KCNJ13

Summary

KCNJ13 (potassium inwardly rectifying channel subfamily J member 13, HGNC:6259) is a protein-coding gene on chromosome 2q37.1, encoding Inward rectifier potassium channel 13 (O60928). Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it.

This gene encodes a member of the inwardly rectifying potassium channel family of proteins. Members of this family form ion channel pores that allow potassium ions to pass into a cell. The encoded protein belongs to a subfamily of low signal channel conductance proteins that have a low dependence on potassium concentration. Mutations in this gene are associated with snowflake vitreoretinal degeneration. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 3769 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inherited retinal dystrophy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 8
• Clinical variants (ClinVar): 54 total — 3 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 39
• Druggable target: yes
• MANE Select transcript: NM_002242

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6259
Approved symbol	KCNJ13
Name	potassium inwardly rectifying channel subfamily J member 13
Location	2q37.1
Locus type	gene with protein product
Status	Approved
Aliases	Kir7.1, Kir1.4, LCA16
Ensembl gene	ENSG00000115474
Ensembl biotype	protein_coding
OMIM	603208
Entrez	3769

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000233826, ENST00000409779, ENST00000410029, ENST00000438786, ENST00000444142

RefSeq mRNA: 3 — MANE Select: NM_002242 NM_001172416, NM_001172417, NM_002242

CCDS: CCDS2498, CCDS54437

Canonical transcript exons

ENST00000233826 — 3 exons

Exon	Start	End
ENSE00000965613	232770903	232771378
ENSE00001029725	232765802	232768813
ENSE00001029727	232776445	232776565

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 99.14.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2394 / max 315.5645, expressed in 214 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34569	2.2394	214

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
choroid plexus epithelium	UBERON:0003911	99.14	gold quality
pigmented layer of retina	UBERON:0001782	98.53	gold quality
retina	UBERON:0000966	98.50	gold quality
jejunal mucosa	UBERON:0000399	92.35	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.76	gold quality
buccal mucosa cell	CL:0002336	83.28	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.00	gold quality
small intestine	UBERON:0002108	80.01	gold quality
sural nerve	UBERON:0015488	79.82	gold quality
ileal mucosa	UBERON:0000331	78.00	gold quality
calcaneal tendon	UBERON:0003701	74.12	gold quality
duodenum	UBERON:0002114	73.03	gold quality
jejunum	UBERON:0002115	70.95	gold quality
adrenal tissue	UBERON:0018303	70.39	gold quality
bone marrow cell	CL:0002092	70.07	gold quality
corpus callosum	UBERON:0002336	70.04	gold quality
colonic epithelium	UBERON:0000397	69.98	gold quality
ventricular zone	UBERON:0003053	66.57	gold quality
cervix squamous epithelium	UBERON:0006922	64.42	gold quality
sperm	CL:0000019	64.16	silver quality
male germ cell	CL:0000015	63.16	silver quality
hindlimb stylopod muscle	UBERON:0004252	62.78	gold quality
seminal vesicle	UBERON:0000998	62.05	silver quality
tendon	UBERON:0000043	61.91	gold quality
cerebellar vermis	UBERON:0004720	58.97	gold quality
kidney	UBERON:0002113	58.67	gold quality
upper leg skin	UBERON:0004262	58.58	gold quality
adult mammalian kidney	UBERON:0000082	58.34	gold quality
gall bladder	UBERON:0002110	57.09	gold quality
islet of Langerhans	UBERON:0000006	56.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	326.48
E-GEOD-135922	yes	15.33
E-MTAB-9388	yes	5.92
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

109 targeting KCNJ13, 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-340-5P	100.00	72.50	4437
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-323A-3P	99.79	70.30	1739

Literature-anchored findings (GeneRIF, showing 18)

• This study confirms the expression of Kir7.1 in human RPE, identifies a Kir7.1 splice variant resulting in predicted changes in protein sequence, and indicates that there is no functional interaction between this splice variant and full-length Kir7.1. (PMID:18035352)
• Kir7.1 channels are modulated by intracellular protons by diverse mechanisms; H26 is important for channel activation at physiological pH(i) and it influences an unidentified proton-induced inhibitory mechanism. (PMID:18094146)
• These results indicate that the KCNJ13 R162W mutation can cause Snowflake vitreoretinal degeneration and further show that vitreoretinal degeneration can arise through mutations in genes whose products are not structural components of the vitreous. (PMID:18179896)
• This study demonstrates the dual regulation of Kir7.1 channel function by PKA and PKC. (PMID:18976636)
• A homozygous nonsense mutation was found in the potassium channel subunit gene KCNJ13 that caused leber congenital amaurosis. (PMID:21763485)
• Kir7.1 expression was found in 100% of choroid plexus tumors and was absent in endolymphatic sac tumors. (PMID:22706862)
• Kir7.1, R162W mutant showed a reduction of IKir7.1 and positive shift in ‘0’ current potential. (PMID:23977131)
• Kir7.1 regulates the transition from quiescence to contractions in the pregnant uterus. (PMID:25056913)
• Juvenile or early-adult-onset cataract in the setting of a congenital vitreo-retinal dystrophy notable for fibrosis over the disc and clumped pigmentation in the posterior pole is a unique phenotype that suggests recessive KCNJ13 mutations. (PMID:25475713)
• Kir7.1 mutations are associated with vision disorders to include novel insights into the molecular mechanism of disease pathobiology in Leber Congenital Amaurosis. (PMID:25921210)
• KCNJ13 mutations are responsible for early-onset retinal dystrophy, featuring remarkable clumpy pigment deposits at the level of the retinal pigment epithelium, suggesting dysfunction and disorganization of this tissue. (PMID:27203561)
• The activated oxytocin receptor was able to inhibit the Kir7.1 channel, an important mediator of sub retinal waste transport and K(+) homeostasis. (PMID:28603013)
• We propose that mutant RPE Kir7.1 channels contribute directly to the abnormal ERG associated with blindness via alterations in sub-retinal space K(+) homeostasis in the vicinity of the photoreceptor outer segment. (PMID:28878288)
• Results confirm earlier findings that the MC4R-Kir7.1 signaling is independent of Gs-AC-cAMP signaling pathway. Furthermore, these data suggest that a noncanonical GPCR signaling pathway may be essential for this interaction. (PMID:29058194)
• Both human and zebrafish variants are missense and located within the conserved transmembrane M2 protein domain, suggesting that disruption of this region may contribute to retinovascular changes as an additional feature to the previously described LCA phenotype. Close monitoring of other patients with similar mutations may be required to minimise the ensuing retinal damage. (PMID:31647904)
• KCNJ13 Gene Deletion Impairs Cell Alignment and Phagocytosis in Retinal Pigment Epithelium Derived from Human-Induced Pluripotent Stem Cells. (PMID:32437550)
• A novel phenotype associated with the R162W variant in the KCNJ13 gene. (PMID:35477418)
• The unique structural characteristics of the Kir 7.1 inward rectifier potassium channel: a novel player in energy homeostasis control. (PMID:36717105)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	kcnj13	ENSDARG00000043443
mus_musculus	Kcnj13	ENSMUSG00000079436
rattus_norvegicus	Kcnj13	ENSRNOG00000016057
drosophila_melanogaster	Irk3	FBGN0032706
drosophila_melanogaster	Irk2	FBGN0039081
drosophila_melanogaster	Irk1	FBGN0265042
caenorhabditis_elegans		WBGENE00002149
caenorhabditis_elegans		WBGENE00002150
caenorhabditis_elegans		WBGENE00002151

