ATF6

Summary

ATF6 (activating transcription factor 6, HGNC:791) is a protein-coding gene on chromosome 1q23.3, encoding Cyclic AMP-dependent transcription factor ATF-6 alpha (P18850). Precursor of the transcription factor form (Processed cyclic AMP-dependent transcription factor ATF-6 alpha), which is embedded in the endoplasmic reticulum membrane.

This gene encodes a transcription factor that activates target genes for the unfolded protein response (UPR) during endoplasmic reticulum (ER) stress. Although it is a transcription factor, this protein is unusual in that it is synthesized as a transmembrane protein that is embedded in the ER. It functions as an ER stress sensor/transducer, and following ER stress-induced proteolysis, it functions as a nuclear transcription factor via a cis-acting ER stress response element (ERSE) that is present in the promoters of genes encoding ER chaperones. This protein has been identified as a survival factor for quiescent but not proliferative squamous carcinoma cells. There have been conflicting reports about the association of polymorphisms in this gene with diabetes in different populations, but another polymorphism has been associated with increased plasma cholesterol levels. This gene is also thought to be a potential therapeutic target for cystic fibrosis.

Source: NCBI Gene 22926 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ATF6-related retinopathy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 525 total — 29 pathogenic, 21 likely-pathogenic
• Phenotypes (HPO): 34
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• Transcription factor: yes — 59 downstream targets (CollecTRI)
• MANE Select transcript: NM_007348

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:791
Approved symbol	ATF6
Name	activating transcription factor 6
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	ATF6A, ATP6alpha
Ensembl gene	ENSG00000118217
Ensembl biotype	protein_coding
OMIM	605537
Entrez	22926

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 18 protein_coding, 6 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

ENST00000367942, ENST00000476437, ENST00000679833, ENST00000679853, ENST00000679886, ENST00000680180, ENST00000680462, ENST00000680481, ENST00000680633, ENST00000680688, ENST00000681001, ENST00000681036, ENST00000681169, ENST00000681187, ENST00000681492, ENST00000681541, ENST00000681557, ENST00000681738, ENST00000681779, ENST00000681801, ENST00000681912, ENST00000862527, ENST00000862528, ENST00000935713, ENST00000951832, ENST00000951833, ENST00000951834, ENST00000951835

RefSeq mRNA: 2 — MANE Select: NM_007348 NM_001410890, NM_007348

CCDS: CCDS1235, CCDS91093

Canonical transcript exons

ENST00000367942 — 16 exons

Exon	Start	End
ENSE00000796532	161863198	161863312
ENSE00000958927	161802052	161802272
ENSE00000958928	161819633	161819818
ENSE00000958929	161821070	161821161
ENSE00000958933	161860207	161860277
ENSE00001042100	161912296	161912380
ENSE00001068178	161778244	161778320
ENSE00001068180	161792124	161792327
ENSE00001068181	161781912	161781999
ENSE00001068184	161783990	161784096
ENSE00001068185	161791408	161791537
ENSE00001445974	161958446	161964070
ENSE00001445975	161766320	161766442
ENSE00003493033	161846449	161846580
ENSE00003594097	161853224	161853323
ENSE00003594227	161851722	161851835

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 92.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.5136 / max 289.5386, expressed in 1806 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6284	23.4949	1794
6283	3.5844	1538
6282	2.5098	945
6286	2.1423	1161
6285	1.5094	1061
6281	0.1931	90
6280	0.0797	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	92.87	gold quality
skin of hip	UBERON:0001554	92.31	gold quality
upper leg skin	UBERON:0004262	92.05	gold quality
pigmented layer of retina	UBERON:0001782	91.69	gold quality
cauda epididymis	UBERON:0004360	91.56	gold quality
synovial joint	UBERON:0002217	90.31	gold quality
caput epididymis	UBERON:0004358	90.24	gold quality
seminal vesicle	UBERON:0000998	90.11	gold quality
saphenous vein	UBERON:0007318	90.09	gold quality
endothelial cell	CL:0000115	89.91	gold quality
bone marrow cell	CL:0002092	89.56	gold quality
mucosa of urinary bladder	UBERON:0001259	89.25	silver quality
islet of Langerhans	UBERON:0000006	89.24	gold quality
mammary duct	UBERON:0001765	89.22	gold quality
colonic epithelium	UBERON:0000397	89.08	gold quality
adrenal tissue	UBERON:0018303	88.62	gold quality
urethra	UBERON:0000057	88.51	gold quality
superficial temporal artery	UBERON:0001614	88.30	gold quality
parotid gland	UBERON:0001831	88.23	gold quality
renal medulla	UBERON:0000362	88.20	gold quality
epithelium of mammary gland	UBERON:0003244	87.83	gold quality
blood	UBERON:0000178	87.80	gold quality
layer of synovial tissue	UBERON:0007616	87.75	gold quality
trigeminal ganglion	UBERON:0001675	87.71	gold quality
lower lobe of lung	UBERON:0008949	87.62	gold quality
monocyte	CL:0000576	87.51	gold quality
visceral pleura	UBERON:0002401	87.37	gold quality
subthalamic nucleus	UBERON:0001906	87.22	gold quality
mononuclear cell	CL:0000842	87.14	gold quality
placenta	UBERON:0001987	87.13	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

59 targets.

