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SASH1 (SAM and SH3 domain containing 1)

Written2013-08Klaus-Peter Janssen
Department of Surgery, Technische Universitaet Muenchen, Ismaninger Str 22, 81675 Munich, Germany

(Note : for Links provided by Atlas : click)


Alias (NCBI)SH3D6A
HGNC Alias symbKIAA0790
LocusID (NCBI) 23328
Atlas_Id 43799
Location 6q24.3  [Link to chromosome band 6q24]
Location_base_pair Starts at 148342838 and ends at 148552044 bp from pter ( according to hg19-Feb_2009)  [Mapping SASH1.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
AFDN (6q27) / SASH1 (6q24.3)BTBD3 (20p12.2) / SASH1 (6q24.3)OXSR1 (3p22.2) / SASH1 (6q24.3)
PKD2 (4q22.1) / SASH1 (6q24.3)SAMD5 (6q24.3) / SASH1 (6q24.3)SASH1 (6q24.3) / AFDN (6q27)
SASH1 (6q24.3) / ARID1B (6q25.3)SASH1 (6q24.3) / DPF3 (14q24.2)SASH1 (6q24.3) / SAMD5 (6q24.3)


Note Entrez Gene: 23328 C, Ensembl: ENSG00000111961 C, UCSC: uc003qme.1 D, Vega:OTTHUMG00000015773.
  Schematic Structure of the Exon structure of human SASH1, as compared to the other members of the SLY-family of signal-adapter proteins, SLy1 (SH3-protein expressed in lymphocytes), and SAMSN1 (or SLy2). At the bottom, the transcribed full-length protein is shown schematically. SASH1 is the largest member of the protein family, it is encoded by 20 exons. All SLY-family proteins share a central conserved NLS (nuclear localisation signal) sequence, a SH3 and a SAM domain (dotted line). SASH1 comprises, in addition, a coiled-coil (CC) motif, a N-terminally located NLS signal (NLS2), a poly-prolin motif (PPP), and a second SAM domain at the C-terminus.
Description SASH1: located on human chromosome 6. Detailed gene locus: 6q24.3: 148593440-148873186 (forward strand).
ENSEMBL Database: Gene ID: ENSG00000111961.
Transcription 20 Protein-coding transcribed Exons, 7700 bp transcript, encoding 1247 amino acid residues.
Pseudogene No known pseudogenes.


Note Human SASH1 is comprised of 1247 amino acid residues, with a pI of 5.7, and a molecular mass of 137 kDa (please note that the apparent mass on denaturing SDS-PAGE is higher, roughly 170 kDa). SASH1 contains the following domains (from amino- to carboxyterminus): a predicted short coiled-coil stretch (CC), two predicted nuclear localisation signals (NLS1 and NLS2), a Src-homology-3 domain (SH3, aa 557 - aa 614), a first sterile alpha motif (SAM1, aa 633 - aa 697), a proline-rich sequence (PPP, aa 978 - aa 1059), and a second sterile alpha motif domain (SAM2, aa 1177 - aa 1241).
  Diagram schematically depicts human SASH1 protein (1247 aa), and the above-mentioned sequence-features: coiled-coil stretch (CC), nuclear localisation signals (NLS1 and NLS2), Src-homology-3 domain (SH3), a sterile alpha motif (SAM), a proline-rich sequence (PPP).
Description Human SASH1 was first described in 2003 as putative tumor suppressor in breast cancer, it encodes a protein with both cytosolic and nuclear localisation. It lacks enzymatic activity, but, due to its multiple protein-protein interactions domains (SH3, SAM, poly-prolin stretches), it is likely to serve as a signal-adapter module that integrates and coordinates other proteins, thereby acting as a negative/positive signal transduction nodule.
Expression SASH1 shows broad expression on protein level in human tissue and cell lines, as well as in mouse tissue. Exception: no or only weak expression has been found in lymphocytes.
Localisation SASH1 is found both in the cytosol, as well as in the nucleus, with the exception of the nucleolus. Enrichment in membrane-proximal areas in migrating cells at the lamellipodia (Martini et al., 2011).
Function SASH1 has no intrinsic enzyme activity, but can form multi-protein complexes due to its protein-protein interaction domains, and can modulate intracellular signal transduction. Moreover, SASH1 is implicated in the regulation of cell adhesion and migration (Martini et al., 2011).
Homology SASH1 belongs to the SLY-family, closest homologues: SLy1 and SLy2 (SH3-domain containing protein expressed in lymphocytes). Of note, SLy1 and SLy2 are much smaller (around 380 aa), and SLy1 is exclusively expressed in lymphocytes.


