GNAT1

Summary

GNAT1 (G protein subunit alpha transducin 1, HGNC:4393) is a protein-coding gene on chromosome 3p21.31, encoding Guanine nucleotide-binding protein G(t) subunit alpha-1 (P11488). Functions as a signal transducer for the rod photoreceptor RHO.

Transducin is a 3-subunit guanine nucleotide-binding protein (G protein) which stimulates the coupling of rhodopsin and cGMP-phoshodiesterase during visual impulses. The transducin alpha subunits in rods and cones are encoded by separate genes. This gene encodes the alpha subunit in rods. This gene is also expressed in other cells, and has been implicated in bitter taste transduction in rat taste cells. Mutations in this gene result in autosomal dominant congenital stationary night blindness. Multiple alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 2779 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inherited retinal dystrophy (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 10
• Clinical variants (ClinVar): 390 total — 15 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 7
• MANE Select transcript: NM_144499

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4393
Approved symbol	GNAT1
Name	G protein subunit alpha transducin 1
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	CSNBAD3
Ensembl gene	ENSG00000114349
Ensembl biotype	protein_coding
OMIM	139330
Entrez	2779

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000232461, ENST00000433068, ENST00000440836, ENST00000467787, ENST00000481246

RefSeq mRNA: 2 — MANE Select: NM_144499 NM_000172, NM_144499

CCDS: CCDS2812

Canonical transcript exons

ENST00000232461 — 9 exons

Exon	Start	End
ENSE00000768715	50193265	50193406
ENSE00000768716	50193506	50193663
ENSE00000768718	50194092	50194221
ENSE00000768719	50194501	50194654
ENSE00000768720	50194765	50194956
ENSE00001374598	50195268	50197696
ENSE00001828203	50191610	50191831
ENSE00003465083	50193133	50193175
ENSE00003669926	50193753	50193881

Expression profiles

Bgee: expression breadth broad, 97 present calls, max score 91.67.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.5331 / max 1126.7662, expressed in 9 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36687	1.3895	8
36686	0.1137	5
36691	0.0112	4
36690	0.0052	2
36692	0.0050	2
36689	0.0049	2
36688	0.0036	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
neuron projection bundle connecting eye with brain	UBERON:0004904	91.67	silver quality
endometrium epithelium	UBERON:0004811	72.34	gold quality
frontal pole	UBERON:0002795	70.96	gold quality
paraflocculus	UBERON:0005351	70.71	gold quality
middle frontal gyrus	UBERON:0002702	70.43	gold quality
parotid gland	UBERON:0001831	68.62	gold quality
buccal mucosa cell	CL:0002336	67.59	gold quality
optic choroid	UBERON:0001776	65.98	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	65.76	gold quality
metanephric glomerulus	UBERON:0004736	65.50	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	65.10	gold quality
biceps brachii	UBERON:0001507	64.76	gold quality
cerebellar vermis	UBERON:0004720	64.22	gold quality
right lobe of liver	UBERON:0001114	64.19	gold quality
lateral nuclear group of thalamus	UBERON:0002736	62.69	gold quality
retina	UBERON:0000966	62.31	gold quality
pigmented layer of retina	UBERON:0001782	62.29	gold quality
quadriceps femoris	UBERON:0001377	61.71	gold quality
cartilage tissue	UBERON:0002418	60.96	gold quality
vastus lateralis	UBERON:0001379	60.88	gold quality
heart right ventricle	UBERON:0002080	60.66	gold quality
tendon of biceps brachii	UBERON:0008188	59.95	gold quality
Brodmann (1909) area 10	UBERON:0013541	59.37	gold quality
esophagus squamous epithelium	UBERON:0006920	59.16	gold quality
liver	UBERON:0002107	58.77	gold quality
gingiva	UBERON:0001828	58.44	gold quality
pons	UBERON:0000988	58.21	gold quality
lower esophagus mucosa	UBERON:0035834	58.17	gold quality
medial globus pallidus	UBERON:0002477	57.96	gold quality
vena cava	UBERON:0004087	57.86	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	6423.01
E-GEOD-137537	yes	5598.80
E-GEOD-98556	yes	3054.59
E-MTAB-11121	yes	2901.30
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting GNAT1, 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-4666A-3P	99.96	71.71	3434
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-4666A-5P	99.41	69.72	1887
HSA-MIR-4797-5P	99.39	68.01	1354

Literature-anchored findings (GeneRIF, showing 7)

