PSPC1

Chr 13

paraspeckle component 1

Also known as: PSP1

NCBI Gene: 55269 ENSG00000121390 UniProt: Q8WXF1

The protein is an RNA-binding protein required for formation of nuclear paraspeckles and regulates gene transcription, circadian clock function, and antiviral immune responses. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delay. This gene is highly constrained against loss-of-function mutations (pLI = 0.99), indicating that such variants are likely to be pathogenic.

ResearchSummary from RefSeq, UniProt

This gene encodes a nucleolar protein that localizes to punctate subnuclear structures that occur close to splicing speckles, known as paraspeckles. These paraspeckles are composed of RNA-protein structures that include a non-coding RNA, NEAT1/Men epsilon/beta, and the Drosophila Behavior Human Splicing family of proteins, which include the product of this gene and the P54NRB/NONO and PSF/SFPQ proteins. Paraspeckles may function in the control of gene expression via an RNA nuclear retention mechanism. The protein encoded by this gene is found in paraspeckles in transcriptionally active cells, but it localizes to unique cap structures at the nucleolar periphery when RNA polymerase II transcription is inhibited, or during telophase. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene, which is also located on chromosome 13, has been identified. [provided by RefSeq, Aug 2011]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.28

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.28LOEUF

pLI 0.990

Z-score 4.03

OE 0.09 (0.04–0.28)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.53Z-score

OE missense 0.59 (0.52–0.67)

177 obs / 300.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.09 (0.04–0.28)

0≤0.351.4

Missense OE?0.59 (0.52–0.67)

0≤0.61.4

Synonymous OE?1.12

0≤1.21.6

LoF obs/exp: 2 / 22.7Missense obs/exp: 177 / 300.1Syn Z: -0.93

Background carrier burden — how many people carry a rare variant somewhere in PSPC1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

493 rare PASS variants

Rare truncating (LoF)

1 in 1,100

33 rare PASS variants

Rare synonymous (reference)

1 in 110

215 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PSPC1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 260	1 in 4,600
South Asian	~43k	1 in 170	≈ 1 in 12,000
Remaining (unassigned)	~30k	1 in 150	1 in 490
European (Finnish)	~27k	1 in 500	none seen
Admixed American	~22k	1 in 200	1 in 1,600
African / African American	~21k	1 in 210	1 in 520
East Asian	~20k	1 in 190	1 in 2,100
Ashkenazi Jewish	~13k	1 in 370	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 330	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 7 of 9 coding exons well covered in gnomAD exomes; exons 4, 5 marginal. Genomes: all 9.? see exons ↓