Target	Regulation
ALG12
ATF6
ATP2A2	Unknown
BGLAP	Unknown
CALR	Activation
CDKN2A
CREB1
CREB3
CRTC2
DDIT3	Unknown
DERL3	Activation
DMP1
DNAJB9
DNAJC3	Activation
DSPP
ESR1
ESRRG
FOS
G6PC1	Repression
HMGCR
HMGCS2	Repression
HSP90B1	Activation
HSPA5	Unknown
HYOU1	Activation
IFRD1	Activation
IL6	Activation
INS	Repression
MAFA	Repression
MANF	Activation
MBTPS1

JASPAR motifs

Motif	Name	Family
MA1466.1	ATF6	Jun-related
MA1466.2	ATF6	Jun-related

JASPAR matrix evidence (PMIDs): PMID:10856300

Upstream regulators (CollecTRI, top): AR, ATF4, ATF6, CEBPB, ESR1, ESRRG, FOXC1, NFKB1, RUNX2

miRNA regulators (miRDB)

228 targeting ATF6, 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-5193	100.00	67.26	1744
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Nitric oxide-induced apoptosis in RAW 264.7 macrophages is mediated by endoplasmic reticulum stress pathway involving ATF6 and CHOP (PMID:11805088)
• luminal domain senses endoplasmic reticulum stress and causes translocation of ATF6 from endoplasmic reticulum to Golgi apparatus (PMID:11821395)
• coordination of transcription and degradation by a domain shared with the viral transcription factor VP16 (PMID:11909875)
• Distinct roles in transcription during the mammalian unfolded protein response (PMID:12014989)
• p38MAPK is activated by phosphorylated ATF6 and induces HSPA5 binding (PMID:12076252)
• stimulated by HCV replicons (PMID:12097557)
• The endoplasmic reticulum stress pathway mediated by ATF6 and by IRE1-XBP1 systems seems essential for the transformation-associated expression of the grp78 gene in hepatocarcinogenesis (PMID:12713871)
• the transport of ATF6 from the ER to the Golgi apparatus and that from the Golgi apparatus to the nucleus are distinct steps (PMID:12782636)
• ATF6 antagonizes SREBP2 to regulate the homeostasis of lipid and glucose (PMID:14765107)
• ATF6 and Ire1p signaling do not define the magnitude of UPR-dependent mRNA increases, even though they may be necessary for gene activation. (PMID:15063770)
• the bulky ATF6 luminal domain blocks its site-2 protease cleavage (PMID:15299016)
• ATF6 and XBP1 have roles in activation of endoplasmic reticulum stress-responsive cis-acting elements (PMID:15598891)
• Our results clearly establish HBx as an inducer of UPR and the activator of the ATF6 and IRE1-XBP1 pathways of UPR. (PMID:17092596)
• Owing to the presence of intra- and intermolecular disulfide bridges formed between the two conserved cysteine residues in the luminal domain, ATF6 occurs in unstressed endoplasmic reticulum in monomer, dimer, and oligomer forms. (PMID:17101776)
• A study evaluting 64 single nucleotide polymorphisms (SNPs) spanning >213 kb in 95 people for their role in the development of type 2 diabetes and the prediabetic state is reported. (PMID:17327457)
• one or more variants in ATF6 are associated with disturbed glucose homeostasis and type 2 diabetes (PMID:17440018)
• Shorter ATF6alpha message lacks exon 7 and may have a regulatory role in the Unfolded protein response. (PMID:17442311)
• the relative levels of ATF6 alpha and -beta, may contribute to regulating the strength and duration of ATF6-dependent ERSR gene induction and cell viability (PMID:17522056)
• NUCB1 is the first-identified, Golgi-localized negative feedback regulator in the ATF6-mediated branch of the UPR (PMID:17686766)
• The aim was to study the activation of ATF6 and Grp78 in transfected human epithelial cells expressing the DeltaF508-CFTR protein. (PMID:18022401)
• Compared with COPD and donor lungs, protein levels of ER stress mediators, such as ATF-6 and ATF-4 and the apoptosis-inductor CHOP as well as XBP-1, were significantly elevated in lung homogenates and AECIIs of IPF lungs (PMID:18635891)
• ATF6alpha-Rheb-mTOR signaling promotes survival of dormant tumor cells in vivo (PMID:18650380)
• Transcriptional induction of the human asparagine synthetase gene during the unfolded protein response does not require the ATF6 (PMID:18840095)
• pXBP1(U) functions as a negative regulator of the unfolded protein response-specific transcription factors ATF6 and pXBP1(S). (PMID:19122331)
• These findings suggest that 8ab could modulate the unfolded protein response by activating ATF6 to facilitate protein folding and processing. (PMID:19304306)
• ATF6alpha induces XBP1-independent expansion of the endoplasmic reticulum. (PMID:19420237)
• The ATF6-Met[67]Val substitution is associated with increased plasma cholesterol levels. (PMID:19667116)
• unglycosylated ATF6beta may directly facilitate the expression of ERSR genes by losing its repressor function to ATF6alpha (PMID:19693772)
• Data show that GRP78 was upregulated following treatment with NAC or PEN, and both the ATF6 protein and XBP1 mRNA were processed, which facilitates the expression of C/EBP homologous protein CHOP. (PMID:19722195)
• Mechanistically, regulation of ER-stress-induced apoptosis by CerS6/C(16)-ceramide was linked to the activation of a specific arm, ATF6/CHOP, of the unfolded protein response pathway. (PMID:19723703)
• Using an in vitro budding reaction that recapitulates the ER-stress induced transport of ATF6, we show that no cytoplasmic proteins other than COPII are necessary for transport. (PMID:19822759)
• Studies show that ATF6, rather than being a soluble nuclear protein, was an active transcription factor and synthesized as a transmembrane protein embedded in the ER. (PMID:20219975)
• The ATF6alpha/Ras homolog enriched in brain (Rheb) pathway is altered in Huntington’s disease, as the decrease in ATF6alpha processing is accompanied by a decrease in the accumulation of Rheb. (PMID:20732420)
• The viral glycoprotein precursor (GPC)was responsible for the induction of ATF6 regulated branch of the host cell’s unfolded protein response. (PMID:21106748)
• these data suggests common SNPs within DUSP12-ATF6 locus may not play a major role in glucose metabolism in the Chinese. (PMID:21211013)
• early DENV-2 infection triggers and then suppresses PERK-mediated eIF2alpha phosphorylation and that in mid and late DENV-2 infection, the IRE1-XBP1 and ATF6 pathways are activated, respectively (PMID:21385877)
• propose that a sensing mechanism operates within the lipid bilayer to trigger the selective activation of ATF6 (PMID:21521793)
• Mcl-1 is a determinant of cell fate, and ATF6 mediates apoptosis via specific suppression of Mcl-1 through up-regulation of WBP1 (PMID:21841196)
• activation of the ATF6 pathway of the UPR limits ATZ-dependent cell toxicity by selectively promoting ER-associated degradation of ATZ (PMID:21976666)
• Alteration of ceramide synthase 6/C16-ceramide induces activating transcription factor 6-mediated endoplasmic reticulum (ER) stress and apoptosis via perturbation of cellular Ca2+ and ER/Golgi membrane network (PMID:22013072)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	atf6	ENSDARG00000012656
mus_musculus	Atf6	ENSMUSG00000026663
rattus_norvegicus	Atf6	ENSRNOG00000024632
drosophila_melanogaster	CrebA	FBGN0004396
drosophila_melanogaster	Atf6	FBGN0033010
drosophila_melanogaster	CrebB	FBGN0265784
caenorhabditis_elegans		WBGENE00000222
caenorhabditis_elegans		WBGENE00000793
caenorhabditis_elegans		WBGENE00016162