• Expression of GNAT1 gene is down-regulated or absent in nasopharyngeal carcinoma tissues. (PMID:17222360)
• These data suggest that a homozygous missense mutation in GNAT1 is associated with autosomal recessive stationary night blindness. (PMID:22190596)
• Three candidate tumor-suppressor genes, SEMA3B, AXUD1 and GNAT1 may be involved in oral squamous cell carcinoma. (PMID:23292452)
• These data suggest that some truncating GNAT1 variants can indeed cause a recessive, mild, late-onset retinal degeneration in human beings rather than just stationary night-blindness as reported previously. (PMID:26472407)
• Our family’s ERG showed essentially no rod response, consistent with a Danish GNAT1 pedigree but different from the Nougaret GNAT1 pedigree that shows partial preservation of rod signal. A genetic connection between Complete congenital stationary night blindness and postural orthostatic tachycardia syndrome would be intriguing, but we found no evidence for this. (PMID:30051303)
• This is the second report of a Nougaret-type congenital stationary night blindness (CSNB) family with the GNAT1 variant. Our novel findings suggest that coexistence of the GNAT1 and biallelic ABCA4 variants is associated with an overlapping phenotype with both Nougaret-type CSNB and cone-rod dystrophy. (PMID:31583501)
• Homozygous in-frame deletion of GNAT1 gene is associated with Stationary night blindness, Oguchi type. (PMID:31696758)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	gnat1	ENSDARG00000044199
mus_musculus	Gnat1	ENSMUSG00000034837
rattus_norvegicus	Gnat1	ENSRNOG00000017589
drosophila_melanogaster	Galphaf	FBGN0010223
caenorhabditis_elegans		WBGENE00001664
caenorhabditis_elegans		WBGENE00001665
caenorhabditis_elegans		WBGENE00001667
caenorhabditis_elegans		WBGENE00001668
caenorhabditis_elegans		WBGENE00001670
caenorhabditis_elegans		WBGENE00001671
caenorhabditis_elegans		WBGENE00001673
caenorhabditis_elegans		WBGENE00001675
caenorhabditis_elegans	gpa-14	WBGENE00001676
caenorhabditis_elegans	gsa-1	WBGENE00001745

Paralogs (15): GNA15 (ENSG00000060558), GNAI3 (ENSG00000065135), GNAO1 (ENSG00000087258), GNAS (ENSG00000087460), GNA11 (ENSG00000088256), GNAI2 (ENSG00000114353), GNA13 (ENSG00000120063), GNAI1 (ENSG00000127955), GNAZ (ENSG00000128266), GNAT2 (ENSG00000134183), GNAL (ENSG00000141404), GNA12 (ENSG00000146535), GNA14 (ENSG00000156049), GNAQ (ENSG00000156052), GNAT3 (ENSG00000214415)

Protein

Protein identifiers

Guanine nucleotide-binding protein G(t) subunit alpha-1 — P11488 (reviewed: P11488)

Alternative names: Transducin alpha-1 chain

All UniProt accessions (2): C9JCV8, P11488

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a signal transducer for the rod photoreceptor RHO. Required for normal RHO-mediated light perception by the retina. Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs), such as the photoreceptor RHO. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Activated RHO promotes GDP release and GTP binding. Signaling is mediated via downstream effector proteins, such as cGMP-phosphodiesterase.

Subunit / interactions. Heterotrimeric G proteins are composed of 3 subunits alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. Interacts with RHO. Interacts with RGS9 and PDE6G. Interacts (when myristoylated) with UNC119; interaction is required for localization in sensory neurons.

Subcellular location. Cell projection. Cilium. Photoreceptor outer segment. Membrane. Photoreceptor inner segment.

Tissue specificity. Rod photoreceptor cells. Predominantly expressed in the retina followed by the ciliary body, iris and retinal pigment epithelium.

Disease relevance. Night blindness, congenital stationary, autosomal dominant 3 (CSNBAD3) [MIM:610444] A non-progressive retinal disorder characterized by impaired night vision, often associated with nystagmus and myopia. The disease is caused by variants affecting the gene represented in this entry. Night blindness, congenital stationary, 1G (CSNB1G) [MIM:616389] An autosomal recessive form of congenital stationary night blindness, a non-progressive retinal disorder characterized by impaired night vision or in dim light, with good vision only on bright days. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the G-alpha family. G(i/o/t/z) subfamily.

