Cys199Tyr)	Pathogenic
1066823	NC_000009.11:g.(?2729426)(2729727_?)del	Pathogenic
1074242	NM_133497.4(KCNV2):c.613G>T (p.Glu205Ter)	Pathogenic
1184555	NM_133497.4(KCNV2):c.1199del (p.Phe400fs)	Pathogenic
1184889	NM_133497.4(KCNV2):c.741G>A (p.Trp247Ter)	Pathogenic
1350298	NM_133497.4(KCNV2):c.430G>T (p.Glu144Ter)	Pathogenic
1358901	NM_133497.4(KCNV2):c.361del (p.Thr121fs)	Pathogenic
1425692	NM_133497.4(KCNV2):c.951C>G (p.Tyr317Ter)	Pathogenic
1434970	NM_133497.4(KCNV2):c.656_657del (p.Glu219fs)	Pathogenic
1442966	NM_133497.4(KCNV2):c.781del (p.Ala261fs)	Pathogenic
1446160	NM_133497.4(KCNV2):c.649C>T (p.Gln217Ter)	Pathogenic
1451899	NM_133497.4(KCNV2):c.547G>T (p.Glu183Ter)	Pathogenic
1451943	NM_133497.4(KCNV2):c.889_901del (p.Asp297fs)	Pathogenic
1452213	NM_133497.4(KCNV2):c.325C>T (p.Gln109Ter)	Pathogenic
1456099	NM_133497.4(KCNV2):c.491del (p.Phe164fs)	Pathogenic
1468960	NM_133497.4(KCNV2):c.564G>C (p.Trp188Cys)	Pathogenic
1911474	NM_133497.4(KCNV2):c.1336dup (p.His446fs)	Pathogenic
1936062	NM_133497.4(KCNV2):c.625G>T (p.Glu209Ter)	Pathogenic
1955508	NM_133497.4(KCNV2):c.39C>G (p.Tyr13Ter)	Pathogenic
1973248	NM_133497.4(KCNV2):c.196C>T (p.Gln66Ter)	Pathogenic
2023676	NM_133497.4(KCNV2):c.153T>A (p.Tyr51Ter)	Pathogenic
2102755	NM_133497.4(KCNV2):c.1108_1195del (p.Gly370fs)	Pathogenic
2427218	NC_000009.11:g.(?2717755)(2728666_?)del	Pathogenic
2427219	NC_000009.11:g.(?2717758)(2728666_?)del	Pathogenic
2427220	NC_000009.11:g.(?2717738)(2719115_?)del	Pathogenic
265419	NM_133497.4(KCNV2):c.778A>T (p.Lys260Ter)	Pathogenic
2735239	NM_133497.4(KCNV2):c.563G>A (p.Trp188Ter)	Pathogenic
2745186	NM_133497.4(KCNV2):c.700dup (p.Arg234fs)	Pathogenic
2745187	NM_133497.4(KCNV2):c.1057G>T (p.Glu353Ter)	Pathogenic
2872939	NM_133497.4(KCNV2):c.856C>T (p.Gln286Ter)	Pathogenic

SpliceAI

236 predictions. Top by Δscore:

Variant	Effect	Δscore
9:2729440:CTACA:C	acceptor_loss	0.9900
9:2729441:TACA:T	acceptor_loss	0.9900
9:2729443:CAG:C	acceptor_loss	0.9900
9:2729444:AGG:A	acceptor_loss	0.9900
9:2729445:G:GT	acceptor_loss	0.9900
9:2729445:GGTGA:G	acceptor_gain	0.9800
9:2729357:G:GT	donor_gain	0.9700
9:2729358:G:T	donor_gain	0.9700
9:2729444:AGGT:A	acceptor_gain	0.9700
9:2729445:GGT:G	acceptor_gain	0.9700
9:2729445:GGTG:G	acceptor_gain	0.9700
9:2719094:CGGTG:C	donor_loss	0.9600
9:2719096:G:GG	donor_gain	0.9600
9:2719097:T:G	donor_loss	0.9600
9:2719098:GAGT:G	donor_loss	0.9600
9:2719099:AG:A	donor_loss	0.9600
9:2719093:GCG:G	donor_gain	0.9500
9:2719100:G:C	donor_loss	0.9500
9:2729444:A:AG	acceptor_gain	0.9400
9:2729445:G:GG	acceptor_gain	0.9400
9:2719085:G:GA	donor_gain	0.9200
9:2719216:A:AG	acceptor_gain	0.9200
9:2719285:GTAA:G	donor_gain	0.9200
9:2723731:CTG:C	acceptor_gain	0.9200
9:2729442:A:AG	acceptor_gain	0.9100
9:2719289:G:GG	donor_gain	0.8900
9:2729442:ACAG:A	acceptor_gain	0.8800
9:2729443:C:G	acceptor_gain	0.8800
9:2729444:AG:A	acceptor_gain	0.8800
9:2729445:GG:G	acceptor_gain	0.8800

AlphaMissense

3572 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:2729449:A:C	S454R	0.999
9:2729451:C:A	S454R	0.999
9:2729451:C:G	S454R	0.999
9:2729575:T:C	F496L	0.998
9:2729577:T:A	F496L	0.998
9:2729577:T:G	F496L	0.998
9:2718301:T:A	W188R	0.997
9:2718301:T:C	W188R	0.997
9:2718303:G:C	W188C	0.997
9:2718303:G:T	W188C	0.997
9:2719087:T:A	W450R	0.997
9:2719087:T:C	W450R	0.997
9:2729531:G:A	G481E	0.997
9:2718197:G:C	R153P	0.995
9:2719084:T:A	W449R	0.995
9:2719084:T:C	W449R	0.995
9:2718211:T:C	F158L	0.994
9:2718213:C:A	F158L	0.994
9:2718213:C:G	F158L	0.994
9:2719012:T:C	F425L	0.994
9:2719014:C:A	F425L	0.994
9:2719014:C:G	F425L	0.994
9:2729518:T:C	C477R	0.994
9:2729520:C:G	C477W	0.994
9:2729530:G:A	G481R	0.994
9:2729530:G:C	G481R	0.994
9:2718190:T:C	F151L	0.993
9:2718191:T:C	F151S	0.993
9:2718192:C:A	F151L	0.993
9:2718192:C:G	F151L	0.993

dbSNP variants (sampled 300 via entrez): RS1000149904 (9:2719723 T>A), RS1000161880 (9:2726497 AAAG>A), RS1000249744 (9:2724038 T>C,G), RS1000390475 (9:2728450 T>C), RS1000762221 (9:2727330 G>A,C,T), RS1000777419 (9:2719057 A>T), RS1000808999 (9:2727578 T>A), RS1000893299 (9:2724455 A>T), RS1000991645 (9:2716948 C>G,T), RS1001120678 (9:2723062 T>C), RS1001258989 (9:2720016 A>C), RS1001568970 (9:2719597 T>A), RS1001581750 (9:2728658 C>T), RS1001628230 (9:2720189 G>C), RS1001868163 (9:2727989 C>A,G)

Disease associations

OMIM: gene MIM:607604 | disease phenotypes: MIM:610356, MIM:602093, MIM:120970, MIM:248200, MIM:601777

GenCC curated gene-disease

Disease	Classification	Inheritance
cone dystrophy with supernormal rod response	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
inherited retinal dystrophy	Definitive	AR

Mondo (10): cone dystrophy with supernormal rod response (MONDO:0012475), inherited retinal dystrophy (MONDO:0019118), cone dystrophy 3 (MONDO:0011193), optic atrophy (MONDO:0003608), cone dystrophy (MONDO:0000455), cone-rod dystrophy (MONDO:0015993), congenital nervous system disorder (MONDO:0002320), pathologic nystagmus (MONDO:0004843), Stargardt disease (MONDO:0019353), cone-rod dystrophy 6 (MONDO:0011143)

Orphanet (5): Cone dystrophy with supernormal rod response (Orphanet:209932), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Cone rod dystrophy (Orphanet:1872), Progressive cone dystrophy (Orphanet:1871), Stargardt disease (Orphanet:827)

HPO phenotypes

11 total (12 of 11 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000545	Myopia
HP:0000548	Cone/cone-rod dystrophy
HP:0000575	Scotoma
HP:0000613	Photophobia
HP:0000662	Nyctalopia
HP:0000666	Horizontal nystagmus
HP:0007401	Macular atrophy
HP:0007663	Reduced visual acuity
HP:0000556	Retinal dystrophy

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001155_3	Vascular endothelial growth factor levels	1.000000e-39
GCST001280_4	Alzheimer’s disease (age of onset)	4.000000e-06
GCST001762_499	Obesity-related traits	1.000000e-06
GCST002039_5	Blood trace element (Se levels)	3.000000e-06
GCST003403_7	Vascular endothelial growth factor levels	9.000000e-99
GCST009391_1143	Metabolite levels	3.000000e-06
GCST009391_1172	Metabolite levels	3.000000e-06
GCST90000584_11	Inflammatory biomarkers (multivariate analysis)	2.000000e-17

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0004344	birth weight
EFO:0010457	Alpha ketoglutarate measurement
EFO:0006524	L-arginine measurement
EFO:0004872	inflammatory biomarker measurement

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D000077765	Cone Dystrophy	C11.270.151; C11.768.216
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D009759	Nystagmus, Pathologic	C10.292.562.675; C11.590.400
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D058499	Retinal Dystrophies	C11.768.585.658
D000080362	Stargardt Disease	C11.270.872; C11.768.585.439.339; C16.320.290.724
C563678	Retinal Cone Dystrophy 3B (supp.)
C538363	Retinal cone dystrophy 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2362996 (PROTEIN FAMILY)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: vgic — Voltage-gated potassium channels (K_v)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.82	Ki	0.15	nM	CHEMBL5722941
9.74	IC50	0.18	nM	CHEMBL5722941

PubChem BioAssay actives

2 with measured affinity, of 34 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-[(1R,2aS,4S,5aS,8aS,10S,11aR,14aS,16S,17aS,19S,20aS,22S,23aS,25S,26aS,28S,29aS,31R,32aS,35aS,36R,38aS,39S,41aS,42S,44aS,45S,48R,50aS,51S,53aS,54S,56aS,57S,59aS,60S,63S,66S,69S,72S,75S,78S,87R,93S,96S,99S)-17a,20a,23a,53a,63-pentakis(4-aminobutyl)-31-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-5-carbamimidamido-2-[[(2S)-5-carbamimidamido-2-[[(2S)-1-[(2S)-5-oxopyrrolidine-2-carbonyl]pyrrolidine-2-carbonyl]amino]pentanoyl]amino]pentanoyl]amino]hexanoyl]amino]-4-methylpentanoyl]amino]-16,29a,72,78-tetrakis(2-amino-2-oxoethyl)-14a,26a-bis(3-amino-3-oxopropyl)-2a,38a,66-tribenzyl-28,50a,57-tris[(2S)-butan-2-yl]-4,5a,19,42,45,69-hexakis(3-carbamimidamidopropyl)-51,54-bis(2-carboxyethyl)-56a,99-bis(carboxymethyl)-36-[[(2S,3S)-1-(carboxymethylamino)-3-methyl-1-oxopentan-2-yl]carbamoyl]-39,60-bis[(1R)-1-hydroxyethyl]-75,93-bis(hydroxymethyl)-32a,35a,59a-tris[(4-hydroxyphenyl)methyl]-22-(1H-imidazol-4-ylmethyl)-96-(1H-indol-3-ylmethyl)-41a-methyl-25-(2-methylpropyl)-1a,3,4a,6,7a,9,10a,13a,15,16a,18,19a,21,22a,24,25a,27,28a,30,31a,34a,37a,38,40a,41,43a,44,47,49a,50,52a,53,55a,56,58a,59,61a,62,65,68,71,74,77,80,83,86,89,92,95,98-pentacontaoxo-33,34,63a,64a,67a,68a-hexathia-a,2,3a,5,6a,8,9a,12a,14,15a,17,18a,20,21a,23,24a,26,27a,29,30a,33a,36a,37,39a,40,42a,43,46,48a,49,51a,52,54a,55,57a,58,60a,61,64,67,70,73,76,79,82,85,88,91,94,97-pentacontazapentacyclo[85.74.4.448,111.010,14.0144,148]nonahexacontahectan-8a-yl]propanoic acid	2198828: Binding affinity to KV channel (unknown origin) assessed as inhibition constant	ki	0.0001	uM

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
cypermethrin	decreases expression	1
sodium arsenite	decreases expression	1
tanespimycin	decreases expression, affects cotreatment	1
STA 9090	decreases expression	1
VER 155008	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Endosulfan	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1

ChEMBL screening assays

21 unique, capped per target: 20 binding, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1787442	Binding	Inhibition of human recombinant Kv channel at 10 uM by radioligand binding assay	Structure-activity relationships of pyrrole based S-nitrosoglutathione reductase inhibitors: pyrrole regioisomers and propionic acid replacement. — Bioorg Med Chem Lett
CHEMBL5522525	Toxicity	Inhibition of human K+ channel by automated electrophysiology	Discovery of Clinical Candidate AZD5462, a Selective Oral Allosteric RXFP1 Agonist for Treatment of Heart Failure. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C6TI	ABi001-A	Induced pluripotent stem cell	Female
CVCL_C6TJ	ABi002-A	Induced pluripotent stem cell	Male
CVCL_E3QS	ABi004-A	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

102 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03772665	PHASE3	COMPLETED	Safety and Efficacy of Emixustat in Stargardt Disease
NCT05244304	PHASE3	COMPLETED	Phase 3, Randomized, Placebo-Controlled Study of Tinlarebant to Explore Safety and Efficacy in Adolescent Stargardt Disease
NCT07419334	PHASE3	RECRUITING	Study of ALK-001 on the Progression of Stargardt Disease
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02402660	PHASE2	ENROLLING_BY_INVITATION	Phase 2 Tolerability and Effects of ALK-001 on Stargardt Disease
NCT03033108	PHASE2	COMPLETED	Pharmacodynamic Study of Emixustat Hydrochloride in Subjects With Macular Atrophy Secondary to Stargardt Disease
NCT04239625	PHASE2	ACTIVE_NOT_RECRUITING	Open-Label Extension: Tolerability and Effects of ALK-001 on Stargardt Disease (TEASE)
NCT04489511	PHASE2	COMPLETED	Study of STG-001 in Subjects With Stargardt Disease
NCT05417126	PHASE2	COMPLETED	Safety and Effects of a Single Intravitreal Injection of vMCO-010 Optogenetic Therapy in Subjects With Stargardt Disease
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT01064505	PHASE1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT05147701	PHASE1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT02230228	PHASE1	COMPLETED	Phase 1 Safety Study of ALK-001 in Healthy Volunteers
NCT03772938	PHASE1	UNKNOWN	Stem Cells Therapy in Degenerative Diseases of the Retina
NCT07417566	PHASE1	RECRUITING	A Study of DC6001 Tablet in Healthy Chinese Adult Subjects
NCT07594236	PHASE1	RECRUITING	Phase 1 Study of C.001 in Retinal Degeneration
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT