GNAT2

Summary

GNAT2 (G protein subunit alpha transducin 2, HGNC:4394) is a protein-coding gene on chromosome 1p13.3, encoding Guanine nucleotide-binding protein G(t) subunit alpha-2 (P19087). Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems.

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 cones.

Source: NCBI Gene 2780 — RefSeq curated summary.

At a glance

• Gene–disease (curated): GNAT2-related retinopathy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 29
• Clinical variants (ClinVar): 258 total — 27 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 26
• MANE Select transcript: NM_001377295

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4394
Approved symbol	GNAT2
Name	G protein subunit alpha transducin 2
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Aliases	ACHM4
Ensembl gene	ENSG00000134183
Ensembl biotype	protein_coding
OMIM	139340
Entrez	2780

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000351050, ENST00000622865, ENST00000679935, ENST00000872462, ENST00000872463, ENST00000872464

RefSeq mRNA: 3 — MANE Select: NM_001377295 NM_001377295, NM_001379232, NM_005272

CCDS: CCDS803

Canonical transcript exons

ENST00000679935 — 9 exons

Exon	Start	End
ENSE00000826822	109603951	109604104
ENSE00000913047	109606308	109606436
ENSE00000913049	109608631	109608788
ENSE00000913051	109610040	109610181
ENSE00001642926	109610465	109610507
ENSE00001707925	109605970	109606099
ENSE00003752967	109612753	109612923
ENSE00003911971	109603091	109603544
ENSE00003913067	109619483	109619616

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 91.32.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5387 / max 257.4410, expressed in 75 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13714	0.2927	39
13716	0.1089	44
13715	0.0628	22
13712	0.0397	7
13711	0.0346	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	91.32	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.00	gold quality
secondary oocyte	CL:0000655	87.58	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.13	gold quality
adrenal tissue	UBERON:0018303	70.40	gold quality
apex of heart	UBERON:0002098	63.63	gold quality
monocyte	CL:0000576	62.85	gold quality
leukocyte	CL:0000738	62.77	gold quality
islet of Langerhans	UBERON:0000006	62.15	gold quality
stromal cell of endometrium	CL:0002255	62.11	gold quality
blood	UBERON:0000178	60.50	gold quality
granulocyte	CL:0000094	59.25	gold quality
calcaneal tendon	UBERON:0003701	58.57	gold quality
bone marrow cell	CL:0002092	58.31	gold quality
heart left ventricle	UBERON:0002084	58.20	gold quality
right adrenal gland cortex	UBERON:0035827	57.63	gold quality
cardiac ventricle	UBERON:0002082	57.59	gold quality
tendon	UBERON:0000043	57.17	gold quality
right adrenal gland	UBERON:0001233	56.62	gold quality
heart	UBERON:0000948	56.02	gold quality
right atrium auricular region	UBERON:0006631	55.91	gold quality
descending thoracic aorta	UBERON:0002345	55.59	gold quality
cardiac atrium	UBERON:0002081	55.51	gold quality
pancreas	UBERON:0001264	55.11	gold quality
rectum	UBERON:0001052	54.73	gold quality
adrenal gland	UBERON:0002369	54.55	gold quality
gall bladder	UBERON:0002110	54.41	gold quality
left testis	UBERON:0004533	54.25	gold quality
left adrenal gland	UBERON:0001234	54.14	gold quality
testis	UBERON:0000473	54.08	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-98556	yes	803.56
E-MTAB-7316	yes	526.65
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 9)