RefSeq proteins (2): NP_000163, NP_653082* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001019	Gprotein_alpha_su	Family
IPR001408	Gprotein_alpha_I	Family
IPR011025	GproteinA_insert	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily

Pfam: PF00503

UniProt features (32 total): binding site 8, region of interest 7, sequence conflict 4, modified residue 3, sequence variant 3, initiator methionine 1, chain 1, compositionally biased region 1, domain 1, lipid moiety-binding region 1, mutagenesis site 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3RBQ	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11488-F1	94.41	0.88

Functional residue map

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

Ligand- & substrate-binding residues (8): 36–43; 43; 146; 171–177; 177; 199; 265–268; 322

Post-translational modifications (4): 142, 174, 347, 2

Mutagenesis-validated functional residues (1):

Position	Phenotype
2	abolishes myristoylation, interaction with unc119 and localization.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2485179	Activation of the phototransduction cascade
R-HSA-2514859	Inactivation, recovery and regulation of the phototransduction cascade
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 232 (showing top): GOBP_BEHAVIOR, GOBP_RESPONSE_TO_ELECTRICAL_STIMULUS, AAGTCCA_MIR422B_MIR422A, GOBP_CELLULAR_RESPONSE_TO_LIGHT_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_HYDROLASE_ACTIVITY, GOBP_GROWTH, GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, AREB6_01, GOBP_PHOTOTRANSDUCTION, GOBP_REGENERATION, GOBP_NEUROGENESIS, GOBP_NEURAL_RETINA_DEVELOPMENT, GOBP_CELL_CELL_SIGNALING, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_PIGMENTATION

GO Biological Process (25): detection of chemical stimulus involved in sensory perception of bitter taste (GO:0001580), signal transduction (GO:0007165), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), visual perception (GO:0007601), phototransduction, visible light (GO:0007603), visual behavior (GO:0007632), cell population proliferation (GO:0008283), response to light stimulus (GO:0009416), dopamine secretion (GO:0014046), G protein-coupled opsin signaling pathway (GO:0016056), regulation of opsin-mediated signaling pathway (GO:0022400), eye photoreceptor cell development (GO:0042462), retinal cone cell differentiation (GO:0042670), detection of light stimulus involved in visual perception (GO:0050908), sensory perception of umami taste (GO:0050917), negative regulation of cyclic-nucleotide phosphodiesterase activity (GO:0051344), retinal rod cell differentiation (GO:0060221), cellular response to electrical stimulus (GO:0071257), neural tissue regeneration (GO:0097719), background adaptation (GO:0120302), G protein-coupled receptor signaling pathway (GO:0007186), phototransduction (GO:0007602), detection of light stimulus (GO:0009583), response to light intensity (GO:0009642), retina development in camera-type eye (GO:0060041)

GO Molecular Function (10): acyl binding (GO:0000035), G protein-coupled receptor binding (GO:0001664), GTPase activity (GO:0003924), GTP binding (GO:0005525), GDP binding (GO:0019003), protein kinase binding (GO:0019901), G-protein beta/gamma-subunit complex binding (GO:0031683), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), guanyl nucleotide binding (GO:0019001)

GO Cellular Component (13): photoreceptor outer segment (GO:0001750), photoreceptor inner segment (GO:0001917), cytoplasm (GO:0005737), cytosol (GO:0005829), heterotrimeric G-protein complex (GO:0005834), plasma membrane (GO:0005886), membrane (GO:0016020), apical plasma membrane (GO:0016324), photoreceptor connecting cilium (GO:0032391), photoreceptor outer segment membrane (GO:0042622), neuronal cell body (GO:0043025), photoreceptor disc membrane (GO:0097381), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
The phototransduction cascade	2
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
cellular process	2
G protein-coupled receptor signaling pathway	2
phototransduction	2
camera-type eye photoreceptor cell differentiation	2
guanyl ribonucleotide binding	2
photoreceptor cell cilium	2
photoreceptor outer segment	2
detection of chemical stimulus involved in sensory perception of taste	1
sensory perception of bitter taste	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
adenylate cyclase activity	1
sensory perception of light stimulus	1
detection of visible light	1
behavior	1
response to light stimulus	1
response to radiation	1
signal release	1
catecholamine secretion	1
phototransduction, visible light	1
cellular response to light stimulus	1
regulation of G protein-coupled receptor signaling pathway	1
G protein-coupled opsin signaling pathway	1
regulation of response to external stimulus	1
eye photoreceptor cell differentiation	1
photoreceptor cell development	1
visual perception	1
detection of light stimulus involved in sensory perception	1
sensory perception of taste	1
cyclic-nucleotide phosphodiesterase activity	1
negative regulation of hydrolase activity	1
response to electrical stimulus	1
cellular response to abiotic stimulus	1
tissue regeneration	1
response to light intensity	1
regulation of pigmentation	1
small molecule binding	1

Protein interactions and networks

STRING

1842 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GNAT1	RHO	P08100	951
GNAT1	OPN4	Q9UHM6	895
GNAT1	RPE65	Q16518	873
GNAT1	CNGA3	Q16281	871
GNAT1	LRAT	O95237	833
GNAT1	PDE6B	P35913	829
GNAT1	NRL	P54845	729
GNAT1	CNGB1	Q14028	725
GNAT1	SEMA4B	Q9NPR2	691
GNAT1	GNB1	P04697	649
GNAT1	GNGT1	P63211	633
GNAT1	PDE6A	P16499	631
GNAT1	GUCA1B	Q9UMX6	628
GNAT1	GRK1	Q15835	627
GNAT1	PDE6H	Q13956	621

IntAct

10 interactions, top by confidence:

A	B	Type	Score
GNAT1	UNC119	psi-mi:“MI:0407”(direct interaction)	0.440
GNAT1	UNC119B	psi-mi:“MI:0407”(direct interaction)	0.440
Arl2	GNAT1	psi-mi:“MI:0407”(direct interaction)	0.440
Arl3	GNAT1	psi-mi:“MI:0407”(direct interaction)	0.440
Haus1	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
GNAT1	DNAJC6	psi-mi:“MI:0915”(physical association)	0.400
CD177	MYO1G	psi-mi:“MI:0914”(association)	0.350
GNAT1	DNAJC6	psi-mi:“MI:0914”(association)	0.350

BioGRID (13): DNAJC6 (Affinity Capture-MS), ARL5B (Affinity Capture-MS), GNAT1 (Proximity Label-MS), GNAT1 (Affinity Capture-MS), DNAJC6 (Affinity Capture-MS), GNAT1 (Affinity Capture-MS), GNAT1 (Affinity Capture-MS), GNAT1 (Affinity Capture-MS), RPL4 (Cross-Linking-MS (XL-MS)), GNAT1 (Affinity Capture-MS), CDC42BPA (Cross-Linking-MS (XL-MS)), GNAT1 (Affinity Capture-MS), GNAT1 (Affinity Capture-MS)

ESM2 similar proteins: A8MTJ3, B2RSH2, G1XJZ0, O13055, O14438, O15976, P04695, P04696, P04897, P04899, P08752, P08753, P08754, P0C7Q4, P10824, P10825, P11488, P16894, P19087, P20353, P20612, P27044, P28052, P29348, P38400, P38401, P38402, P38403, P38407, P38408, P41776, P50146, P50147, P50149, P51876, P63096, P63097, P87034, P87383, Q18434

Diamond homologs: A2Y3B5, A8MTJ3, B0XRA0, B2RSH2, O04278, O04279, O13055, O13315, O14438, O15976, O42784, O74227, O74259, O95837, P04695, P04696, P04897, P04899, P08239, P08752, P08753, P08754, P09471, P0C7Q4, P0CN96, P0CN97, P10824, P10825, P11488, P16378, P16894, P18064, P18872, P19087, P20353, P20612, P26981, P27044, P27045, P28051

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
SMO	up-regulates	GNAT1	binding
RHO	“up-regulates activity”	GNAT1	binding
GNAT1	“down-regulates activity”	PDE6G	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	15
Likely pathogenic	7
Uncertain significance	201
Likely benign	127
Benign	21

Top pathogenic / likely-pathogenic (22)

Variant ID	HGVS	Classification
1070533	NM_144499.3(GNAT1):c.255_273del (p.Thr86fs)	Pathogenic
1375618	NM_144499.3(GNAT1):c.51del (p.Lys18fs)	Pathogenic
1379751	NM_144499.3(GNAT1):c.499G>T (p.Glu167Ter)	Pathogenic
1414433	NM_144499.3(GNAT1):c.146_149dup (p.Lys50fs)	Pathogenic
1453289	NM_144499.3(GNAT1):c.607G>T (p.Glu203Ter)	Pathogenic
15926	NM_144499.3(GNAT1):c.113G>A (p.Gly38Asp)	Pathogenic
190967	NM_144499.3(GNAT1):c.598C>G (p.Gln200Glu)	Pathogenic
190968	NM_144499.3(GNAT1):c.386A>G (p.Asp129Gly)	Pathogenic
2125040	NM_144499.3(GNAT1):c.210C>G (p.Tyr70Ter)	Pathogenic
2853836	NM_144499.3(GNAT1):c.678C>G (p.Tyr226Ter)	Pathogenic
2877753	NM_144499.3(GNAT1):c.419C>A (p.Ser140Ter)	Pathogenic
2966092	NM_144499.3(GNAT1):c.171C>G (p.Tyr57Ter)	Pathogenic
4727185	NM_144499.3(GNAT1):c.435del (p.Asn145fs)	Pathogenic
812324	NM_144499.3(GNAT1):c.8del (p.Ala3fs)	Pathogenic
812325	NM_144499.3(GNAT1):c.460G>T (p.Asp154Tyr)	Pathogenic
1472808	NM_144499.3(GNAT1):c.578+1G>C	Likely pathogenic
1931171	NM_144499.3(GNAT1):c.579-1G>A	Likely pathogenic
3247058	NC_000003.11:g.(?50230626)(50232011_?)del	Likely pathogenic
3366905	NM_144499.3(GNAT1):c.98T>C (p.Leu33Pro)	Likely pathogenic
3366971	NM_144499.3(GNAT1):c.124A>G (p.Lys42Glu)	Likely pathogenic
3381794	NM_144499.3(GNAT1):c.1053A>G (p.Ter351Trp)	Likely pathogenic
546937	NM_144499.3(GNAT1):c.82C>T (p.Arg28Ter)	Likely pathogenic

SpliceAI

1308 predictions. Top by Δscore:

Variant	Effect	Δscore
3:50191789:G:GT	donor_gain	1.0000
3:50191801:G:GT	donor_gain	1.0000
3:50191815:G:GT	donor_gain	1.0000
3:50191819:C:G	donor_gain	1.0000
3:50193176:G:GG	donor_gain	1.0000
3:50193263:A:AG	acceptor_gain	1.0000
3:50193263:A:C	acceptor_loss	1.0000
3:50193263:AG:A	acceptor_gain	1.0000
3:50193264:G:GG	acceptor_gain	1.0000
3:50193264:GG:G	acceptor_gain	1.0000
3:50193264:GGA:G	acceptor_gain	1.0000
3:50193264:GGATT:G	acceptor_gain	1.0000
3:50193385:G:GG	donor_gain	1.0000
3:50193416:G:GT	donor_gain	1.0000
3:50194954:GAG:G	donor_gain	1.0000
3:50191828:CTGGG:C	donor_loss	0.9900
3:50191829:TGG:T	donor_loss	0.9900
3:50191830:GG:G	donor_gain	0.9900
3:50191831:GG:G	donor_gain	0.9900
3:50191831:GGTAG:G	donor_loss	0.9900
3:50191832:G:GA	donor_loss	0.9900
3:50191833:T:A	donor_loss	0.9900
3:50193127:TTTCA:T	acceptor_loss	0.9900
3:50193128:TTCA:T	acceptor_loss	0.9900
3:50193129:TCA:T	acceptor_loss	0.9900
3:50193130:CAG:C	acceptor_loss	0.9900
3:50193131:A:AC	acceptor_loss	0.9900
3:50193131:A:AG	acceptor_gain	0.9900
3:50193132:G:GT	acceptor_gain	0.9900
3:50193132:GGT:G	acceptor_gain	0.9900

AlphaMissense

2345 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:50191823:T:C	L33P	1.000
3:50191831:G:C	G36R	1.000
3:50193147:G:A	G41R	1.000
3:50193147:G:C	G41R	1.000
3:50193147:G:T	G41W	1.000
3:50193148:G:A	G41E	1.000
3:50193150:A:C	K42Q	1.000
3:50193151:A:T	K42M	1.000
3:50193152:G:C	K42N	1.000
3:50193152:G:T	K42N	1.000
3:50193170:G:C	Q48H	1.000
3:50193170:G:T	Q48H	1.000
3:50193797:C:A	P165H	1.000
3:50193833:C:T	T177I	1.000
3:50194100:A:G	D196G	1.000
3:50194106:G:A	G198D	1.000
3:50194108:G:A	G199R	1.000
3:50194108:G:C	G199R	1.000
3:50194108:G:T	G199W	1.000
3:50194109:G:A	G199E	1.000
3:50194123:C:A	R204S	1.000
3:50194124:G:C	R204P	1.000
3:50194132:T:A	W207R	1.000
3:50194132:T:C	W207R	1.000
3:50194134:G:C	W207C	1.000
3:50194134:G:T	W207C	1.000
3:50194144:T:C	F211L	1.000
3:50194146:C:A	F211L	1.000
3:50194146:C:G	F211L	1.000
3:50194168:T:C	F219L	1.000

