ATF6-related retinopathy

Summary

ATF6-related retinopathy (MONDO:0100447) is a disease caused by ATF6 (GenCC Definitive), with 1 cohort gene and 1 clinical trial.

At a glance

• Causal gene: ATF6 (GenCC Definitive)
• Cohort genes: 1
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	ATF6-related retinopathy
Mondo ID	MONDO:0100447
GARD	0026222
Is cancer (heuristic)	no

Also known as: ACHM7 · achromatopsia 7 · achromatopsia caused by mutation in ATF6 · achromatopsia type 7 · ATF6 achromatopsia · ATF6 retinopathy · ATF6-related retinopathy

Data availability: 1 GenCC gene-disease record.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › retinal disorder › retinal degeneration › inherited retinal dystrophy › ATF6-related retinopathy

Related subtypes (104): retinal dystrophies primarily involving Bruch’s membrane, vitreoretinal dystrophy, dystrophies primarily involving the retinal pigment epithelium, retinal dystrophy in systemic or cerebroretinal lipidoses, age-related macular degeneration, helicoid peripapillary chorioretinal degeneration, Sorsby fundus dystrophy, microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability, pigmented paravenous retinochoroidal atrophy, retinoschisis, autosomal dominant, retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations, amaurosis-hypertrichosis syndrome, familial benign flecked retina, microcephaly and chorioretinopathy 1, ornithine aminotransferase deficiency, retinal degeneration-nanophthalmos-glaucoma syndrome, retinoschisis of fovea, Revesz syndrome, choroideremia, choroideremia-deafness-obesity syndrome, X-linked retinal dysplasia, X-linked retinoschisis, progressive bifocal chorioretinal atrophy, aceruloplasminemia, late-onset retinal degeneration, infantile cerebellar-retinal degeneration, progressive retinal dystrophy due to retinol transport defect, microcornea-myopic chorioretinal atrophy, retinal dystrophy with inner retinal dysfunction and ganglion cell anomalies, macular degeneration, early-onset, cone-rod dystrophy, ectopia lentis-chorioretinal dystrophy-myopia syndrome, foveal hypoplasia-presenile cataract syndrome, MRCS syndrome, X-linked intellectual disability-limb spasticity-retinal dystrophy-diabetes insipidus syndrome, Leber congenital amaurosis, oligocone trichromacy, Oguchi disease, retinitis pigmentosa, hereditary macular dystrophy, RPE65-related recessive retinopathy, RPGR-related retinopathy, AIPL1-related retinopathy, RP2-related retinopathy, RDH5-related retinopathy, RLBP1-related retinopathy, LCA5-related retinopathy, RAB28-related retinopathy, FLVCR1-related retinopathy with or without ataxia, RPE65-related dominant retinopathy, GUCY2D retinopathy, PDE6A-related retinopathy, ELOVL4-related maculopathy, MAK-related retinopathy, KIZ-related retinopathy, TOPORS-related retinopathy, PRPF8-related retinopathy, RD3-related retinopathy, BEST1-related dominant retinopathy, BEST1-related recessive retinopathy, IMPG2-related recessive retinopathy, IMPG2-related dominant retinopathy, CACNA1F-related retinopathy, CACNA2D4-related retinopathy, CDHR1-related retinopathy, GUCA1A-related retinopathy, RHO-related retinopathy, SNRNP200-related dominant retinopathy, RDH12-related recessive retinopathy, RDH12-related dominant retinopathy, NMNAT1-related retinopathy, CNGA3-related retinopathy, EYS-related retinopathy, GNAT2-related retinopathy, IDH3B-related retinopathy, MERTK-related retinopathy, PRPF31-related retinopathy, GPR179-related retinopathy, GRM6-related retinopathy, ADAM9-related retinopathy, RP1-related recessive retinopathy, RP1-related dominant retinopathy, CERKL-related retinopathy, TRPM1-related retinopathy, CNGB1-related retinopathy, PCARE-related retinopathy, CNGA1-related retinopathy, ABCA4-related retinopathy, NYX-related retinopathy, retinal dystrophy, X-linked, Gardner-Hardcastle type, PDE6C-related retinopathy, PDE6G-related retinopathy, LRIT3-related retinopathy, IMPG1-related dominant retinopathy, IMPG1-related recessive retinopathy, TTLL5-related retinopathy, HGSNAT-related retinopathy, IMPDH1-related retinopathy, PRPH2-related retinopathy, PROM1-related retinopathy, KCNV2-related retinopathy, CRX-related retinopathy, REEP6-related retinopathy, SPATA7-related retinopathy

Subtypes (1): achromatopsia 7

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
ATF6	Definitive	Autosomal recessive	ATF6-related retinopathy	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATF6	Orphanet:1872	Cone rod dystrophy
ATF6	Orphanet:49382	Achromatopsia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
ATF6	HGNC:791	ENSG00000118217	P18850	Cyclic AMP-dependent transcription factor ATF-6 alpha	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATF6	Cyclic AMP-dependent transcription factor ATF-6 alpha	Precursor of the transcription factor form (Processed cyclic AMP-dependent transcription factor ATF-6 alpha), which is embedded in the endoplasmic reticulum membrane.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transcription factor	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
ATF6	Transcription factor	no		bZIP, bZIP_sf, ATF_bZIP_TF

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
corpus epididymis	1
skin of hip	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATF6	283	ubiquitous	marker	corpus epididymis, skin of hip, upper leg skin

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATF6	3,053

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ATF6	P18850	56.09

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
ATF6 (ATF6-alpha) activates chaperones	1	1903.3×	0.004	ATF6
ATF6 (ATF6-alpha) activates chaperone genes	1	1142.0×	0.004	ATF6
PERK regulates gene expression	1	815.7×	0.004	ATF6
Modulation of host responses by IFN-stimulated genes	1	601.0×	0.005	ATF6
ATF4 activates genes in response to endoplasmic reticulum stress	1	407.9×	0.005	ATF6
Unfolded Protein Response (UPR)	1	356.9×	0.005	ATF6
Interferon Signaling	1	120.2×	0.013	ATF6
Cytokine Signaling in Immune system	1	40.8×	0.033	ATF6
Cellular responses to stress	1	36.8×	0.033	ATF6
Cellular responses to stimuli	1	31.5×	0.035	ATF6
Immune System	1	13.0×	0.077	ATF6

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of ATF6-mediated unfolded protein response	1	16852.0×	8e-04	ATF6
ATF6-mediated unfolded protein response	1	2106.5×	0.003	ATF6
eye development	1	351.1×	0.011	ATF6
endoplasmic reticulum unfolded protein response	1	295.6×	0.011	ATF6
positive regulation of autophagy	1	208.1×	0.011	ATF6
ERAD pathway	1	181.2×	0.011	ATF6
response to endoplasmic reticulum stress	1	166.8×	0.011	ATF6
protein folding	1	103.4×	0.016	ATF6
visual perception	1	79.5×	0.018	ATF6
positive regulation of apoptotic process	1	56.7×	0.023	ATF6
signal transduction	1	16.1×	0.073	ATF6
positive regulation of transcription by RNA polymerase II	1	14.9×	0.073	ATF6
regulation of transcription by RNA polymerase II	1	11.7×	0.086	ATF6

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATF6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	ATF6

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
ATF6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04041232	EARLY_PHASE1	SUSPENDED	PBA Use for Treatment of ATF6-/- Patients