Details for: PKHD1L1

Gene ID: 93035

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: PKHD1L1

Ensembl ID: ENSG00000205038

Description: PKHD1 like 1

Cell Significance Landscape

Associated with

Significant Cells

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

  • IgG plasma cell CL0000985
    CSI 15.32
    rCSI 18.35%
    PRS 98.45
  • plasmablast CL0000980
    CSI 14.61
    rCSI 11.49%
    PRS 98.54
  • endocardial cell CL0002350
    CSI 11.2
    rCSI 53.61%
    PRS 98.14
  • cardiac muscle cell CL0000746
    CSI 10.43
    rCSI 14.97%
    PRS 96.54
  • cardiac endothelial cell CL0010008
    CSI 8.89
    rCSI 35.86%
    PRS 99.07
  • retinal blood vessel endothelial cell CL0002585
    CSI 6.1
    rCSI 9.74%
    PRS 99.37
  • platelet CL0000233
    CSI 5.57
    rCSI 23.1%
    PRS 96.5
  • secretory cell CL0000151
    CSI 5.56
    rCSI 5.8%
    PRS 98.75
  • adipocyte CL0000136
    CSI 5.26
    rCSI 6.75%
    PRS 97.06
  • endothelial cell of lymphatic vessel CL0002138
    CSI 5.02
    rCSI 9.95%
    PRS 98.89
  • cardiac blood vessel endothelial cell CL0010006
    CSI 4.64
    rCSI 32.78%
    PRS 97.6
  • ciliated epithelial cell CL0000067
    CSI 3.13
    rCSI 2.75%
    PRS 96.7
  • epithelial cell CL0000066
    CSI 2.97
    rCSI 4.56%
    PRS 94.93
  • megakaryocyte CL0000556
    CSI 2.7
    rCSI 11.7%
    PRS 97.91
  • mesothelial cell CL0000077
    CSI 1.75
    rCSI 6.83%
    PRS 95.28

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 [PKHD1L1](/details-gene/93035) (Polycystic Kidney And Hepatic Disease 1 Like 1) encodes the protein Fibrocystin-L, a large receptor-like protein. While its precise function is still under investigation, data suggests it plays significant roles in both the immune system and sensory perception. **Overall**, expression analysis reveals that [PKHD1L1](/details-gene/93035) is a highly significant marker for terminally differentiated antibody-secreting cells, including [IgG plasma cells](/details-cell/CL0000985) and [plasmablasts](/details-cell/CL0000980). It also shows prominent expression in various cardiovascular cell types, such as [endocardial cells](/details-cell/CL0002350) and [cardiac muscle cells](/details-cell/CL0000746). Clinically, mutations in [PKHD1L1](/details-gene/93035) have been linked to autosomal recessive nonsyndromic hearing loss, underscoring its critical role in the auditory system ([Link](https://doi.org/10.1007/s00439-024-02649-2)). ## Cellular Roles and Expression Landscape The expression profile of [PKHD1L1](/details-gene/93035) highlights its specialized roles in distinct cellular contexts. **Overall**, the gene's most significant expression is observed within the humoral immune system, where it serves as a top marker for [IgG plasma cells](/details-cell/CL0000985) (CSI: 15.32) and [plasmablasts](/details-cell/CL0000980) (CSI: 14.61). This strong and specific expression pattern suggests a key function in the late stages of B-cell differentiation and the maintenance or function of antibody-producing cells. One study also reported inducible expression in T lymphocytes, suggesting a broader role in adaptive immunity ([Link](https://doi.org/10.1093/hmg/ddg068)). Beyond the immune system, [PKHD1L1](/details-gene/93035) demonstrates a notable presence in the cardiovascular system. It is highly significant in [endocardial cells](/details-cell/CL0002350) (CSI: 11.20), [cardiac muscle cells](/details-cell/CL0000746) (CSI: 10.43), and various other endothelial cell populations, including [cardiac endothelial cells](/details-cell/CL0010008) and [retinal blood vessel endothelial cells](/details-cell/CL0002585). This pattern points towards a potential, though less characterized, role in cardiac function or vascular biology. Additionally, significant expression is noted in [platelets](/details-cell/CL0000233) and their precursors, [megakaryocytes](/details-cell/CL0000556), hinting at a function in hemostasis. ## Pathways and Molecular Function The functional annotations for [PKHD1L1](/details-gene/93035) align well with its expression landscape and clinical associations. Its involvement in the 'Immune response' ([GO:0006955](https://www.ebi.ac.uk/QuickGO/term/GO:0006955)) is consistent with its high significance in plasma cells. The gene's connection to 'Sensory perception of sound' ([GO:0007605](https://www.ebi.ac.uk/QuickGO/term/GO:0007605)) is strongly supported by its established role in the inner ear and its association with hereditary hearing loss ([Link](https://doi.org/10.1007/s00439-024-02649-2)). At the molecular level, [PKHD1L1](/details-gene/93035) is annotated with 'Signaling receptor activity' ([GO:0038023](https://www.ebi.ac.uk/QuickGO/term/GO:0038023)), which is consistent with its predicted protein structure. Cellular component analysis places the protein in the [membrane](/details-cell/GO:0016020) and [extracellular space](/details-cell/GO:0005615), as well as in highly specialized structures like the stereocilium. Its specific localization to the 'Stereocilium coat' ([GO:0120234](https://www.ebi.ac.uk/QuickGO/term/GO:0120234)) and 'Stereocilium tip' ([GO:0032426](https://www.ebi.ac.uk/QuickGO/term/GO:0032426)) directly explains its essential function in the mechanotransduction process of hearing. ## Research Directions While the role of [PKHD1L1](/details-gene/93035) in hearing is becoming clearer, its function in the immune and cardiovascular systems remains largely unexplored and presents compelling avenues for future research. **Proposed Hypotheses:** 1. Given its high expression in antibody-secreting cells and its function as a signaling receptor, [PKHD1L1](/details-gene/93035) may be critical for the long-term survival, maintenance, or antibody secretion capacity of terminally differentiated plasma cells in bone marrow niches. 2. The significant expression of [PKHD1L1](/details-gene/93035) in [cardiac muscle cells](/details-cell/CL0000746) and [endocardial cells](/details-cell/CL0002350) suggests it may function as an adhesion or signaling molecule essential for maintaining the structural or functional integrity of heart tissue. **Experimental Approach:** To test the hypothesis regarding its role in plasma cell biology, a conditional knockout mouse model could be employed. Specifically, deleting [Pkhd1l1](/details-gene/93035) in B-lineage cells (e.g., using a *Cd19-Cre* driver) would allow for a detailed investigation. Following immunization with a T-dependent antigen, key parameters such as the formation of germinal centers, the generation of antigen-specific plasma cells, and the maintenance of long-lived plasma cells in the bone marrow could be quantified via flow cytometry and ELISpot assays. A significant reduction in long-lived plasma cell populations or serum antibody titers in knockout animals compared to controls would confirm a vital role for [PKHD1L1](/details-gene/93035) in humoral immunity. **Therapeutic Potential:** The high and specific expression of [PKHD1L1](/details-gene/93035) on the surface of plasma cells makes it an attractive therapeutic target for diseases driven by pathogenic antibodies or malignant plasma cells, such as multiple myeloma or certain autoimmune disorders. As a surface receptor, it is amenable to targeting by monoclonal antibodies, antibody-drug conjugates (ADCs), or chimeric antigen receptor (CAR)-T cell therapies. Such a strategy, focused on **inhibition** or targeted depletion of plasma cells, could offer a highly specific treatment modality with potentially fewer off-target effects compared to broadly immunosuppressive agents.

Genular Protein ID: 1981858453

Symbol: PKHL1_HUMAN

Name: Fibrocystin-L

UniProtKB Accession Codes:

Q86WI1 Q567P2 Q9UF27

Database IDs:

AGR 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 2 CTD 1 CarbonylDB 1 ChiTaRS 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 1 ExpressionAtlas 1 GO 8 Gene3D 3 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyCosmos 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 11 KEGG 1 MANE-Select 1 MIM 3 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PIR 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMART 4 SMR 1 STRING 1 SUPFAM 4 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12620974

Title: PKHDL1, a homolog of the autosomal recessive polycystic kidney disease gene, encodes a receptor with inducible T lymphocyte expression.

PubMed ID: 12620974

DOI: 10.1093/hmg/ddg068

PubMed ID: 16421571

Title: DNA sequence and analysis of human chromosome 8.

PubMed ID: 16421571

DOI: 10.1038/nature04406

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: 38459354

Title: PKHD1L1, a gene involved in the stereocilia coat, causes autosomal recessive nonsyndromic hearing loss.

PubMed ID: 38459354

DOI: 10.1007/s00439-024-02649-2

Sequence Information:

  • Length: 4243
  • Mass: 465734
  • Checksum: A3A50CA85C5DA500
  • Sequence:
    • MGHLWLLGIW GLCGLLLCAA DPSTDGSQII PKVTEIIPKY GSINGATRLT IRGEGFSQAN 
QFNYGVDNAE LGNSVQLISS FQSITCDVEK DASHSTQITC YTRAMPEDSY TVRVSVDGVP 
VTENNTCKGH INSWECTFNA KSFRTPTIRS ITPLSGTPGT LITIQGRIFT DVYGSNIALS 
SNGKNVRILR VYIGGMPCEL LIPQSDNLYG LKLDHPNGDM GSMVCKTTGT FIGHHNVSFI 
LDNDYGRSFP QKMAYFVSSL NKIAMFQTYA EVTMIFPSQG SIRGGTTLTI SGRFFDQTDF 
PVRVLVGGEP CDILNVTENS ICCKTPPKPH ILKTVYPGGR GLKLEVWNNS RPIRLEEILE 
YNEKTPGYMG ASWVDSASYI WLMEQDTFVA RFSGFLVAPD SDVYRFYIKG DDRYAIYFSQ 
TGLPEDKVRI AYHSANANSY FSSPTQRSDD IHLQKGKEYY IEILLQEYRL SAFVDVGLYQ 
YRNVYTEQQT GDAVNEEQVI KSQSTILQEV QVITLENWET TNAINEVQKI KVTSPCVEAN 
SCSLYQYRLI YNMEKTVFLP ADASEFILQS ALNDLWSIKP DTVQVIRTQN PQSYVYMVTF 
ISTRGDFDLL GYEVVEGNNV TLDITEQTKG KPNLETFTLN WDGIASKPLT LWSSEAEFQG 
AVEEMVSTKC PPQIANFEEG FVVKYFRDYE TDFNLEHINR GQKTAETDAY CGRYSLKNPA 
VLFDSADVKP NRRPYGDILL FPYNQLCLAY KGFLANYIGL KFQYQDNSKI TRSTDTQFTY 
NFAYGNNWTY TCIDLLDLVR TKYTGTNVSL QRISLHKASE SQSFYVDVVY IGHTSTISTL 
DEMPKRRLPA LANKGIFLEH FQVNQTKTNG PTMTNQYSVT MTSYNCSYNI PMMAVSFGQI 
ITHETENEFV YRGNNWPGES KIHIQRIQAA SPPLSGSFDI QAYGHILKGL PAAVSAADLQ 
FALQSLEGMG RISVTREGTC AGYAWNIKWR STCGKQNLLQ INDSNIIGEK ANMTVTRIKE 
GGLFRQHVLG DLLRTPSQQP QVEVYVNGIP AKCSGDCGFT WDSNITPLVL AISPSQGSYE 
EGTILTIVGS GFSPSSAVTV SVGPVGCSLL SVDEKELKCQ ILNGSAGHAP VAVSMADVGL 
AQNVGGEEFY FVYQSQISHI WPDSGSIAGG TLLTLSGFGF NENSKVLVGN ETCNVIEGDL 
NRITCRTPKK TEGTVDISVT TNGFQATARD AFSYNCLQTP IITDFSPKVR TILGEVNLTI 
KGYNFGNELT QNMAVYVGGK TCQILHWNFT DIRCLLPKLS PGKHDIYVEV RNWGFASTRD 
KLNSSIQYVL EVTSMFPQRG SLFGGTEITI RGFGFSTIPA ENTVLLGSIP CNVTSSSENV 
IKCILHSTGN IFRITNNGKD SVHGLGYAWS PPVLNVSVGD TVAWHWQTHP FLRGIGYRIF 
SVSSPGSVIY DGKGFTSGRQ KSTSGSFSYQ FTSPGIHYYS SGYVDEAHSI FLQGVINVLP 
AETRHIPLHL FVGRSEATYA YGGPENLHLG SSVAGCLATE PLCSLNNTRV KNSKRLLFEV 
SSCFSPSISN ITPSTGTVNE LITIIGHGFS NLPWANKVTI GSYPCVVEES SEDSITCHID 
PQNSMDVGIR ETVTLTVYNL GTAINTLSNE FDRRFVLLPN IDLVLPNAGS TTGMTSVTIK 
GSGFAVSSAG VKVLMGHFPC KVLSVNYTAI ECETSPAAQQ LVDVDLLIHG VPAQCQGNCT 
FSYLESITPY ITGVFPNSVI GSVKVLIEGE GLGTVLEDIA VFIGNQQFRA IEVNENNITA 
LVTPLPVGHH SVSVVVGSKG LALGNLTVSS PPVASLSPTS GSIGGGTTLV ITGNGFYPGN 
TTVTIGDEPC QIISINPNEV YCRTPAGTTG MVDVKIFVNT IAYPPLLFTY ALEDTPFLRG 
IIPSRGPPGT EIEITGSNFG FEILEISVMI NNIQCNVTMA NDSVVQCIVG DHAGGTFPVM 
MHHKTKGSAM STVVFEYPLN IQNINPSQGS FGGGQTMTVT GTGFNPQNSI ILVCGSECAI 
DRLRSDYTTL LCEIPSNNGT GAEQACEVSV VNGKDLSQSM TPFTYAVSLT PLITAVSPKR 
GSTAGGTRLT VVGSGFSENM EDVHITIAEA KCDVEYSNKT HIICMTDAHT LSGWAPVCVH 
IRGVGMAKLD NADFLYVDAW SSNFSWGGKS PPEEGSLVVI TKGQTILLDQ STPILKMLLI 
QGGTLIFDEA DIELQAENIL ITDGGVLQIG TETSPFQHKA VITLHGHLRS PELPVYGAKT 
LAVREGILDL HGVPVPVTWT RLAHTAKAGE RILILQEAVT WKPGDNIVIA STGHRHSQGE 
NEKMTIASVS ADGINITLSN PLNYTHLGIT VTLPDGTLFE ARAEVGILTR NILIRGSDNV 
EWNNKIPACP DGFDTGEFAT QTCLQGKFGE EIGSDQFGGC VMFHAPVPGA NMVTGRIEYV 
EVFHAGQAFR LGRYPIHWHL LGDLQFKSYV RGCAIHQAYN RAVTIHNTHH LLVERNIIYD 
IKGGAFFIED GIEHGNILQY NLAVFVQQST SLLNDDVTPA AFWVTNPNNT IRHNAVAGGT 
HFGFWYRMNN HPDGPSYDRN ICQKRVPLGE FFNNTVHSQG WFGMWIFEEY FPMQTGSCTS 
TVPAPAIFNS LTTWNCQKGA EWVNGGALQF HNFVMVNNYE AGIETKRILA PYVGGWGETN 
GAVIKNAKIV GHLDELGMGS AFCTAKGLVL PFSEGLTVSS VHFMNFDRPN CVALGVTSIS 
GVCNDRCGGW SAKFVDVQYS HTPNKAGFRW EHEMVMIDVD GSLTGHKGHT VIPHSSLLDP 
SHCTQEAEWS IGFPGSVCDA SVSFHRLAFN QPSPVSLLEK DVVLSDSFGT SIIPFQKKRL 
THMSGWMALI PNANHINWYF KGVDHITNIS YTSTFYGFKE EDYVIISHNF TQNPDMFNII 
DMRNGSSNPL NWNTSKNGDW HLEANTSTLY YLVSGRNDLH QSQLISGNLD PDVKDVVINF 
QAYCCILQDC FPVHPPSRKP IPKKRPATYN LWSNDSFWQS SRENNYTVPH PGANVIIPEG 
TWIVADIDMP SMERLIIWGV LELEDKYNVG AAESSYREVV LNATYISLQG GRLIGGWEDN 
PFKGDLKIVL RGNHTTQDWA LPEGPNQGAK VLGVFGELDL HGIPHSIYKT KLSETAFAGS 
KVLSLMDAVD WQEGEEIVIT TTSYDFHQTE TRSIVKILHD HKILILNDSL SYTHFAEKYH 
VPGTGESYTL AADVGILSRN IKIVGEDYPG WSEDSFGARV LVGSFTENMM TFKGNARISN 
VEFYHSGQEG FRDSTDPRYA VTFLNLGQIQ EHGSSYIRGC AFHHGFSPAI GVFGTDGLDI 
DDNIIHFTVG EGIRIWGNAN RVRGNLIALS VWPGTYQNRK DLSSTLWHAA IEINRGTNTV 
LQNNVVAGFG RAGYRIDGEP CPGQFNPVEK WFDNEAHGGL YGIYMNQDGL PGCSLIQGFT 
IWTCWDYGIY FQTTESVHIY NVTLVDNGMA IFPMIYMPAA ISHKISSKNV QIKSSLIVGS 
SPGFNCSDVL TNDDPNIELT AAHRSPRSPS GGRSGICWPT FASAHNMAPR KPHAGIMSYN 
AISGLLDISG STFVGFKNVC SGETNVIFIT NPLNEDLQHP IHVKNIKLVD TTEQSKIFIH 
RPDISKVNPS DCVDMVCDAK RKSFLRDIDG SFLGNAGSVI PQAEYEWDGN SQVGIGDYRI 
PKAMLTFLNG SRIPVTEKAP HKGIIRDSTC KYLPEWQSYQ CFGMEYAMMV IESLDPDTET 
RRLSPVAIMG NGYVDLINGP QDHGWCAGYT CQRRLSLFHS IVALNKSYEV YFTGTSPQNL 
RLMLLNVDHN KAVLVGIFFS TLQRLDVYVN NLLVCPKTTI WNAQQKHCEL NNHLYKDQFL 
PNLDSTVLGE NYFDGTYQML YLLVKGTIPV EIHTATVIFV SFQLSVATED DFYTSHNLVK 
NLALFLKIPS DKIRISKIRG KSLRRKRSMG FIIEIEIGDP PIQFISNGTT GQMQLSELQE 
IAGSLGQAVI LGNISSILGF NISSMSITNP LPSPSDSGWI KVTAQPVERS AFPVHHVAFV 
SSLLVITQPV AAQPGQPFPQ QPSVKATDSD GNCVSVGITA LTLRAILKDS NNNQVNGLSG 
NTTIPFSSCW ANYTDLTPLR TGKNYKIEFI LDNVVGVESR TFSLLAESVS SSGSSSSSNS 
KASTVGTYAQ IMTVVISCLV GRMWLLEIFM AAVSTLNITL RSY