SAMD9L | ENSG00000177409 | NCBI 219285

Details for: SAMD9L

Gene ID: 219285

Gene Type: Protein-coding - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: SAMD9L

Ensembl ID: ENSG00000177409

Description: sterile alpha motif domain containing 9 like

Cell Significance Landscape

Display Count:

Associated with

Cytoplasm
(GO:0005737)
Early endosome
(GO:0005769)
Mitochondrion
(GO:0005739)
Protein binding
(GO:0005515)

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

CD14-positive, CD16-positive monocyte CL0002397

CSI 20.55

rCSI 26.93%

PRS 79.56
T follicular helper cell CL0002038

CSI 11.64

rCSI 8.71%

PRS 81.24
erythrocyte CL0000232

CSI 10.23

rCSI 23.21%

PRS 69.35
lung macrophage CL1001603

CSI 8.85

rCSI 19.77%

PRS 74.26
granulocyte CL0000094

CSI 7.72

rCSI 11.79%

PRS 75.67
group 3 innate lymphoid cell CL0001071

CSI 7.52

rCSI 5.65%

PRS 72.23
class switched memory B cell CL0000972

CSI 6.01

rCSI 4.49%

PRS 82.16
goblet cell CL0000160

CSI 5.64

rCSI 5.33%

PRS 65.53
mature T cell CL0002419

CSI 5.32

rCSI 4.14%

PRS 83.45
CD4-positive, alpha-beta thymocyte CL0000810

CSI 4.82

rCSI 3.86%

PRS 85.12
alpha-beta T cell CL0000789

CSI 4.54

rCSI 5.32%

PRS 82.21
fallopian tube secretory epithelial cell CL4030006

CSI 4.39

rCSI 4.22%

PRS 66.13
tracheal goblet cell CL1000329

CSI 4.28

rCSI 9.34%

PRS 78.16
pulmonary capillary endothelial cell CL4028001

CSI 4.2

rCSI 8.01%

PRS 80.35
astrocyte of the cerebral cortex CL0002605

CSI 3.98

rCSI 8.92%

PRS 48.38
microcirculation associated smooth muscle cell CL0008035

CSI 3.97

rCSI 11.49%

PRS 67.35
blood vessel smooth muscle cell CL0019018

CSI 3.91

rCSI 31.78%

PRS 59.76
effector CD8-positive, alpha-beta T cell CL0001050

CSI 3.9

rCSI 2.96%

PRS 79.68
effector memory CD8-positive, alpha-beta T cell, terminally differentiated CL0001062

