GET3

Chr 19AR

guided entry of tail-anchored proteins factor 3, ATPase

Also known as: ARSA-I, ARSA1, ASNA-I, ASNA1, CMD2H, TRC40

NCBI Gene: 439 ENSG00000198356 OMIM: 601913

The GET3 protein functions as an ATPase that delivers tail-anchored proteins from the cytosol to the endoplasmic reticulum by recognizing their transmembrane domains and facilitating their membrane insertion through ATP-dependent conformational changes. Biallelic mutations cause autosomal recessive dilated cardiomyopathy, though the complete phenotypic spectrum remains to be fully defined. The gene shows high constraint against loss-of-function variants, suggesting mutations predominantly cause disease through loss of function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene represents the human homolog of the bacterial arsA gene, encoding the arsenite-stimulated ATPase component of the arsenite transporter responsible for resistance to arsenicals. This protein is also a central component of a transmembrane domain (TMD) recognition complex (TRC) that is involved in the post-translational delivery of tail-anchored (TA) proteins from the cytosol to the endoplasmic reticulum (ER). It recognizes and selectively binds the TMD of TA proteins in the cytosol, and delivers them to the ER for insertion. [provided by RefSeq, Oct 2011]

OMIM ResearchGenerating clinical summary…

ARLOEUF 0.351 OMIM phenotype

Clinical Summary— GET3

🧬

Gene-Disease Validity (ClinGen)

cardiomyopathy, dilated, 2H · ARLimited

Limited evidence — not for standalone diagnostic reporting

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 31 VUS of 45 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.35LOEUF

pLI 0.943

Z-score 3.15

OE 0.07 (0.03–0.35)

Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.21Z-score

OE missense 0.57 (0.49–0.67)

120 obs / 210.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.07 (0.03–0.35)

0≤0.351.4

Missense OE?0.57 (0.49–0.67)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 1 / 13.5Missense obs/exp: 120 / 210.0Syn Z: -0.80

ClinVar Variant Classifications

45 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS31

Likely Benign1

Pathogenic

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	1	1	0	2
Likely Pathogenic	0	0	0	0
VUS	0	31	0	31
Likely Benign	0	0	1	1
Benign	0	0	0	0
Total	1	32	1	34

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

19 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap GET3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →