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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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NSRP1
nuclear speckle splicing regulatory protein 1
Chromosome 17 Β· 17q11.2
NCBI Gene: 84081Ensembl: ENSG00000126653.18HGNC: HGNC:25305UniProt: A0A024QZ33
74PubMed Papers
21Diseases
0Drugs
5Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
ribonucleoprotein complexmRNA bindingprotein bindingregulation of alternative mRNA splicing, via spliceosomeneurodevelopmental disorder with spasticity, seizures, and brain abnormalitiesmicrocephalySevere global developmental delaySeizure
✦AI Summary

NSRP1 (Nuclear Speckle Splicing Regulatory Protein 1) is an RNA-binding protein that regulates alternative pre-mRNA splicing with critical roles in development and disease. The protein functions as a splicing regulator in nuclear speckles, controlling the alternative processing of various RNA splicing factors including the oncogenic factor SRSF1 1. NSRP1 demonstrates tissue-specific expression patterns, being selectively expressed in developing thymocytes where it controls cell cycle and survival during T cell maturation 1. In breast cancer, NSRP1 acts as a tumor suppressor by regulating alternative splicing of genes like NUMB and NSD2, influencing interferon signaling pathways and epithelial-mesenchymal transition 23. Mechanistically, NSRP1 requires proper nuclear localization through C-terminal nuclear localization signals for function 45. Biallelic loss-of-function variants in NSRP1 cause a severe autosomal recessive neurodevelopmental disorder characterized by developmental delay, epilepsy, microcephaly, hypotonia, and spastic cerebral palsy 5. Milder phenotypes can result from missense variants affecting nuclear localization 4. The gene also hosts miR-423-5p, which regulates cardiac pacemaking through HCN4 targeting 6.

Sources cited
1
NSRP1 is selectively expressed in developing thymocytes and regulates alternative splicing of RNA splicing factors including SRSF1
PMID: 34037780
2
NSRP1 regulates alternative splicing of NSD2 and interferon signaling pathways in breast cancer
PMID: 39667501
3
NSRP1 acts as a metastasis suppressor by regulating NUMB alternative splicing and TGFΞ²/SMAD-mediated epithelial-mesenchymal transition
PMID: 35568738
4
Missense variants affecting nuclear localization can cause milder NSRP1-associated neurodevelopmental phenotypes
PMID: 38808951
5
Biallelic loss-of-function variants cause severe neurodevelopmental disorder with developmental delay, epilepsy, and spastic cerebral palsy
PMID: 34385670
6
NSRP1 hosts miR-423-5p which regulates cardiac pacemaking through HCN4 targeting
PMID: 28821541
Disease Associationsβ“˜21
neurodevelopmental disorder with spasticity, seizures, and brain abnormalitiesOpen Targets
0.64Moderate
microcephalyOpen Targets
0.45Moderate
SeizureOpen Targets
0.45Moderate
Severe global developmental delayOpen Targets
0.45Moderate
SpasticityOpen Targets
0.45Moderate
systemic lupus erythematosusOpen Targets
0.29Weak
spontaneous coronary artery dissectionOpen Targets
0.27Weak
chronic obstructive pulmonary diseaseOpen Targets
0.21Weak
information processing speedOpen Targets
0.18Weak
diabetes mellitusOpen Targets
0.16Weak
type 2 diabetes mellitusOpen Targets
0.13Weak
COVID-19Open Targets
0.09Suggestive
breast cancerOpen Targets
0.08Suggestive
Familial exudative vitreoretinopathyOpen Targets
0.05Suggestive
intelligenceOpen Targets
0.05Suggestive
response to statinOpen Targets
0.05Suggestive
X-linked retinal dysplasiaOpen Targets
0.04Suggestive
severe early-childhood-onset retinal dystrophyOpen Targets
0.04Suggestive
Stargardt diseaseOpen Targets
0.04Suggestive
Familial drusenOpen Targets
0.04Suggestive
Neurodevelopmental disorder with spasticity, seizures, and brain abnormalitiesUniProt
Pathogenic Variants5
NM_032141.4(NSRP1):c.1324del (p.Glu441_Val442insTer)Pathogenic
Neurodevelopmental disorder with spasticity, seizures, and brain abnormalities
β˜…β˜†β˜†β˜†2024β†’ Residue 441
NM_032141.4(NSRP1):c.1048_1054dup (p.Arg352delinsLysSerTer)Likely pathogenic
Neurodevelopmental disorder with spasticity, seizures, and brain abnormalities
β˜…β˜†β˜†β˜†2023β†’ Residue 352
NM_032141.4(NSRP1):c.24T>G (p.Tyr8Ter)Likely pathogenic
not specified
β˜…β˜†β˜†β˜†2022β†’ Residue 8
NM_032141.4(NSRP1):c.1272dup (p.Lys425fs)Pathogenic
Microcephaly;Seizure;Spasticity;Severe global developmental delay|Neurodevelopmental disorder with spasticity, seizures, and brain abnormalities
β˜†β˜†β˜†β˜†2022β†’ Residue 425
NM_032141.4(NSRP1):c.1359_1362del (p.Glu455fs)Pathogenic
Microcephaly;Seizure;Spasticity;Severe global developmental delay|Neurodevelopmental disorder with spasticity, seizures, and brain abnormalities
β˜†β˜†β˜†β˜†2022β†’ Residue 455
View on ClinVar β†—
Related Genes
CDC5LProtein interaction96%CTNNBL1Protein interaction77%EFCAB5Protein interaction73%TCF24Shared pathway33%BHLHA9Shared pathway33%ZNF674Shared pathway33%
Tissue Expression6 tissues
Heart
100%
Brain
75%
Lung
71%
Ovary
65%
Bone Marrow
62%
Liver
58%
Gene Interaction Network
Click a node to explore
NSRP1CDC5LCTNNBL1EFCAB5TCF24BHLHA9ZNF674
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q9H0G5
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.58Moderately Constrained
pLIβ“˜
0.53Intermediate
Observed/Expected LoF0.39 [0.27–0.58]
RankingsWhere NSRP1 stands among ~20K protein-coding genes
  • #6,416of 20,598
    Most Researched74
  • #3,549of 5,498
    Most Pathogenic Variants5
  • #3,899of 17,882
    Most Constrained (LOEUF)0.58 Β· top quartile
Genes detectedNSRP1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
NSrp70 is a lymphocyte-essential splicing factor that controls thymocyte development.
PMID: 34037780
Nucleic Acids Res Β· 2021
1.00
2
Downregulation of the splicing regulator NSRP1 confers resistance to CDK4/6 inhibitors via activation of interferon signaling in breast cancer.
PMID: 39667501
J Biol Chem Β· 2025
0.90
3
The CCDC55 couples cannabinoid receptor CNR1 to a putative DISC1 schizophrenia pathway.
PMID: 26475744
Neuroscience Β· 2015
0.80
4
A milder form of NSRP1-associated neurodevelopmental disorder, caused by a missense variant in the nuclear localization signal.
PMID: 38808951
Am J Med Genet A Β· 2024
0.70
5
Biallelic loss-of-function variants in the splicing regulator NSRP1 cause a severe neurodevelopmental disorder with spastic cerebral palsy and epilepsy.
PMID: 34385670
Genet Med Β· 2021
0.60