GET4

guided entry of tail-anchored proteins factor 4, the group of GET4-GET5 transmembrane domain recognition complex subunits|BAG6 complex

Basic information

Region (hg38): 7:876554-896436

Previous symbols: [ "C7orf20" ]

Links

ENSG00000239857 ∙ NCBI:51608 ∙ OMIM:612056 ∙ HGNC:21690 ∙ Uniprot:Q7L5D6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital disorder of glycosylation, type IIy (Limited), mode of inheritance: Unknown
• congenital disorder of glycosylation, type IIy (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Congenital disorder of glycosylation,, type IIy	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	Biochemical; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	32395830

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GET4 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GET4 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				5	1	6
missense			32			32
nonsense						0
start loss			1			1
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	33	5	1

Variants in GET4

This is a list of pathogenic ClinVar variants found in the GET4 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-876719-G-A		not specified	Uncertain significance (Aug 01, 2024)
7-876754-G-A		not specified	Uncertain significance (Jan 07, 2025)
7-876755-G-A		not specified	Uncertain significance (Apr 23, 2024)
7-886060-A-G		not specified	Uncertain significance (Mar 31, 2024)
7-886103-C-T		not specified	Uncertain significance (Jul 19, 2022)
7-886106-G-C		not specified	Uncertain significance (Nov 23, 2021)
7-886127-A-G		not specified	Uncertain significance (Jan 02, 2024)
7-886589-G-A			Likely benign (Mar 01, 2022)
7-886626-G-A		not specified	Uncertain significance (Mar 11, 2025)
7-886641-G-A		not specified	Uncertain significance (Jan 07, 2025)
7-887385-T-C		not specified	Uncertain significance (Jun 08, 2022)
7-887418-G-A		GET4 deficiency • Congenital disorder of glycosylation, type IIy	Pathogenic/Likely pathogenic (Mar 08, 2023)
7-887420-G-A		not specified	Uncertain significance (Jan 18, 2025)
7-887465-G-A		not specified	Uncertain significance (Mar 06, 2023)
7-887481-C-G		not specified	Uncertain significance (Jun 24, 2022)
7-887504-C-T		not specified	Uncertain significance (Nov 14, 2023)
7-887508-C-G		not specified	Uncertain significance (Jul 20, 2021)
7-890993-A-G		not specified	Uncertain significance (Sep 16, 2021)
7-891012-C-T		not specified	Uncertain significance (Feb 01, 2023)
7-891020-G-A		not specified	Uncertain significance (Feb 12, 2024)
7-891035-G-T		not specified	Uncertain significance (Oct 31, 2022)
7-891050-G-A		not specified	Uncertain significance (Nov 20, 2024)
7-892310-C-T		not specified	Uncertain significance (Jun 10, 2022)
7-892317-C-T			Benign (May 15, 2018)
7-892348-A-G		not specified	Uncertain significance (Feb 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GET4	protein_coding	protein_coding	ENST00000265857	9	19885

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.562	0.438	125709	0	9	125718	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.168	184	191	0.966	0.0000123	2097
Missense in Polyphen		30	56.365	0.53224		610
Synonymous	-4.86	144	86.5	1.66	0.00000624	637
Loss of Function	2.93	3	15.4	0.194	6.59e-7	193

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000584	0.0000584
Ashkenazi Jewish	0.000101	0.0000993
East Asian	0.00	0.00
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.0000358	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000166	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: As part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, maintains misfolded and hydrophobic patches-containing proteins in a soluble state and participates to their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation (PubMed:20676083, PubMed:21636303, PubMed:21743475, PubMed:28104892). The BAG6/BAT3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane. Recruited to ribosomes, it interacts with the transmembrane region of newly synthesized tail-anchored proteins and together with SGTA and ASNA1 mediates their delivery to the endoplasmic reticulum (PubMed:20676083, PubMed:28104892, PubMed:25535373). Client proteins that cannot be properly delivered to the endoplasmic reticulum are ubiquitinated and sorted to the proteasome (PubMed:28104892). Similarly, the BAG6/BAT3 complex also functions as a sorting platform for proteins of the secretory pathway that are mislocalized to the cytosol either delivering them to the proteasome for degradation or to the endoplasmic reticulum (PubMed:21743475). The BAG6/BAT3 complex also plays a role in the endoplasmic reticulum-associated degradation (ERAD), a quality control mechanism that eliminates unwanted proteins of the endoplasmic reticulum through their retrotranslocation to the cytosol and their targeting to the proteasome. It maintains these retrotranslocated proteins in an unfolded yet soluble state condition in the cytosol to ensure their proper delivery to the proteasome (PubMed:21636303). {ECO:0000269|PubMed:20676083, ECO:0000269|PubMed:21636303, ECO:0000269|PubMed:21743475, ECO:0000269|PubMed:25535373, ECO:0000269|PubMed:28104892}.

Recessive Scores

• pRec: 0.0954

Intolerance Scores

• rvis_EVS: -1.27
• rvis_percentile_EVS: 5.24

Haploinsufficiency Scores

• pHI: 0.187
• hipred: Y
• hipred_score: 0.640
• ghis: 0.636

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.969

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Get4

Gene ontology

• Biological process: protein insertion into ER membrane;cytoplasmic sequestering of protein;tail-anchored membrane protein insertion into ER membrane;maintenance of unfolded protein involved in ERAD pathway
• Cellular component: nucleoplasm;nucleolus;cytoplasm;cytosol;BAT3 complex
• Molecular function: protein binding;chaperone binding