Paralogs (15): KCNJ5 (ENSG00000120457), KCNJ8 (ENSG00000121361), KCNJ2 (ENSG00000123700), KCNJ1 (ENSG00000151704), KCNJ16 (ENSG00000153822), KCNJ6 (ENSG00000157542), KCNJ15 (ENSG00000157551), KCNJ9 (ENSG00000162728), KCNJ3 (ENSG00000162989), KCNJ4 (ENSG00000168135), KCNJ10 (ENSG00000177807), KCNJ14 (ENSG00000182324), KCNJ12 (ENSG00000184185), KCNJ11 (ENSG00000187486), KCNJ18 (ENSG00000260458)

Protein

Protein identifiers

Inward rectifier potassium channel 13 — O60928 (reviewed: O60928)

Alternative names: Inward rectifier K(+) channel Kir7.1, Potassium channel, inwardly rectifying subfamily J member 13

All UniProt accessions (3): C9JWD6, O60928, H7C4D1

UniProt curated annotations — full annotation on UniProt →

Function. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. KCNJ13 has a very low single channel conductance, low sensitivity to block by external barium and cesium, and no dependence of its inward rectification properties on the internal blocking particle magnesium.

Subunit / interactions. Homotetramer. Interacts with RAB28; the interaction may facilitate cone outer segments phagocytosis. Forms a complex with OPN3 and MC4R; OPN3 potentiates KCNJ13 activity.

Subcellular location. Membrane. Cell membrane.

Tissue specificity. Predominantly expressed in small intestine. Expression is also detected in stomach, kidney, and all central nervous system regions tested with the exception of spinal cord.

Post-translational modifications. Phosphorylation at Ser-201 by PKC strongly inhibits ionic currents, while phosphorylation at Ser-287 by PKA increases them.

Disease relevance. Snowflake vitreoretinal degeneration (SVD) [MIM:193230] Developmental and progressive hereditary eye disorder that affects multiple tissues within the eye. Diagnostic features of SVD include fibrillar degeneration of the vitreous humor, early-onset cataract, minute crystalline deposits in the neurosensory retina, and retinal detachment. The disease is caused by variants affecting the gene represented in this entry. Leber congenital amaurosis 16 (LCA16) [MIM:614186] A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by Ba(2+) and Cs(+), although sensitivity to those inhibitors is much lower than in other Kir channels.

Similarity. Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ13 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
O60928-1	1	yes
O60928-2	2, Kir7.1S

RefSeq proteins (3): NP_001165887, NP_001165888, NP_002233* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008062	KCNJ13	Family
IPR013518	K_chnl_inward-rec_Kir_cyto	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR016449	K_chnl_inward-rec_Kir	Family
IPR040445	Kir_TM	Domain
IPR041647	IRK_C	Domain

Pfam: PF01007, PF17655

Catalyzed reactions (Rhea), 1 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)

UniProt features (25 total): sequence variant 8, topological domain 4, mutagenesis site 3, modified residue 2, splice variant 2, transmembrane region 2, chain 1, intramembrane region 1, short sequence motif 1, site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9PR5	ELECTRON MICROSCOPY	3.3
9NMS	ELECTRON MICROSCOPY	3.5
9NMT	ELECTRON MICROSCOPY	3.9
9PR6	ELECTRON MICROSCOPY	3.9
9PR7	ELECTRON MICROSCOPY	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60928-F1	83.26	0.56

Functional residue map

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

Catalytic / active sites (1): 149 (role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesium)

Post-translational modifications (2): 201, 287

Mutagenesis-validated functional residues (3):

Position	Phenotype
111	no effect on channel activity.
125	increased channel activity and increased sensitivity to inhibition by ba(2+).
129	loss of channel activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 205 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, CAGCTG_AP4_Q5, CEBPB_01, GOBP_MONOATOMIC_CATION_TRANSPORT, EVI1_05, TCF4_Q5, CEBP_Q2, FREAC3_01, NKX22_01, AACTTT_UNKNOWN, FREAC4_01, LEF1_Q6, GATA1_02, IK3_01, GOBP_IMPORT_INTO_CELL

