Details for: SHROOM4

Gene ID: 57477

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: SHROOM4

Ensembl ID: ENSG00000158352

Description: shroom family member 4

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

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

  • blood vessel endothelial cell CL0000071
    CSI 7.6
    rCSI 15.76%
    PRS 83.68
  • Mueller cell CL0000636
    CSI 6.14
    rCSI 14.01%
    PRS 78.76
  • retinal blood vessel endothelial cell CL0002585
    CSI 5.48
    rCSI 8.75%
    PRS 89.36
  • epithelial cell of proximal tubule CL0002306
    CSI 4.98
    rCSI 12.17%
    PRS 79.01
  • cerebral cortex endothelial cell CL1001602
    CSI 4.21
    rCSI 7.28%
    PRS 79.37
  • melanocyte CL0000148
    CSI 4.1
    rCSI 3.04%
    PRS 81.22
  • pulmonary capillary endothelial cell CL4028001
    CSI 3.84
    rCSI 7.31%
    PRS 93.09
  • kidney interstitial alternatively activated macrophage CL1000695
    CSI 3.64
    rCSI 9.48%
    PRS 87.5
  • lung secretory cell CL1000272
    CSI 3.28
    rCSI 8.11%
    PRS 86.71
  • fibroblast of cardiac tissue CL0002548
    CSI 3.11
    rCSI 14.87%
    PRS 86.56
  • endothelial cell of pericentral hepatic sinusoid CL0019022
    CSI 3.06
    rCSI 9.44%
    PRS 88.95
  • neural crest cell CL0011012
    CSI 3.04
    rCSI 2.4%
    PRS 77.24
  • lung endothelial cell CL1001567
    CSI 2.75
    rCSI 6.42%
    PRS 93.43
  • chondrocyte CL0000138
    CSI 2.74
    rCSI 4.36%
    PRS 80.45
  • hepatic stellate cell CL0000632
    CSI 2.63
    rCSI 9.84%
    PRS 80.17
  • kidney loop of Henle thick ascending limb epithelial cell CL1001106
    CSI 2.51
    rCSI 21.71%
    PRS 80.84
  • cardiac neuron CL0010022
    CSI 2.3
    rCSI 7.36%
    PRS 84.18
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 2.23
    rCSI 3.16%
    PRS 83.45
  • renal principal cell CL0005009
    CSI 2.12
    rCSI 5.51%
    PRS 85.95
  • Schwann cell CL0002573
    CSI 2.12
    rCSI 6.02%
    PRS 81.97
  • renal interstitial pericyte CL1001318
    CSI 1.99
    rCSI 5.49%
    PRS 82.43
  • endocardial cell CL0002350
    CSI 1.94
    rCSI 9.31%
    PRS 82.31
  • pulmonary artery endothelial cell CL1001568
    CSI 1.94
    rCSI 2.64%
    PRS 92.08
  • kidney connecting tubule epithelial cell CL1000768
    CSI 1.8
    rCSI 4.56%
    PRS 78.36
  • cardiac endothelial cell CL0010008
    CSI 1.7
    rCSI 6.85%
    PRS 86.65
  • pulmonary alveolar type 2 cell CL0002063
    CSI 1.64
    rCSI 2.54%
    PRS 88.32
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 1.52
    rCSI 3.94%
    PRS 82.63
  • differentiation-committed oligodendrocyte precursor CL4023059
    CSI 1.45
    rCSI 2.63%
    PRS 78.68
  • parietal epithelial cell CL1000452
    CSI 1.18
    rCSI 3.15%
    PRS 79.38
  • endothelial cell of vascular tree CL0002139
    CSI 1.15
    rCSI 6.29%
    PRS 82.49
  • pulmonary alveolar type 1 cell CL0002062
    CSI 1.06
    rCSI 6.09%
    PRS 82.78
  • endothelial cell of venule CL1000414
    CSI 1.05
    rCSI 9.36%
    PRS 91.2
  • glial cell CL0000125
    CSI 0.93
    rCSI 3.55%
    PRS 78.47
  • endothelial cell of placenta CL0009092
    CSI 0.88
    rCSI 4.35%
    PRS 91.51
  • cardiac blood vessel endothelial cell CL0010006
    CSI 0.86
    rCSI 6.09%
    PRS 79.67
  • lung microvascular endothelial cell CL2000016
    CSI 0.82
    rCSI 15.75%
    PRS 91.44
  • blood vessel smooth muscle cell CL0019018
    CSI 0.45
    rCSI 3.69%
    PRS 82.04
  • vein endothelial cell of respiratory system CL4033008
    CSI 0.42
    rCSI 2.89%
    PRS 90.34
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 0.27
    rCSI 2.88%
    PRS 82.45

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 [SHROOM4](/details-gene/57477) (shroom family member 4) is a protein-coding gene located on the X chromosome, identified as a member of the Shroom family of proteins known for their roles in regulating cell morphology. Functionally, [SHROOM4](/details-gene/57477) is primarily associated with the organization of the [actin cytoskeleton](/details-cell/GO:0015629), binding directly to [actin filaments](/details-cell/GO:0051015) and influencing cellular architecture. Its expression is particularly significant in various types of endothelial cells, including those of blood vessels and specialized tissues like the retina and brain. Clinically, mutations in [SHROOM4](/details-gene/57477) are associated with X-linked mental retardation (OMIM: [300579](https://omim.org/entry/300579)), consistent with its annotated roles in [brain development](/details-cell/GO:0007420) and synaptic structure. ## Cellular Roles and Expression Landscape The expression profile of [SHROOM4](/details-gene/57477) indicates a prominent role in the vascular endothelium and in other specialized cell types requiring robust cytoskeletal regulation. **Overall**, the gene shows the highest significance in [blood vessel endothelial cell](/details-cell/CL0000071) (CSI: 7.60), a pattern reinforced by its high scores in more specialized endothelial populations such as [retinal blood vessel endothelial cell](/details-cell/CL0002585) (CSI: 5.48), [cerebral cortex endothelial cell](/details-cell/CL1001602) (CSI: 4.21), and [pulmonary capillary endothelial cell](/details-cell/CL4028001) (CSI: 3.84). This consistent, high-level significance across diverse endothelial beds suggests a fundamental function in establishing or maintaining the structure and integrity of the vascular lining. Beyond the endothelium, [SHROOM4](/details-gene/57477) is a key marker for several other distinct cell types. It is highly significant in [Mueller cell](/details-cell/CL0000636) (CSI: 6.14), a type of retinal glial cell critical for retinal structure and homeostasis. Its expression is also notable in [epithelial cell of proximal tubule](/details-cell/CL0002306) in the kidney (CSI: 4.98), [melanocyte](/details-cell/CL0000148) (CSI: 4.10), and various mesenchymal-like cells including [fibroblast of cardiac tissue](/details-cell/CL0002548) and [hepatic stellate cell](/details-cell/CL0000632). This expression pattern points to a conserved role in regulating cell shape and adhesion in barrier tissues and in cells that undergo morphological changes. The general absence of hematopoietic immune cells from the top expressed list suggests a more specialized role in structural and barrier-forming cells. ## Pathways and Molecular Function The functions of [SHROOM4](/details-gene/57477) are intrinsically linked to the dynamic regulation of the actin cytoskeleton. Gene Ontology annotations highlight its involvement in processes such as [actin cytoskeleton organization](/details-cell/GO:0030036), [actin filament organization](/details-cell/GO:0007015), and [cell morphogenesis](/details-cell/GO:0000902). At the molecular level, it functions through direct [actin filament binding](/details-cell/GO:0051015) and [myosin ii binding](/details-cell/GO:0045159), which are key interactions for generating cytoskeletal tension and driving changes in cell shape. This molecular activity provides a clear basis for its cellular roles. The high expression in endothelial and epithelial cells is consistent with its localization to the [apical junction complex](/details-cell/GO:0043296) and [adherens junction](/details-cell/GO:0005912), where it likely contributes to cell-cell adhesion and barrier integrity. Furthermore, its clinical relevance is supported by its annotated roles in [brain development](/details-cell/GO:0007420), [cognition](/details-cell/GO:0050890), and its localization to both [GABA-ergic synapse](/details-cell/GO:0098982) and [glutamatergic synapse](/details-cell/GO:0098978), where it may regulate the structure of the postsynaptic density. A publication by Kutsche et al. first linked disruptions of this gene to X-linked mental retardation, highlighting its critical role in the central nervous system [Link](https://doi.org/10.1007/s00439-005-0072-2). ## Research Directions The available data on [SHROOM4](/details-gene/57477) function and expression suggests several avenues for future investigation, particularly concerning its role in vascular biology and neurodevelopment. **Proposed Hypotheses:** 1. Given its high and widespread expression across endothelial cell types and its core function in organizing the actin cytoskeleton, [SHROOM4](/details-gene/57477) is likely a critical regulator of endothelial barrier function. Its dysregulation may contribute to pathological conditions characterized by vascular leakage, such as acute respiratory distress syndrome (ARDS) or sepsis. 2. Based on its association with X-linked intellectual disability and its annotated role in regulating neurotransmitter receptor levels ([GO:0099072](https://www.ebi.ac.uk/QuickGO/term/GO:0099072)), [SHROOM4](/details-gene/57477) likely modulates synaptic plasticity and strength by controlling the actin-dependent trafficking and anchoring of receptors at the postsynaptic membrane. Loss-of-function mutations would therefore disrupt synaptic integrity and cognitive processes. **Experimental Approach:** To test the first hypothesis regarding its role in endothelial barrier integrity, one could utilize an in vitro model with human umbilical vein endothelial cells (HUVECs) or human brain microvascular endothelial cells (HBMECs). [SHROOM4](/details-gene/57477) expression could be knocked down using siRNA. The impact on barrier function could be quantified by measuring transendothelial electrical resistance (TEER). Concurrently, changes to the actin cytoskeleton and the localization of junctional proteins like VE-cadherin could be visualized via immunofluorescence microscopy to determine the structural basis of any observed functional deficit. **Therapeutic Potential:** As [SHROOM4](/details-gene/57477) is associated with a loss-of-function developmental disorder, it is not a conventional therapeutic target for inhibition. However, its role in regulating endothelial barriers may present context-specific therapeutic opportunities. For conditions involving pathological vascular permeability, such as in solid tumors or inflammatory diseases, modulating [SHROOM4](/details-gene/57477) activity or its downstream pathways could be a strategy to restore barrier function. Given its widespread expression in healthy endothelium, any systemic inhibitory strategy would carry a high risk of side effects. Therefore, therapeutic approaches would need to be highly targeted, perhaps via localized delivery or by targeting interacting partners that are more specific to the disease state.

Genular Protein ID: 1482791757

Symbol: SHRM4_HUMAN

Name: Protein Shroom4

UniProtKB Accession Codes:

Q9ULL8 A7E2X9 D6RFW0 Q96LA0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 3 EvolutionaryTrace 1 GO 18 Gene3D 2 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 2 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 1 SMART 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: 10574462

Title: Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.

PubMed ID: 10574462

DOI: 10.1093/dnares/6.5.337

PubMed ID: 15772651

Title: The DNA sequence of the human X chromosome.

PubMed ID: 15772651

DOI: 10.1038/nature03440

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: 16615870

Title: A new standard nomenclature for proteins related to Apx and Shroom.

PubMed ID: 16615870

DOI: 10.1186/1471-2121-7-18

PubMed ID: 16684770

Title: Differential actin-dependent localization modulates the evolutionarily conserved activity of Shroom family proteins.

PubMed ID: 16684770

DOI: 10.1074/jbc.m512463200

PubMed ID: 16249884

Title: Disruptions of the novel KIAA1202 gene are associated with X-linked mental retardation.

PubMed ID: 16249884

DOI: 10.1007/s00439-005-0072-2

PubMed ID: 24700572

Title: A novel EBP c.224T>A mutation supports the existence of a male-specific disorder independent of CDPX2.

PubMed ID: 24700572

DOI: 10.1002/ajmg.a.36508

PubMed ID: 26522270

Title: NAA10 mutation causing a novel intellectual disability syndrome with Long QT due to N-terminal acetyltransferase impairment.

PubMed ID: 26522270

DOI: 10.1038/srep16022

PubMed ID: 26740508

Title: Identification of novel genetic causes of Rett syndrome-like phenotypes.

PubMed ID: 26740508

DOI: 10.1136/jmedgenet-2015-103568

Sequence Information:

  • Length: 1493
  • Mass: 164857
  • Checksum: 40260DC12A24EAFF
  • Sequence:
    • MENRPGSFQY VPVQLQGGAP WGFTLKGGLE HCEPLTVSKI EDGGKAALSQ KMRTGDELVN 
INGTPLYGSR QEALILIKGS FRILKLIVRR RNAPVSRPHS WHVAKLLEGC PEAATTMHFP 
SEAFSLSWHS GCNTSDVCVQ WCPLSRHCST EKSSSIGSME SLEQPGQATY ESHLLPIDQN 
MYPNQRDSAY SSFSASSNAS DCALSLRPEE PASTDCIMQG PGPTKAPSGR PNVAETSGGS 
RRTNGGHLTP SSQMSSRPQE GYQSGPAKAV RGPPQPPVRR DSLQASRAQL LNGEQRRASE 
PVVPLPQKEK LSLEPVLPAR NPNRFCCLSG HDQVTSEGHQ NCEFSQPPES SQQGSEHLLM 
QASTKAVGSP KACDRASSVD SNPLNEASAE LAKASFGRPP HLIGPTGHRH SAPEQLLASH 
LQHVHLDTRG SKGMELPPVQ DGHQWTLSPL HSSHKGKKSP CPPTGGTHDQ SSKERKTRQV 
DDRSLVLGHQ SQSSPPHGEA DGHPSEKGFL DPNRTSRAAS ELANQQPSAS GSLVQQATDC 
SSTTKAASGT EAGEEGDSEP KECSRMGGRR SGGTRGRSIQ NRRKSERFAT NLRNEIQRRK 
AQLQKSKGPL SQLCDTKEPV EETQEPPESP PLTASNTSLL SSCKKPPSPR DKLFNKSMML 
RARSSECLSQ APESHESRTG LEGRISPGQR PGQSSLGLNT WWKAPDPSSS DPEKAHAHCG 
VRGGHWRWSP EHNSQPLVAA AMEGPSNPGD NKELKASTAQ AGEDAILLPF ADRRKFFEES 
SKSLSTSHLP GLTTHSNKTF TQRPKPIDQN FQPMSSSCRE LRRHPMDQSY HSADQPYHAT 
DQSYHSMSPL QSETPTYSEC FASKGLENSM CCKPLHCGDF DYHRTCSYSC SVQGALVHDP 
CIYCSGEICP ALLKRNMMPN CYNCRCHHHQ CIRCSVCYHN PQHSALEDSS LAPGNTWKPR 
KLTVQEFPGD KWNPITGNRK TSQSGREMAH SKTSFSWATP FHPCLENPAL DLSSYRAISS 
LDLLGDFKHA LKKSEETSVY EEGSSLASMP HPLRSRAFSE SHISLAPQST RAWGQHRREL 
FSKGDETQSD LLGARKKAFP PPRPPPPNWE KYRLFRAAQQ QKQQQQQQKQ QEEEEEEEEE 
EEEEEEEEEE EAEEEEEELP PQYFSSETSG SCALNPEEVL EQPQPLSFGH LEGSRQGSQS 
VPAEQESFAL HSSDFLPPIR GHLGSQPEQA QPPCYYGIGG LWRTSGQEAT ESAKQEFQHF 
SPPSGAPGIP TSYSAYYNIS VAKAELLNKL KDQPEMAEIG LGEEEVDHEL AQKKIQLIES 
ISRKLSVLRE AQRGLLEDIN ANSALGEEVE ANLKAVCKSN EFEKYHLFVG DLDKVVNLLL 
SLSGRLARVE NALNSIDSEA NQEKLVLIEK KQQLTGQLAD AKELKEHVDR REKLVFGMVS 
RYLPQDQLQD YQHFVKMKSA LIIEQRELEE KIKLGEEQLK CLRESLLLGP SNF