Details for: DNAH17

Gene ID: 8632

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: DNAH17

Ensembl ID: ENSG00000187775

Description: dynein axonemal heavy chain 17

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • retinal bipolar neuron CL0000748
    CSI 4.91
    rCSI 9.2%
    PRS 97.3
  • cerebellar granule cell CL0001031
    CSI 4.33
    rCSI 6.37%
    PRS 97.51
  • rod bipolar cell CL0000751
    CSI 3.93
    rCSI 7.06%
    PRS 97.83
  • ON-bipolar cell CL0000749
    CSI 3.72
    rCSI 5.52%
    PRS 98.29
  • retinal cone cell CL0000573
    CSI 2.83
    rCSI 4.55%
    PRS 97.21
  • retinal rod cell CL0000604
    CSI 2.56
    rCSI 4.5%
    PRS 97.82
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 2.55
    rCSI 6.6%
    PRS 98.94
  • invaginating midget bipolar cell CL4033034
    CSI 2.39
    rCSI 14.12%
    PRS 95.42
  • alveolar macrophage CL0000583
    CSI 2.01
    rCSI 3.31%
    PRS 99.28
  • basal cell of epidermis CL0002187
    CSI 1.69
    rCSI 3%
    PRS 88.03
  • pulmonary alveolar type 1 cell CL0002062
    CSI 1.68
    rCSI 9.68%
    PRS 98.58
  • CD8-positive, alpha-beta memory T cell, CD45RO-positive CL0001203
    CSI 1.5
    rCSI 1.82%
    PRS 91.27
  • flat midget bipolar cell CL4033033
    CSI 0.88
    rCSI 6.31%
    PRS 95.3

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 [DNAH17](/details-gene/8632), or Dynein Axonemal Heavy Chain 17, is a protein-coding gene located on chromosome 17q25.3. It encodes a large component of the outer dynein arm of motile cilia and flagella. As a microtubule-dependent motor protein, [DNAH17](/details-gene/8632) utilizes ATP hydrolysis to generate force, which is essential for ciliary beating and flagellar propulsion. Expression data indicates its high significance in specialized cell types, most notably in neuronal populations of the retina such as [retinal bipolar neuron](/details-cell/CL0000748)s and [cerebellar granule cell](/details-cell/CL0001031)s. Functionally, it is critically involved in cilium movement, and mutations in this gene have been directly linked to male infertility due to defects in sperm motility ([Link](https://doi.org/10.1016/j.ajhg.2019.04.015)). ## Cellular Roles and Expression Landscape The expression profile of [DNAH17](/details-gene/8632) points to a specialized role in cells possessing motile cilia, flagella, or highly developed microtubule-based structures. **Overall**, the gene shows the highest significance in distinct neuronal populations. It is a top marker for [retinal bipolar neuron](/details-cell/CL0000748) (CSI: 4.91), [cerebellar granule cell](/details-cell/CL0001031) (CSI: 4.33), and photoreceptor cells, including [retinal cone cell](/details-cell/CL0000573) and [retinal rod cell](/details-cell/CL0000604). The high expression in photoreceptors is consistent with the presence of a modified primary cilium (the connecting cilium) that is vital for transporting proteins to the outer segment. Its role in other retinal neurons may relate to primary cilia function or other intracellular transport processes. Beyond the nervous system, [DNAH17](/details-gene/8632) is significant in other ciliated or specialized cell types. This includes epithelial cells such as [kidney loop of Henle thin ascending limb epithelial cell](/details-cell/CL1001107) and [pulmonary alveolar type 1 cell](/details-cell/CL0002062), suggesting a potential role in the function of primary cilia in these tissues. Its moderate significance in immune cells like the [alveolar macrophage](/details-cell/CL0000583) and [CD8-positive, alpha-beta memory T cell, CD45RO-positive](/details-cell/CL0001203) may also point to a role for primary cilia in immune sensing and signaling. The established role of [DNAH17](/details-gene/8632) in sperm motility is strongly supported by its functional annotation as a component of the [sperm flagellum](/details-cell/GO:0036126). ## Pathways and Molecular Function Functional annotations provide a clear molecular basis for the role of [DNAH17](/details-gene/8632) as a motor protein within the axoneme. * **Molecular Function:** [DNAH17](/details-gene/8632) exhibits [microtubule motor activity](/details-cell/GO:0003777) and specifically [minus-end-directed microtubule motor activity](/details-cell/GO:0008569). Its function is powered by [ATP binding](/details-cell/GO:0005524) and subsequent hydrolysis. It acts as part of a larger structure, demonstrated by its binding to other dynein components like the dynein intermediate and light intermediate chains ([GO:0045505](/details-cell/GO:0045505), [GO:0051959](/details-cell/GO:0051959)). * **Biological Process:** The primary biological process involving [DNAH17](/details-gene/8632) is [cilium movement involved in cell motility](/details-cell/GO:0060294). It is also integral to the biogenesis of the motor complex itself, specifically in [outer dynein arm assembly](/details-cell/GO:0036158). * **Cellular Component:** [DNAH17](/details-gene/8632) is a core component of the [axonemal dynein complex](/details-cell/GO:0005858), localizing specifically to the [outer dynein arm](/details-cell/GO:0036157) of the [axoneme](/details-cell/GO:0005930). This structural role places it within the [9+2 motile cilium](/details-cell/GO:0097729) and the [sperm flagellum](/details-cell/GO:0036126), explaining its direct impact on the motility of these structures. ## Research Directions The well-defined role of [DNAH17](/details-gene/8632) in sperm motility and its newly highlighted significance in retinal neurons open several avenues for future research. **Proposed Hypotheses:** 1. Mutations in [DNAH17](/details-gene/8632) may underlie certain forms of retinal degenerative diseases. Given its high significance in photoreceptor cells, it is plausible that [DNAH17](/details-gene/8632) is essential for intraflagellar transport (IFT) through the connecting cilium, and its disruption could impair the renewal of the outer segment, leading to cell death and vision loss. 2. Beyond the known severe asthenozoospermia, a spectrum of hypomorphic (partially functional) [DNAH17](/details-gene/8632) variants may contribute to subfertility or reduced sperm motility in the general male population, representing a currently underdiagnosed genetic factor. 3. [DNAH17](/details-gene/8632) dysfunction in respiratory epithelial cells could contribute to subtle primary ciliary dyskinesia (PCD)-like phenotypes, potentially increasing susceptibility to chronic respiratory infections without presenting as classic, full-blown PCD. **Key Experimental Approach:** To test the hypothesis that [DNAH17](/details-gene/8632) is critical for retinal health (Hypothesis 1), a targeted experimental approach could be employed. A conditional knockout mouse model using the Cre-lox system with a photoreceptor-specific Cre driver (e.g., *Opn1-Cre*) would be generated to ablate *Dnah17* specifically in rod and/or cone cells. The retinal health of these mice would be assessed over time using non-invasive electroretinography (ERG) to measure functional decline. Histological analysis and transmission electron microscopy would be used to examine the ultrastructure of the photoreceptor connecting cilium and outer segments for defects. Furthermore, immunohistochemistry could be used to determine if key proteins, such as rhodopsin, are mislocalized within the photoreceptor cell body instead of being transported to the outer segment. **Therapeutic Potential:** As mutations in [DNAH17](/details-gene/8632) lead to a loss of function, therapeutic strategies would likely focus on gene replacement rather than inhibition. For potential retinopathies linked to [DNAH17](/details-gene/8632), adeno-associated virus (AAV)-mediated gene therapy delivered to the subretinal space could be a viable approach, as this method has proven successful for other genetic retinal diseases. However, the large size of the [DNAH17](/details-gene/8632) coding sequence may pose a significant challenge for packaging into conventional AAV vectors, potentially requiring dual-vector strategies. For infertility, genetic intervention is currently more complex, but future advances in germline editing or spermatogonial stem cell therapies could theoretically address this condition.

Genular Protein ID: 4043638187

Symbol: DYH17_HUMAN

Name: Axonemal beta dynein heavy chain 17

UniProtKB Accession Codes:

Q9UFH2 O00431 O15206 Q2M2Y1 Q6ZRQ2 Q8N7Q7

Database IDs:

AGR 1 Antibodypedia 1 Bgee 1 BioMuta 1 CCDS 1 CTD 1 ChEBI 4 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 8 Ensembl 1 ExpressionAtlas 1 GO 15 Gene3D 14 GeneCards 1 GeneTree 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 18 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 12 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 RefSeq 1 SIGNOR 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 16625196

Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage.

PubMed ID: 16625196

DOI: 10.1038/nature04689

PubMed ID: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

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: 9373155

Title: Identification of dynein heavy chain genes expressed in human and mouse testis: chromosomal localization of an axonemal dynein gene.

PubMed ID: 9373155

DOI: 10.1016/s0378-1119(97)00417-4

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: 9545504

Title: A potential human axonemal dynein heavy-chain gene maps to 17q25.

PubMed ID: 9545504

DOI: 10.1007/s003359900782

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 31178125

Title: Mutations in DNAH17, Encoding a Sperm-Specific Axonemal Outer Dynein Arm Heavy Chain, Cause Isolated Male Infertility Due to Asthenozoospermia.

PubMed ID: 31178125

DOI: 10.1016/j.ajhg.2019.04.015

Sequence Information:

  • Length: 4462
  • Mass: 509313
  • Checksum: AEDDF56145E1F2A8
  • Sequence:
    • MTMAPDVRLE YLEEVASIVL KFKPDKWSKL IGAEENVALF TEFFEKPDVQ VLVLTLNAAG 
MIIPCLGFPQ SLKSKGVYFI KTKSENINKD NYRARLLYGD ISPTPVDQLI AVVEEVLSSL 
LNQSENMAGW PQVVSEDIVK QVHRLKNEMF VMSGKIKGKT LLPIPEHLGS LDGTLESMER 
IPSSLDNLLL HAIETTIIDW SHQIRDVLSK DSAQALLDGL HPLPQVEFEF WDTRLLNLKC 
IHEQLNRPKV NKIVEILEKA KSCYWPALQN VYTNVTEGLK EANDIVLYLK PLRILLEEME 
QADFTMLPTF IAKVLDTICF IWATSEYYNT PARIIVILQE FCNQIIEMTR TFLSPEEVLK 
GLQGEIEEVL SGISLAVNVL KELYQTYDFC CVNMKLFFKD KEPVPWEFPS SLAFSRINSF 
FQRIQTIEEL YKTAIEFLKL EKIELGGVRG NLLGSLVTRI YDEVFELVKV FADCKYDPLD 
PGDSNFDRDY ADFEIKIQDL DRRLATIFCQ GFDDCSCIKS SAKLLYMCGG LMERPLILAE 
VAPRYSVMLE LFDAELDNAK ILYDAQMAAS EEGNIPLIHK NMPPVAGQLK WSLELQERLE 
VSMKHLKHVE HPVMSGAEAK LTYQKYDEMM ELLRCHREKI YQQWVAGVDQ DCHFNLGQPL 
ILRDAASNLI HVNFSKALVA VLREVKYLNF QQQKEIPDSA ESLFSENETF RKFVGNLELI 
VGWYNEIKTI VKAVEFLLIK SELEAIDVKL LSAETTLFWN GEGVFQYIQE VREILHNLQN 
RMQKAKQNIE GISQAMKDWS ANPLFERKDN KKEALLDLDG RIANLNKRYA AVRDAGVKIQ 
AMVAENAELF RADTLSLPWK DYVIYIDDMV LDEFDQFIRK SLSFLMDNMV IDESIAPLFE 
IRMELDEDGL TFNPTLEVGS DRGFLALIEG LVNDIYNVAR LIPRLAKDRM NYKMDLEDNT 
DLIEMREEVS SLVINAMKEA EEYQDSFERY SYLWTDNLQE FMKNFLIYGC AVTAEDLDTW 
TDDTIPKTPP TLAQFQEQID SYEKLYEEVS KCENTKVFHG WLQCDCRPFK QALLSTIRRW 
GFMFKRHLSN HVTNSLADLE AFMKVARMGL TKPLKEGDYD GLVEVMGHLM KVKERQAATD 
NMFEPLKQTI ELLKTYGEEM PEEIHLKLQE LPEHWANTKK LAIQVKLTVA PLQANEVSIL 
RRKCQQFELK QHEFRERFRR EAPFSFSDPN PYKSLNKQQK SISAMEGIME ALSKSGGLFE 
VPVPDYKQLK ACHREVRLLK ELWDMVVVVN TSIEDWKTTK WKDINVEQMD IDCKKFAKDM 
RSLDKEMKTW DAFVGLDNTV KNVITSLRAV SELQNPAIRE RHWQQLMQAT QVKFKMSEET 
TLADLLQLNL HSYEDEVRNI VDKAVKESGM EKVLKALDST WSMMEFQHEP HPRTGTMMLK 
SSEVLVETLE DNQVQLQNLM MSKYLAHFLK EVTSWQQKLS TADSVISIWF EVQRTWSHLE 
SIFIGSEDIR TQLPGDSQRF DDINQEFKAL MEDAVKTPNV VEATSKPGLY NKLEALKKSL 
AICEKALAEY LETKRLAFPR FYFVSSADLL DILSNGNDPV EVSRHLSKLF DSLCKLKFRL 
DASDKPLKVG LGMYSKEDEY MVFDQECDLS GQVEVWLNRV LDRMCSTLRH EIPEAVVTYE 
EKPREQWILD YPAQVALTCT QIWWTTEVGL AFARLEEGYE NAIRDYNKKQ ISQLNVLITL 
LMGNLNAGDR MKIMTICTID VHARDVVAKM IVAKVESSQA FTWQAQLRHR WDEEKRHCFA 
NICDAQIQYS YEYLGNTPRL VITPLTDRCY ITLTQSLHLI MGGAPAGPAG TGKTETTKDL 
GRALGTMVYV FNCSEQMDYK SCGNIYKGLA QTGAWGCFDE FNRISVEVLS VIAVQVKCVQ 
DAIRAKKKAF NFLGEIIGLI PTVGIFITMN PGYAGRAELP ENLKALFRPC AMVVPDFELI 
CEIMLMAEGF LEARLLARKF ITLYTLCKEL LSKQDHYDWG LRAIKSVLVV AGSLKRGDPS 
RAEDQVLMRA LRDFNIPKIV TDDLPVFMGL IGDLFPALDV PRKRDLNFEK IIKQSIVELK 
LQAEDSFVLK VVQLEELLQV RHSVFIVGNA GSGKSQVLKS LNKTYQNLKR KPVAVDLDPK 
AVTCDELFGI INPVTREWKD GLFSTIMRDL ANITHDGPKW IILDGDIDPM WIESLNTVMD 
DNKVLTLASN ERIPLNRTMR LVFEISHLRT ATPATVSRAG ILYINPADLG WNPVVSSWIE 
RRKVQSEKAN LMILFDKYLP TCLDKLRFGF KKITPVPEIT VIQTILYLLE CLLTEKTVPP 
DSPRELYELY FVFTCFWAFG GAMFQDQLVD YRVEFSKWWI NEFKTIKFPS QGTIFDYYID 
PDTKKFLPWT DKVPSFELDP DVPLQASLVH TTETIRIRYF MDLLMEKSWP VMLVGNAGTG 
KSVLMGDKLE SLNTDNYLVQ AVPFNFYTTS AMLQGVLEKP LEKKSGRNYG PPGTKKLVYF 
IDDMNMPEVD KYGTVAPHTL IRQHMDHRHW YDRHKLTLKD IHNCQYVACM NPTSGSFTID 
SRLQRHFCVF AVSFPGQEAL TTIYNTILTQ HLAFRSVSMA IQRISSQLVA AALALHQKIT 
ATFLPTAIKF HYVFNLRDLS NIFQGLLFST AEVLKTPLDL VRLWLHETER VYGDKMVDEK 
DQETLHRVTM ASTKKFFDDL GDELLFAKPN IFCHFAQGIG DPKYVPVTDM APLNKLLVDV 
LDSYNEVNAV MNLVLFEDAV AHICRINRIL ESPRGNALLV GVGGSGKQSL SRLAAYISGL 
DVFQITLKKG YGIPDLKIDL AAQYIKAAVK NVPSVFLMTD SQVAEEQFLV LINDLLASGE 
IPGLFMEDEV ENIISSMRPQ VKSLGMNDTR ETCWKFFIEK VRRQLKVILC FSPVGSVLRV 
RARKFPAVVN CTAIDWFHEW PEDALVSVSA RFLEETEGIP WEVKASISFF MSYVHTTVNE 
MSRVYLATER RYNYTTPKTF LEQIKLYQNL LAKKRTELVA KIERLENGLM KLQSTASQVD 
DLKAKLAIQE AELKQKNESA DQLIQVVGIE AEKVSKEKAI ADQEEVKVEV INKNVTEKQK 
ACETDLAKAE PALLAAQEAL DTLNKNNLTE LKSFGSPPDA VVNVTAAVMI LTAPGGKIPK 
DKSWKAAKIM MGKVDTFLDS LKKFDKEHIP EACLKAFKPY QGNPTFDPEF IRSKSTAAAG 
LCSWCINIVR FYEVYCDVAP KRQALEEANA ELAEAQEKLS RIKNKIAELN ANLSNLTSAF 
EKATAEKIKC QQEADATNRV ILLANRLVGG LASENIRWAE SVENFRSQGV TLCGDVLLIS 
AFVSYVGYFT KKYRNELMEK FWIPYIHNLK VPIPITNGLD PLSLLTDDAD VATWNNQGLP 
SDRMSTENAT ILGNTERWPL IVDAQLQGIK WIKNKYRSEL KAIRLGQKSY LDVIEQAISE 
GDTLLIENIG ETVDPVLDPL LGRNTIKKGK YIKIGDKEVE YHPKFRLILH TKYFNPHYKP 
EMQAQCTLIN FLVTRDGLED QLLAAVVAKE RPDLEQLKAN LTKSQNEFKI VLKELEDSLL 
ARLSAASGNF LGDTALVENL ETTKHTASEI EEKVVEAKIT EVKINEAREN YRPAAERASL 
LYFILNDLNK INPVYQFSLK AFNVVFEKAI QRTTPANEVK QRVINLTDEI TYSVYMYTAR 
GLFERDKLIF LAQVTFQVLS MKKELNPVEL DFLLRFPFKA GVVSPVDFLQ HQGWGGIKAL 
SEMDEFKNLD SDIEGSAKRW KKLVESEAPE KEIFPKEWKN KTALQKLCMV RCLRPDRMTY 
AIKNFVEEKM GSKFVEGRSV EFSKSYEESS PSTSIFFILS PGVDPLKDVE ALGKKLGFTI 
DNGKLHNVSL GQGQEVVAEN ALDVAAEKGH WVILQNIHLV ARWLGTLDKK LEHYSTGSHE 
DYRVFISAEP APSPETHIIP QGILENAIKI TNEPPTGMHA NLHKALDLFT QDTLEMCTKE 
MEFKCMLFAL CYFHAVVAER RKFGAQGWNR SYPFNNGDLT ISINVLYNYL EANPKVPWDD 
LRYLFGEIMY GGHITDDWDR RLCRTYLAEY IRTEMLEGDV LLAPGFQIPP NLDYKGYHEY 
IDENLPPESP YLYGLHPNAE IGFLTVTSEK LFRTVLEMQP KETDSGAGTG VSREEKVKAV 
LDDILEKIPE TFNMAEIMAK AAEKTPYVVV AFQECERMNI LTNEMRRSLK ELNLGLKGEL 
TITTDVEDLS TALFYDTVPD TWVARAYPSM MGLAAWYADL LLRIRELEAW TTDFALPTTV 
WLAGFFNPQS FLTAIMQSMA RKNEWPLDKM CLSVEVTKKN REDMTAPPRE GSYVYGLFME 
GARWDTQTGV IAEARLKELT PAMPVIFIKA IPVDRMETKN IYECPVYKTR IRGPTYVWTF 
NLKTKEKAAK WILAAVALLL QV