AUP1

protein-coding

AUP1 lipid droplet regulating VLDL assembly factor

Gene summary

The protein encoded this gene is involved in several pathways including quality control of misfolded proteins in the endoplasmic reticulum and lipid droplet accumulation. Lipid droplets are organelles in the cytoplasm that store neutral lipids such as cholesterol esters and trigylycerides to prevent the overabundance of free cholesterol and fatty acids in cells, but also to act as storage for other metabolic processes, such as membrane biogenesis. Reduced expression of this gene results in reduced lipid droplet clustering, a function that is dependent on ubiquitination of the protein. This protein contains multiple domains including a hydrophobic N-terminal domain, an acetyltranferase domain, a ubiquitin-binding CUE domain, and a UBE2B2-binding domain (G2BR). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

MANE transcript

NM_181575.5

Inheritance

—

ClinVar variants

U:85B:2

Top phenotype

Parkinson disease 13, autosomal dominant, susceptibility to

gnomAD constraint

pLI —, LoF o/e 0.45

Max pathogenic AF

—

Genomic locus

chr2:74,526,645-74,529,760

External References & Databases

Ensembl (ENSG00000115307)

Transcript & Mutation Effects

hg38 • Region Span ~3.1 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 AUP1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 65

not providedTotal: 4

Parkinson disease 13, autosomal dominant, susceptibility toTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_181575.5. 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			4 clinvar	1 clinvar		5
missense			69 clinvar	1 clinvar		70
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			11 clinvar			11
Total	0	0	85	2	0	87

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 94 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_181575.5	RefSeq	NP_853553.1	12	MANE Select
ENST00000377526.4	Ensembl	ENSP00000366748.3	12	MANE Select
ENST00000425118.5	Ensembl	ENSP00000403430.1	11	Standard
ENST00000890021.1	Ensembl	ENSP00000560080.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

ubiquitin-dependent ERAD pathway
retrograde protein transport, ER to cytosol
regulation of catalytic activity

Molecular Function

protein binding
ubiquitin binding
ubiquitin-protein transferase activator activity

Cellular Component

Hrd1p ubiquitin ligase ERAD-L complex
membrane
integral component of endoplasmic reticulum membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377526
Coding exons: 12
Length: 3295
Individuals with no LoFs: 124785
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 124798
p: 0.0000521

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.586	212	237	0.893	0.0000129	2595
Missense (PolyPhen)		70	95.708	0.73139		1061
Synonymous	0.117	93	94.4	0.985	0.00000466	879
Loss of Function	2.41	10	22.3	0.448	0.00000105	241

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00019	0.00019	rare
European (Non-Finnish)	0.000054	0.000053	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in the translocation of terminally misfolded proteins from the endoplasmic reticulum lumen to the cytoplasm and their degradation by the proteasome. {ECO:0000269|PubMed:18711132}.;

Recessive Scores

pRec: 0.120

Intolerance Scores

LoFtool: 0.246
RVIS EVS: 0.22
RVIS percentile EVS: 68.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.823

Gene Damage Prediction

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