ZSWIM9
Zinc finger SWIM-type containing 9 is a protein encoded in humans by the ZSWIM9 gene.{{Cite web |title=ZSWIM9 zinc finger SWIM-type containing 9 [Homo sapiens (human)] - Gene - NCBI |url=https://www.ncbi.nlm.nih.gov/gene/374920 |access-date=2024-12-04 |website=www.ncbi.nlm.nih.gov}} It is a member of zinc finger SWIM-type family. This gene is expressed in embryonic development and predicted to act in cell differentiation.
{{Infobox protein
| name = Zinc finger SWIM-type containing 9
| AltNames = c19orf68
| image = File:Tertiary structure of ZSWIM9.png
| width =
| caption = Tertiary structure of ZSWIM9 rainbow colored from N-terminus to C-terminus
| Symbol = ZSWIM9
| AltSymbols =
| IUPHAR_id =
| ATC_prefix =
| ATC_suffix =
| ATC_supplemental =
| CAS_number =
| CAS_supplemental =
| DrugBank =
| EntrezGene =
| HGNCid = 34495
| OMIM =
| PDB =
| RefSeq = NM_199341.4
| UniProt = Q86XI8
| ECnumber =
| Chromosome = 19
| Arm = q
| Band = 13.33
| LocusSupplementaryData =
| Wikidata =
}}
Gene
The ZSWIM9 gene is located on the plus strand at 19q13.33 from 48,170,680 to 48,197,620 spanning 26,941 base pairs.{{Cite web |date=December 10, 2024 |title=ZSWIM9 Gene - Zinc Finger SWIM-Type Containing 9 |url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=ZSWIM9&keywords=ZSWIM9 |website=GeneCards}} Also known as C19orf68, this gene has orthologs in placental mammals, marsupials, reptiles (turtles), birds (flightless birds), and amphibians.{{Cite web |title=BLAST: Basic Local Alignment Search Tool |url=https://blast.ncbi.nlm.nih.gov/Blast.cgi#alnHdr_XP_069056600 |access-date=2024-12-11 |website=blast.ncbi.nlm.nih.gov}} ZSWIM9 has 4 exons, with variation between isoforms.
mRNA and transcriptional variants
= Transcripts =
ZSWIM9 has a total of six transcriptional variants with isoform 1 being the most complete and understood. All isoforms contain a conserved domain, FAR1, except X3 and X5, as well as the SWIM-type domain.
class="wikitable" style="text-align: center;"
|+Transcript variants of ZSWIM9 !Transcript Variant !Accession number !mRNA length (nucelotides) !Protein length (amino acids) !Molecular weight (kDa) |
1
|NM_199341.4 |3600 |920 |101.7 |
X1
|XM_006723204.4 |3914 |947 |104.6 |
X2
|XM_005259449.4 |4281 |933 |103.2 |
X3
|XM_006723205.3 |3596 |920 |101.6 |
X4
|XM_011526936.3 |3624 |848 |93.1 |
X5
|XM_047438788.1 |3130 |720 |80.0 |
class="wikitable" style="text-align: center;
|+Exons present in each isoform of ZSWIM9 !Isoform !Exon 1 !Exon 2 !Exon 3 !Exon 4 |
1
!✓ !✓ !✓ !✓ |
---|
X1
|✓ |✓ |✓ |✓ |
X2
|✓ |✓ |✓ |✓ |
X3
|✓ |✓ |✓ |✓ |
X4
|x |x |✓ |✓ |
X5
|x |x |x |✓ |
Protein
The human ZSWIM9 protein is 920 amino acids long with a molecular weight of 101.7 kDA and a theoretical isoelectric point of 8.51.{{Cite web |title=Expasy - Compute pI/Mw tool |url=https://web.expasy.org/compute_pi/ |access-date=2024-12-11 |website=web.expasy.org}}
= Composition =
The human ZSWIM9 protein along with orthologs has higher than normal amounts of arginine, specifically around amino acids 379-421. Arginine has been seen to play a crucial role in genome stability{{Cite journal |last1=Sanchez-Bailon |first1=Maria Pilar |last2=Choi |first2=Soo-Youn |last3=Dufficy |first3=Elizabeth R. |last4=Sharma |first4=Karan |last5=McNee |first5=Gavin S. |last6=Gunnell |first6=Emma |last7=Chiang |first7=Kelly |last8=Sahay |first8=Debashish |last9=Maslen |first9=Sarah |last10=Stewart |first10=Grant S. |last11=Skehel |first11=J. Mark |last12=Dreveny |first12=Ingrid |last13=Davies |first13=Clare C. |date=2021-11-02 |title=Arginine methylation and ubiquitylation crosstalk controls DNA end-resection and homologous recombination repair |journal=Nature Communications |language=en |volume=12 |issue=1 |pages=6313 |doi=10.1038/s41467-021-26413-6 |pmid=34728620 |pmc=8564520 |bibcode=2021NatCo..12.6313S |issn=2041-1723}} and typically associated with interactions with nucleic acids, specific cellular localization (nucleus), or involvement in structural or enzymatic roles. The high concentration of arginine residues influences the protein's charge, binding properties, and potential regulatory functions. Arginine-rich proteins can play crucial roles in cell differentiation during embryonic development due to their involvement in processes that regulate gene expression, chromatin remodeling, and signaling pathways.{{Cite journal |last1=Lee |first1=Yun Hwa |last2=Ma |first2=Hui |last3=Tan |first3=Tuan Zea |last4=Ng |first4=Swee Siang |last5=Soong |first5=Richie |last6=Mori |first6=Seiichi |last7=Fu |first7=Xin-Yuan |last8=Zernicka-Goetz |first8=Magdalena |last9=Wu |first9=Qiang |date=2012-09-20 |title=Protein Arginine Methyltransferase 6 Regulates Embryonic Stem Cell Identity |journal=Stem Cells and Development |language=en |volume=21 |issue=14 |pages=2613–2622 |doi=10.1089/scd.2011.0330 |issn=1547-3287 |pmc=5729635 |pmid=22455726}}
= Conserved domains/motifs =
File:ZSWIM9 MSA of FAR1 domain.png
ZSWIM9 contains a zinc finger SWIM-type profile, a pattern recognized in human protein ZSWIM9 and its orthologs that represent a shared zinc-binding motif.{{Cite journal |last1=Makarova |first1=Kira S. |last2=Aravind |first2=L. |last3=Koonin |first3=Eugene V. |date=August 2002 |title=SWIM, a novel Zn-chelating domain present in bacteria, archaea and eukaryotes |url=https://pubmed.ncbi.nlm.nih.gov/12151216/ |journal=Trends in Biochemical Sciences |volume=27 |issue=8 |pages=384–386 |doi=10.1016/s0968-0004(02)02140-0 |issn=0968-0004 |pmid=12151216}}{{Cite web |title=Gene group {{!}} HUGO Gene Nomenclature Committee |url=https://www.genenames.org/data/genegroup/#!/group/90 |access-date=2024-12-11 |website=www.genenames.org}} The acronym "SWIM" stands for SWI2/SNF2 and MuDR and detects conserved cysteine- and histidine-rich regions involved in zinc coordination, which facilitates protein-DNA or protein-protein interactions.
There is a conserved FAR1 DNA-binding domain from amino acids 97-128.{{Cite web |title=Motif Scan |url=https://myhits.sib.swiss/cgi-bin/motif_scan |access-date=2024-12-11 |website=myhits.sib.swiss |language=en}} This indicates that ZSWIM9, a member of the FRS family, shares a domain architecture with mutator-like transposases, including an N-terminal C2H2 zinc finger domain, a central transposase-like domain, and a C-terminal SWIM motif. This structure, coupled with its FAR1-like DNA-binding domain, suggests ZSWIM9 functions as a transcriptional regulator, potentially co-opted from transposases to play roles in gene expression, DNA repair, or transposon splicing.{{Cite web |title=InterPro |url=https://www.ebi.ac.uk/interpro/entry/InterPro/IPR004330/ |access-date=2024-12-11 |website=www.ebi.ac.uk}}
There is a family of unknown function (DUF5575) from amino acids 12-320.{{Cite web |title=uncharacterized protein ZSWIM9 [Homo sapiens] - Protein - NCBI |url=https://www.ncbi.nlm.nih.gov/protein/NP_955373.3 |access-date=2024-12-11 |website=www.ncbi.nlm.nih.gov}}
Regulation
= Gene level regulation =
Located in the nucleoplasm,{{Cite web |title=ZSWIM9 protein expression summary - The Human Protein Atlas |url=https://www.proteinatlas.org/ENSG00000185453-ZSWIM9 |access-date=2024-12-11 |website=www.proteinatlas.org}} ZSWIM9 in humans is ubiquitously expressed in medium abundance in the brain (fetal brain, and cerebellum), fat, and kidneys.{{Cite journal |last1=Fagerberg |first1=Linn |last2=Hallström |first2=Björn M. |last3=Oksvold |first3=Per |last4=Kampf |first4=Caroline |last5=Djureinovic |first5=Dijana |last6=Odeberg |first6=Jacob |last7=Habuka |first7=Masato |last8=Tahmasebpoor |first8=Simin |last9=Danielsson |first9=Angelika |last10=Edlund |first10=Karolina |last11=Asplund |first11=Anna |last12=Sjöstedt |first12=Evelina |last13=Lundberg |first13=Emma |last14=Szigyarto |first14=Cristina Al-Khalili |last15=Skogs |first15=Marie |date=February 2014 |title=Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics |journal=Molecular & Cellular Proteomics |volume=13 |issue=2 |pages=397–406 |doi=10.1074/mcp.M113.035600 |doi-access=free |issn=1535-9484 |pmc=3916642 |pmid=24309898}}{{Cite journal |last1=Duff |first1=Michael O. |last2=Olson |first2=Sara |last3=Wei |first3=Xintao |last4=Garrett |first4=Sandra C. |last5=Osman |first5=Ahmad |last6=Bolisetty |first6=Mohan |last7=Plocik |first7=Alex |last8=Celniker |first8=Susan E. |last9=Graveley |first9=Brenton R. |date=2015-05-21 |title=Genome-wide identification of zero nucleotide recursive splicing in Drosophila |journal=Nature |volume=521 |issue=7552 |pages=376–379 |doi=10.1038/nature14475 |issn=1476-4687 |pmc=4529404 |pmid=25970244|bibcode=2015Natur.521..376D }} Ubiquitously expressed, with some variability, in low abundance in early developed fetal hearts and fetal lungs.{{Cite journal |last1=Szabo |first1=Linda |last2=Morey |first2=Robert |last3=Palpant |first3=Nathan J. |last4=Wang |first4=Peter L. |last5=Afari |first5=Nastaran |last6=Jiang |first6=Chuan |last7=Parast |first7=Mana M. |last8=Murry |first8=Charles E. |last9=Laurent |first9=Louise C. |last10=Salzman |first10=Julia |date=2015-06-16 |title=Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development |journal=Genome Biology |volume=16 |issue=1 |pages=126 |doi=10.1186/s13059-015-0690-5 |doi-access=free |issn=1474-760X |pmc=4506483 |pmid=26076956}}
While ZSWIM9 is expresses in low levels among fetal hearts, it has been predicted that there is a higher expression in earlier developed embryoid stem cells and embryoid bodies with beating cardiomyocytes, then a decreased level of expression later on in development such as in mature cardiomyocytes from fetal hearts.{{Cite web |title=GDS3513 / 3394 |url=https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS3513:3394 |access-date=2024-12-13 |website=www.ncbi.nlm.nih.gov}} This suggests ZSWIM9 might play a role in early differentiation stages and cellular commitment processes.
Additionally, higher expression of ZSWIM9 was seen in myotonic dystrophy type 2, which is muscle dysfunction in numerous muscle types including cardiac,{{Citation |last=Schoser |first=Benedikt |title=Myotonic Dystrophy Type 2 |date=2020-03-19 |work=GeneReviews® [Internet] |url=https://www.ncbi.nlm.nih.gov/sites/books/NBK1466/#:~:text=Myotonic%20dystrophy%20type%202%20(DM2,mellitus,%20and%20other%20endocrine%20abnormalities. |access-date=2024-12-13 |publisher=University of Washington, Seattle |language=en |pmid=20301639}} compared to a control from DM2 vastus lateralis muscle tissue.{{Cite web |title=GDS5276 / ILMN_1792828 |url=https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS5276:ILMN_1792828 |access-date=2024-12-13 |website=www.ncbi.nlm.nih.gov}} Higher expression suggests that ZSWIM9 may have a role in the muscle’s response to chronic disease-related stress, regeneration process, or damage repair. This pattern of expression may reflect ZSWIM9’s involvement in cellular pathways that become more active or dysregulated in the disease state.
= Protein level regulation =
The human ZSWIM9 protein is predicted to be primarily localized in the nucleus{{Cite web |title=DeepLoc-2.0 |url=https://services.healthtech.dtu.dk/cgi-bin/webface2.cgi?jobid=675C4CF9000EAFF8777ABA77&wait=20 |access-date=2024-12-13 |website=services.healthtech.dtu.dk}} and cytoplasm,{{Cite web |title=PSORT II Prediction |url=https://psort.hgc.jp/form2.html |access-date=2024-12-13 |website=psort.hgc.jp}} however, it has also been visualized via immunofluorescence in the nucleoplasm.{{Cite web |title=Search: ZSWIM9 - The Human Protein Atlas |url=https://www.proteinatlas.org/search/ZSWIM9 |access-date=2024-12-13 |website=www.proteinatlas.org}} It was also predicted ZSWIM9 has nuclear export signals, which direct proteins from the nucleus to the cytoplasm.{{Cite journal |last1=Xu |first1=Darui |last2=Farmer |first2=Alicia |last3=Collett |first3=Garen |last4=Grishin |first4=Nick V. |last5=Chook |first5=Yuh Min |date=2012-09-15 |editor-last=Weis |editor-first=Karsten |title=Sequence and structural analyses of nuclear export signals in the NESdb database |journal=Molecular Biology of the Cell |language=en |volume=23 |issue=18 |pages=3677–3693 |doi=10.1091/mbc.e12-01-0046 |issn=1059-1524 |pmc=3442415 |pmid=22833565}} The presence of an NES indicates the protein may shuttle between the nucleus and cytoplasm, depending on cellular conditions or specific signals (e.g., stress, phosphorylation).
Phosphorylation
Interacting proteins
ZSWIM9 was found to primarily interact with proteins involved with DNA maintenance in the nucleus, cytoplasm, and nucleoplasm.{{Cite web |title=PSICQUIC View |url=http://www.ebi.ac.uk/Tools/webservices/psicquic/view/results.xhtml?conversationContext=1 |access-date=2024-12-13 |website=www.ebi.ac.uk}}
class="wikitable" style="text-align: center;"
|+ZSWIM9 interacting proteins !Protein !Detection method !Subcellular localization !Function |
Chromobox protein homolog 1
|Tandem affinity purification |Nucleus, nucleoplasm, chromosome, cytoskeleton |Component of heterochromatin. Recognizes and binds histone H3 tails methylated at 'Lys-9', leading to epigenetic repression. Interaction with lamin B receptor (LBR) can contribute to the association of the heterochromatin with the inner nuclear membrane. |
BMI1 (Polycomb complex protein)
|Co-immunoprecipitation |Nucleus, nucleoplasm, chromosome, cytosol |Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. |
CBX3
(Chromobox 3) |Co-immunoprecipitation |Nucleus, nuclear envelope, nucleoplasm, chromosome, cytoskeleton |Seems to be involved in transcriptional silencing in heterochromatin-like complexes. Recognizes and binds histone H3 tails methylated at 'Lys-9', leading to epigenetic repression. May contribute to the association of the heterochromatin with the inner nuclear membrane through its interaction with the lamin B receptor (LBR). |
FHL3 (Human four-and-a-half LIM-only protein 3)
|Co-immunoprecipitation |Nucleus, cytoskeleton |Recruited by SOX15 to FOXK1 promoters where it acts as a transcriptional coactivator of FOXK1. |
Histone 3 (H3) is an arginine-rich histone and is linked active chromatin structures and gene activation.{{Cite journal |last1=Di Lorenzo |first1=Alessandra |last2=Bedford |first2=Mark T. |date=2011 |title=Histone arginine methylation |journal=FEBS Letters |language=en |volume=585 |issue=13 |pages=2024–2031 |doi=10.1016/j.febslet.2010.11.010 |issn=1873-3468 |pmc=3409563 |pmid=21074527|bibcode=2011FEBSL.585.2024D }}
Hox genes are a group of related genes that play a critical role in the development and organization of an organism's body plan during embryonic development.{{Cite web |title=Hox Genes in Development: The Hox Code {{!}} Learn Science at Scitable |url=https://www.nature.com/scitable/topicpage/hox-genes-in-development-the-hox-code-41402/ |access-date=2024-12-13 |website=www.nature.com |language=en}} This is indicative of ZSWIM9 protein function.
SOX15 binds to the DNA consensus sequence 5'-AACAATG-3' and can function as both an activator and repressor. It synergistically interacts with POU5F1 (OCT3/4) at gene promoters and activates the FOXK1 promoter by recruiting FHL3, promoting myoblast proliferation. Additionally, it inhibits myoblast differentiation by repressing muscle-specific genes like MYOD and MYOG.{{Cite web |title=UniProt |url=https://www.uniprot.org/uniprotkb/O60248/entry |access-date=2024-12-13 |website=www.uniprot.org}}
Evolution
= Paralogs =
= Orthologs =
Orthologs of ZSWIM9 were found in placental mammals, marsupials, reptiles, birds, and amphibians. ZSWIM9 is found in reptiles, but only in turtles and in birds, but only in flightless birds. This could indicate a key point of divergence or a result of ZSWIM9 protein function.{{Cite journal |last1=Matsuda |first1=Yoichi |last2=Nishida-Umehara |first2=Chizuko |last3=Tarui |first3=Hiroshi |last4=Kuroiwa |first4=Asato |last5=Yamada |first5=Kazuhiko |last6=Isobe |first6=Taku |last7=Ando |first7=Junko |last8=Fujiwara |first8=Atushi |last9=Hirao |first9=Yukako |last10=Nishimura |first10=Osamu |last11=Ishijima |first11=Junko |last12=Hayashi |first12=Akiko |last13=Saito |first13=Toshiyuki |last14=Murakami |first14=Takahiro |last15=Murakami |first15=Yasunori |date=2005-08-01 |title=Highly conserved linkage homology between birds and turtles: Bird and turtle chromosomes are precise counterparts of each other |url=https://link.springer.com/article/10.1007/s10577-005-0986-5 |journal=Chromosome Research |language=en |volume=13 |issue=6 |pages=601–615 |doi=10.1007/s10577-005-0986-5 |pmid=16170625 |issn=1573-6849|hdl=2115/30315 |hdl-access=free }}
File:ZSWIM9 sequence divergence.png
class="wikitable mw-collapsible" style="text-align: center;"
|+Selected Orthologs of ZSWIM9 !Organism type !Species name !Common name !Taxonomic group !Date of divergence (MYA) !% Identity !% Similarity !AC# !Protein length |
rowspan="6" |Placental
|Homo sapiens |Primate |0 |100 |100 |NP_955373 |920 |
Oryctolagus cuniculus
|Lagomorpha |87 |69 |73 |XP_051693391 |913 |
Mus musculus
|Rodentia |87 |67.9 |74.2 |NP_796286.2 |849 |
Camelus ferus
|Artiodactyla |94 |85.4 |89.2 |XP_032341552.1 |923 |
Vulpes lagopus
|Carnivora |94 |84.8 |69.6 |XP_041600653 |915 |
Equus przewalskii
|Perissodactyla |94 |47.8 |51.4 |XP_008525788 |611 |
rowspan="4" |Marsupial
|Trichosurus vulpecula |Diprotodotia |160 |80.2 |48.1 |XP_036599503.1 |717 |
Vombatus ursinus
|Diprotodotia |160 |75.6 |65.2 |XP_027715069.1 |966 |
Antechinus flavipes
|Dasyuromorphia |160 |74.4 |56.2 |XP_051845809 |898 |
Sarcophilus harrisii
|Dasyuromorphia |160 |74.3 |62.7 |XP_031817585 |1030 |
rowspan="2" |Reptile
|Dermochelys coriacea |Testudines |319 |61.9 |43.2 |XP_043357605.1 |538 |
Emydura macquarii
|Testudines |319 |61.8 |43.6 |XP_067413334.1 |538 |
rowspan="3" |Bird
|Rhea pennata |Rheiformes |319 |44.2 |33.5 |XP_062449005.1 |535 |
Apteryx rowi
|Apterygiformes |319 |43.3 |33.4 |XP_025945372.1 |535 |
Dromaius novaehollandiae
|Emu |Palaeognathae |319 |43.1 |33.5 |XP_025976311.1 |535 |
rowspan="6" |Amphibian
|Rhinatrema bivittatum |Gymnophiona |352 |51.9 |39.7 |XP_029440252.1 |548 |
Geotrypetes seraphini
|Gymnophiona |352 |50.1 |38.5 |XP_038816602.1 |548 |
Microcaecilia unicolor
|Tiny cayenne caecilian |Gymnophiona |352 |50 |38.5 |XP_030053572.1 |544 |
Ascaphus truei
|Coastal tailed frog |Anura |352 |49.3 |38.3 |MEE6483311.1 |536 |
Ambystoma mexicanum
|Urodela |352 |46.9 |36.6 |XP_069493689.1 |544 |
Pleurodeles waltl
|Urodela |352 |45.8 |34.9 |XP_069056600.1 |580 |
Function
Zinc-finger proteins contain a short finger-like structural motif stabilized by zinc-ions [https://symposium.cshlp.org/content/52/473] which are involved in critical biological processes including cell differentiation{{Cite journal |last1=Powell |first1=Michael D. |last2=Read |first2=Kaitlin A. |last3=Sreekumar |first3=Bharath K. |last4=Oestreich |first4=Kenneth J. |date=2019-06-06 |title=Ikaros Zinc Finger Transcription Factors: Regulators of Cytokine Signaling Pathways and CD4+ T Helper Cell Differentiation |journal=Frontiers in Immunology |language=English |volume=10 |page=1299 |doi=10.3389/fimmu.2019.01299 |doi-access=free |pmid=31244845 |pmc=6563078 |issn=1664-3224}} and embryonic development.{{Cite journal |last1=Close |first1=Renaud |last2=Toro |first2=Sabrina |last3=Martial |first3=Joseph A. |last4=Muller |first4=Marc |date=2002-10-01 |title=Expression of the zinc finger Egr1 gene during zebrafish embryonic development |url=https://www.sciencedirect.com/science/article/pii/S0925477302002836 |journal=Mechanisms of Development |volume=118 |issue=1 |pages=269–272 |doi=10.1016/S0925-4773(02)00283-6 |pmid=12351200 |hdl=2268/13012 |issn=0925-4773|hdl-access=free }} ZSWIM9, however, is classified by the SWIM domain, characterized by a CxCxnCxH molecular structure.{{Cite journal |last1=Hassan |first1=Imtiaz Ul |last2=Rehman |first2=Hafiz Mamoon |last3=Liu |first3=Ziran |last4=Zhou |first4=Liangji |last5=Samma |first5=Muhammad Kaleem |last6=Wang |first6=Chengdong |last7=Rong |first7=Zixin |last8=Qi |first8=Xufeng |last9=Cai |first9=Dongqing |last10=Zhao |first10=Hui |date=2023-05-18 |title=Genome-wide identification and spatiotemporal expression profiling of zinc finger SWIM domain-containing protein family genes |journal=Zoological Research |language=en |volume=44 |issue=3 |pages=663–674 |doi=10.24272/j.issn.2095-8137.2022.418 |issn=2095-8137 |pmc=10236294 |pmid=37161653}} The SWIM domain is predicted to have DNA-binding and protein-protein interaction functions.{{Cite journal |last1=Makarova |first1=Kira S |last2=Aravind |first2=L |last3=Koonin |first3=Eugene V |date=2002-08-01 |title=SWIM, a novel Zn-chelating domain present in bacteria, archaea and eukaryotes |url=https://www.sciencedirect.com/science/article/abs/pii/S0968000402021400 |journal=Trends in Biochemical Sciences |volume=27 |issue=8 |pages=384–386 |doi=10.1016/S0968-0004(02)02140-0 |pmid=12151216 |issn=0968-0004|url-access=subscription }}
Clinical significance
A couple of single nucleotide polymorphisms (SNPs) were identified as clinically significant and associated with ZSWIM9.{{Cite web |title=Variation Viewer |url=https://www.ncbi.nlm.nih.gov/variation/view |access-date=2024-12-13 |website=www.ncbi.nlm.nih.gov}} One study associate a SNP in ZSWIM9 with acute Graft versus Host Disease (aGvHD) which affects patients undergoing allogeneic hematopoietic stem-cell transplantation (allo-HSCT). This condition is triggered by the damage to normal tissue caused by pre-transplant conditioning regimens, with DNA-repair mechanisms potentially playing a key role in mitigating this damage.{{Cite journal |last1=Uppugunduri |first1=C. R. S. |last2=Huezo-Diaz Curtis |first2=P. |last3=Nava |first3=T. |last4=Rezgui |first4=M. A. |last5=Mlakar |first5=V. |last6=Mlakar |first6=S. Jurkovic |last7=Waespe |first7=N. |last8=Théoret |first8=Y. |last9=Gumy-Pause |first9=F. |last10=Bernard |first10=F. |last11=Chalandon |first11=Y. |last12=Boelens |first12=J. J. |last13=Bredius |first13=R. G. M. |last14=Dalle |first14=J. H. |last15=Nath |first15=C. |date=February 2022 |title=Association study of candidate DNA-repair gene variants and acute graft versus host disease in pediatric patients receiving allogeneic hematopoietic stem-cell transplantation |journal=The Pharmacogenomics Journal |language=en |volume=22 |issue=1 |pages=9–18 |doi=10.1038/s41397-021-00251-7 |issn=1470-269X |pmc=8794787 |pmid=34711928}} This could be associated with proteins involved in cell differentiation through several mechanisms related to DNA repair, gene expression regulation, and cellular responses to stress or injury.
References
{{Reflist}}