dbSNP variants (sampled 300 via entrez): RS1000466596 (3:50196882 G>A,C), RS1000767350 (3:50197913 G>A), RS1000820026 (3:50197497 C>T), RS1001568081 (3:50192810 T>A,G), RS1002165777 (3:50191327 G>A), RS1002518158 (3:50191645 C>A,G), RS1002726144 (3:50198070 G>A), RS1003086839 (3:50194010 G>A), RS1004131014 (3:50195944 C>T), RS1004474187 (3:50193959 C>A), RS1004914296 (3:50196400 A>C), RS1005574197 (3:50194993 C>T), RS1006464987 (3:50190321 A>T), RS1006478252 (3:50197887 A>G), RS1006504717 (3:50190787 C>A,T)

Disease associations

OMIM: gene MIM:139330 | disease phenotypes: MIM:610444, MIM:616389, MIM:268000, MIM:613216

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital stationary night blindness autosomal dominant 3	Definitive	Autosomal dominant
congenital stationary night blindness 1G	Strong	Autosomal recessive
retinal degeneration	Strong	Autosomal recessive
congenital stationary night blindness	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
inherited retinal dystrophy	Definitive	AD
inherited retinal dystrophy	Definitive	AR

Mondo (7): inherited retinal dystrophy (MONDO:0019118), congenital stationary night blindness autosomal dominant 3 (MONDO:0012497), congenital stationary night blindness 1G (MONDO:0014614), retinitis pigmentosa (MONDO:0019200), congenital stationary night blindness 1C (MONDO:0013183), congenital stationary night blindness (MONDO:0016293), retinal degeneration (MONDO:0004580)

Orphanet (3): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Congenital stationary night blindness (Orphanet:215), Retinitis pigmentosa (Orphanet:791)

HPO phenotypes

7 total (8 of 7 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000543	Optic disc pallor
HP:0001133	Constriction of peripheral visual field
HP:0007642	Early-onset non-progressive night blindness
HP:0000556	Retinal dystrophy

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST005951_49	Body mass index	1.000000e-08
GCST006269_1190	General cognitive ability	3.000000e-08
GCST007044_11	Extremely high intelligence	4.000000e-08
GCST007201_139	Schizophrenia	2.000000e-06
GCST007559_24	Sleep duration (short sleep)	3.000000e-08
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004337	intelligence
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D012162	Retinal Degeneration	C11.270.612; C11.768.585
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C567704	CSNB1C (supp.)
C566475	Night Blindness, Congenital Stationary, Autosomal Dominant 3 (supp.)
C536122	Night blindness, congenital stationary (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	2
aristolochic acid I	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
perfluorooctanoic acid	affects expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	decreases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	increases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Atrazine	increases expression	1
Cadmium	increases abundance, increases expression	1
Lead	increases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	increases abundance, increases expression	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00716586	PHASE4	COMPLETED	Treatment of Cystoid Macular Edema in Patients With Retinal Degeneration
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT02157077	PHASE3	COMPLETED	Aflibercept After Ranibizumab in Exudative Age-related Macular Degeneration
NCT03954626	PHASE3	COMPLETED	Study to Collect Safety and ECG Data on Brolucizumab 6 mg Intravitreal Treatment in Patients With Wet AMD
NCT06305416	PHASE3	RECRUITING	A Efficacy and Safety Study of Ranibizumab 10mg/ml Injection (Incepta) in Patients With Diabetic Macular Edema
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
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT02348359	PHASE2	TERMINATED	X-82 to Treat Age-related Macular Degeneration
NCT04643886	PHASE2	TERMINATED	A Multiple Dose Study of Repeat Intravitreal Injections of GEM103 in Dry Age-related Macular Degeneration
NCT04684394	PHASE2	TERMINATED	A Multiple Dose Study of Repeat Intravitreal Injections of GEM103 in Neovascular Age-related Macular Degeneration
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT06011798	PHASE2	COMPLETED	Assess the Efficacy and Safety of Repeat Intravitreal Injections of Foselutoclax (UBX1325) in Patients With DME (ASPIRE)
NCT07174687	PHASE2	RECRUITING	SGLT2 Inhibitors in Geographic Atrophy
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
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
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)