Paralogs (9): CREB3L3 (ENSG00000060566), CREM (ENSG00000095794), CREB3 (ENSG00000107175), CREB1 (ENSG00000118260), ATF1 (ENSG00000123268), CREB3L4 (ENSG00000143578), CREB3L1 (ENSG00000157613), CREB3L2 (ENSG00000182158), ATF6B (ENSG00000213676)

Protein

Protein identifiers

Cyclic AMP-dependent transcription factor ATF-6 alpha — P18850 (reviewed: P18850)

Alternative names: Activating transcription factor 6 alpha

All UniProt accessions (14): A0A7P0T8R5, P18850, A0A7P0T8Y1, A0A7P0T992, A0A7P0T9H5, A0A7P0T9V3, A0A7P0TAB8, A0A7P0TAD1, A0A7P0TAF2, A0A7P0TAH1, A0A7P0TAI7, A0A7P0TB89, A0A7P0Z421, A0A7P0Z4I7

UniProt curated annotations — full annotation on UniProt →

Function. Precursor of the transcription factor form (Processed cyclic AMP-dependent transcription factor ATF-6 alpha), which is embedded in the endoplasmic reticulum membrane. Endoplasmic reticulum stress promotes processing of this form, releasing the transcription factor form that translocates into the nucleus, where it activates transcription of genes involved in the unfolded protein response (UPR). Transcription factor that initiates the unfolded protein response (UPR) during endoplasmic reticulum stress by activating transcription of genes involved in the UPR. Binds DNA on the 5’-CCAC[GA]-3’half of the ER stress response element (ERSE) (5’-CCAAT-N(9)-CCAC[GA]-3’) and of ERSE II (5’-ATTGG-N-CCACG-3’). Binding to ERSE requires binding of NF-Y to ERSE. Could also be involved in activation of transcription by the serum response factor. May play a role in foveal development and cone function in the retina.

Subunit / interactions. Interacts with XBP1 isoform 2; the interaction occurs in a ER stress-dependent manner. Interacts with LACC1. Interacts with THBS4 (via EGF-like 3; calcium-binding domain) which facilitates its processing, activation and nuclear translocation. Interacts (via lumenal domain) with THBS1. Homodimer and heterodimer with ATF6-beta. The dimer interacts with the nuclear transcription factor Y (NF-Y) trimer through direct binding to NF-Y subunit C (NF-YC). Also interacts with the transcription factors GTF2I, YY1 and SRF.

Subcellular location. Endoplasmic reticulum membrane. Golgi apparatus membrane Nucleus.

Tissue specificity. Ubiquitous.

Post-translational modifications. During unfolded protein response, a fragment of approximately 50 kDa containing the cytoplasmic transcription factor domain is released by proteolysis. The cleavage seems to be performed sequentially by site-1 (MBTPS1, S1P) and site-2 (MBTPS2, S2P) proteases. N-glycosylated; in its luminal domain. The glycosylation status may serve as a sensor for ER homeostasis, resulting in ATF6 activation to trigger the unfolded protein response (UPR). Ubiquitinated by RNF186 at Lys-152, which is required for pattern recognition receptor-induced unfolded protein response-associated outcomes.

Disease relevance. Achromatopsia 7 (ACHM7) [MIM:616517] A form of achromatopsia, 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.

Domain organisation. The basic domain functions as a nuclear localization signal. The basic leucine-zipper domain is sufficient for association with the NF-Y trimer and binding to ERSE.

Similarity. Belongs to the bZIP family. ATF subfamily.

RefSeq proteins (2): NP_001397819, NP_031374* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004827	bZIP	Domain
IPR046347	bZIP_sf	Homologous_superfamily
IPR051882	ATF_bZIP_TF	Family

Pfam: PF00170

UniProt features (40 total): mutagenesis site 8, sequence conflict 7, sequence variant 6, region of interest 5, glycosylation site 3, chain 2, compositionally biased region 2, cross-link 2, topological domain 2, site 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P18850-F1	56.09	0.15

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): 419–420 (cleavage; by mbtps1)

Post-translational modifications (2): 87, 152

Glycosylation sites (3): 472, 584, 643

Mutagenesis-validated functional residues (8):

Position	Phenotype
152	almost complete loss of rnf186-mediated ubiquitination.
391	loss of proteolytic cleavage; when associated with l-394.
394	loss of proteolytic cleavage; when associated with f-391.
415–416	reduces proteolytic cleavage.
419	reduces proteolytic cleavage.
474	loss of glycosylation at asn-472 and increase of golgi translocation rate.
586	loss of glycosylation at asn-584 and increase of golgi translocation rate. higher increase in golgi translocation rate;
645	loss of glycosylation at asn-643 and increase of golgi translocation rate. higher increase in golgi translocation rate;

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-380994	ATF4 activates genes in response to endoplasmic reticulum stress
R-HSA-381033	ATF6 (ATF6-alpha) activates chaperones
R-HSA-381183	ATF6 (ATF6-alpha) activates chaperone genes
R-HSA-9909505	Modulation of host responses by IFN-stimulated genes
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168256	Immune System
R-HSA-2262752	Cellular responses to stress
R-HSA-381042	PERK regulates gene expression
R-HSA-381119	Unfolded Protein Response (UPR)
R-HSA-8953897	Cellular responses to stimuli
R-HSA-913531	Interferon Signaling

MSigDB gene sets: 353 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_BCELL_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, AREB6_03, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, TGACCTY_ERR1_Q2, MODULE_308, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN

GO Biological Process (16): eye development (GO:0001654), regulation of transcription by RNA polymerase II (GO:0006357), protein folding (GO:0006457), signal transduction (GO:0007165), visual perception (GO:0007601), positive regulation of autophagy (GO:0010508), endoplasmic reticulum unfolded protein response (GO:0030968), response to endoplasmic reticulum stress (GO:0034976), ATF6-mediated unfolded protein response (GO:0036500), ERAD pathway (GO:0036503), positive regulation of apoptotic process (GO:0043065), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of ATF6-mediated unfolded protein response (GO:1903893), regulation of DNA-templated transcription (GO:0006355), response to unfolded protein (GO:0006986), regulation of ATF6-mediated unfolded protein response (GO:1903891)

GO Molecular Function (13): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), enzyme binding (GO:0019899), identical protein binding (GO:0042802), sequence-specific DNA binding (GO:0043565), protein heterodimerization activity (GO:0046982), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (11): Golgi membrane (GO:0000139), chromatin (GO:0000785), nucleus (GO:0005634), nuclear envelope (GO:0005635), nucleoplasm (GO:0005654), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), cytosol (GO:0005829), membrane (GO:0016020), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Unfolded Protein Response (UPR)	2
PERK regulates gene expression	1
ATF6 (ATF6-alpha) activates chaperones	1
Interferon Signaling	1
Immune System	1
Cellular responses to stimuli	1
Cellular responses to stress	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
intracellular membrane-bounded organelle	3
endomembrane system	3
cytoplasm	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
cellular process	2
response to endoplasmic reticulum stress	2
regulation of transcription by RNA polymerase II	2
ATF6-mediated unfolded protein response	2
transcription cis-regulatory region binding	2
protein binding	2
sensory organ development	1
visual system development	1
protein maturation	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
sensory perception of light stimulus	1
autophagy	1
positive regulation of catabolic process	1
regulation of autophagy	1
cellular response to unfolded protein	1
intracellular signal transduction	1
cellular response to stress	1
ER-nucleus signaling pathway	1
endoplasmic reticulum unfolded protein response	1
proteasomal protein catabolic process	1
response to chemical	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
positive regulation of DNA-templated transcription	1
positive regulation of endoplasmic reticulum unfolded protein response	1
regulation of ATF6-mediated unfolded protein response	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1

