ATF6

activating transcription factor 6, the group of Basic leucine zipper proteins

Basic information

Region (hg38): 1:161766298-161977574

Links

ENSG00000118217 ∙ NCBI:22926 ∙ OMIM:605537 ∙ HGNC:791 ∙ Uniprot:P18850 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• achromatopsia 7 (Strong), mode of inheritance: AR
• achromatopsia 7 (Strong), mode of inheritance: AR
• cone-rod dystrophy (Supportive), mode of inheritance: AD
• achromatopsia (Supportive), mode of inheritance: AR
• achromatopsia 7 (Definitive), mode of inheritance: AR
• achromatopsia (Strong), mode of inheritance: AR
• ATF6-related retinopathy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Achromatopsia 7	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Ophthalmologic	26029869; 26063662

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATF6 gene.

• not provided (16 variants)
• Achromatopsia 7 (10 variants)
• ATF6-related disorder (1 variants)
• Achromatopsia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATF6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	80	8	90
missense	2		183	3	7	195
nonsense	11		1			12
start loss						0
frameshift	7		2			9
inframe indel			5			5
splice donor/acceptor (+/-2bp)	1	9				10
splice region	2		12	15	3	32
non coding			4	51	4	59
Total	21	9	197	134	19

Highest pathogenic variant AF is 0.0000526

Variants in ATF6

This is a list of pathogenic ClinVar variants found in the ATF6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-161766363-G-T		Achromatopsia 7	Pathogenic (-)
1-161766364-G-C			Uncertain significance (Aug 02, 2022)
1-161766367-G-T			Pathogenic (Aug 09, 2022)
1-161766373-G-A			Uncertain significance (Oct 25, 2022)
1-161766375-T-C			Likely benign (Jul 28, 2021)
1-161766377-G-C			Uncertain significance (May 29, 2022)
1-161766377-G-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 14, 2024)
1-161766381-T-C			Likely benign (Jan 16, 2022)
1-161766381-T-G			Likely benign (Oct 09, 2023)
1-161766387-C-T			Likely benign (Nov 22, 2022)
1-161766393-G-A			Uncertain significance (Nov 08, 2022)
1-161766400-C-T			Uncertain significance (Jul 09, 2022)
1-161766401-C-A			Uncertain significance (Oct 14, 2022)
1-161766401-C-T			Uncertain significance (Sep 13, 2022)
1-161766401-C-CT			Pathogenic (Sep 08, 2023)
1-161766407-G-T		ATF6-related disorder	Benign/Likely benign (Jan 31, 2024)
1-161766419-T-C			Benign (Jan 30, 2024)
1-161766421-C-T		Inborn genetic diseases	Uncertain significance (Jun 06, 2023)
1-161766422-A-G			Uncertain significance (Aug 22, 2022)
1-161766426-G-A			Likely benign (Feb 08, 2023)
1-161766427-C-T			Uncertain significance (Feb 23, 2022)
1-161766437-A-G			Uncertain significance (Jun 20, 2022)
1-161766443-G-T			Likely pathogenic (Apr 23, 2021)
1-161766447-G-A			Uncertain significance (Oct 24, 2022)
1-161766447-G-T		Achromatopsia 7	Pathogenic (Nov 01, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATF6	protein_coding	protein_coding	ENST00000367942	16	197777

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.23e-7	0.999	125714	0	34	125748	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.557	323	352	0.917	0.0000177	4350
Missense in Polyphen		80	90.227	0.88666		1148
Synonymous	-0.441	136	130	1.05	0.00000668	1323
Loss of Function	3.00	17	36.6	0.465	0.00000192	436

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000242	0.000241
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000168	0.000158
Middle Eastern	0.0000545	0.0000544
South Asian	0.000297	0.000294
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transmembrane glycoprotein of the endoplasmic reticulum that functions as a transcription activator and initiates the unfolded protein response (UPR) during endoplasmic reticulum stress. Cleaved upon ER stress, the N-terminal processed cyclic AMP-dependent transcription factor ATF-6 alpha translocates to the nucleus where it activates 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. {ECO:0000269|PubMed:10564271, ECO:0000269|PubMed:11158310, ECO:0000269|PubMed:11779464, ECO:0000269|PubMed:26029869}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:26029869, ECO:0000269|PubMed:26063662}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Protein processing in endoplasmic reticulum - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Sterol Regulatory Element-Binding Proteins (SREBP) signalling;Alzheimers Disease;Photodynamic therapy-induced unfolded protein response;VEGFA-VEGFR2 Signaling Pathway;ATF6 (ATF6-alpha) activates chaperones;Unfolded Protein Response (UPR);Metabolism of proteins;Signaling mediated by p38-alpha and p38-beta (Consensus)

Recessive Scores

• pRec: 0.280

Intolerance Scores

• loftool: 0.768
• rvis_EVS: 0.42
• rvis_percentile_EVS: 77.23

Haploinsufficiency Scores

• pHI: 0.241
• hipred: Y
• hipred_score: 0.747
• ghis: 0.498

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.986

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Atf6
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: atf6
• Affected structure: endoplasmic reticulum unfolded protein response
• Phenotype tag: abnormal
• Phenotype quality: process quality

Gene ontology

• Biological process: eye development;regulation of transcription by RNA polymerase II;protein folding;signal transduction;visual perception;endoplasmic reticulum unfolded protein response;ATF6-mediated unfolded protein response;positive regulation of apoptotic process;positive regulation of transcription by RNA polymerase II;positive regulation of ATF6-mediated unfolded protein response;positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress
• Cellular component: Golgi membrane;nucleus;nuclear envelope;nucleoplasm;endoplasmic reticulum;endoplasmic reticulum membrane;Golgi apparatus;cytosol;membrane;integral component of endoplasmic reticulum membrane
• Molecular function: transcription regulatory region sequence-specific DNA binding;RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;transcription coactivator activity;protein binding;ubiquitin protein ligase binding;cAMP response element binding;identical protein binding;sequence-specific DNA binding;protein heterodimerization activity