GO Biological Process (8): potassium ion transport (GO:0006813), regulation of monoatomic ion transmembrane transport (GO:0034765), regulation of membrane potential (GO:0042391), potassium ion import across plasma membrane (GO:1990573), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), potassium ion transmembrane transport (GO:0071805), monoatomic cation transmembrane transport (GO:0098655)

GO Molecular Function (1): inward rectifier potassium channel activity (GO:0005242)

GO Cellular Component (3): plasma membrane (GO:0005886), monoatomic ion channel complex (GO:0034702), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monoatomic ion transmembrane transport	3
metal ion transport	1
regulation of transmembrane transport	1
regulation of monoatomic ion transport	1
regulation of biological quality	1
potassium ion transmembrane transport	1
inorganic cation import across plasma membrane	1
transport	1
monoatomic ion transport	1
transmembrane transport	1
potassium ion transport	1
monoatomic cation transmembrane transport	1
monoatomic cation transport	1
voltage-gated potassium channel activity	1
ligand-gated monoatomic cation channel activity	1
membrane	1
cell periphery	1
transmembrane transporter complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

924 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCNJ13	MC4R	P32245	671
KCNJ13	COL11A1	P12107	642
KCNJ13	IQCB1	Q15051	632
KCNJ13	SPATA7	Q9P0W8	599
KCNJ13	KCNS1	Q96KK3	593
KCNJ13	RD3	Q7Z3Z2	580
KCNJ13	AIPL1	Q9NZN9	544
KCNJ13	LCA5	Q86VQ0	540
KCNJ13	COL4A3	Q01955	524
KCNJ13	KCNK6	Q9Y257	523
KCNJ13	CABP4	P57796	519
KCNJ13	RDH12	Q96NR8	506
KCNJ13	TULP1	O00294	505
KCNJ13	CEP290	O15078	503
KCNJ13	IMPDH1	P20839	493

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0KAL7, A1UZM8, A1VTW0, A2S6C4, A3MQC3, A3N5K9, A3NRA5, A4JHY7, A5ESW9, A6UM20, A6UMS8, A7IBQ1, A9AEZ6, B2AGU8, B2JCP7, B2SXH3, B2UES6, B4EAS1, B7JBL0, C5CJ68, D9N164, E1BN00, O60928, O70617, O82859, P19449, P37177, P37178, P54932, P86046, Q0AKD8, Q0BBR3, Q0KEN8, Q145W4, Q1BTH4, Q1MEX2, Q2K711, Q2T1A9, Q39CU8, Q3JW78

Diamond homologs: B7U540, E1BN00, E1BNE9, F1MYR9, F1NHE9, O02670, O02822, O18839, O19182, O60928, O70339, O70596, O70617, O88335, O88932, P35560, P35561, P48048, P48050, P48051, P48542, P48543, P48544, P48545, P48548, P48549, P48550, P49655, P49656, P49658, P52185, P52186, P52187, P52188, P52189, P52190, P52191, P52192, P63250, P63251

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
PRKACA	up-regulates	KCNJ13	phosphorylation
PRKCA	down-regulates	KCNJ13	phosphorylation
4-aminopyridine	“down-regulates activity”	KCNJ13	“chemical inhibition”
barium(2+)	“down-regulates activity”	KCNJ13	“chemical inhibition”
caesium(1+)	“down-regulates activity”	KCNJ13	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	2
Uncertain significance	38
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
224857	NM_002242.4(KCNJ13):c.158G>A (p.Trp53Ter)	Pathogenic
30332	NM_002242.4(KCNJ13):c.722T>C (p.Leu241Pro)	Pathogenic
978433	NM_002242.4(KCNJ13):c.655C>T (p.Gln219Ter)	Pathogenic
916717	NM_002242.4(KCNJ13):c.431T>C (p.Leu144Pro)	Likely pathogenic
978434	NM_002242.4(KCNJ13):c.314G>T (p.Ser105Ile)	Likely pathogenic

