Exspanding the Knowledge About TNPO2-Associated Disorders (Target-TNPO2)

Development of New Therapeutic Approaches for TNPO2-Associated Disorders

The Target-TNPO2 is an international, multicenter observational registry designed to collect comprehensive clinical, genetic, neurodevelopmental, and longitudinal data from individuals with pathogenic or likely pathogenic variants in the TNPO2 gene.

This aids to improve the knowledge and clinical progression on TNPO2-associated disorders.

The investigators further aim to provide new insides into the pathomechanism of TNPO2 variants using blood samples.

Study Overview

• Status: Recruiting
• Conditions: TNPO2

Detailed Description

Transportin-2 (TNPO2) encodes a member of the importin-β family of nuclear transport receptors, which mediate the selective transport of proteins containing nuclear localization signals from the cytoplasm into the nucleus. Nucleocytoplasmic transport is essential for numerous cellular processes, including gene regulation, RNA metabolism, cell differentiation, and neuronal development. Proper nuclear import is particularly critical during embryonic brain development, where tightly regulated trafficking of transcription factors and RNA-binding proteins is required for normal neurodevelopment.

Pathogenic germline variants in TNPO2 have recently been identified as the cause of a rare neurodevelopmental disorder. Reported individuals commonly present with global developmental delay, intellectual disability, hypotonia, delayed motor and language development, epilepsy in a subset of patients, and variable behavioral abnormalities, including features of autism spectrum disorder and schizophrenia. Additional manifestations, such as movement disorders, feeding difficulties, and dysmorphic features, have been described in some individuals. However, the phenotypic spectrum, disease mechanisms, and long-term clinical course remain incompletely understood due to the limited number of reported cases.

As additional patients are identified through genome and exome sequencing, the spectrum of TNPO2-associated disorders is expected to expand. Systematic collection of standardized clinical and molecular data is therefore essential to improve understanding of disease pathogenesis, define genotype-phenotype correlations, and establish evidence-based recommendations for clinical care.

Purpose of the Registry The TNPO2- Registry is an international, multicenter observational registry designed to collect comprehensive clinical, genetic, neurodevelopmental, and longitudinal data from individuals with pathogenic or likely pathogenic variants in the TNPO2 gene, as well as selected individuals with variants of uncertain significance supported by compatible clinical phenotypes.

The registry aims to create a centralized resource that facilitates collaboration among clinicians, researchers, and patient organizations while advancing knowledge of the natural history, clinical variability, and molecular basis of TNPO2-associated disorders.

Aditionally this study aims to characterize the variants and identify the underlying pathomachanism that is causative for the disorder using PBMCs from patients. These findings aim to test multiple FDA approved drugs to identify novel treatment options.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Lena-Luise Becker, Dr. med.; Phone Number: 0049 30 450 566 112; Email: lena-luise.becker@charite.de
• Study Contact Backup: Name: Angela M. Kaindl, Prof. Dr.; Phone Number: 0049 30 450 566112; Email: angela.kaindl@charite.de

Study Locations

• Germany
  • State of Berlin
    • Berlin, State of Berlin, Germany, 13353
      • Recruiting
      • Charite- Universitatsmedizin Berlin
      • Contact: Lena-Luise Becker, Dr. med.; Phone Number: 004903450566112; Email: lena-luise.becker@charite.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

All patients with variants in the TNPO2 gene.

Description

Inclusion Criteria:

• TNPO2 variant

Exclusion Criteria:

• no consent

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
intelligence quotient	Developmental Outcome using standardized testing (BAYLEY III or WISC-V)	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psychiatric disorders	Number of patients with a psychiatric disorders	10 years
Functional anaylsis of variants	Number of gain-of-function variants in cohort	2 years

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2026
• Primary Completion (Estimated): June 30, 2036
• Study Completion (Estimated): December 31, 2036

Study Registration Dates

• First Submitted: July 2, 2026
• First Submitted That Met QC Criteria: July 8, 2026
• First Posted (Actual): July 13, 2026

Study Record Updates

• Last Update Posted (Actual): July 13, 2026
• Last Update Submitted That Met QC Criteria: July 8, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: TNPO2
• Other Study ID Numbers: Target-TNPO2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No