Germinal Heterozygous germline mutations have been identified in the three nonconsanguineous families with benign dermatologic features in a Chinese study (Zhou et al., 2013). However, no correlation between these mutations and occurrence of malignoma has been reported so far:
1) T → G substitution at nucleotide 2126 (TAC → GAC) in exon 14, resulting in amino acid substitutions of Tyr to Asp (Y551D) at codon 551
2) T → C substitution at nucleotide 2019 (CTC → CCC) in exon 13, resulting in Leu to Pro at codon 515 (L515P)
3) G → A substitution (GAA → AAA) at position 2000 in exon 13, causing Glu to Lys at codon 509 (E509K).
Somatic No truncating or nonsense mutations have been identified in somatic cells for SASH1 in a study on human breast cancer (Zeller et al., 2003).

Implicated in

Entity Breast cancer
Note Loss of the gene-internal microsatellite DNA marker D6S311 was found in 30% of samples of primary breast carcinoma, and the LOH was significantly correlated with poor survival and increase in tumor size. In established human mammary cancer cell lines, SASH1 is expressed at relatively low levels. SASH1 is downregulated in the majority (74%) of breast tumors in comparison with corresponding normal breast epithelia. In addition, SASH1 is also downregulated in tumors of the lung and thyroid. (Zeller et al., 2003).
Entity Colorectal cancer
Note The mRNA as well as protein expression of SASH1 was strongly and significantly reduced in colon cancer of UICC stage II, III, and IV, as well as in colorectal liver metastases. In contrast, SASH1 expression was not significantly altered in benign adenomas and in early stage lesions (UICC I). Around 40% of primary colon tumours tested (n=113) showed a 10-fold or stronger reduction in SASH1 expression, compared to normal colon mucosa. Decreased SASH1 mRNA expression was correlated with the occurrence of metachronous distant metastasis, and multivariate analysis identified SASH1 downregulation as an independent negative prognostic parameter for patient survival (Rimkus et al., 2006). Recently, these results were confirmed on an independent patient collective of stage II colon cancer (n=179 patients), confirming that decreased SASH1 expression is an independent negative prognostic factor in colon cancer, allowing to distinguish high-risk patients in early, locally restriced stages of the disease (Nitsche et al., 2012).
Entity Pancreatic cancer (unpublished observations)
Note In a collective of n=103 patients with pancreatic ductal adenocarcinoma, 38% of the tumors showed no or strongly reduced SASH1 protein expression by immunohistochemistry. Decreased SASH1 expression was significantly reduced with poor survival in Kaplan-Meier analysis (Tiago de Oliveira and Klaus-Peter Janssen, unpublished data).
Entity Benign dyskeratosis
Note SASH1 germline mutations have been identified in patients with a kind of dyschromatosis. Of note, three independent heterozygous germline mutations have been identified, that cause amino acid substitutions in the central SH3/SAM-containing region in the SASH1 gene. In epidermal tissues from an affected individual, increased transepithelial migration of melanocytes was observed (Zhou et al., 2013).
Entity Osteosarcoma
Note SASH1 protein was significantly down-regulated in osteosarcoma tissues compared to normal bone tissue. Moreover, SASH1 protein showed significant down-regulation in osteosarcoma tissues from patients with lung metastasis compared to those without lung metastasis, and, lastly, a gradual decrease of SASH1 expression occurred with increasing Enneking stage (Meng et al., 2013).