• mutations in GNAT2 are implicated in achromatopsia (PMID:12077706)
• We detected a deletion of a highly conserved lysine at codon 270 in a critical functional area of the alpha-cone transducin molecule, and therefore is not the disease causing mutation. (PMID:15094710)
• Expression of GNAT2 transgene, when found in rod photoreceptor cells rather than in cones, demonstrates different mechanisms of amplification in the body’s G-protein alpha cascades and the activation of phosphodiesterase 6. (PMID:20603337)
• Clinical and genetic investigation of a large Tunisian family with complete achromatopsia: identification of a new nonsense mutation in GNAT2 gene. (PMID:21107338)
• Missense mutations, nonsense mutations, splice mutations, and small deletions and insertions in the affected genes cause achromatopsia. (PMID:21267001)
• The majority (n = 12) of patients were either homozygotes or compound heterozygotes for known achromatopsia alleles, two in CNGB3 (p.T383fsX and p.T296YfsX9) and three in CNGA3 (p.R283Q, p.R427C and p.L527R). (PMID:23362848)
• Single nucleotide polymorphisms in GNAT2 gene is associated with obesity. (PMID:23563607)
• Study identified a total 22 different potentially Achromatopsia-causing variants, of which 12 are novel. The mutation spectrum also includes a novel copy number variation, a heterozygous duplication of exon 4, of which the breakpoint matches exactly that of the previously reported exon 4 deletion. (PMID:31058429)
• The cone mosaic in GNAT2-ACHM (GNAT2-achromatopsia) is relatively well preserved, potentially allowing for a wide therapeutic window for cone-directed interventions. (PMID:32203983)

Cross-species orthologs

19 orthologs

Organism	Symbol	Gene ID
danio_rerio	gnat2	ENSDARG00000042529
mus_musculus	Gnat2	ENSMUSG00000009108
rattus_norvegicus	Gnat2	ENSRNOG00000019296
drosophila_melanogaster	cta	FBGN0000384
drosophila_melanogaster	Galphai	FBGN0001104
drosophila_melanogaster	Galphaf	FBGN0010223
caenorhabditis_elegans		WBGENE00001664
caenorhabditis_elegans		WBGENE00001665
caenorhabditis_elegans		WBGENE00001666
caenorhabditis_elegans		WBGENE00001667
caenorhabditis_elegans		WBGENE00001668
caenorhabditis_elegans		WBGENE00001670
caenorhabditis_elegans		WBGENE00001671
caenorhabditis_elegans		WBGENE00001673
caenorhabditis_elegans		WBGENE00001674
caenorhabditis_elegans		WBGENE00001675
caenorhabditis_elegans	gpa-14	WBGENE00001676
caenorhabditis_elegans	gpa-16	WBGENE00001678
caenorhabditis_elegans	gsa-1	WBGENE00001745

Paralogs (15): GNA15 (ENSG00000060558), GNAI3 (ENSG00000065135), GNAO1 (ENSG00000087258), GNAS (ENSG00000087460), GNA11 (ENSG00000088256), GNAT1 (ENSG00000114349), GNAI2 (ENSG00000114353), GNA13 (ENSG00000120063), GNAI1 (ENSG00000127955), GNAZ (ENSG00000128266), GNAL (ENSG00000141404), GNA12 (ENSG00000146535), GNA14 (ENSG00000156049), GNAQ (ENSG00000156052), GNAT3 (ENSG00000214415)

Protein

Protein identifiers

Guanine nucleotide-binding protein G(t) subunit alpha-2 — P19087 (reviewed: P19087)

Alternative names: Transducin alpha-2 chain

All UniProt accessions (3): A0A087WZE5, P19087, Q5T697

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Transducin is an amplifier and one of the transducers of a visual impulse that performs the coupling between rhodopsin and cGMP-phosphodiesterase.

Subunit / interactions. G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site.

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

Tissue specificity. Retinal rod outer segment.

Disease relevance. Achromatopsia 4 (ACHM4) [MIM:613856] An ocular stationary disorder due to the absence of functioning cone photoreceptors in the retina. It is characterized by total colorblindness, low visual acuity, photophobia and nystagmus. 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 (3): NP_001364224, NP_001366161, NP_005263 (=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 (25 total): binding site 7, region of interest 6, sequence variant 3, modified residue 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, domain 1, sequence conflict 1, helix 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6N84	X-RAY DIFFRACTION	1.75
6N85	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P19087-F1	94.21	0.89

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 (7): 40–47; 47; 175–181; 181; 200–204; 269–272; 326

Post-translational modifications (3): 178, 351, 2

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-4086398	Ca2+ pathway
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 217 (showing top): GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, GOBP_BEHAVIOR, GOBP_INFLAMMATORY_RESPONSE, GOBP_GROWTH, GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_PHOTOTRANSDUCTION, GOBP_REGENERATION, GOBP_NEUROGENESIS, GOBP_NEURAL_RETINA_DEVELOPMENT, PID_CONE_PATHWAY, GOBP_ORGANIC_ACID_TRANSPORT, NKX61_01, GOBP_PIGMENTATION, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY

GO Biological Process (29): cell morphogenesis (GO:0000902), detection of chemical stimulus involved in sensory perception of bitter taste (GO:0001580), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), positive regulation of cytosolic calcium ion concentration (GO:0007204), visual perception (GO:0007601), phototransduction (GO:0007602), visual behavior (GO:0007632), intracellular protein localization (GO:0008104), response to UV (GO:0009411), gene expression (GO:0010467), dopamine metabolic process (GO:0042417), retinal cone cell development (GO:0046549), tissue remodeling (GO:0048771), homeostasis of number of retina cells (GO:0048877), detection of light stimulus involved in visual perception (GO:0050908), L-glutamate import (GO:0051938), retinal rod cell differentiation (GO:0060221), neural tissue regeneration (GO:0097719), background adaptation (GO:0120302), reactive gliosis (GO:0150103), cone retinal bipolar cell differentiation (GO:1904390), signal transduction (GO:0007165), response to light stimulus (GO:0009416), detection of light stimulus (GO:0009583), detection of visible light (GO:0009584), response to light intensity (GO:0009642), retinal cone cell differentiation (GO:0042670), camera-type eye development (GO:0043010)

GO Molecular Function (8): G protein-coupled receptor binding (GO:0001664), GTPase activity (GO:0003924), GTP binding (GO:0005525), G protein-coupled photoreceptor activity (GO:0008020), 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 (9): photoreceptor outer segment (GO:0001750), photoreceptor inner segment (GO:0001917), cytoplasm (GO:0005737), heterotrimeric G-protein complex (GO:0005834), plasma membrane (GO:0005886), photoreceptor outer segment membrane (GO:0042622), synapse (GO:0045202), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Beta-catenin independent WNT signaling	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
G protein-coupled receptor activity	2
signal transduction	2
response to light stimulus	2
anatomical structure morphogenesis	1
detection of chemical stimulus involved in sensory perception of taste	1
sensory perception of bitter taste	1
adenylate cyclase activity	1
G protein-coupled receptor signaling pathway	1
regulation of biological quality	1
sensory perception of light stimulus	1
detection of light stimulus	1
behavior	1
macromolecule localization	1
macromolecule biosynthetic process	1
catecholamine metabolic process	1
eye photoreceptor cell development	1
retinal cone cell differentiation	1
multicellular organismal process	1
retina homeostasis	1
homeostasis of number of cells within a tissue	1
visual perception	1
detection of light stimulus involved in sensory perception	1
dicarboxylic acid transport	1
acidic amino acid transport	1
L-amino acid transport	1
camera-type eye photoreceptor cell differentiation	1
tissue regeneration	1
response to light intensity	1
regulation of pigmentation	1
signaling receptor binding	1
ribonucleoside triphosphate phosphatase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
detection of visible light	1
photoreceptor activity	1
protein-containing complex binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1

Protein interactions and networks

STRING

1625 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GNAT2	CNGB3	Q9NQW8	988
GNAT2	CNGA3	Q16281	982
GNAT2	PDE6C	P51160	980
GNAT2	PDE6H	Q13956	881
GNAT2	OPN4	Q9UHM6	822
GNAT2	GLYATL1	Q969I3	739
GNAT2	GNGT2	O14610	721
GNAT2	ARR3	P36575	690
GNAT2	OPN1SW	P03999	676
GNAT2	RHO	P08100	659
GNAT2	NR2E3	Q9Y5X4	647
GNAT2	CRX	O43186	640
GNAT2	PDE6A	P16499	637
GNAT2	GNB3	P16520	624
GNAT2	GNB2	P11016	617
GNAT2	EYS	Q5T1H1	617

IntAct

13 interactions, top by confidence:

A	B	Type	Score
GNAI3	RGS12	psi-mi:“MI:0914”(association)	0.640
Haus1	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
GNAT2	ACSL4	psi-mi:“MI:0914”(association)	0.350
GNG3	GNAI2	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
GNAT2	UNC119B	psi-mi:“MI:0914”(association)	0.350
GPSM3	PHF1	psi-mi:“MI:0914”(association)	0.350
GNG3	GNAS	psi-mi:“MI:0914”(association)	0.350