Protein interactions and networks

STRING

2756 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATF6	HSPA5	P11021	999
ATF6	XBP1	P17861	990
ATF6	EIF2AK3	Q9NZJ5	971
ATF6	ERN1	O75460	968
ATF6	ATF4	P18848	942
ATF6	ATF5	Q9Y2D1	932
ATF6	CEBPB	P17676	927
ATF6	HSP90B1	P14625	926
ATF6	EIF2S1	P05198	923
ATF6	MBTPS2	O43462	915
ATF6	THBS4	P35443	911
ATF6	EIF2AK2	P19525	906
ATF6	MBTPS1	Q14703	899
ATF6	VAPB	O95292	895
ATF6	DDIT3	P35638	894

IntAct

114 interactions, top by confidence:

A	B	Type	Score
ATF6	ATF6	psi-mi:“MI:0407”(direct interaction)	0.790
ATF6	ATF6	psi-mi:“MI:0914”(association)	0.790
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ATF6	XBP1	psi-mi:“MI:0407”(direct interaction)	0.620
XBP1	ATF6	psi-mi:“MI:0407”(direct interaction)	0.620
MGAT4C	GXYLT2	psi-mi:“MI:0914”(association)	0.530
PCDHB16	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
OS9	AGRN	psi-mi:“MI:0914”(association)	0.530
GABRD	ATF6	psi-mi:“MI:0914”(association)	0.530
ERLEC1	ATF6	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
BTNL3	FAM171A2	psi-mi:“MI:0914”(association)	0.530
CLEC3A	ZZEF1	psi-mi:“MI:0914”(association)	0.530
DNAJC3	DEDD	psi-mi:“MI:0914”(association)	0.530
Crtc2	ATF6	psi-mi:“MI:0915”(physical association)	0.520
ATF6	CREB3L3	psi-mi:“MI:0915”(physical association)	0.520
ATF6	DAPK1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (183): ATF6 (Affinity Capture-MS), ATF6 (Affinity Capture-MS), APOD (Affinity Capture-MS), SH3TC1 (Affinity Capture-MS), RFWD2 (Affinity Capture-MS), STK40 (Affinity Capture-MS), ACLY (Affinity Capture-MS), PARG (Affinity Capture-MS), ATF6 (Affinity Capture-MS), ATF6 (Affinity Capture-MS), ATF6 (Affinity Capture-MS), ATF6 (Affinity Capture-MS), ATF6 (Affinity Capture-MS), ATF6 (Affinity Capture-MS), ATF6 (Affinity Capture-MS)

ESM2 similar proteins: A1L224, A2VD01, D3ZLB7, F6VAN0, G3V909, O02761, O35451, O43889, O77628, O88479, O94983, O97930, P01100, P01101, P01102, P0C0N8, P0C0N9, P11939, P12841, P18850, P20389, P38532, Q00613, Q08CW8, Q08DJ8, Q1LYG4, Q3SYZ3, Q502F0, Q56TN0, Q56TT7, Q5FVM5, Q5RCM9, Q5UEM7, Q5UEM8, Q61817, Q64210, Q66HA2, Q68CJ9, Q6QDP7, Q6ZPJ0

Diamond homologs: F6VAN0, G3V909, O35451, P18850, Q5FVM5, Q6Z312, Q91XE9, Q99941, Q9D2A5, Q9M7Q2, Q08CW8, Q1LYG4, Q3SYZ3, Q502F0, Q5RCM9, Q5UEM7, Q5UEM8, Q68CJ9, Q6QDP7, Q70SY1, Q8BH52, Q8TEY5, A1L224, A2VD01, O43889, O44743, P29747, Q4JFH9, Q61817, Q66HA2, Q8SQ19, Q96BA8, Q9Z125, P27699, Q03060, Q03061, Q1LZH5, Q54RZ9, P42777, Q0JHF1