CSI 3.82

rCSI 19.18%

PRS 79.16
CD16-positive, CD56-dim natural killer cell, human CL0000939

CSI 3.77

rCSI 2.51%

PRS 84.44
parietal epithelial cell CL1000452

CSI 3.66

rCSI 9.78%

PRS 57.18
myeloid dendritic cell CL0000782

CSI 3.25

rCSI 4.7%

PRS 81.86
CD14-positive monocyte CL0001054

CSI 3.1

rCSI 3.86%

PRS 77.02
activated type II NK T cell CL0000931

CSI 3.05

rCSI 3.43%

PRS 82.51
alternatively activated macrophage CL0000890

CSI 3.01

rCSI 3.78%

PRS 77.98
double negative thymocyte CL0002489

CSI 3

rCSI 2.08%

PRS 77.87
naive T cell CL0000898

CSI 2.97

rCSI 2.07%

PRS 81.66
secretory cell CL0000151

CSI 2.96

rCSI 3.09%

PRS 66.46
hematopoietic multipotent progenitor cell CL0000837

CSI 2.81

rCSI 6.75%

PRS 83.03
nasal mucosa goblet cell CL0002480

CSI 2.73

rCSI 3.17%

PRS 73.26
CD4-positive, CD25-positive, alpha-beta regulatory T cell CL0000792

CSI 2.63

rCSI 2.58%

PRS 82.04
ciliated cell CL0000064

CSI 2.57

rCSI 4.16%

PRS 62.52
CD4-positive, alpha-beta memory T cell CL0000897

CSI 2.5

rCSI 1.79%

PRS 80.48
BEST4+ enteroycte CL4030026

CSI 2.37

rCSI 2.95%

PRS 67.99
plasmacytoid dendritic cell, human CL0001058

CSI 2.35

rCSI 1.64%

PRS 69.35
intestine goblet cell CL0019031

CSI 2.26

rCSI 2%

PRS 64.16
CD14-low, CD16-positive monocyte CL0002396

CSI 2.24

rCSI 1.72%

PRS 67.51
monocyte CL0000576

CSI 2.21

rCSI 4%

PRS 78.32
Kupffer cell CL0000091

CSI 2.17

rCSI 4.96%

PRS 66.53
central memory CD8-positive, alpha-beta T cell CL0000907

CSI 2.15

rCSI 1.45%

PRS 79.95
double-positive, alpha-beta thymocyte CL0000809

CSI 2.11

rCSI 2.15%

PRS 78.3
central memory CD4-positive, alpha-beta T cell CL0000904

CSI 2.09

rCSI 1.24%

PRS 83.58
retinal blood vessel endothelial cell CL0002585

CSI 2.09

rCSI 3.34%

PRS 70.74
lung interstitial macrophage CL4033043

CSI 2.04

rCSI 4.57%

PRS 82.43
plasmablast CL0000980

CSI 2.02

rCSI 1.59%

PRS 73.09
Schwann cell CL0002573

CSI 1.97

rCSI 5.61%

PRS 64.22
elicited macrophage CL0000861

CSI 1.96

rCSI 1.8%

PRS 75.45
squamous epithelial cell CL0000076

CSI 1.92

rCSI 4.57%

PRS 69.38
kidney interstitial alternatively activated macrophage CL1000695

CSI 1.87

rCSI 4.89%

PRS 66.17
blood vessel endothelial cell CL0000071

CSI 1.86

rCSI 3.86%

PRS 63.42
hematopoietic stem cell CL0000037

CSI 1.82

rCSI 1.21%

PRS 69.39
immature B cell CL0000816

CSI 1.78

rCSI 1.32%

PRS 79.74
hematopoietic precursor cell CL0008001

CSI 1.75

rCSI 1.8%

PRS 81.69
cerebral cortex endothelial cell CL1001602

CSI 1.73

rCSI 2.99%

PRS 56.67
transitional stage B cell CL0000818

CSI 1.73

rCSI 5.65%

PRS 88.45
intermediate monocyte CL0002393

CSI 1.72

rCSI 2.59%

PRS 71.19
cardiac endothelial cell CL0010008

CSI 1.72

rCSI 6.93%

PRS 65.44
mature B cell CL0000785

CSI 1.61

rCSI 1.4%

PRS 77.22
mononuclear phagocyte CL0000113

CSI 1.61

rCSI 3.53%

PRS 70.41
megakaryocyte-erythroid progenitor cell CL0000050

CSI 1.46

rCSI 1.32%

PRS 63.53
lung endothelial cell CL1001567

CSI 1.46

rCSI 3.4%

PRS 82.91
multi-ciliated epithelial cell CL0005012

CSI 1.45

rCSI 1.45%

PRS 59.84
activated CD4-positive, alpha-beta T cell, human CL0001043

CSI 1.4

rCSI 3.38%

PRS 92.62
dendritic cell, human CL0001056

CSI 1.31

rCSI 2.01%

PRS 75.72
T-helper 17 cell CL0000899

CSI 1.3

rCSI 1.03%

PRS 86.59
CD8-positive, alpha-beta cytotoxic T cell CL0000794

CSI 1.3

rCSI 1.55%

PRS 84.86
IgG plasma cell CL0000985

CSI 1.25

rCSI 1.5%

PRS 81.67
alveolar macrophage CL0000583

CSI 1.19

rCSI 1.96%

PRS 71.66
myeloid leukocyte CL0000766

CSI 1.15

rCSI 1.06%

PRS 68.16
activated CD8-positive, alpha-beta T cell, human CL0001049

CSI 1.12

rCSI 1.91%

PRS 83.18
antibody secreting cell CL0000946

CSI 1.08

rCSI 4.79%

PRS 92.88
vasa recta ascending limb cell CL1001131

CSI 1.05

rCSI 4.74%

PRS 80.76
myeloid dendritic cell, human CL0001057

CSI 0.99

rCSI 5.56%

PRS 86.53
CD1c-positive myeloid dendritic cell CL0002399

CSI 0.97

rCSI 1.17%

PRS 75.31
Hofbauer cell CL3000001

CSI 0.88

rCSI 1.66%

PRS 76.66
mature alpha-beta T cell CL0000791

CSI 0.86

rCSI 3.13%

PRS 85.12
erythroid lineage cell CL0000764

CSI 0.76

rCSI 4.89%

PRS 82.07
exhausted T cell CL0011025

CSI 0.54

rCSI 9.13%

PRS 85.08
CD14-positive, CD16-negative classical monocyte CL0002057

CSI 0.53

rCSI 3.23%

PRS 83.34
cytotoxic T cell CL0000910

CSI 0.22

rCSI 1.26%

PRS 74.7

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Context Genes (max 20):

Interaction Source:

Pathway Categories (for ONTOLOGY source):

Baseline Cell Type:

Baseline Cell Context(s): Comma-separated if multiple.