BioGRID (37): GNAT2 (Affinity Capture-MS), UNC119 (Affinity Capture-MS), UNC119B (Affinity Capture-MS), ACSL3 (Affinity Capture-MS), ACSL4 (Affinity Capture-MS), SNX1 (Affinity Capture-MS), SNX2 (Affinity Capture-MS), SNX5 (Affinity Capture-MS), VPS13A (Affinity Capture-MS), OCIAD1 (Affinity Capture-MS), EPHA4 (Affinity Capture-MS), ARMCX3 (Affinity Capture-MS), GNAT2 (Affinity Capture-MS), GNAT2 (Affinity Capture-MS), ACSL4 (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

2 interactions.

A	Effect	B	Mechanism
SMO	up-regulates	GNAT2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 12 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
ADORA2B mediated anti-inflammatory cytokines production	5	126.9×	4e-09
GPER1 signaling	5	124.1×	4e-09
G alpha (z) signalling events	5	116.5×	4e-09
G alpha (s) signalling events	5	36.6×	8e-07
G alpha (i) signalling events	7	27.3×	9e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	27
Likely pathogenic	8
Uncertain significance	117
Likely benign	82
Benign	3

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1047871	GRCh37/hg19 1p21.2-12(chr1:102021465-119737478)	Pathogenic
1075981	NM_001377295.2(GNAT2):c.5del (p.Gly2fs)	Pathogenic
1446938	NM_001377295.2(GNAT2):c.826del (p.Glu276fs)	Pathogenic
1455635	NM_001377295.2(GNAT2):c.590+1del	Pathogenic
15922	NM_001377295.2(GNAT2):c.235C>T (p.Gln79Ter)	Pathogenic
15923	NM_001377295.2(GNAT2):c.842_843insTCAG (p.His282fs)	Pathogenic
1953648	NM_001377295.2(GNAT2):c.172C>T (p.Gln58Ter)	Pathogenic
1958714	NM_001377295.2(GNAT2):c.496del (p.Glu166fs)	Pathogenic
2065503	NM_001377295.2(GNAT2):c.821_822del (p.Leu273_Phe274insTer)	Pathogenic
2102140	NM_001377295.2(GNAT2):c.495_496insAG (p.Glu166fs)	Pathogenic
2425335	NC_000001.10:g.(?110151229)(110151430_?)del	Pathogenic
2812390	NM_001377295.2(GNAT2):c.421G>T (p.Glu141Ter)	Pathogenic
3250281	NM_001377295.2(GNAT2):c.503del (p.Leu168fs)	Pathogenic
3544452	NM_001377295.2(GNAT2):c.591_597delinsCA (p.Arg197fs)	Pathogenic
4769017	NM_001377295.2(GNAT2):c.526C>T (p.Arg176Ter)	Pathogenic
522772	NM_001377295.2(GNAT2):c.481C>T (p.Arg161Ter)	Pathogenic
623271	NM_001377295.2(GNAT2):c.285_291delinsCTGTAT (p.Ala96fs)	Pathogenic
623272	NM_001377295.2(GNAT2):c.303+365_461+974dup	Pathogenic
623273	NM_001377295.2(GNAT2):c.303+365_461+974del	Pathogenic
623274	NM_001377295.2(GNAT2):c.313C>T (p.Arg105Ter)	Pathogenic
623275	NM_001377295.2(GNAT2):c.503dup (p.Pro169_Ser170insTer)	Pathogenic
623276	NM_001377295.2(GNAT2):c.591-2A>C	Pathogenic
623278	NM_001377295.2(GNAT2):c.620A>T (p.Glu207Val)	Pathogenic
623282	NM_001377295.2(GNAT2):c.803_806dup (p.Lys270fs)	Pathogenic
623285	NM_001377295.2(GNAT2):c.937C>T (p.Arg313Ter)	Pathogenic
623287	NM_001377295.2(GNAT2):c.955del (p.Ile319fs)	Pathogenic
812114	NM_001377295.2(GNAT2):c.605G>A (p.Gly202Glu)	Pathogenic
1999298	NM_001377295.2(GNAT2):c.162-2A>G	Likely pathogenic
2031990	NM_001377295.2(GNAT2):c.304-1G>A	Likely pathogenic
438058	NM_001377295.2(GNAT2):c.906C>A (p.Tyr302Ter)	Likely pathogenic

