# The role of Septin6 Group in Murine and Human Hematopoiesis

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2024 · $339,840

## Abstract

(PLEASE KEEP IN WORD, DO NOT PDF)
Title: The role of Septin6 Group in Murine and Human Hematopoiesis
1 R01 DK137172-01
Septins are highly conserved GTPase proteins which regulate a variety of cellular functions including cytokinesis, polarity, cell cycle, vesicle trafficking, exocytosis, and creation of diffusion barriers. We have recently identified a non-syndromic newborn with severe neutropenia (Renella, AJH 2022) with a novel X-linked germline mutation in the C-terminus of SEPTIN6 gene (SEPTIN6 c.1282T>C p.428Glnext*9) associated with dysmyelopoiesis. Editing the germline mutation into normal male CD34+ hematopoietic stem and progenitor cells (HSC/P) phenocopied key pathologic features of the clinical syndrome, including large, multinucleated nuclei and reduced myeloid progenitor growth in vitro (preliminary data). The C-terminus has been proposed to play a key role in filament stabilization, bundling and bending as well as interactions with other septins and in silico modeling suggest the addition of 9 amino acids (aa) associated with the SEPTIN6 c.1282T>C p.428Glnext*9 mutation would alter function by interfering with SEPTIN6 protein interactions. Based on our initial publication, a second patient with severe neutropenia has since been identified in Seattle with a distinct mutation in the same codon (SEPTIN6 c.1282T>A) (Mohamad, Allensbach, Williams, accepted for presentation, ASH 2022). While the aa substitution is different, modeling predicts that SEPTIN6 variants adopt the same structure. Both identified patients had a high degree of myeloid tetraploidy in the marrow and were refractory to G-CSF.

## Key facts

- **NIH application ID:** 10895582
- **Project number:** 5R01DK137172-02
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** DAVID A WILLIAMS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $339,840
- **Award type:** 5
- **Project period:** 2023-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10895582

## Citation

> US National Institutes of Health, RePORTER application 10895582, The role of Septin6 Group in Murine and Human Hematopoiesis (5R01DK137172-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10895582. Licensed CC0.

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