GET3

guided entry of tail-anchored proteins factor 3, ATPase, the group of Guided entry of tail-anchored proteins complex subunits|GET4-GET5 transmembrane domain recognition complex subunits

Basic information

Region (hg38): 19:12737139-12748323

Previous symbols: [ "ASNA1" ]

Links

ENSG00000198356 ∙ NCBI:439 ∙ OMIM:601913 ∙ HGNC:752 ∙ Uniprot:O43681 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, dilated, 2H	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	Cardiovascular	31461301

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GET3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GET3 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						0
missense			20			20
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	20	0	0

Variants in GET3

This is a list of pathogenic ClinVar variants found in the GET3 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-12737528-G-C		not specified	Uncertain significance (Sep 30, 2022)
19-12737533-G-T		not specified	Uncertain significance (Feb 06, 2023)
19-12737591-G-A		not specified	Uncertain significance (Oct 26, 2024)
19-12737608-C-T		not specified	Uncertain significance (Oct 09, 2024)
19-12738542-C-T		not specified	Uncertain significance (May 24, 2023)
19-12738543-G-A		not specified	Uncertain significance (May 26, 2024)
19-12738573-C-G		Prostate cancer	Uncertain significance (-)
19-12738593-G-A		not specified	Uncertain significance (Jan 22, 2025)
19-12738629-G-A		not specified	Uncertain significance (Jul 05, 2023)
19-12745398-G-A		not specified	Uncertain significance (Dec 16, 2024)
19-12745402-C-T		not specified	Uncertain significance (Mar 04, 2024)
19-12745405-A-G		not specified	Uncertain significance (Jul 27, 2024)
19-12745622-A-G		not specified	Uncertain significance (Nov 15, 2021)
19-12745638-T-C		Cardiomyopathy, dilated, 2H	Pathogenic (Jan 23, 2025)
19-12747206-A-T		not specified	Uncertain significance (Mar 02, 2023)
19-12747269-G-A		not specified	Uncertain significance (Nov 10, 2022)
19-12747276-G-A		not specified	Uncertain significance (May 24, 2023)
19-12747527-G-A		not specified	Uncertain significance (Mar 23, 2023)
19-12747530-C-T		not specified	Uncertain significance (Sep 24, 2024)
19-12747533-G-A		not specified	Uncertain significance (Aug 10, 2021)
19-12747544-C-G		-	no classification for the single variant (-)
19-12747587-G-C		not specified	Uncertain significance (Apr 29, 2024)
19-12747590-C-T		-	no classification for the single variant (-)
19-12748000-A-G		not specified	Uncertain significance (May 30, 2024)
19-12748013-C-T		not specified	Uncertain significance (Nov 13, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GET3	protein_coding	protein_coding	ENST00000591090	7	11185

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.943	0.0568	125741	0	3	125744	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.21	120	210	0.571	0.0000119	2307
Missense in Polyphen		15	65.723	0.22823		782
Synonymous	-0.801	100	90.3	1.11	0.00000575	670
Loss of Function	3.15	1	13.5	0.0742	5.70e-7	167

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: ATPase required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum. Recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. This complex then targets to the endoplasmic reticulum by membrane-bound receptors, where the tail- anchored protein is released for insertion. This process is regulated by ATP binding and hydrolysis. ATP binding drives the homodimer towards the closed dimer state, facilitating recognition of newly synthesized TA membrane proteins. ATP hydrolysis is required for insertion. Subsequently, the homodimer reverts towards the open dimer state, lowering its affinity for the membrane-bound receptor, and returning it to the cytosol to initiate a new round of targeting (By similarity). May be involved in insulin signaling. {ECO:0000255|HAMAP-Rule:MF_03112, ECO:0000269|PubMed:17382883, ECO:0000269|PubMed:18477612, ECO:0000269|PubMed:25535373}.
• Pathway: XBP1(S) activates chaperone genes;IRE1alpha activates chaperones;Unfolded Protein Response (UPR);Metabolism of proteins (Consensus)

Recessive Scores

• pRec: 0.178

Intolerance Scores

• loftool: 0.361
• rvis_EVS: -0.54
• rvis_percentile_EVS: 20.26

Haploinsufficiency Scores

• pHI: 0.390
• hipred: Y
• hipred_score: 0.685
• ghis: 0.633

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.963

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Asna1
• 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)

Zebrafish Information Network

• Gene name: asna1
• Affected structure: retinal outer plexiform layer
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: posttranslational protein targeting to endoplasmic reticulum membrane;arsenite transport;IRE1-mediated unfolded protein response;tail-anchored membrane protein insertion into ER membrane
• Cellular component: nucleus;nucleolus;cytoplasm;endoplasmic reticulum membrane;GET complex;extracellular exosome
• Molecular function: transporter activity;protein binding;ATP binding;arsenite transmembrane transporter activity;ATPase activity;metal ion binding