SpliceAI

1508 predictions. Top by Δscore:

Variant	Effect	Δscore
1:109605965:CTCA:C	donor_loss	1.0000
1:109605967:CA:C	donor_loss	1.0000
1:109605969:C:A	donor_loss	1.0000
1:109605969:CCA:C	donor_gain	1.0000
1:109606096:CATC:C	acceptor_gain	1.0000
1:109606303:CTTA:C	donor_loss	1.0000
1:109606304:TTAC:T	donor_loss	1.0000
1:109606305:TACC:T	donor_loss	1.0000
1:109606306:A:AC	donor_gain	1.0000
1:109606306:AC:A	donor_gain	1.0000
1:109606306:ACC:A	donor_loss	1.0000
1:109606307:C:A	donor_loss	1.0000
1:109606307:C:CT	donor_gain	1.0000
1:109606307:CC:C	donor_gain	1.0000
1:109606432:GGTAG:G	acceptor_gain	1.0000
1:109606433:GTAG:G	acceptor_gain	1.0000
1:109606434:TAG:T	acceptor_gain	1.0000
1:109606435:AG:A	acceptor_gain	1.0000
1:109606437:C:CC	acceptor_gain	1.0000
1:109608629:A:AC	donor_gain	1.0000
1:109608630:C:CC	donor_gain	1.0000
1:109608707:T:TA	donor_gain	1.0000
1:109610177:TGATC:T	acceptor_gain	1.0000
1:109610180:TC:T	acceptor_gain	1.0000
1:109610181:CC:C	acceptor_gain	1.0000
1:109612747:A:AC	donor_gain	1.0000
1:109612748:C:CC	donor_gain	1.0000
1:109612748:CTCA:C	donor_gain	1.0000
1:109612749:TCA:T	donor_loss	1.0000
1:109612750:CAC:C	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000222513 (1:109608124 C>A,T), RS1000319383 (1:109610758 T>C), RS1000829586 (1:109615793 A>G,T), RS1000850803 (1:109617907 C>T), RS1001270991 (1:109612024 C>T), RS1001323337 (1:109612405 T>C), RS1001447195 (1:109604847 T>C), RS1001458065 (1:109604563 T>G), RS1001458611 (1:109619662 G>A,C), RS1001929707 (1:109610121 A>G), RS1002057655 (1:109606493 G>A,C,T), RS1002270105 (1:109613904 G>A), RS1002412938 (1:109602685 T>C), RS1002451283 (1:109617006 T>C), RS1002549975 (1:109613338 A>G)

Disease associations

OMIM: gene MIM:139340 | disease phenotypes: MIM:613856

GenCC curated gene-disease

Disease	Classification	Inheritance
achromatopsia 4	Definitive	Autosomal recessive
cone dystrophy	Supportive	Autosomal dominant
achromatopsia	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
GNAT2-related retinopathy	Definitive	AR

Mondo (4): inherited retinal dystrophy (MONDO:0019118), achromatopsia 4 (MONDO:0013465), achromatopsia (MONDO:0018852), cone dystrophy (MONDO:0000455)

Orphanet (3): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Achromatopsia (Orphanet:49382), Progressive cone dystrophy (Orphanet:1871)

HPO phenotypes

26 total (27 of 26 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000505	Visual impairment
HP:0000512	Abnormal electroretinogram
HP:0000539	Abnormality of refraction
HP:0000540	Hypermetropia
HP:0000545	Myopia
HP:0000551	Color vision defect
HP:0000603	Central scotoma
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0001103	Abnormal macular morphology
HP:0007663	Reduced visual acuity
HP:0007695	Abnormal pupillary light reflex
HP:0007703	Abnormal retinal pigmentation
HP:0007722	Retinal pigment epithelial atrophy
HP:0007750	Hypoplasia of the fovea
HP:0007803	Monochromacy
HP:0007814	Retinal pigment epithelial mottling
HP:0007843	Attenuation of retinal blood vessels
HP:0011516	Achromatopsia
HP:0012043	Pendular nystagmus
HP:0025549	Eccentric visual fixation
HP:0030465	Undetectable light-adapted electroretinogram
HP:0030584	Color vision test abnormality
HP:0030620	Inner retinal layer loss on macular OCT
HP:0030825	Absent foveal reflex
HP:0000556	Retinal dystrophy

