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SAMD9
sterile alpha motif domain containing 9
SAMD9 is located on the long (q) arm of chromosome 7, at band 7q21.2. Arm ratio per GRCh38 - banding schematic.
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Overview
SAMD9 (sterile alpha motif domain containing 9) is located on chromosome 7 and encodes a large protein of 1,589 amino acids involved in cellular regulation. The gene controls cell proliferation and supports immune system function, particularly in the development and maintenance of blood cells. Pathogenic variants in SAMD9 are associated with rare inherited conditions affecting bone marrow function and immunity, following an autosomal dominant inheritance pattern. The gene appears on multiple NHS Genomic Medicine Service panels related to cytopenia, immunodeficiency, and developmental disorders, reflecting its clinical significance in paediatric medicine.
What the gene does
The SAMD9 protein functions as a negative regulator of cell growth and proliferation, helping to control when cells divide and how they respond to external signals. Evidence suggests the protein plays a role in restricting cellular responses to certain growth factors and inflammatory signals, thereby maintaining appropriate immune cell populations. The protein appears to be particularly important during haematopoiesis, the process by which blood cells are formed in the bone marrow. Research indicates SAMD9 may influence the interferon signalling pathway, which is critical for antiviral immune responses and regulation of cell growth. When the protein functions normally, it helps ensure balanced production of white blood cells, red blood cells, and platelets. Disruption of SAMD9 function can therefore lead to abnormalities in blood cell counts and immune system performance.
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Chromosome location
SAMD9 is located at chromosomal position 7q21.2 on the long arm of chromosome 7. This region of chromosome 7 contains several genes involved in immune regulation and cellular growth control. The genomic organisation and detailed exon structure of SAMD9 contribute to the generation of the full-length protein through standard transcription and splicing mechanisms.
Protein structure
The SAMD9 protein contains a SAM (sterile alpha motif) domain near its N-terminus, spanning amino acids 14 to 78. The SAM domain is a protein interaction module found in many signalling and regulatory proteins, enabling SAMD9 to interact with other cellular components. A disordered region extends from amino acids 83 to 135, which may provide flexibility for protein interactions or regulatory modifications. The remaining bulk of the 1,589-amino-acid protein likely contains additional functional elements that contribute to its role in growth regulation, though detailed structural characterisation of these regions remains an area of ongoing research.
Key variants
Pathogenic variants in SAMD9 typically result in gain-of-function effects, meaning the altered protein has increased or abnormal activity that disrupts normal cellular regulation. Most disease-causing variants are de novo mutations, arising newly in an affected individual rather than being inherited from a parent. The spectrum of SAMD9 variants is associated with variable clinical presentations, ranging from isolated cytopenia to more complex syndromes involving growth restriction and developmental features.
No pathogenic or likely-pathogenic ClinVar variants recorded yet for this gene.
Associated conditions
SAMD9-related disorders encompass a spectrum of conditions primarily affecting bone marrow function and immune system development. These conditions are characterised by low blood cell counts (cytopenia), which can involve reduced numbers of white blood cells, red blood cells, or platelets. Some individuals with SAMD9 variants also experience growth restriction, developmental differences, or increased susceptibility to infections due to impaired immune function. The severity and specific features can vary considerably between affected individuals, even within the same family. Early recognition of SAMD9-related conditions is important for appropriate monitoring and supportive care.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic SAMD9 variants typically follow autosomal dominant inheritance.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
UK clinical status
SAMD9 appears on numerous NHS Genomic Medicine Service gene panels, reflecting its broad clinical relevance. The gene is included on panels for cytopenia disorders, including the Cytopenia - NOT Fanconi anaemia panel (R91) and Cytopenias and congenital anaemias panel. It also features on the Primary immunodeficiency or monogenic inflammatory bowel disease panel (R15), recognising its role in immune function. Additional panel memberships include Intellectual disability (R29), Fetal anomalies (R21), Differences in sex development (R146), and Congenital adrenal hypoplasia (R150), indicating the diverse clinical presentations that may prompt SAMD9 testing. SAMD9 has achieved green classification status across these panels, meaning there is strong evidence supporting its role in the associated conditions and its inclusion in NHS diagnostic pathways.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
How is SAMD9 inherited?
SAMD9-related conditions follow an autosomal dominant pattern, meaning a pathogenic variant in one copy of the gene is sufficient to cause disease. Many cases result from new (de novo) variants rather than inheritance from a parent.
What types of blood cell problems can SAMD9 variants cause?
SAMD9 variants can lead to low counts of various blood cell types, including white blood cells, red blood cells, and platelets. The specific pattern and severity of cytopenia varies between individuals.
Why is SAMD9 on so many different NHS gene panels?
SAMD9 appears on multiple panels because pathogenic variants can produce diverse clinical features affecting blood counts, immune function, growth, and development. This broad clinical spectrum means the gene is relevant to several different diagnostic pathways in the NHS Genomic Medicine Service.