Effects of SASH1 on lung cancer cell proliferation, apoptosis, and invasion in vitro.
Chen EG, Chen Y, Dong LL, Zhang JS.
Tumour Biol. 2012 Oct;33(5):1393-401. doi: 10.1007/s13277-012-0387-2. Epub 2012 Apr 10.
PMID 22488244
Effects of SASH1 on melanoma cell proliferation and apoptosis in vitro.
Lin S, Zhang J, Xu J, Wang H, Sang Q, Xing Q, He L.
Mol Med Rep. 2012 Dec;6(6):1243-8. doi: 10.3892/mmr.2012.1099. Epub 2012 Sep 26.
PMID 23023727
The candidate tumor suppressor SASH1 interacts with the actin cytoskeleton and stimulates cell-matrix adhesion.
Martini M, Gnann A, Scheikl D, Holzmann B, Janssen KP.
Int J Biochem Cell Biol. 2011 Nov;43(11):1630-40. doi: 10.1016/j.biocel.2011.07.012. Epub 2011 Jul 28.
PMID 21820526
SASH1 regulates proliferation, apoptosis, and invasion of osteosarcoma cell.
Meng Q, Zheng M, Liu H, Song C, Zhang W, Yan J, Qin L, Liu X.
Mol Cell Biochem. 2013 Jan;373(1-2):201-10. doi: 10.1007/s11010-012-1491-8. Epub 2012 Oct 29.
PMID 23108792
Integrative marker analysis allows risk assessment for metastasis in stage II colon cancer.
Nitsche U, Rosenberg R, Balmert A, Schuster T, Slotta-Huspenina J, Herrmann P, Bader FG, Friess H, Schlag PM, Stein U, Janssen KP.
Ann Surg. 2012 Nov;256(5):763-71; discussion 771. doi: 10.1097/SLA.0b013e318272de87.
PMID 23095620
Prognostic significance of downregulated expression of the candidate tumour suppressor gene SASH1 in colon cancer.
Rimkus C, Martini M, Friederichs J, Rosenberg R, Doll D, Siewert JR, Holzmann B, Janssen KP.
Br J Cancer. 2006 Nov 20;95(10):1419-23. Epub 2006 Oct 31.
PMID 17088907
Overexpression of SASH1 related to the decreased invasion ability of human glioma U251 cells.
Yang L, Liu M, Gu Z, Chen J, Yan Y, Li J.
Tumour Biol. 2012 Dec;33(6):2255-63. doi: 10.1007/s13277-012-0487-z. Epub 2012 Aug 23.
PMID 22915266
SASH1: a candidate tumor suppressor gene on chromosome 6q24.3 is downregulated in breast cancer.
Zeller C, Hinzmann B, Seitz S, Prokoph H, Burkhard-Goettges E, Fischer J, Jandrig B, Schwarz LE, Rosenthal A, Scherneck S.
Oncogene. 2003 May 15;22(19):2972-83.
PMID 12771949
SASH1 regulates melanocyte transepithelial migration through a novel Gαs-SASH1-IQGAP1-E-Cadherin dependent pathway.
Zhou D, Wei Z, Deng S, Wang T, Zai M, Wang H, Guo L, Zhang J, Zhong H, He L, Xing Q.
Cell Signal. 2013 Jun;25(6):1526-38. doi: 10.1016/j.cellsig.2012.12.025. Epub 2013 Jan 16.
PMID 23333244


This paper should be referenced as such :
Janssen, KP
SASH1 (SAM, SH3 domain containing 1)
Atlas Genet Cytogenet Oncol Haematol. 2014;18(4):236-238.
Free journal version : [ pdf ]   [ DOI ]

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 4 ]
  Lung: Translocations in Squamous Cell Carcinoma
SASH1/SAMD5 (6q24)
t(6;6)(q24;q25) SASH1/ARID1B
t(6;14)(q24;q24) SASH1/DPF3

External links

HGNC (Hugo)SASH1   19182
Entrez_Gene (NCBI)SASH1  23328  SAM and SH3 domain containing 1
AliasesCAPOK; DUH1; SH3D6A; dJ323M4.1
GeneCards (Weizmann)SASH1
Ensembl hg19 (Hinxton)ENSG00000111961 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000111961 [Gene_View]  ENSG00000111961 [Sequence]  chr6:148342838-148552044 [Contig_View]  SASH1 [Vega]
ICGC DataPortalENSG00000111961
TCGA cBioPortalSASH1
Genatlas (Paris)SASH1
SOURCE (Princeton)SASH1
Genetics Home Reference (NIH)SASH1
Genomic and cartography
GoldenPath hg38 (UCSC)SASH1  -     chr6:148342838-148552044 +  6q24.3-q25.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)SASH1  -     6q24.3-q25.1   [Description]    (hg19-Feb_2009)
GoldenPathSASH1 - 6q24.3-q25.1 [CytoView hg19]  SASH1 - 6q24.3-q25.1 [CytoView hg38]
genome Data Viewer NCBISASH1 [Mapview hg19]  
OMIM127500   607955   618373   
Gene and transcription
Genbank (Entrez)AB018333 AI632133 AJ420508 AJ507735 AK023607
RefSeq transcript (Entrez)NM_001346505 NM_001346506 NM_001346507 NM_001346508 NM_001346509 NM_015278
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)SASH1
Alternative Splicing GalleryENSG00000111961
Gene ExpressionSASH1 [ NCBI-GEO ]   SASH1 [ EBI - ARRAY_EXPRESS ]   SASH1 [ SEEK ]   SASH1 [ MEM ]
Gene Expression Viewer (FireBrowse)SASH1 [ Firebrowse - Broad ]
GenevisibleExpression of SASH1 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)23328
GTEX Portal (Tissue expression)SASH1
Human Protein AtlasENSG00000111961-SASH1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO94885   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO94885  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO94885
Splice isoforms : SwissVarO94885
Domaine pattern : Prosite (Expaxy)SAM_DOMAIN (PS50105)    SH3 (PS50002)   
Domains : Interpro (EBI)rSAM/SH3_domain-containing    SAM    SAM/pointed_sf    SASH1_SAM_repeat1    SASH1_SAM_repeat2    SASH1_SH3    SH3-like_dom_sf    SH3_domain   
Domain families : Pfam (Sanger)SAM_1 (PF00536)    SAM_2 (PF07647)    SH3_2 (PF07653)    SLY (PF12485)   
Domain families : Pfam (NCBI)pfam00536    pfam07647    pfam07653    pfam12485   
Domain families : Smart (EMBL)SAM (SM00454)  SH3 (SM00326)  
Conserved Domain (NCBI)SASH1
DMDM Disease mutations23328
Blocks (Seattle)SASH1
PDB (RSDB)2DL0    2EBP   
PDB Europe2DL0    2EBP   
PDB (PDBSum)2DL0    2EBP   
PDB (IMB)2DL0    2EBP   
Structural Biology KnowledgeBase2DL0    2EBP   
SCOP (Structural Classification of Proteins)2DL0    2EBP   
CATH (Classification of proteins structures)2DL0    2EBP   
Human Protein Atlas [tissue]ENSG00000111961-SASH1 [tissue]
Peptide AtlasO94885
IPIIPI00304817   IPI01010180   IPI01011555   IPI00871313   IPI00478570   
Protein Interaction databases
IntAct (EBI)O94885
Ontologies - Pathways
Ontology : AmiGOprotein polyubiquitination  G-protein alpha-subunit binding  protein binding  cytoplasm  protein C-terminus binding  positive regulation of endothelial cell migration  regulation of epithelial cell migration  protein kinase binding  mitogen-activated protein kinase kinase kinase binding  mitogen-activated protein kinase kinase kinase binding  positive regulation of lipopolysaccharide-mediated signaling pathway  protein-containing complex  positive regulation of JUN kinase activity  positive regulation of JUN kinase activity  positive regulation of angiogenesis  molecular adaptor activity  regulation of protein K63-linked ubiquitination  positive regulation of p38MAPK cascade  positive regulation of NIK/NF-kappaB signaling  positive regulation of NIK/NF-kappaB signaling  regulation of protein autoubiquitination  