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
ATF6	“up-regulates quantity by expression”	HYOU1	“transcriptional regulation”
ATF6	“up-regulates quantity by expression”	NUCB1	“transcriptional regulation”
HSPA5	“down-regulates activity”	ATF6	binding
ATF6	“up-regulates quantity by expression”	DDIT3	“transcriptional regulation”
ATF6	up-regulates	“Chaperone-mediated protein folding”
ATF6	“up-regulates quantity by expression”	XBP1	“transcriptional regulation”
S	“down-regulates quantity by repression”	ATF6	“transcriptional regulation”
ATF6	“up-regulates quantity by expression”	HSPA5	“transcriptional regulation”
PCSK7	up-regulates	ATF6	phosphorylation
MAPK14	“up-regulates activity”	ATF6	phosphorylation
ATF6	“up-regulates activity”	ATF6	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 116 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
SLC-mediated transmembrane transport	8	6.8×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
endoplasmic reticulum unfolded protein response	6	18.1×	2e-04
ERAD pathway	9	16.6×	3e-06
response to endoplasmic reticulum stress	7	11.9×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	29
Likely pathogenic	21
Uncertain significance	251
Likely benign	169
Benign	24

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068673	NM_007348.4(ATF6):c.1337C>G (p.Ser446Ter)	Pathogenic
1457758	NM_007348.4(ATF6):c.7G>T (p.Glu3Ter)	Pathogenic
1951902	NM_007348.4(ATF6):c.45dup (p.Ser16Ter)	Pathogenic
2002232	NM_007348.4(ATF6):c.222G>A (p.Trp74Ter)	Pathogenic
208171	NC_000001.11:g.161791408dup	Pathogenic
208172	NM_007348.4(ATF6):c.970C>T (p.Arg324Cys)	Pathogenic
208176	NM_007348.4(ATF6):c.1699T>A (p.Tyr567Asn)	Pathogenic
209096	NM_007348.4(ATF6):c.82+5G>T	Pathogenic
209097	NM_007348.4(ATF6):c.353del (p.Pro118fs)	Pathogenic
209098	NM_007348.4(ATF6):c.1187+5G>C	Pathogenic
209099	NM_007348.4(ATF6):c.1533+1G>C	Pathogenic
209100	NM_007348.4(ATF6):c.797dup (p.Pro266_Asn267insTer)	Pathogenic
209101	NM_007348.4(ATF6):c.1110dup (p.Val371fs)	Pathogenic
2121684	NM_007348.4(ATF6):c.1450C>T (p.Arg484Ter)	Pathogenic
217302	NM_007348.3:c.355_356dupG	Pathogenic
2700662	NM_007348.4(ATF6):c.206G>A (p.Trp69Ter)	Pathogenic
2700673	NM_007348.4(ATF6):c.1330del (p.Ser444fs)	Pathogenic
2718613	NM_007348.4(ATF6):c.1457G>A (p.Trp486Ter)	Pathogenic
2845171	NM_007348.4(ATF6):c.1381del (p.Tyr461fs)	Pathogenic
2863567	NM_007348.4(ATF6):c.1156del (p.Ala386fs)	Pathogenic
2959328	NM_007348.4(ATF6):c.1714C>T (p.Arg572Ter)	Pathogenic
3064177	NM_007348.4(ATF6):c.949C>T (p.Arg317Ter)	Pathogenic
3250227	NM_007348.4(ATF6):c.1485dup (p.Lys496fs)	Pathogenic
4081052	NM_007348.4(ATF6):c.1126C>T (p.Arg376Ter)	Pathogenic
505015	NC_000001.11:g.161781912dup	Pathogenic
620421	NM_007348.4(ATF6):c.1108A>T (p.Lys370Ter)	Pathogenic
800907	NM_007348.4(ATF6):c.511del (p.Ile171fs)	Pathogenic
801569	NM_007348.4(ATF6):c.709C>T (p.Gln237Ter)	Pathogenic
977965	NM_007348.4(ATF6):c.3G>T (p.Met1Ile)	Pathogenic
1068149	NM_007348.4(ATF6):c.484+1G>A	Likely pathogenic

SpliceAI

2979 predictions. Top by Δscore:

Variant	Effect	Δscore
1:161766439:TGGGG:T	donor_loss	1.0000
1:161766443:G:GA	donor_loss	1.0000
1:161766444:T:A	donor_loss	1.0000
1:161778235:T:A	acceptor_gain	1.0000
1:161778239:CAAAG:C	acceptor_loss	1.0000
1:161778240:A:AG	acceptor_gain	1.0000
1:161778240:AAAGA:A	acceptor_loss	1.0000
1:161778241:A:G	acceptor_gain	1.0000
1:161778242:A:AG	acceptor_gain	1.0000
1:161778242:A:AT	acceptor_loss	1.0000
1:161778243:G:GG	acceptor_gain	1.0000
1:161778314:GAC:G	donor_gain	1.0000
1:161778317:GTAT:G	donor_gain	1.0000
1:161778318:TAT:T	donor_gain	1.0000
1:161778319:AT:A	donor_gain	1.0000
1:161778320:TG:T	donor_loss	1.0000
1:161778321:G:GG	donor_gain	1.0000
1:161778321:GTAA:G	donor_loss	1.0000
1:161778322:TA:T	donor_loss	1.0000
1:161781882:A:AG	acceptor_gain	1.0000
1:161781883:A:G	acceptor_gain	1.0000
1:161781895:T:TA	acceptor_gain	1.0000
1:161781900:T:TA	acceptor_gain	1.0000
1:161781907:TACAG:T	acceptor_loss	1.0000
1:161781908:ACAGG:A	acceptor_loss	1.0000
1:161781909:CAGG:C	acceptor_loss	1.0000
1:161781910:A:AC	acceptor_loss	1.0000
1:161781910:A:AG	acceptor_gain	1.0000
1:161781911:G:GG	acceptor_gain	1.0000
1:161781995:TACAG:T	donor_loss	1.0000