Target Cell Type:

Target Cell Context(s): Comma-separated if multiple.

Legend:

Query Gene
Node Color (Target Cell CSI, relative to current network):
- Very High
- High
- Medium
- Low
- Very Low
- CSI N/A
Node Size: Proportional to Target Cell CSI magnitude
STRING PPI Edge
Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

Description
Proteins

## Summary [SAMD9L](/details-gene/219285) (Sterile Alpha Motif Domain Containing 9 Like) is a protein-coding gene located on human chromosome 7q21.2. Functionally, it is implicated in endosomal and mitochondrial processes, with established roles in protein binding. Expression data from the **Overall** context highlights its significant role in the hematopoietic system, where it is a particularly strong marker for [CD14-positive, CD16-positive monocyte](/details-cell/CL0002397). Its importance extends to other immune cell types, including [T follicular helper cell](/details-cell/CL0002038) and [lung macrophage](/details-cell/CL1001603). Clinically, mutations in [SAMD9L](/details-gene/219285) are associated with severe genetic disorders, including Ataxia-pancytopenia syndrome ([252270](https://omim.org/entry/252270)) and Myelodysplastic syndrome ([159550](https://omim.org/entry/159550)), underscoring its critical function in both hematopoiesis and neurological homeostasis ([Link](https://doi.org/10.1016/j.ajhg.2016.04.009); [Link](https://doi.org/10.1016/j.ccr.2013.08.011)). ## Cellular Roles and Expression Landscape The expression profile of [SAMD9L](/details-gene/219285) indicates a prominent role in the immune system, particularly within the myeloid lineage. In the **Overall** context, it shows the highest significance in [CD14-positive, CD16-positive monocyte](/details-cell/CL0002397) (CSI: 20.55), suggesting it is a key component of the molecular machinery in this cell type. Its importance is further emphasized by high significance scores in other myeloid cells such as [lung macrophage](/details-cell/CL1001603) and [granulocyte](/details-cell/CL0000094). Beyond the myeloid compartment, [SAMD9L](/details-gene/219285) is also a significant marker in several lymphoid populations, including [T follicular helper cell](/details-cell/CL0002038), [group 3 innate lymphoid cell](/details-cell/CL0001071), [class switched memory B cell](/details-cell/CL0000972), and various T cell subsets. This suggests a broad, yet specific, function across both innate and adaptive immunity. Interestingly, the gene also shows notable expression in non-hematopoietic cells such as [erythrocyte](/details-cell/CL0000232), [goblet cell](/details-cell/CL0000160), and [pulmonary capillary endothelial cell](/details-cell/CL4028001), pointing towards more widespread physiological roles than immunology alone. ## Pathways and Molecular Function Functional annotations indicate that the [SAMD9L](/details-gene/219285) protein is primarily located in the [cytoplasm](/details-cell/GO:0005737), with specific enrichment in the [early endosome](/details-cell/GO:0005769) and [mitochondrion](/details-cell/GO:0005739). Its primary molecular function is annotated as [protein binding](/details-cell/GO:0005515). This localization is consistent with published research. Studies have described [SAMD9L](/details-gene/219285) as an endosome fusion facilitator, a role that aligns with its high expression in professional phagocytes like monocytes and macrophages, which rely on endosomal trafficking for antigen processing and presentation ([Link](https://doi.org/10.1016/j.ccr.2013.08.011)). Furthermore, the mitochondrial localization is supported by findings that link mutations in [SAMD9L](/details-gene/219285) to mitochondrial dysregulation in a novel subtype of spinocerebellar ataxia ([Link](https://doi.org/10.1093/braincomms/fcac030)). These dual roles in endosomal and mitochondrial pathways suggest [SAMD9L](/details-gene/219285) may act as a crucial regulator at the interface of cellular trafficking, metabolism, and immune signaling. ## Research Directions The established links between [SAMD9L](/details-gene/219285) mutations, hematological malignancies, and neurological syndromes provide a strong basis for further investigation. Its high significance in myeloid cells suggests that its dysfunction could be a primary driver of these pathologies. **Testable Hypotheses:** 1. Given its role as an endosome fusion facilitator and its high expression in monocytes, haploinsufficiency of [SAMD9L](/details-gene/219285) may impair phagosome maturation and subsequent antigen presentation, leading to a compromised immune surveillance state that permits the outgrowth of malignant hematopoietic clones. 2. Considering its mitochondrial localization and association with Ataxia-pancytopenia syndrome, pathogenic mutations in [SAMD9L](/details-gene/219285) likely disrupt critical mitochondrial quality control pathways (e.g., mitophagy) in hematopoietic stem cells and neurons, resulting in the accumulation of cellular damage that manifests as bone marrow failure and neurodegeneration. **Proposed Experiment:** To test the first hypothesis regarding its role in monocyte function, one could perform a CRISPR-Cas9-mediated knockdown of [SAMD9L](/details-gene/219285) in primary human CD14+ monocytes. The functional consequences could then be evaluated by profiling their response to pathogen-associated molecular patterns (PAMPs). A comprehensive analysis using RNA-sequencing would reveal changes in inflammatory gene expression, while flow cytometry could quantify defects in the upregulation of co-stimulatory molecules (e.g., CD80, CD86) and MHC class II. Additionally, a phagocytosis assay using pH-sensitive fluorescently-labeled bioparticles could directly measure the impact on phagosome maturation. **Therapeutic Potential:** The diseases associated with [SAMD9L](/details-gene/219285), such as Ataxia-pancytopenia syndrome and certain myelodysplastic syndromes, are often caused by loss-of-function mutations or haploinsufficiency ([Link](https://doi.org/10.1016/j.ajhg.2016.04.009); [Link](https://doi.org/10.1016/j.ccr.2013.08.011)). This suggests that [SAMD9L](/details-gene/219285) is a poor candidate for therapeutic inhibition. Instead, strategies aimed at **activation or functional restoration** would be more appropriate. Potential therapeutic avenues could include gene therapy to deliver a functional copy of the gene to affected hematopoietic stem cells or the development of small-molecule chaperones or stabilizers that enhance the function of the remaining wild-type protein in cases of haploinsufficiency.

Disclaimer: This in-silico analysis is generated by an AI language model and may contain inaccuracies or hallucinations. However, it is cross-referenced with curated gene expression data from major biological sources. Please verify the information before use.

Sterile alpha motif domain-containing protein 9-like

Genular Protein ID: 3715666289

Symbol: SAM9L_HUMAN

Name: Sterile alpha motif domain-containing protein 9-like

UniProtKB Accession Codes:

Q8IVG5 A0JP23 A0JP24 A0PJG8 A4D1G8 D6W5Q6 Q2TV71 Q2TV75 Q2UZV8 Q8IWI4 Q8N3L9 Q8N875

Database IDs:

Citations:

PubMed ID: 17407603

Title: Human sterile alpha motif domain 9, a novel gene identified as down-regulated in aggressive fibromatosis, is absent in the mouse.

PubMed ID: 17407603

DOI: 10.1186/1471-2164-8-92

PubMed ID: 12690205

Title: Human chromosome 7: DNA sequence and biology.

PubMed ID: 12690205

DOI: 10.1126/science.1083423

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 24029230

Title: Haploinsufficiency of SAMD9L, an endosome fusion facilitator, causes myeloid malignancies in mice mimicking human diseases with monosomy 7.

PubMed ID: 24029230

DOI: 10.1016/j.ccr.2013.08.011

PubMed ID: 27259050

Title: Ataxia-pancytopenia syndrome is caused by missense mutations in SAMD9L.

PubMed ID: 27259050

DOI: 10.1016/j.ajhg.2016.04.009

PubMed ID: 30046003

Title: Germline SAMD9 and SAMD9L mutations are associated with extensive genetic evolution and diverse hematologic outcomes.

PubMed ID: 30046003

DOI: 10.1172/jci.insight.121086

PubMed ID: 35310830

Title: New spinocerebellar ataxia subtype caused by SAMD9L mutation triggering mitochondrial dysregulation (SCA49).

PubMed ID: 35310830

DOI: 10.1093/braincomms/fcac030

Sequence Information:

Length: 1584
Mass: 184533
Checksum: A9C52976D47AE79B
Sequence:

