Details for: WDR72

Gene ID: 256764

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: WDR72

Ensembl ID: ENSG00000166415

Description: WD repeat domain 72

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • renal principal cell CL0005009
    CSI 10.39
    rCSI 26.99%
    PRS 95.64
  • midzonal region hepatocyte CL0019028
    CSI 6.76
    rCSI 15.86%
    PRS 93.47
  • mononuclear phagocyte CL0000113
    CSI 6.2
    rCSI 13.64%
    PRS 97.64
  • ionocyte CL0005006
    CSI 6.12
    rCSI 6.56%
    PRS 96.66
  • kidney collecting duct principal cell CL1001431
    CSI 5.75
    rCSI 28.95%
    PRS 93.18
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 5.65
    rCSI 14.62%
    PRS 94.83
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 5.47
    rCSI 14.27%
    PRS 97.36
  • periportal region hepatocyte CL0019026
    CSI 5.33
    rCSI 20.71%
    PRS 93.09
  • pancreatic ductal cell CL0002079
    CSI 5.08
    rCSI 9.89%
    PRS 96.46
  • kidney connecting tubule epithelial cell CL1000768
    CSI 4.91
    rCSI 12.47%
    PRS 93.17
  • epithelial cell of proximal tubule CL0002306
    CSI 4.91
    rCSI 12%
    PRS 91.91
  • renal interstitial pericyte CL1001318
    CSI 3.82
    rCSI 10.52%
    PRS 95.33
  • parietal epithelial cell CL1000452
    CSI 3.76
    rCSI 10.05%
    PRS 93.49
  • renal alpha-intercalated cell CL0005011
    CSI 3.68
    rCSI 4.92%
    PRS 97.34
  • retina horizontal cell CL0000745
    CSI 3.66
    rCSI 5.59%
    PRS 94.2
  • duct epithelial cell CL0000068
    CSI 3.55
    rCSI 5.2%
    PRS 97.84
  • epithelial cell CL0000066
    CSI 3.19
    rCSI 4.9%
    PRS 87.38
  • kidney proximal convoluted tubule epithelial cell CL1000838
    CSI 2.97
    rCSI 31.46%
    PRS 91.57
  • kidney collecting duct intercalated cell CL1001432
    CSI 2.8
    rCSI 20.01%
    PRS 93.13
  • retinal ganglion cell CL0000740
    CSI 2.73
    rCSI 6.03%
    PRS 90.06
  • intrahepatic cholangiocyte CL0002538
    CSI 2.73
    rCSI 6.55%
    PRS 95.72
  • centrilobular region hepatocyte CL0019029
    CSI 2.7
    rCSI 7.05%
    PRS 92.59
  • hepatocyte CL0000182
    CSI 2.67
    rCSI 4.78%
    PRS 94.6
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.45
    rCSI 3.48%
    PRS 95.09
  • renal beta-intercalated cell CL0002201
    CSI 1.55
    rCSI 3.69%
    PRS 96.06
  • kidney loop of Henle thick ascending limb epithelial cell CL1001106
    CSI 1.34
    rCSI 11.58%
    PRS 92.57
  • podocyte CL0000653
    CSI 1.14
    rCSI 5.05%
    PRS 96.05
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 0.96
    rCSI 10.16%
    PRS 93.44
  • ON midget ganglion cell CL4033046
    CSI 0.87
    rCSI 17.82%
    PRS 90.43
  • H2 horizontal cell CL0004218
    CSI 0.86
    rCSI 4.29%
    PRS 92.5
  • OFF midget ganglion cell CL4033047
    CSI 0.36
    rCSI 7.25%
    PRS 90.7

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)

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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 [WDR72](/details-gene/256764) (WD repeat domain 72) is a protein-coding gene located on chromosome 15q21.3. It encodes a protein characterized by multiple WD40 repeats, which typically function as a scaffold for protein-protein interactions. Functionally, [WDR72](/details-gene/256764) is critically involved in biomineralization, with mutations in the gene being the causative factor for a form of autosomal-recessive hypomaturation amelogenesis imperfecta, a developmental disorder affecting tooth enamel ([Link](https://doi.org/10.1016/j.ajhg.2009.09.014)). This is consistent with its annotated roles in `[Ameloblast differentiation](/details-go/GO:0036305)` and `[Enamel mineralization](/details-go/GO:0070166)` ([Link](https://doi.org/10.1016/j.matbio.2014.06.005)). Beyond this specialized function, expression data reveals a prominent and significant role in specific epithelial cell types, particularly within the kidney and liver, such as `[renal principal cell](/details-cell/CL0005009)` and `[midzonal region hepatocyte](/details-cell/CL0019028)`, suggesting broader functions in transport and secretion. ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [WDR72](/details-gene/256764) points to a specialized role in epithelial cells responsible for highly regulated transport and metabolic processes. The gene shows the highest significance in `[renal principal cell](/details-cell/CL0005009)` (CSI: 10.39), a cell type critical for water and electrolyte balance in the kidney's collecting duct. This strong renal signature is further supported by its high significance in multiple other nephron segments, including `[kidney collecting duct principal cell](/details-cell/CL1001431)`, `[kidney loop of Henle thin ascending limb epithelial cell](/details-cell/CL1001107)`, and `[epithelial cell of proximal tubule](/details-cell/CL0002306)`. Beyond the kidney, [WDR72](/details-gene/256764) is also a significant gene in hepatocytes, with high CSI scores in both `[midzonal region hepatocyte](/details-cell/CL0019028)` and `[periportal region hepatocyte](/details-cell/CL0019026)`. This suggests a potential involvement in the liver's metabolic or secretory functions. A secondary signal is observed in phagocytic cells, including `[mononuclear phagocyte](/details-cell/CL0000113)` and `[kidney interstitial alternatively activated macrophage](/details-cell/CL1000695)`, indicating a possible, albeit less prominent, role in these immune cells. The collective data portrays [WDR72](/details-gene/256764) as a key operational gene in a specific subset of epithelial tissues responsible for maintaining organismal homeostasis. ## Pathways and Molecular Function The known functions of [WDR72](/details-gene/256764) are primarily linked to its role in tooth development, as evidenced by its association with `[Ameloblast differentiation](/details-go/GO:0036305)` and `[Enamel mineralization](/details-go/GO:0070166)`. Research suggests it acts as a stage-specific regulator during this process ([Link](https://doi.org/10.1016/j.matbio.2014.06.005)). Its broader functions, implied by its high expression in renal and hepatic cells, are likely related to its involvement in intracellular trafficking and protein localization. This is supported by annotations for `[Endocytosis](/details-go/GO:0006897)`, `[Vesicle organization](/details-go/GO:0016050)`, and `[Protein localization to plasma membrane](/details-go/GO:0072659)`. These processes are fundamental to the physiological roles of the cells where it is highly expressed. For instance, in `[renal principal cell](/details-cell/CL0005009)`, vesicle-mediated transport is essential for regulating the insertion of aquaporin water channels into the plasma membrane. Similarly, its role in `[Regulation of ph](/details-go/GO:0006885)` may be relevant to the function of intercalated cells in the kidney. The protein's localization to the `[Cytoplasm](/details-go/GO:0005737)` and `[Endosome](/details-go/GO:0005768)` is consistent with a role as a scaffolding component in these intracellular pathways. ## Research Directions The well-established role of [WDR72](/details-gene/256764) in amelogenesis provides a strong foundation, but its high and specific expression in other major organs like the kidney and liver suggests uncharacterized functions that warrant investigation. ### Proposed Hypotheses: 1. **Hypothesis 1:** Given its exceptionally high significance in `[renal principal cell](/details-cell/CL0005009)` and its annotated function in vesicle transport, [WDR72](/details-gene/256764) may function as a key scaffolding protein that regulates the trafficking and plasma membrane insertion of aquaporins (e.g., AQP2) or epithelial sodium channels (ENaC) in response to hormonal stimuli like vasopressin, thereby playing a critical role in renal water and sodium homeostasis. 2. **Hypothesis 2:** Based on its high expression in `[midzonal region hepatocyte](/details-cell/CL0019028)` and its link to `[Endocytosis](/details-go/GO:0006897)`, [WDR72](/details-gene/256764) could be involved in receptor-mediated endocytosis of lipoproteins or other circulating molecules, or alternatively, in the vesicular transport pathways required for bile acid secretion, thus contributing to hepatic lipid metabolism and detoxification. ### Suggested Experimental Approach: To test the primary hypothesis regarding its renal function, a conditional knockout mouse model could be developed using a Cre-Lox system with an *Aqp2*-Cre driver to specifically delete [WDR72](/details-gene/256764) in the principal cells of the collecting duct. The physiological consequences could be assessed by subjecting these mice to dehydration or water-loading challenges and measuring key parameters such as urine volume, osmolality, and electrolyte levels. Cellular-level validation could involve isolating primary collecting duct cells from these mice and using immunofluorescence microscopy to determine if the loss of [WDR72](/details-gene/256764) impairs the vasopressin-induced translocation of AQP2 from intracellular vesicles to the apical membrane. ### Therapeutic Potential: Currently, the only known pathology linked to [WDR72](/details-gene/256764) is a congenital disorder, which is not amenable to conventional therapeutic intervention in adults. However, its high tissue-specificity in the kidney and liver makes it an intriguing protein to study in the context of acquired diseases like chronic kidney disease or non-alcoholic steatohepatitis (NASH). If its function is implicated in the pathophysiology of these more common conditions, it could become a potential therapeutic target. As an intracellular scaffolding protein, it would be challenging to target directly with small molecules. Therefore, therapeutic strategies would more likely focus on inhibiting or activating the downstream signaling or transport pathways that it regulates.

Genular Protein ID: 1408636576

Symbol: WDR72_HUMAN

Name: WD repeat-containing protein 72

UniProtKB Accession Codes:

Q3MJ13 Q7Z3I3 Q8N8X2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 7 Ensembl 2 ExpressionAtlas 1 GO 6 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HPA 1 InParanoid 1 IntAct 1 InterPro 5 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 4 SMART 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

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: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

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: 14702039

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

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 19853237

Title: Mutations in the beta propeller WDR72 cause autosomal-recessive hypomaturation amelogenesis imperfecta.

PubMed ID: 19853237

DOI: 10.1016/j.ajhg.2009.09.014

PubMed ID: 25008349

Title: WDR72 models of structure and function: a stage-specific regulator of enamel mineralization.

PubMed ID: 25008349

DOI: 10.1016/j.matbio.2014.06.005

Sequence Information:

  • Length: 1102
  • Mass: 123425
  • Checksum: 0C32B03612C1BE6C
  • Sequence:
    • MRTSLQAVAL WGQKAPPHSI TAIMITDDQR TIVTGSQEGQ LCLWNLSHEL KISAKELLFG 
HSASVTCLAR ARDFSKQPYI VSAAENGEMC VWNVTNGQCM EKATLPYRHT AICYYHCSFR 
MTGEGWLLCC GEYQDVLIID AKTLAVVHSF RSSQFPDWIN CMCIVHSMRI QEDSLLVVSV 
AGELKVWDLS SSINSIQEKQ DVYEKESKFL ESLNCQTIRF CTYTERLLLV VFSKCWKVYD 
YCDFSLLLTE VSRNGQFFAG GEVIAAHRIL IWTEDGHSYI YQLLNSGLSK SIYPADGRVL 
KETIYPHLLC STSVQENKEQ SRPFVMGYMN ERKEPFYKVL FSGEVSGRIT LWHIPDVPVS 
KFDGSPREIP VTATWTLQDN FDKHDTMSQS IIDYFSGLKD GAGTAVVTSS EYIPSLDKLI 
CGCEDGTIII TQALNAAKAR LLEGGSLVKD SPPHKVLKGH HQSVTSLLYP HGLSSKLDQS 
WMLSGDLDSC VILWDIFTEE ILHKFFLEAG PVTSLLMSPE KFKLRGEQII CCVCGDHSVA 
LLHLEGKSCL LHARKHLFPV RMIKWHPVEN FLIVGCADDS VYIWEIETGT LERHETGERA 
RIILNCCDDS QLVKSVLPIA SETLKHKSIE QRSSSPYQLG PLPCPGLQVE SSCKVTDAKF 
CPRPFNVLPV KTKWSNVGFH ILLFDLENLV ELLLPTPLSD VDSSSSFYGG EVLRRAKSTV 
EKKTLTLRKS KTACGPLSAE ALAKPITESL AQGDNTIKFS EENDGIKRQK KMKISKKMQP 
KPSRKVDASL TIDTAKLFLS CLLPWGVDKD LDYLCIKHLN ILKLQGPISL GISLNEDNFS 
LMLPGWDLCN SGMIKDYSGV NLFSRKVLDL SDKYTATLPN QVGIPRGLEN NCDSLRESDT 
IVYLLSRLFL VNKLVNMPLE LACRVGSSFR MESIHNKMRG AGNDILNMSS FYSCLRNGKN 
ESHVPEADLS LLKLISCWRD QSVQVTEAIQ AVLLAEVQQH MKSLGKIPVN SQPVSMAENG 
NCEMKQMLPK LEWTEELELQ CVRNTLPLQT PVSPVKHDSN SNSANFQDVE DMPDRCALEE 
SESPGEPRHH SWIAKVCPCK VS

Genular Protein ID: 2096285454

Symbol: A0A087WTC3_HUMAN

Name: N/A

UniProtKB Accession Codes:

A0A087WTC3

Database IDs:

AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID-ORCS 1 CTD 1 ChiTaRS 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 2 ExpressionAtlas 1 GeneTree 1 HGNC 1 HOGENOM 1 MassIVE 1 NCBI Taxonomy 1 OrthoDB 1 PeptideAtlas 2 Proteomes 2 ProteomicsDB 1 RefSeq 1 SAM 1 UCSC 1 VEuPathDB 1

Citations:

PubMed ID: 11237011

Title: Initial sequencing and analysis of the human genome.

PubMed ID: 11237011

DOI: 10.1038/35057062

PubMed ID: 15496913

Title: Finishing the euchromatic sequence of the human genome.

PubMed ID: 15496913

DOI: 10.1038/nature03001

PubMed ID: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

Sequence Information:

  • Length: 88
  • Mass: 9340
  • Checksum: D29929B7B54E9E3E
  • Sequence:
    • MAGVPPPAWL PPCSLISDCC ASNQRDSVGV GPSEPAPVSP VKHDSNSNSA NFQDVEDMPD 
RCALEESESP GEPRHHSWIA KVCPCKVS