GWAS associations

29 associations (top):

Study	Trait	p-value
GCST000578_3	Major depressive disorder	1.000000e-06
GCST001953_39	Obesity	9.000000e-12
GCST002783_29	Body mass index	4.000000e-10
GCST002783_294	Body mass index	2.000000e-13
GCST002783_550	Body mass index	7.000000e-14
GCST002783_61	Body mass index	2.000000e-07
GCST004066_106	Hip circumference	2.000000e-10
GCST004066_65	Hip circumference	3.000000e-10
GCST004495_126	BMI (adjusted for smoking behaviour)	3.000000e-06
GCST004495_49	BMI (adjusted for smoking behaviour)	8.000000e-09
GCST004495_50	BMI (adjusted for smoking behaviour)	5.000000e-13
GCST004497_97	Body mass index (joint analysis main effects and smoking interaction)	2.000000e-11
GCST004497_98	Body mass index (joint analysis main effects and smoking interaction)	2.000000e-07
GCST004499_59	BMI in non-smokers	1.000000e-09
GCST004499_60	BMI in non-smokers	4.000000e-06
GCST004557_124	Body mass index	4.000000e-06
GCST004557_151	Body mass index	2.000000e-15
GCST004557_175	Body mass index	8.000000e-07
GCST004557_256	Body mass index	9.000000e-11
GCST004557_8	Body mass index	2.000000e-15
GCST004558_192	Body mass index (joint analysis main effects and physical activity interaction)	7.000000e-14
GCST004558_203	Body mass index (joint analysis main effects and physical activity interaction)	3.000000e-09
GCST004558_51	Body mass index (joint analysis main effects and physical activity interaction)	1.000000e-09
GCST004558_70	Body mass index (joint analysis main effects and physical activity interaction)	1.000000e-13
GCST004559_147	Body mass index in physically active individuals	9.000000e-13
GCST004559_39	Body mass index in physically active individuals	2.000000e-09
GCST004559_67	Body mass index in physically active individuals	9.000000e-13
GCST005830_59	Hand grip strength	2.000000e-08
GCST006802_31	Body mass index	6.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0006941	grip strength measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D000077765	Cone Dystrophy	C11.270.151; C11.768.216
D058499	Retinal Dystrophies	C11.768.585.658
C564206	Achromatopsia 4 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
2-palmitoylglycerol	increases expression	1
Scutellaria barbata extract	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Endosulfan	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

53 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
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]
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)
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT03990727	Not specified	UNKNOWN	Phenotype Correlates Genotype of Inherited Retina Dystrophies, Retinitis Pigmentosa, Con>Rod Dystrophies.
NCT04658251	Not specified	TERMINATED	Study of New Mutations in Cone Disorders
NCT05355415	Not specified	RECRUITING	Adaptive Optics Imaging of Outer Retinal Diseases
NCT01648452	PHASE1/PHASE2	COMPLETED	CNTF Implants for CNGB3 Achromatopsia
NCT02599922	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGB3 Achromatopsia (A Clarity Clinical Trial)
NCT02610582	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety and Efficacy of rAAV.hCNGA3 Gene Therapy in Patients With CNGA3-linked Achromatopsia
NCT02935517	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Safety and Efficacy Trial of AAV Gene Therapy in Patients With CNGA3 Achromatopsia (A Clarity Clinical Trial)
NCT03001310	PHASE1/PHASE2	COMPLETED	Gene Therapy for Achromatopsia (CNGB3)
NCT03758404	PHASE1/PHASE2	COMPLETED	Gene Therapy for Achromatopsia (CNGA3)
NCT04041232	EARLY_PHASE1	SUSPENDED	PBA Use for Treatment of ATF6-/- Patients
NCT01846052	Not specified	COMPLETED	Clinical and Genetic Characterization of Individuals With Achromatopsia
NCT03278873	Not specified	TERMINATED	Long-Term Follow-Up Gene Therapy Study for Achromatopsia CNGB3 and CNGA3
NCT04124185	Not specified	COMPLETED	Natural History Study for Achromatopsia
NCT07085533	Not specified	RECRUITING	Natural History Study of Inherited Retinal Diseases
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