Achromatopsia 7

Summary

Achromatopsia 7 (MONDO:0014677) 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
• ClinVar variants: 31
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	achromatopsia 7
Mondo ID	MONDO:0014677
OMIM	616517
DOID	DOID:0110009
UMLS	C4225297
MedGen	904646
GARD	0016129
Is cancer (heuristic)	no

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

Data availability: 31 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › perceptual disorders › vision disorder › color vision disorder › achromatopsia › achromatopsia 7

Related subtypes (5): achromatopsia 2, achromatopsia 3, blue cone monochromacy, achromatopsia 6, achromatopsia 4

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

ClinVar germline variants

31 retrieved; paginated sample, class counts are floors:

15 pathogenic, 7 benign, 5 likely pathogenic, 2 uncertain significance, 1 conflicting classifications of pathogenicity, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
208171	NC_000001.11:g.161791408dup	ATF6	Pathogenic	no assertion criteria provided
208172	NM_007348.4(ATF6):c.970C>T (p.Arg324Cys)	ATF6	Pathogenic	criteria provided, multiple submitters, no conflicts
208176	NM_007348.4(ATF6):c.1699T>A (p.Tyr567Asn)	ATF6	Pathogenic	criteria provided, single submitter
209096	NM_007348.4(ATF6):c.82+5G>T	ATF6	Pathogenic	criteria provided, multiple submitters, no conflicts
209097	NM_007348.4(ATF6):c.353del (p.Pro118fs)	ATF6	Pathogenic	criteria provided, multiple submitters, no conflicts
209098	NM_007348.4(ATF6):c.1187+5G>C	ATF6	Pathogenic	criteria provided, single submitter
209099	NM_007348.4(ATF6):c.1533+1G>C	ATF6	Pathogenic	criteria provided, multiple submitters, no conflicts
209100	NM_007348.4(ATF6):c.797dup (p.Pro266_Asn267insTer)	ATF6	Pathogenic	criteria provided, single submitter
209101	NM_007348.4(ATF6):c.1110dup (p.Val371fs)	ATF6	Pathogenic	criteria provided, single submitter
217302	NM_007348.3:c.355_356dupG	ATF6	Pathogenic	no assertion criteria provided
3064177	NM_007348.4(ATF6):c.949C>T (p.Arg317Ter)	ATF6	Pathogenic	criteria provided, single submitter
4081052	NM_007348.4(ATF6):c.1126C>T (p.Arg376Ter)	ATF6	Pathogenic	criteria provided, single submitter
800907	NM_007348.4(ATF6):c.511del (p.Ile171fs)	ATF6	Pathogenic	criteria provided, single submitter
801569	NM_007348.4(ATF6):c.709C>T (p.Gln237Ter)	ATF6	Pathogenic	criteria provided, multiple submitters, no conflicts
977965	NM_007348.4(ATF6):c.3G>T (p.Met1Ile)	ATF6	Pathogenic	no assertion criteria provided
3064150	NM_007348.4(ATF6):c.1720-2A>T	ATF6	Likely pathogenic	criteria provided, single submitter
3377706	NM_007348.4(ATF6):c.780_784del (p.Gly261fs)	ATF6	Likely pathogenic	criteria provided, single submitter
592152	NM_007348.4(ATF6):c.1784del (p.Leu595fs)	ATF6	Likely pathogenic	no assertion criteria provided
977964	NM_007348.4(ATF6):c.950G>A (p.Arg317Gln)	ATF6	Likely pathogenic	no assertion criteria provided
977966	NM_007348.4(ATF6):c.854A>G (p.Lys285Arg)	ATF6	Likely pathogenic	no assertion criteria provided
3220935	NM_007348.4(ATF6):c.1805-2A>C	ATF6	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1031735	NM_007348.4(ATF6):c.677C>A (p.Ala226Glu)	ATF6	Uncertain significance	criteria provided, multiple submitters, no conflicts
801570	NM_007348.4(ATF6):c.1190_1191insTTTTT (p.Met397fs)	ATF6	Uncertain significance	criteria provided, single submitter
1164403	NM_007348.4(ATF6):c.105C>T (p.Leu35=)	ATF6	Benign	criteria provided, multiple submitters, no conflicts
1164404	NM_007348.4(ATF6):c.270T>C (p.Pro90=)	ATF6	Benign	criteria provided, multiple submitters, no conflicts
1164405	NM_007348.4(ATF6):c.309G>A (p.Ser103=)	ATF6	Benign	criteria provided, multiple submitters, no conflicts
1167834	NM_007348.4(ATF6):c.1896A>G (p.Ser632=)	ATF6	Benign	criteria provided, multiple submitters, no conflicts
3338252	NM_007348.4(ATF6):c.1605-154G>A	ATF6	Benign	criteria provided, single submitter
801568	NM_007348.4(ATF6):c.199A>G (p.Met67Val)	ATF6	Benign	criteria provided, multiple submitters, no conflicts
801571	NM_007348.4(ATF6):c.1191G>T (p.Met397Ile)	ATF6	Likely benign	criteria provided, single submitter

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	achromatopsia 7	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,clinvar

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