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 (388 variants)
Inborn_genetic_diseases (82 variants)
Achromatopsia_7 (23 variants)
Retinal_dystrophy (8 variants)
ATF6-related_disorder (6 variants)
not_specified (3 variants)
Achromatopsia (3 variants)
Bilateral_sensorineural_hearing_impairment (2 variants)
Retinal_disorders (1 variants)
Macular_dystrophy (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. These statistics are base on transcript: NM_000007348.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	89 clinvar	5 clinvar	97
missense	2 clinvar	3 clinvar	214 clinvar	7 clinvar	4 clinvar	230
nonsense	12 clinvar	1 clinvar	1 clinvar			14
start loss	1					1
frameshift	11 clinvar	3 clinvar	3 clinvar			17
splice donor/acceptor (+/-2bp)	1 clinvar	10 clinvar				11
Total	27	17	221	96	9

Highest pathogenic variant AF is 0.000062648

Loading clinvar variants...

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