AlphaMissense

4369 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:161819668:A:C	K315N	1.000
1:161819668:A:T	K315N	1.000
1:161819669:A:G	N316D	1.000
1:161819673:G:C	R317P	1.000
1:161819693:C:A	R324S	1.000
1:161853238:T:C	L483P	1.000
1:161853246:T:A	W486R	1.000
1:161853246:T:C	W486R	1.000
1:161853248:G:C	W486C	1.000
1:161853248:G:T	W486C	1.000
1:161863296:T:A	V568D	1.000
1:161912303:T:C	L576P	1.000
1:161912306:T:C	L577P	1.000
1:161958493:T:C	C618R	1.000
1:161819657:C:A	R312S	0.999
1:161819658:G:C	R312P	0.999
1:161819661:T:C	M313T	0.999
1:161819666:A:G	K315E	0.999
1:161819667:A:T	K315I	0.999
1:161819670:A:C	N316T	0.999
1:161819670:A:G	N316S	0.999
1:161819670:A:T	N316I	0.999
1:161819671:T:A	N316K	0.999
1:161819671:T:G	N316K	0.999
1:161819678:T:C	S319P	0.999
1:161819682:C:A	A320D	0.999
1:161819690:T:C	S323P	0.999
1:161819693:C:G	R324G	0.999
1:161819694:G:C	R324P	0.999
1:161819766:T:C	L348P	0.999

dbSNP variants (sampled 300 via entrez): RS1000027879 (1:161890764 G>A), RS1000028866 (1:161941162 T>C,G), RS1000029861 (1:161794631 A>G), RS1000031645 (1:161850433 A>G), RS1000065721 (1:161801355 T>C), RS1000073134 (1:161810269 C>G,T), RS1000099453 (1:161765283 A>C), RS1000126490 (1:161810474 C>A,T), RS1000134947 (1:161764366 T>A,G), RS1000159298 (1:161959932 T>C), RS1000166035 (1:161870637 G>A), RS1000173152 (1:161823678 T>C), RS1000221352 (1:161877994 T>G), RS1000254666 (1:161816197 T>C), RS1000254767 (1:161857630 C>T)

Disease associations

OMIM: gene MIM:605537 | disease phenotypes: MIM:616517

GenCC curated gene-disease

Disease	Classification	Inheritance
ATF6-related retinopathy	Definitive	Autosomal recessive
achromatopsia 7	Definitive	Autosomal recessive
cone-rod 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
ATF6-related retinopathy	Definitive	AR

Mondo (7): inherited retinal dystrophy (MONDO:0019118), achromatopsia 7 (MONDO:0014677), Charcot-Marie-Tooth disease type 1 (MONDO:0019011), achromatopsia (MONDO:0018852), retinal disorder (MONDO:0005283), ATF6-related retinopathy (MONDO:0100447), cone-rod dystrophy (MONDO:0015993)

Orphanet (3): OBSOLETE: Inherited retinal disorder (Orphanet:71862), Achromatopsia (Orphanet:49382), Charcot-Marie-Tooth disease type 1 (Orphanet:65753)

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000505	Visual impairment
HP:0000529	Progressive visual loss
HP:0000539	Abnormality of refraction
HP:0000540	Hypermetropia
HP:0000543	Optic disc pallor
HP:0000545	Myopia
HP:0000551	Color vision defect
HP:0000603	Central scotoma
HP:0000613	Photophobia
HP:0000639	Nystagmus
HP:0000662	Nyctalopia
HP:0001103	Abnormal macular morphology
HP:0001105	Retinal atrophy
HP:0007401	Macular atrophy
HP:0007641	Dyschromatopsia
HP:0007663	Reduced visual acuity
HP:0007695	Abnormal pupillary light reflex
HP:0007703	Abnormal retinal pigmentation
HP:0007722	Retinal pigment epithelial atrophy
HP:0007737	Spicular pigmentation of the retina
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:0012508	Metamorphopsia
HP:0025549	Eccentric visual fixation
HP:0030465	Undetectable light-adapted electroretinogram

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000490_3	Parkinson’s disease (age of onset)	8.000000e-06
GCST002621_1	Chronic bronchitis in chronic obstructive pulmonary disease	5.000000e-07
GCST006493_9	Systemic sclerosis	7.000000e-06
GCST90026413_5	Severe insulin-deficient type 2 diabetes	9.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D012164	Retinal Diseases	C11.768
D058499	Retinal Dystrophies	C11.768.585.658