MSKQVSLPEM IKDWTKEHVK KWVNEDLKIN EQYGQILLSE EVTGLVLQEL TEKDLVEMGL 
PWGPALLIKR SYNKLNSKSP ESDNHDPGQL DNSKPSKTEH QKNPKHTKKE EENSMSSNID 
YDPREIRDIK QEESILMKEN VLDEVANAKH KKKGKLKPEQ LTCMPYPFDQ FHDSHRYIEH 
YTLQPETGAL NLIDPIHEFK ALTNTETATE VDIKMKFSNE VFRFASACMN SRTNGTIHFG 
VKDKPHGEIV GVKITSKAAF IDHFNVMIKK YFEESEINEA KKCIREPRFV EVLLQNNTPS 
DRFVIEVDTI PKHSICNDKY FYIQMQICKD KIWKQNQNLS LFVREGASSR DILANSKQRD 
VDFKAFLQNL KSLVASRKEA EEEYGMKAMK KESEGLKLVK LLIGNRDSLD NSYYDWYILV 
TNKCHPNQIK HLDFLKEIKW FAVLEFDPES MINGVVKAYK ESRVANLHFP NQYEDKTTNM 
WEKISTLNLY QQPSWIFCNG RSDLKSETYK PLEPHLWQRE RASEVRKLIL FLTDENIMTR 
GKFLVVFLLL SSVESPGDPL IETFWAFYQA LKGMENMLCI SVNSHIYQRW KDLLQTRMKM 
EDELTNHSIS TLNIELVNST ILKLKSVTRS SRRFLPARGS SSVILEKKKE DVLTALEILC 
ENECTETDIE KDKSKFLEFK KSKEEHFYRG GKVSWWNFYF SSENYSSDFV KRDSYEKLKD 
LIHCWAESPK PIFAKIINLY HHPGCGGTTL AMHVLWDLKK NFRCAVLKNK TTDFAEIAEQ 
VINLVTYRAK SHQDYIPVLL LVDDFEEQEN VYFLQNAIHS VLAEKDLRYE KTLVIILNCM 
RSRNPDESAK LADSIALNYQ LSSKEQRAFG AKLKEIEKQH KNCENFYSFM IMKSNFDETY 
IENVVRNILK GQDVDSKEAQ LISFLALLSS YVTDSTISVS QCEIFLGIIY TSTPWEPESL 
EDKMGTYSTL LIKTEVAEYG RYTGVRIIHP LIALYCLKEL ERSYHLDKCQ IALNILEENL 
FYDSGIGRDK FQHDVQTLLL TRQRKVYGDE TDTLFSPLME ALQNKDIEKV LSAGSRRFPQ 
NAFICQALAR HFYIKEKDFN TALDWARQAK MKAPKNSYIS DTLGQVYKSE IKWWLDGNKN 
CRSITVNDLT HLLEAAEKAS RAFKESQRQT DSKNYETENW SPQKSQRRYD MYNTACFLGE 
IEVGLYTIQI LQLTPFFHKE NELSKKHMVQ FLSGKWTIPP DPRNECYLAL SKFTSHLKNL 
QSDLKRCFDF FIDYMVLLKM RYTQKEIAEI MLSKKVSRCF RKYTELFCHL DPCLLQSKES 
QLLQEENCRK KLEALRADRF AGLLEYLNPN YKDATTMESI VNEYAFLLQQ NSKKPMTNEK 
QNSILANIIL SCLKPNSKLI QPLTTLKKQL REVLQFVGLS HQYPGPYFLA CLLFWPENQE 
LDQDSKLIEK YVSSLNRSFR GQYKRMCRSK QASTLFYLGK RKGLNSIVHK AKIEQYFDKA 
QNTNSLWHSG DVWKKNEVKD LLRRLTGQAE GKLISVEYGT EEKIKIPVIS VYSGPLRSGR 
NIERVSFYLG FSIEGPLAYD IEVI

Details for: SAMD9L

Cell Significance Landscape

Associated with

Significant Cells

Network Configuration

Legend:

Other Information

Human sterile alpha motif domain 9, a novel gene identified as down-regulated in aggressive fibromatosis, is absent in the mouse. PubMed ID: 17407603

Human chromosome 7: DNA sequence and biology. PubMed ID: 12690205

The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). PubMed ID: 15489334

Complete sequencing and characterization of 21,243 full-length human cDNAs. PubMed ID: 14702039

The full-ORF clone resource of the German cDNA consortium. PubMed ID: 17974005

Initial characterization of the human central proteome. PubMed ID: 21269460

Haploinsufficiency of SAMD9L, an endosome fusion facilitator, causes myeloid malignancies in mice mimicking human diseases with monosomy 7. PubMed ID: 24029230

Ataxia-pancytopenia syndrome is caused by missense mutations in SAMD9L. PubMed ID: 27259050

Germline SAMD9 and SAMD9L mutations are associated with extensive genetic evolution and diverse hematologic outcomes. PubMed ID: 30046003

New spinocerebellar ataxia subtype caused by SAMD9L mutation triggering mitochondrial dysregulation (SCA49). PubMed ID: 35310830