NSRP1

Chr 17

nuclear speckle splicing regulatory protein 1

Also known as: CCDC55, HSPC095, NEDSSBA, NSrp70

NCBI Gene: 84081 ENSG00000126653 UniProt: Q9H0G5

The NSRP1 protein is an RNA-binding protein that regulates alternative splicing of pre-mRNA and is localized to nuclear speckles as part of ribonucleoprotein complexes. Mutations cause autosomal recessive neurodevelopmental disorder with spasticity, seizures, and brain abnormalities. This condition primarily affects the central nervous system with early developmental onset.

ResearchSummary from RefSeq, OMIM, UniProt

Enables mRNA binding activity. Involved in developmental process and regulation of alternative mRNA splicing, via spliceosome. Located in nuclear speck. Part of ribonucleoprotein complex. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with spasticity, seizures, and brain abnormalities

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · neurodevelopmental disorder with spasticity, seizures, and brain abnormalities · AR · ClinGen 2024

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.58

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.58LOEUF

pLI 0.012

Z-score 3.16

OE 0.32 (0.19–0.58)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.15Z-score

OE missense 0.98 (0.88–1.08)

273 obs / 279.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.32 (0.19–0.58)

0≤0.351.4

Missense OE?0.98 (0.88–1.08)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 8 / 25.1Missense obs/exp: 273 / 279.9Syn Z: -0.47

Background carrier burden — how many people carry a rare variant somewhere in NSRP1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 80

687 rare PASS variants

Rare truncating (LoF)

1 in 1,100

96 rare PASS variants

Rare synonymous (reference)

1 in 210

237 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NSRP1. 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 120	1 in 1,100
South Asian	~43k	1 in 73	1 in 640
Remaining (unassigned)	~30k	1 in 69	1 in 740
European (Finnish)	~27k	1 in 260	1 in 1,300
Admixed American	~22k	1 in 78	1 in 750
African / African American	~21k	1 in 88	1 in 720
East Asian	~20k	1 in 97	1 in 2,500
Ashkenazi Jewish	~13k	1 in 220	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 75	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): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