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

147 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Thapsigargin	increases expression, increases reaction, increases activity, affects localization, increases cleavage (+1 more)	11
4-phenylbutyric acid	affects cotreatment, decreases expression, decreases reaction, increases expression	9
Tunicamycin	decreases reaction, increases expression, decreases cleavage, increases cleavage	7
Arsenic Trioxide	decreases reaction, decreases expression, increases reaction, increases expression, increases phosphorylation	6
Cyclosporine	affects reaction, increases expression, affects cotreatment	6
sodium arsenite	increases abundance, increases expression, increases reaction, decreases expression	4
Particulate Matter	decreases reaction, increases cleavage, decreases expression, increases abundance, increases expression	4
bisphenol A	affects cotreatment, decreases methylation, decreases expression, increases expression, increases methylation	3
Acetylcysteine	increases expression, increases activity, increases metabolic processing, decreases expression, decreases reaction	3
Glucosamine	increases expression, decreases expression, decreases reaction	3
Indomethacin	affects cotreatment, increases activity, increases expression	3
Lipopolysaccharides	increases expression, increases cleavage, decreases reaction	3
Valproic Acid	decreases expression, increases expression, affects expression	3
bisphenol F	increases expression, affects cotreatment	2
beta-N-methylamino-L-alanine	decreases expression, increases expression	2
deoxynivalenol	increases expression	2
geraniol	decreases reaction, increases expression	2
perhexiline maleate	decreases reaction, increases abundance, increases expression	2
ochratoxin A	increases expression	2
hydroquinone	increases lipidation, affects cotreatment, decreases reaction, increases expression, decreases expression (+2 more)	2
Resveratrol	decreases reaction, increases expression	2
Arsenic	increases expression, increases reaction, affects binding, increases cleavage, affects reaction (+1 more)	2
Vehicle Emissions	decreases expression, increases abundance, increases expression	2
Calcitriol	increases expression, affects cotreatment	2
Glucose	decreases reaction, increases expression, increases reaction	2
Methamphetamine	decreases reaction, affects reaction, increases cleavage, increases expression, affects localization (+1 more)	2
Paraquat	increases expression, increases cleavage	2
Tobacco Smoke Pollution	increases expression	2
Tretinoin	increases expression	2
aristolochic acid I	decreases expression	1

Cellosaurus cell lines

9 cell lines: 9 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1KA	Abcam HeLa ATF6 KO	Cancer cell line	Female
CVCL_B8BL	Abcam HCT 116 ATF6 KO	Cancer cell line	Male
CVCL_B9DR	Abcam A-549 ATF6 KO	Cancer cell line	Male
CVCL_D2DX	Abcam MCF-7 ATF6 KO	Cancer cell line	Female
CVCL_D9Y1	Ubigene HeLa ATF6 KO	Cancer cell line	Female
CVCL_SD86	HAP1 ATF6 (-) 1	Cancer cell line	Male
CVCL_SD87	HAP1 ATF6 (-) 2	Cancer cell line	Male
CVCL_SD88	HAP1 ATF6 (-) 3	Cancer cell line	Male
CVCL_SD89	HAP1 ATF6 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01955135	PHASE4	COMPLETED	Anesthesia for Retinopathy of Prematurity
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
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
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]
NCT01373476	PHASE2	COMPLETED	Multicentre, Randomized, Controlled Trial of Qideng Mingmu Capsule in The Treatment of Diabetic Retinopathy
NCT01793090	PHASE2	COMPLETED	EPI-743 in Cobalamin C Defect: Effects on Visual and Neurological Impairment
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)
NCT04041232	EARLY_PHASE1	SUSPENDED	PBA Use for Treatment of ATF6-/- Patients
NCT06467344	PHASE1/PHASE2	RECRUITING	Study to Evaluate ACDN-01 in ABCA4-related Stargardt Retinopathy (STELLAR)
NCT06789445	PHASE1/PHASE2	RECRUITING	A Study to Investigate the Safety of OpCT-001 in Adults Who Have Primary Photoreceptor Disease (CLARICO)
NCT00427180	Not specified	UNKNOWN	IRIS PILOT - Extended Pilot Study With a Retinal Implant System
NCT01864486	Not specified	COMPLETED	Restoring Vision With the Intelligent Retinal Implant System (IRIS V1)in Patients With Retinal Dystrophy
NCT02435940	Not specified	RECRUITING	Inherited Retinal Degenerative Disease Registry
NCT02670980	Not specified	COMPLETED	Compensation for Blindness With the Intelligent Retinal Implant System (IRIS V2) in Patients With Retinal Dystrophy
NCT04658251	Not specified	TERMINATED	Study of New Mutations in Cone Disorders
NCT05355415	Not specified	RECRUITING	Adaptive Optics Imaging of Outer Retinal Diseases
NCT06445322	Not specified	RECRUITING	Prescreening Study to Identify Potential Stargardt Participants for ACDN-01 Clinical Trials (STARPATH)
NCT07548944	Not specified	RECRUITING	Observational Study to Investigate the Short-term Effects of Transcorneal Electrical Stimulation on Visual Performance
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)
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