GET1

protein-coding

guided entry of tail-anchored proteins factor 1, the group of Guided entry of tail-anchored proteins complex subunits

Gene summary

This gene is located in the candidate region for congenital heart disease (CHD) in Down syndrome (DS). It encodes a basic protein that functions as a receptor that promotes insertion of tail-anchored proteins in the endoplasmic reticulum membrane. This gene is located at a maternally-methylated differentially methylated region (DMR); however, its transcription may be biallelic, not imprinted. Alternative splicing results in different transcript variants. A pseudogene has been defined on chromosome 4. [provided by RefSeq, Apr 2017]

Previous symbols:

MANE transcript

NM_004627.6

Inheritance

—

ClinVar variants

U:37

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr21:39,377,698-39,428,528

External References & Databases

Ensembl (ENSG00000182093)

Transcript & Mutation Effects

hg38 • Region Span ~50.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GET1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 33

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004627.6. 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			1 clinvar			1
missense			33 clinvar			33
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	37	0	0	37

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004627.6	RefSeq	NP_004618.2	5	MANE Select
ENST00000649170.1	Ensembl	ENSP00000496813.1	5	MANE Select
NM_001146218.3	RefSeq	NP_001139690.1	4	Standard
NM_001350293.1	RefSeq	NP_001337222.1	5	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
wrb	Danio rerio	Structure: neuromast hair cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

wrb

Danio rerio

Structure: neuromast hair cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

tail-anchored membrane protein insertion into ER membrane

Cellular Component

nucleus
endoplasmic reticulum membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000333781
Coding exons: 5
Length: 48285
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125747
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.618	85	103	0.828	0.00000558	1136
Missense (PolyPhen)		16	21.796	0.73408		264
Synonymous	-1.44	54	42.1	1.28	0.00000276	327
Loss of Function	1.11	6	9.73	0.616	4.22e-7	110

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for ASNA1/TRC40-mediated insertion of tail- anchored (TA) proteins into the ER membrane. {ECO:0000269|PubMed:21444755}.;

Recessive Scores

pRec: 0.149

Intolerance Scores

LoFtool: 0.749
RVIS EVS: -0.03
RVIS percentile EVS: 51.4

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.450

Gene Damage Prediction

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