SpliceAI

713 predictions. Top by Δscore:

Variant	Effect	Δscore
2:232776443:A:AC	donor_gain	1.0000
2:232776444:C:CC	donor_gain	1.0000
2:232768811:CAC:C	acceptor_gain	0.9900
2:232768812:ACCT:A	acceptor_loss	0.9900
2:232768813:CCTA:C	acceptor_loss	0.9900
2:232768814:C:CA	acceptor_loss	0.9900
2:232768814:C:CC	acceptor_gain	0.9900
2:232776439:ACTC:A	donor_loss	0.9900
2:232776441:TCACC:T	donor_loss	0.9900
2:232776442:CACCA:C	donor_loss	0.9900
2:232776443:A:C	donor_loss	0.9900
2:232776443:AC:A	donor_gain	0.9900
2:232776444:C:CG	donor_loss	0.9900
2:232776444:CC:C	donor_gain	0.9900
2:232776444:CCA:C	donor_gain	0.9900
2:232776444:CCAG:C	donor_gain	0.9900
2:232771062:TG:T	donor_gain	0.9800
2:232776444:CCAGT:C	donor_gain	0.9700
2:232771255:T:TA	donor_gain	0.9600
2:232774038:TTGGG:T	donor_gain	0.9600
2:232768809:AGCAC:A	acceptor_gain	0.9500
2:232771379:C:G	acceptor_gain	0.9500
2:232768810:GCAC:G	acceptor_gain	0.9400
2:232768811:CACC:C	acceptor_gain	0.9400
2:232774018:ATG:A	donor_gain	0.9400
2:232771161:A:T	acceptor_gain	0.9300
2:232770973:G:C	donor_gain	0.9200
2:232776437:GTAC:G	donor_loss	0.9200
2:232776438:TACT:T	donor_loss	0.9200
2:232770995:CCA:C	donor_gain	0.8900

AlphaMissense

2388 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:232771007:G:A	T119I	0.999
2:232771140:A:G	W75R	0.999
2:232771140:A:T	W75R	0.999
2:232768758:A:C	F172L	0.998
2:232768758:A:T	F172L	0.998
2:232768760:A:G	F172L	0.998
2:232770972:A:G	C131R	0.998
2:232770995:C:A	G123V	0.998
2:232770996:C:A	G123C	0.998
2:232770999:A:G	Y122H	0.998
2:232771001:C:T	G121D	0.998
2:232771004:A:T	I120N	0.998
2:232771010:A:G	L118P	0.998
2:232771018:C:A	E115D	0.998
2:232771018:C:G	E115D	0.998
2:232771027:G:C	F112L	0.998
2:232771027:G:T	F112L	0.998
2:232771028:A:G	F112S	0.998
2:232771029:A:G	F112L	0.998
2:232771064:A:T	V100D	0.998
2:232771067:C:G	C99S	0.998
2:232771067:C:T	C99Y	0.998
2:232771068:A:G	C99R	0.998
2:232771068:A:T	C99S	0.998
2:232771150:A:C	F71L	0.998
2:232771150:A:T	F71L	0.998
2:232771152:A:G	F71L	0.998
2:232771161:A:G	W68R	0.998
2:232771161:A:T	W68R	0.998
2:232768414:G:A	S287F	0.997

dbSNP variants (sampled 300 via entrez): RS1000157635 (2:232769258 T>A), RS1000548585 (2:232767032 A>G), RS1000654692 (2:232773928 A>G), RS1000857075 (2:232775050 A>C), RS1001431318 (2:232769124 G>A), RS1001445215 (2:232773654 T>C), RS1001462459 (2:232769325 G>A), RS1001616344 (2:232769560 C>A,T), RS1002329572 (2:232776164 T>C), RS1002594554 (2:232777220 A>C), RS1002663837 (2:232775804 T>C), RS1003101674 (2:232770640 A>G), RS1003135933 (2:232771159 C>T), RS1003156858 (2:232777212 A>C), RS1003341328 (2:232769281 G>A)

