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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

ACTN4 Gene

protein-coding GIFtS: 67
GCID: GC19P039138

actinin, alpha 4

(Previous name: focal segmental glomerulosclerosis 1 )
(Previous symbol: FSGS1)

Explore 40 diseases affiliated with
ACTN4 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Actinin, Alpha 4¹ ²		FSGS² ⁵
FSGS1¹ ² ⁵		ACTININ-4²
Focal Segmental Glomerulosclerosis 1¹ ²		Actinin Alpha4 Isoform²
Non-Muscle Alpha-Actinin 4² ³		Alpha-Actinin-4¹
F-Actin Cross-Linking Protein² ³

External Ids:	HGNC: 166¹	Entrez Gene: 81²	Ensembl: ENSG00000130402⁷	OMIM: 604638⁵	UniProtKB: O43707³

Export aliases for ACTN4 gene to outside databases

Previous GC identifers: GC19P039725 GC19P039529 GC19P043814 GC19P043830 GC19P035584

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for ACTN4:

Alpha actinins belong to the spectrin gene superfamily which represents a diverse group of cytoskeletal proteins,

including the alpha and beta spectrins and dystrophins. Alpha actinin is an actin-binding protein with multiple roles

in different cell types. In nonmuscle cells, the cytoskeletal isoform is found along microfilament bundles and

adherens-type junctions, where it is involved in binding actin to the membrane. In contrast, skeletal, cardiac, and

smooth muscle isoforms are localized to the Z-disc and analogous dense bodies, where they help anchor the myofibrillar

actin filaments. This gene encodes a nonmuscle, alpha actinin isoform which is concentrated in the cytoplasm, and

thought to be involved in metastatic processes. Mutations in this gene have been associated with focal and segmental

glomerulosclerosis. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: ACTN4_HUMAN, O43707

Function: F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This

is a bundling protein. Probably involved in vesicular trafficking via its association with the CART complex. The CART

complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation

Gene Wiki entry for ACTN4 (Actinin alpha 4)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000019.9 NC_018930.1 NT_011109.16

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the ACTN4 gene promoter:
Oct-B1 oct-B3 oct-B2 ATF-2 CUTL1 YY1 POU2F1 POU2F1a c-Jun
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): ACTN4 promoter sequence

Search SABiosciences Chromatin IP Primers for ACTN4

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat ACTN4

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 19q13 Ensembl cytogenetic band: 19q13.2 HGNC cytogenetic band: 19q13

ACTN4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ACTN4 gene location

GeneLoc information about chromosome 19 GeneLoc Exon Structure

GeneLoc location for GC19P039138: view genomic region (about GC identifiers)

Start:	39,138,289 bp from pter	End:	39,222,223 bp from pter
Size:	83,935 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: ACTN4_HUMAN, O43707 (See protein sequence)

Recommended Name: Alpha-actinin-4

Size: 911 amino acids; 104854 Da

Subunit: Homodimer; antiparallel (By similarity). Binds TRIM3 at the N-terminus (By similarity). Identified in a

complex with CASK, IQGAP1, MAGI2, NPHS1, SPTAN1 and SPTBN1 (By similarity). Identified in a mRNP granule complex, at

least composed of ACTB, ACTN4, DHX9, ERG, HNRNPA1, HNRNPA2B1, HNRNPAB, HNRNPD, HNRNPL, HNRNPR, HNRNPU, HSPA1, HSPA8,

IGF2BP1, ILF2, ILF3, NCBP1, NCL, PABPC1, PABPC4, PABPN1, RPLP0, RPS3, RPS3A, RPS4X, RPS8, RPS9, SYNCRIP, TROVE2, YBX1

and untranslated mRNAs. Component of the CART complex, at least composed of ACTN4, HGS/HRS, MYO5B and TRIM3. Interacts

with BAIAP1 and PDLIM2

Subcellular location: Nucleus. Cytoplasm. Note=Localized in cytoplasmic mRNP granules containing untranslated mRNAs.

Colocalizes with actin stress fibers. Nuclear translocation can be induced by the PI3 kinase inhibitor wortmannin or

by cytochalasin D. Exclusively localized in the nucleus in a limited number of cell lines (breast cancer cell line

MCF-7, oral floor cancer IMC-2, and bladder cancer KU-7)

Sequence caution: Sequence=AAC17470.1; Type=Frameshift; Positions=19, 26, 124, 130, 589, 594, 787, 806;

Sequence=BAA24447.1; Type=Erroneous initiation;

3 PDB 3D structures from and Proteopedia for ACTN4:

1WLX (3D)

1YDI (3D)

2R0O (3D)

Secondary accessions: O76048

Explore the universe of human proteins at neXtProt for ACTN4: NX_O43707

Post-translational modifications:

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_O43707

ACTN4 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_004915.2

ENSEMBL proteins:

ENSP00000252699 ENSP00000439497 ENSP00000467190 ENSP00000465176 ENSP00000398393

ENSP00000411187

Reactome Protein details: O43707
Human Recombinant Protein Products for ACTN4:

	Browse Purified and Recombinant Proteins at EMD Millipore
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	Browse recombinant and purified proteins available from Enzo Life Sciences
	OriGene Purified Protein: ACTN4 OriGene Protein Over-expression Lysate: ACTN4 OriGene Custom Protein Services for ACTN4
	GenScript Custom Purified and Recombinant Proteins Services for ACTN4
	Novus Biologicals ACTN4 Proteins Novus Biologicals ACTN4 Lysates
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for ACTN4

Gene Ontology (GO): 5/12 cellular component terms (GO ID links to tree view) (see all 12): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001725	stress fiber	--	--
GO:0005576	extracellular region	TAS	--
GO:0005634	nucleus	IDA	9508771
GO:0005737	cytoplasm	IDA	9508771
GO:0030018	Z disc	IEA	--

ACTN4 for ontologies About GeneDecksing

ACTN4 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of ACTN4
	Browse R&D Systems for Antibodies
	OriGene Antibodies (see all 3): ACTN4 OriGene Custom Antibody Services for ACTN4
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	Novus Biologicals ACTN4 Antibodies
	Abcam antibodies for ACTN4
	Uscn Antibodies for ACTN4
	ThermoFisher Antibody for ACTN4

Assay Products for ACTN4:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for ACTN4
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for ACTN4

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

ACTN4 for domains About GeneDecksing

5/9 InterPro domains/families (see all 9):

IPR014837 EF-hand_Ca_insen

IPR018247 EF_Hand_1_Ca_BS

IPR002017 Spectrin_repeat

IPR001715 CH-domain

IPR011992 EF-hand-like_dom

Graphical View of Domain Structure for InterPro Entry O43707

ProtoNet protein and cluster: O43707

3 Blocks protein families:

IPB001589 Actin-binding

IPB001715 Calponin-like actin-binding

IPB002017 Spectrin repeat

UniProtKB/Swiss-Prot: ACTN4_HUMAN, O43707

Similarity: Belongs to the alpha-actinin family

Similarity: Contains 1 actin-binding domain

Similarity: Contains 2 CH (calponin-homology) domains

Similarity: Contains 2 EF-hand domains

Similarity: Contains 4 spectrin repeats

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase, shRNA from OriGene, Sirion Biotech, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Sirion Biotech, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, Sirion Biotech, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Molecular Function:

UniProtKB/Swiss-Prot Summary: ACTN4_HUMAN, O43707

Function: F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This

is a bundling protein. Probably involved in vesicular trafficking via its association with the CART complex. The CART

complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation

Gene Ontology (GO): 5/9 molecular function terms (GO ID links to tree view) (see all 9): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001882	nucleoside binding	IDA	12411747
GO:0003779	actin binding	TAS	8104223
GO:0005178	integrin binding	TAS	8104223
GO:0005509	calcium ion binding	IEA	--
GO:0005515	protein binding	IPI	16944923

ACTN4 for ontologies About GeneDecksing

Phenotypes:
7 MGI mutant phenotypes (inferred from 3 alleles) (MGI details for Actn4):

cardiovascular system	cellular	growth/size	homeostasis/metabolism	immune system
mortality/aging	renal/urinary system

