GET3

Chr 19AR

guided entry of tail-anchored proteins factor 3, ATPase

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

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.351 OMIM phenotype
Clinical SummaryGET3
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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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.35LOEUF
pLI 0.943
Z-score 3.15
OE 0.07 (0.030.35)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.21Z-score
OE missense 0.57 (0.490.67)
120 obs / 210.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.07 (0.030.35)
00.351.4
Missense OE0.57 (0.490.67)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 1 / 13.5Missense obs/exp: 120 / 210.0Syn Z: -0.80

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

GET3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