Disease associations

OMIM: gene MIM:603208 | disease phenotypes: MIM:614186, MIM:193230, MIM:268000

GenCC curated gene-disease

Disease	Classification	Inheritance
snowflake vitreoretinal degeneration	Definitive	Autosomal dominant
Leber congenital amaurosis 16	Definitive	Autosomal recessive
Leber congenital amaurosis	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
snowflake vitreoretinal degeneration	Moderate	AD
inherited retinal dystrophy	Definitive	AR

Mondo (5): Leber congenital amaurosis 16 (MONDO:0013613), snowflake vitreoretinal degeneration (MONDO:0008663), inherited retinal dystrophy (MONDO:0019118), retinitis pigmentosa (MONDO:0019200), Leber congenital amaurosis (MONDO:0018998)

Orphanet (4): Leber congenital amaurosis (Orphanet:65), Snowflake vitreoretinal degeneration (Orphanet:91496), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Retinitis pigmentosa (Orphanet:791)

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000365	Hearing impairment
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000512	Abnormal electroretinogram
HP:0000518	Cataract
HP:0000540	Hypermetropia
HP:0000541	Retinal detachment
HP:0000543	Optic disc pallor
HP:0000563	Keratoconus
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000662	Nyctalopia
HP:0000729	Autistic behavior
HP:0001123	Visual field defect
HP:0001141	Severely reduced visual acuity
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001483	Eye poking
HP:0002084	Encephalocele
HP:0002269	Abnormality of neuronal migration
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0004374	Hemiplegia/hemiparesis
HP:0006817	Aplasia/Hypoplasia of the cerebellar vermis
HP:0007663	Reduced visual acuity

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002149_18	Schizophrenia	2.000000e-08
GCST002539_44	Schizophrenia	2.000000e-12
GCST004521_189	Autism spectrum disorder or schizophrenia	3.000000e-10
GCST004521_38	Autism spectrum disorder or schizophrenia	1.000000e-08
GCST004787_50	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	2.000000e-06
GCST005196_218	Coronary artery disease	3.000000e-10
GCST006803_9	Schizophrenia	4.000000e-16
GCST008559_2	Anxiety and stress-related disorders	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010098	stress-related disorder

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D057130	Leber Congenital Amaurosis	C11.270.516; C11.768.364
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C536677	Snowflake vitreoretinal degeneration (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2146349 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: vgic — Inwardly rectifying potassium channels (K_IR)

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
Ba2+	Antagonist	3.2	pKi
Cs+	Antagonist	1.6	pKi

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
trichostatin A	affects cotreatment, decreases expression	3
methylmercuric chloride	decreases expression, increases expression	2
entinostat	decreases expression, affects cotreatment	2
belinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
FR900359	increases phosphorylation	1
titanium dioxide	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Acetaminophen	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Phenylmercuric Acetate	decreases expression, affects cotreatment	1
Silicon Dioxide	increases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Sodium Selenite	decreases expression	1
Palmitic Acid	decreases expression	1
Lactic Acid	increases expression	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2148632	Binding	Inhibition of Kir7.1 expressed in HEK293 cells assessed as inhibition of thallium efflux up to 100 uM by fluorescence assay	Discovery of Selective Small Molecule ROMK Inhibitors as Potential New Mechanism Diuretics. — ACS Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00999609	PHASE3	ACTIVE_NOT_RECRUITING	Safety and Efficacy Study in Subjects With Leber Congenital Amaurosis
NCT06891443	PHASE3	RECRUITING	Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION)
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
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
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]
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT00516477	PHASE1	COMPLETED	Safety Study in Subjects With Leber Congenital Amaurosis