Details for: CFAP65

Gene ID: 255101

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: CFAP65

Ensembl ID: ENSG00000181378

Description: cilia and flagella associated protein 65

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • retinal rod cell CL0000604
    CSI 5
    rCSI 8.81%
    PRS 92.06
  • squamous epithelial cell CL0000076
    CSI 4.63
    rCSI 10.99%
    PRS 91.7
  • ciliated cell CL0000064
    CSI 4.44
    rCSI 7.2%
    PRS 90
  • pancreatic A cell CL0000171
    CSI 3.56
    rCSI 3.73%
    PRS 95.78
  • pancreatic D cell CL0000173
    CSI 3.29
    rCSI 3.24%
    PRS 95.75
  • intestine goblet cell CL0019031
    CSI 3.14
    rCSI 2.78%
    PRS 93.38
  • ependymal cell CL0000065
    CSI 3.13
    rCSI 6.35%
    PRS 81.64
  • multi-ciliated epithelial cell CL0005012
    CSI 2.92
    rCSI 2.91%
    PRS 90.89
  • ciliated epithelial cell CL0000067
    CSI 2.88
    rCSI 2.53%
    PRS 88.73
  • enteroendocrine cell CL0000164
    CSI 2.8
    rCSI 3.83%
    PRS 93.18
  • lung ciliated cell CL1000271
    CSI 2.76
    rCSI 3.19%
    PRS 91.2
  • mucus secreting cell CL0000319
    CSI 2.33
    rCSI 3.71%
    PRS 97.37
  • ciliated columnar cell of tracheobronchial tree CL0002145
    CSI 1.55
    rCSI 3.52%
    PRS 89.33
  • deuterosomal cell CL4033044
    CSI 1.12
    rCSI 3.8%
    PRS 90.11
  • enteroendocrine cell of colon CL0009042
    CSI 0.75
    rCSI 3.53%
    PRS 95.19

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.

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 cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

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 cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
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.

Comma-separated if multiple.
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)

Loading network (please wait)...

Other Information

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

## Summary [CFAP65](/details-gene/255101) (Cilia and Flagella Associated Protein 65) is a protein-coding gene located on chromosome 2q35. Functionally, it is integral to the structure and motility of cilia and flagella. This is underscored by its high expression significance in a variety of ciliated cell types, including [retinal rod cell](/details-cell/CL0000604), [ciliated epithelial cell](/details-cell/CL0000067), and [ependymal cell](/details-cell/CL0000065). Clinically, mutations in [CFAP65](/details-gene/255101) are strongly associated with male infertility, specifically causing severe asthenoteratospermia, which is characterized by multiple morphological abnormalities of the sperm flagella ([Link](https://doi.org/10.1111/cge.13644), [Link](https://doi.org/10.1136/jmedgenet-2019-106031)). ## Cellular Roles and Expression Landscape The expression profile of [CFAP65](/details-gene/255101) points to a highly specialized role in cells possessing ciliary or flagellar structures. **Overall**, the gene shows the highest expression significance (CSI: 5.00) in [retinal rod cell](/details-cell/CL0000604), which contain a modified primary cilium essential for photoreception. This is followed by high significance in [squamous epithelial cell](/details-cell/CL0000076) (CSI: 4.63) and a broad range of overtly ciliated cells, such as [ciliated cell](/details-cell/CL0000064) (CSI: 4.44), [multi-ciliated epithelial cell](/details-cell/CL0005012) (CSI: 2.92), and [lung ciliated cell](/details-cell/CL1000271) (CSI: 2.76). The gene's importance extends to other specialized cell types where cilia play critical signaling or sensory roles. For instance, it is a significant marker in secretory and endocrine cells, including [pancreatic A cell](/details-cell/CL0000171) (CSI: 3.56), [intestine goblet cell](/details-cell/CL0019031) (CSI: 3.14), and [enteroendocrine cell](/details-cell/CL0000164) (CSI: 2.80). This widespread expression pattern across diverse tissues—from the retina and respiratory tract to the pancreas and nervous system ([ependymal cell](/details-cell/CL0000065))—highlights [CFAP65](/details-gene/255101) as a fundamental component of ciliary biology, rather than being restricted to a single organ system. ## Pathways and Molecular Function Functional annotation corroborates the expression data, firmly placing [CFAP65](/details-gene/255101) within the molecular machinery of cilia and flagella. The gene is significantly associated with the biological processes of '[Flagellated sperm motility](/details-go/GO:0030317)' and '[Sperm axoneme assembly](/details-go/GO:0007288)'. This aligns perfectly with the clinical phenotype of male infertility caused by biallelic mutations in the gene, which lead to malformed sperm flagella ([Link](https://doi.org/10.1136/jmedgenet-2019-106344)). At the subcellular level, the [CFAP65](/details-gene/255101) protein is a component of the '[Sperm flagellum](/details-go/GO:0036126)', '[Sperm midpiece](/details-go/GO:0097225)', '[Acrosomal vesicle](/details-go/GO:0001669)', and '[Acrosomal membrane](/details-go/GO:0002080)', indicating a role in both the motile apparatus and the structures critical for fertilization. Its annotated molecular functions, including '[Protein binding](/details-go/GO:0005515)' and '[Rna binding](/details-go/GO:0003723)', suggest it may act as a structural scaffold or a regulatory hub within these complex organelles, potentially mediating interactions between other ciliary components or localizing specific mRNA transcripts for protein synthesis. ## Research Directions The established role of [CFAP65](/details-gene/255101) in sperm flagellar integrity provides a strong foundation for further investigation into its broader functions in other ciliated tissues, where its role remains largely unexplored. **Proposed Hypotheses:** 1. Given its top-ranking expression significance in [retinal rod cell](/details-cell/CL0000604), which rely on a modified cilium for function, loss-of-function variants in [CFAP65](/details-gene/255101) may be an unrecognized cause of retinal ciliopathies, such as retinitis pigmentosa or Leber congenital amaurosis. 2. The unexpected annotation for '[Rna binding](/details-go/GO:0003723)' suggests a potential dual function for [CFAP65](/details-gene/255101). It may not only be a static structural component but could also actively participate in the post-transcriptional regulation or localization of mRNAs encoding other key axonemal proteins at the base of the cilium. 3. The significant expression of [CFAP65](/details-gene/255101) in secretory cells like [pancreatic A cell](/details-cell/CL0000171) and [intestine goblet cell](/details-cell/CL0019031) suggests a potential role in cilia-mediated signaling pathways that regulate hormone or mucus secretion, and its dysfunction could contribute to metabolic or gastrointestinal disorders. **Experimental Approach:** To test the hypothesis that [CFAP65](/details-gene/255101) is critical for retinal health (Hypothesis 1), a murine model with a conditional knockout of `Cfap65` specifically in retinal photoreceptors could be generated. These mice would be subjected to detailed ophthalmological examination, including electroretinography (ERG) to assess retinal function and transmission electron microscopy (TEM) to analyze the ultrastructure of the photoreceptor outer segments for defects consistent with ciliopathies. **Therapeutic Potential:** The primary clinical relevance of [CFAP65](/details-gene/255101) is in recessive male infertility. As this is a loss-of-function disorder, the therapeutic strategy would involve gene restoration rather than inhibition. While challenging, this makes [CFAP65](/details-gene/255101) a potential candidate for gene therapy approaches aimed at correcting spermatogenesis in affected individuals. Furthermore, if a link to retinal or other ciliopathies is established, the gene could become an important diagnostic marker for a broader range of human diseases.

Genular Protein ID: 3750796139

Symbol: CFA65_HUMAN

Name: N/A

UniProtKB Accession Codes:

Database IDs:

Citations:

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

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: 17974005

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

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 33472045

Title: Deleterious variants in X-linked CFAP47 induce asthenoteratozoospermia and primary male infertility.

PubMed ID: 33472045

DOI: 10.1016/j.ajhg.2021.01.002

PubMed ID: 28552195

Title: Biallelic mutations in CFAP43 and CFAP44 cause male infertility with multiple morphological abnormalities of the sperm flagella.

PubMed ID: 28552195

DOI: 10.1016/j.ajhg.2017.04.012

PubMed ID: 31571197

Title: A novel homozygous CFAP65 mutation in humans causes male infertility with multiple morphological abnormalities of the sperm flagella.

PubMed ID: 31571197

DOI: 10.1111/cge.13644

PubMed ID: 31413122

Title: Biallelic mutations in CFAP65 lead to severe asthenoteratospermia due to acrosome hypoplasia and flagellum malformations.

PubMed ID: 31413122

DOI: 10.1136/jmedgenet-2019-106031

PubMed ID: 31501240

Title: Biallelic mutations in CFAP65 cause male infertility with multiple morphological abnormalities of the sperm flagella in humans and mice.

PubMed ID: 31501240

DOI: 10.1136/jmedgenet-2019-106344

PubMed ID: 28585349

Title: CSNK2B splice site mutations in patients cause intellectual disability with or without myoclonic epilepsy.

PubMed ID: 28585349

DOI: 10.1002/humu.23270

Sequence Information:

  • Length: 1925
  • Mass: 217250
  • Checksum: 000CFE2B83394B42
  • Sequence:
  • MFTLTGCRLV EKTQKVENPS VSFASSFPLI PLLLRGKSVQ KKQAESKSQI KLHTQSAPFG 
    LCPKDMMLTQ APSSVVRSRN SRNHTVNSGG SCLSASTVAI PAINDSSAAM SACSTISAQP 
    ASSMDTQMHS PKKQERVNKR VIWGIEVAEE LHWKGWELGK ETTRNLVLKN RSLKLQKMKY 
    RPPKTKFFFT VIPQPIFLSP GITLTLPIVF RPLEAKEYMD QLWFEKAEGM FCVGLRATLP 
    CHRLICRPPS LQLPMCAVGD TTEAFFCLDN VGDLPTFFTW EFSSPFQMLP ATGLLEPGQA 
    SQIKVTFQPL TAVIYEVQAT CWYGAGSRQR SSIQLQAVAK CAQLLVSIKH KCPEDQDAEG 
    FQKLLYFGSV AVGCTSERQI RLHNPSAVNA PFRIEISPDE LAEDQAFSCP TAHGIVLPGE 
    KKCVSVFFHP KTLDTRTVDY CSIMPSGCAS KTLLKVVGFC RGPAVSLQHY CVNFSWVNLG 
    ERSEQPLWIE NQSDCTAHFQ FAIDCLESVF TIRPAFGTLV GKARMTLHCA FQPTHPIICF 
    RRVACLIHHQ DPLFLDLMGT CHSDSTKPAI LKPQHLTWYR THLARGLTLY PPDILDAMLK 
    EKKLAQDQNG ALMIPIQDLE DMPAPQYPYI PPMTEFFFDG TSDITIFPPP ISVEPVEVDF 
    GACPGPEAPN PVPLCLMNHT KGKIMVVWTR RSDCPFWVTP ESCDVPPLKS MAMRLHFQPP 
    HPNCLYTVEL EAFAIYKVLQ SYSNIEEDCT MCPSWCLTVR ARGHSYFAGF EHHIPQYSLD 
    VPKLFPAVSS GEPTYRSLLL VNKDCKLLTF SLAPQRGSDV ILRPTSGLVA PGAHQIILIC 
    TYPEGSSWKQ HTFYLQCNAS PQYLKEVSMY SREEPLQLKL DTHKSLYFKP TWVGCSSTSP 
    FTFRNPSRLP LQFEWRVSEQ HRKLLAVQPS RGLIQPNERL TLTWTFSPLE ETKYLFQVGM 
    WVWEAGLSPN ANPAATTHYM LRLVGVGLTS SLSAKEKELA FGNVLVNSKQ SRFLVLLNDG 
    NCTLYYRLYL EQGSPEAVDN HPLALQLDRT EGSMPPRSQD TICLTACPKQ RSQYSWTITY 
    SLLSHRDNKA GEKQELCCVS LVAVYPLLSI LDVSSMGSAE GITRKHLWRL FSLDLLNSYL 
    ERDPTPCELT YKVPTRHSMS QIPPVLTPLR LDFNFGAAPF KAPPSVVFLA LKNSGVVSLD 
    WAFLLPSDQR IDVELWAEQA ELNSTELHQM RVQDNCLFSI SPKAGSLSPG QEQMVELKYS 
    HLFIGTDHLP VLFKVSHGRE ILLNFIGVTV KPEQKYVHFT STTHQFIPIP IGDTLPPRQI 
    YELYNGGSVP VTYEVQTDVL SQVQEKNFDH PIFCCLNPKG EIQPGSTARV LWIFSPIEAK 
    TYTVDVPIHI LGWNSALIHF QGVGYNPHMM GDTAPFHNIS SWDNSSIHSR LVVPGQNVFL 
    SQSHISLGNI PVQSKCSRLL FLNNISKNEE IAFSWQPSPL DFGEVSVSPM IGVVAPEETV 
    PFVVTLRASV HASFYSADLV CKLYSQQLMR QYHKELQEWK DEKVRQEVEF TITDMKVKKR 
    TCCTACEPAR KYKTLPPIKN QQSVSRPASW KLQTPKEEVS WPCPQPPSPG MLCLGLTARA 
    HATDYFLANF FSEFPCHFLH RELPKRKAPR EESETSEEKS PNKWGPVSKQ KKQLLVDILT 
    TIIRGLLEDK NFHEAVDQSL VEQVPYFRQF WNEQSTKFMD QKNSLYLMPI LPVPSSSWED 
    GKGKQPKEDR PEHYPGLGKK EEGEEEKGEE EEEELEEEEE EEEETEEEEL GKEEIEEKEE 
    ERDEKEEKVS WAGIGPTPQP ESQESMQWQW QQQLNVMVKE EQEQDEKEAI RRLPAFANLQ 
    EALLENMIQN ILVEASRGEV VLTSRPRVIA LPPFCVPRSL TPDTLLPTQQ AEVLHPVVPL 
    PTDLP

Genular Protein ID: 2899999798

Symbol: Q49A14_HUMAN

Name: N/A

UniProtKB Accession Codes:

Database IDs:

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

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: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 15815621

Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.

PubMed ID: 15815621

DOI: 10.1038/nature03466

Sequence Information:

  • Length: 271
  • Mass: 30509
  • Checksum: 7C9CA1CB5A83963E
  • Sequence:
  • MTLHCAFQPT HPIICFRRVA CLIHHQDPLF LDLMGTCHSD STKPAILKPQ HLTWYRTHLA 
    RGLTLYPPDI LDAMLKEKKL AQDQNGALMI PIQDLEDMPA PQYPYIPPMT EFFFDGTSDI 
    TIFPPPISVE PVEVDFGACP GPEAPNPVPL CLMNHTKGKI MVVWTRRSDC PFWVTPESCD 
    VPPLKSMAMR LHFQPPHPNC LYTVELEAFA IYKVCARNER EECGVSARSL SGLVGWQEVT 
    EGSFRLHPLR ARLSLGWTVT PMSLSPPKLL A

Genular Protein ID: 3727686392

Symbol: B4DYZ8_HUMAN

Name: N/A

UniProtKB Accession Codes:

Database IDs:

Sequence Information:

  • Length: 729
  • Mass: 81247
  • Checksum: B90873890D8E44A6
  • Sequence:
  • MLTQAPSSVV RSRNSRNHTV NSGGSCLSAS TVAIPAINDS SAAMSACSTI SAQPASSMDT 
    QMHSPKKQER VNKRVIWGIE VAEELHWKGW ELGKETTRNL VLKNRSLKLQ KMKYRPPKTK 
    FFFTVIPQPI FLSPGITLTL PIVFRPLEAK EYMDQLWFEK AEGMFCVGLR ATLPCHRLIC 
    RPPSLQLPMC AVGDTTEAFF CLDNVGDLPT FFTWEFSSPF QMLPATGLLE PGQASQIKVT 
    FQPLTAVIYE VQATCWYGAG SRQRSSIQLQ AVAKCAQLLV SIKHKCPEDQ DAEGFQKLLY 
    FGSVAVGCTS ERQIRLHNPS AVNAPFRIEI SPDELAEDQA FSCPTAHGIV LPGEKKCVSV 
    FFHPKTLDTR TVDYCSIMPS GCASKTLLKV VGFCRGPAVS LQHYCVNFSW VNLGERSEQP 
    LWIENQSDCT AHFQFAIDCL ESVFTIRPAF GTLVGKARMT LHCAFQPTHP IICFRRVACL 
    IHHQDPLFLD LMGTCHSDST KPAILKPQHL TWYRTHLARG LTLYPPDILD AMLKEKKLAQ 
    DQNGALMIPI QDLEDMPAPQ YPYIPPMTEF FFDGTSDITI FPPPISVEPV EVDFGACPGP 
    EAPNPVPLCL MNHTKGKIMV VWTRRSDCPF WVTPESCDVP PLKSMAMRLH FQPPHPNCLY 
    TVELEAFAIY KVCARNEREE CGVSARSLSG LVGWQEVTEG SFRLHPLRAR LSLGWTVTPM 
    SLSPPKLLA

Genular Protein ID: 1475272337

Symbol: B4DZ05_HUMAN

Name: N/A

UniProtKB Accession Codes:

Database IDs:

Sequence Information:

  • Length: 784
  • Mass: 87583
  • Checksum: F6E0DDCE2FCB9447
  • Sequence:
  • METAIWRRSY ISLISSERPV HNWRGKSVQK KQAESKSQIK LHTQSAPFGL CPKDLMLTQA 
    PSSVVRSRNS RNHTVNSGGS CLSASTVAIP AINDSSAAMS ACSTISAQPA SSMDTQMHSP 
    KKQERVNKRV IWGIEVAEEL HWKGWELGKE TTRNLVLKNR SLKLQKMKYR PPKTKFFFTV 
    IPQPIFLSPG ITLTLPIVFR PLEAKEYMDQ LWFEKAEGMF CVGLRATLPC HRLICRPPSL 
    QLPMCAVGDT TEAFFCLDNV GDLPTFFTWE FSSPFQMLPA TGLLEPGQAS QIKVTFQPLT 
    AVIYEVQATC WYGAGSRQRS SIQLQAVAKC AQLLVSIKHK CPEDQDAEGF QKLLYFGSVA 
    VGCTSERQIR LHNPSAVNAP FRIEISPDEL AEDQAFSCPT AHGIVLPGEK KCVSVFFHPK 
    TLDTRTVDYC SIMPSGCASK TLLKVVGFCR GPAVSLQHYC VNFSWVNLGE RSEQPLWIEN 
    QSDCTAHFQF AIDCLESVFT IRPAFGTLVG KARMTLHCAF QPTHPIICFR RVACLIHHQD 
    PLFLDLMGTC HSDSTKPAIL KPQHLTWYRT HLARGLTLYP PDILDAMLKE KKLAQDQNGA 
    LMIPIQDLED MPAPQYPYIP PMTEFFFDGT SDITIFPPPI SVEPVEVDFG ACPGPEAPNP 
    VPLCLMNHTK GKIMVVWTRR SDCPFWVTPE SCDVPPLKSM AMRLHFQPPH PNCLYTVELE 
    AFAIYKVCAR NEREECGVSA RSLSGLVGWQ EVTEGSFRLH PLRARLSLGW TVTPMSLSPP 
    KLLA