GET4

protein-coding

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

Gene summary

Enables protein carrier activity and protein-folding chaperone binding activity. Involved in several processes, including post-translational protein targeting to endoplasmic reticulum membrane; protein catabolic process; and tail-anchored membrane protein insertion into ER membrane. Located in cytosol. Part of BAT3 complex. Implicated in congenital disorder of glycosylation type IIy. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

C7orf20

MANE transcript

NM_015949.3

Inheritance

ClinVar variants

U:67B:10

Top phenotype

Congenital disorder of glycosylation,, type IIy

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr7:876,554-896,436

External References & Databases

Ensembl (ENSG00000239857)

Transcript & Mutation Effects

hg38 • Region Span ~19.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital disorder of glycosylation, type IIyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859356

Submitter: Ambry Genetics

congenital disorder of glycosylation, type IIyLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0859356

Submitter: Labcorp Genetics (formerly Invitae)

congenital disorder of glycosylation, type IIyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859356

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Congenital disorder of glycosylation,, type IIyAR

Manifestation: Biochemical; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: General

Rationale: 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

Refs: 32395830

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GET4 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 66

not providedTotal: 9

Congenital disorder of glycosylation, type IIyTotal: 3

GET4 deficiencyTotal: 2

GET4-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015949.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				7 clinvar	2 clinvar	9
missense			65 clinvar	1 clinvar		66
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	67	8	2	77

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015949.3	RefSeq	NP_057033.2	9	MANE Select
ENST00000265857.8	Ensembl	ENSP00000265857.3	9	MANE Select
ENST00000407192.5	Ensembl	ENSP00000385646.1	8	Standard
ENST00000407192.6	Ensembl	ENSP00000385646.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

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

Molecular Function

protein binding
chaperone binding

Cellular Component

nucleoplasm
nucleolus
cytoplasm
cytosol
BAT3 complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265857
Coding exons: 9
Length: 19885
Individuals with no LoFs: 125709
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 125718
p: 0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.168	184	191	0.966	0.0000123	2097
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0	0.0	absent
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.969

Gene Damage Prediction

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