PAAF1

protein-coding

proteasomal ATPase associated factor 1, the group of WD repeat domain containing

Gene summary

This gene encodes a WD repeat-containing protein involved in regulation of association of proteasome components. During HIV infection, the encoded protein is thought to promote provirus transcription through recruitment of the 19S regulatory complex. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2012]

Previous symbols:

WDR71

MANE transcript

NM_025155.3

Inheritance

—

ClinVar variants

U:50B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.82

Max pathogenic AF

—

Genomic locus

chr11:73,876,699-73,931,114

External References & Databases

Ensembl (ENSG00000175575)

Transcript & Mutation Effects

hg38 • Region Span ~54.4 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 PAAF1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 47

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_025155.3. 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				1 clinvar		1
missense			48 clinvar			48
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	50	1	0	51

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 53 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_025155.3	RefSeq	NP_079431.1	12	MANE Select
ENST00000310571.8	Ensembl	ENSP00000311665.4	12	MANE Select
NM_001267803.2	RefSeq	NP_001254732.1	11	Standard
NM_001267804.2	RefSeq	NP_001254733.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

viral process

Molecular Function

protein binding

Cellular Component

proteasome complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000310571
Coding exons: 12
Length: 51047
Individuals with no LoFs: 125424
Homozygous LoFs: 3
Heterozygous LoFs: 321
Defined: 125748
p: 0.00129

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.925	176	214	0.822	0.0000109	2535
Missense (PolyPhen)		51	60.197	0.84722		651
Synonymous	0.690	71	78.8	0.901	0.00000402	773
Loss of Function	0.787	18	22.0	0.819	0.00000110	260

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00051	0.00049	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00071	0.00065	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00019	0.00019	rare
South Asian	0.0092	0.0086	notable
Other	0.00099	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Inhibits proteasome 26S assembly and proteolytic activity by impairing the association of the 19S regulatory complex with the 20S core. In case of HIV-1 infection, recruited by viral Tat to the HIV-1 promoter, where it promotes the recruitment of 19S regulatory complex through dissociation of the proteasome 26S. This presumably promotes provirus transcription efficiency. Protects SUPT6H from proteasomal degradation. {ECO:0000269|PubMed:15831487, ECO:0000269|PubMed:17289585, ECO:0000269|PubMed:22316138}.;

Recessive Scores

pRec: 0.104

Intolerance Scores

LoFtool: 0.814
RVIS EVS: 0.24
RVIS percentile EVS: 69.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0192

Gene Damage Prediction

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