Ontology : EGO-EBIprotein polyubiquitination  G-protein alpha-subunit binding  protein binding  cytoplasm  protein C-terminus binding  positive regulation of endothelial cell migration  regulation of epithelial cell migration  protein kinase binding  mitogen-activated protein kinase kinase kinase binding  mitogen-activated protein kinase kinase kinase binding  positive regulation of lipopolysaccharide-mediated signaling pathway  protein-containing complex  positive regulation of JUN kinase activity  positive regulation of JUN kinase activity  positive regulation of angiogenesis  molecular adaptor activity  regulation of protein K63-linked ubiquitination  positive regulation of p38MAPK cascade  positive regulation of NIK/NF-kappaB signaling  positive regulation of NIK/NF-kappaB signaling  regulation of protein autoubiquitination  
NDEx NetworkSASH1
Atlas of Cancer Signalling NetworkSASH1
Wikipedia pathwaysSASH1
Orthology - Evolution
GeneTree (enSembl)ENSG00000111961
Phylogenetic Trees/Animal Genes : TreeFamSASH1
Homologs : HomoloGeneSASH1
Homology/Alignments : Family Browser (UCSC)SASH1
Gene fusions - Rearrangements
Fusion : MitelmanMLLT4/SASH1 [6q27/6q24.3]  
Fusion : MitelmanSASH1/ARID1B [6q24.3/6q25.3]  
Fusion : MitelmanSASH1/DPF3 [6q24.3/14q24.2]  
Fusion : MitelmanSASH1/MLLT4 [6q24.3/6q27]  
Fusion PortalMLLT4 6q27 SASH1 6q24.3 LGG
Fusion PortalSASH1 6q24.3 ARID1B 6q25.3 BRCA
Fusion PortalSASH1 6q24.3 MLLT4 6q27 LGG
Fusion : Fusion_HubACPP--SASH1    ARID1B--SASH1    BTBD3--SASH1    CBX3--SASH1    COL1A1--SASH1    GPR155--SASH1    IGFBP7--SASH1    KANSL1L--SASH1    KDM6A--SASH1    MLLT4--SASH1    OXSR1--SASH1    PAQR3--SASH1    PIP5K1A--SASH1    PKD2--SASH1    PKP1--SASH1   
PRH2--SASH1    QKI--SASH1    RRAGD--SASH1    SAMD5--SASH1    SASH1--ARID1B    SASH1--ATP1A1    SASH1--BHLHE40    SASH1--C6ORF103    SASH1--CCDC171    SASH1--COX16    SASH1--DMTF1    SASH1--DOPEY1    SASH1--EYA1    SASH1--FGFR1OP    SASH1--HDDC2   
Fusion : QuiverSASH1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSASH1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SASH1
Exome Variant ServerSASH1
GNOMAD BrowserENSG00000111961
Varsome BrowserSASH1
Genetic variants : HAPMAP23328
Genomic Variants (DGV)SASH1 [DGVbeta]
DECIPHERSASH1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisSASH1 
ICGC Data PortalSASH1 
TCGA Data PortalSASH1 
Broad Tumor PortalSASH1
OASIS PortalSASH1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSASH1  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DSASH1
Mutations and Diseases : HGMDSASH1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch SASH1
DgiDB (Drug Gene Interaction Database)SASH1
DoCM (Curated mutations)SASH1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SASH1 (select a term)
NCG6 (London) select SASH1
Cancer3DSASH1(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
OMIM127500    607955    618373   
Orphanet19148    23554   
Genetic Testing Registry SASH1
NextProtO94885 [Medical]
Target ValidationSASH1
Huge Navigator SASH1 [HugePedia]
snp3D : Map Gene to Disease23328
BioCentury BCIQSASH1
Clinical trials, drugs, therapy
Protein Interactions : CTD23328
Pharm GKB GenePA134984521
Clinical trialSASH1
canSAR (ICR)SASH1 (select the gene name)
DataMed IndexSASH1
PubMed58 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Mon Oct 12 12:51:43 CEST 2020

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