ACTN4 for phenotypes About GeneDecksing

Animal Models:
Mouse knock-out Actn4^tm1Plk for ACTN4

inGenious Targeting Laboratory - Customizable classic, inducible, and humanized mouse model solutions for ACTN4

miRNA Products:		OriGene 3'-UTR Clone: ACTN4 Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat ACTN4
		8/44 QIAGEN miScript miRNA Assays for microRNAs that regulate ACTN4 (see all 44):
		hsa-miR-142-5p hsa-miR-548j hsa-miR-4307 hsa-miR-548k hsa-miR-605 hsa-miR-374a hsa-miR-3921 hsa-miR-548l

		SwitchGear 3'UTR luciferase reporter plasmid: ACTN4 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for ACTN4 (see all 7) OriGene shRNA RFP: ACTN4 OriGene siRNA: ACTN4
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat ACTN4
		Sirion Biotech Custom design and validation of potent shRNA sequences against ACTN4

Gene Editing Products:			DNA2.0 Custom Protein Engineering Service for ACTN4
			Sirion Biotech Customized adenovirus for overexpression of ACTN4 Sirion Biotech Customized adenovirus for potent knockdown of ACTN4

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for ACTN4 (see all 3) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for ACTN4 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: ACTN4 (NM_004924)
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		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat ACTN4

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for ACTN4
		Search LifeMap BioReagents cell lines for ACTN4
		Sirion Biotech Customized stable knockdown cell line services for ACTN4 Sirion Biotech Customized inducible knockdown cell line services for ACTN4 Sirion Biotech Customized stable overexpressing cell line services for ACTN4 Sirion Biotech Customized inducible overexpressing cell line services for ACTN4

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ACTN4

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/20 super-pathways (see all 20) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Cell adhesion_Integrin-mediated cell adhesion and migration

Cell adhesion_Integrin-mediated cell adhesion and migration	1.00	Cytoskeleton remodeling Fibronectin-binding integrins in cell motility	0.32
Cell adhesion Integrin-mediated cell adhesion and migration	1.00	Cytoskeleton remodeling_Fibronectin-binding integrins in cell motility	0.32
Cytoskeleton remodeling_Integrin outside-in signaling	0.37	Cell adhesion_Endothelial cell contacts by non-junctional mechanisms	0.21
Cytoskeleton remodeling Integrin outside-in signaling	0.37	Cell adhesion Endothelial cell contacts by non-junctional mechanisms	0.21

Sertoli-Sertoli Cell Junction Dynamics

	Sertoli-Sertoli Cell Junction Dynamics	1.00			Epithelial Tight Junctions	0.36
	Germ Cell-Sertoli Cell Junction Dynamics	0.38

Platelet activation, signaling and aggregation

Platelet activation, signaling and aggregation

1.00

Hemostasis

0.43

Platelet degranulation

Platelet degranulation

1.00

Response to elevated platelet cytosolic Ca2+

0.94

Cell adhesion Endothelial cell contacts by junctional mechanisms

Cell adhesion Endothelial cell contacts by junctional mechanisms

1.00

Cell adhesion_Endothelial cell contacts by junctional mechanisms

0.97

Pathway sources
See GeneCards unified pathways
Show all pathways

5 EMD Millipore Pathways for ACTN4

	Cell adhesion Integrin-mediated cell adhesion and migration
	Cytoskeleton remodeling Integrin outside-in signaling
	Cytoskeleton remodeling Fibronectin-binding integrins in cell motility
	Cell adhesion Endothelial cell contacts by junctional mechanisms
	Cell adhesion Endothelial cell contacts by non-junctional mechanisms

5/6 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for ACTN4 (see all 6)

	Sertoli-Sertoli Cell Junction Dynamics
	ILK Signaling
	Remodeling of Adherens Junctions
	Epithelial Tight Junctions
	Germ Cell-Sertoli Cell Junction Dynamics

5/6 GeneGo (Thomson Reuters) Pathways for ACTN4 (see all 6)

	Cell adhesion Endothelial cell contacts by non-junctional mechanisms
	Cytoskeleton remodeling Integrin outside-in signaling
	Cell adhesion Integrin-mediated cell adhesion and migration
	Cell adhesion Endothelial cell contacts by junctional mechanisms
	Inhibitory action of Lipoxins on neutrophil migration

2 BioSystems Pathways for ACTN4

	Arrhythmogenic right ventricular cardiomyopathy
	Striated Muscle Contraction

5/6 Reactome Pathways for ACTN4 (see all 6)

	Hemostasis
	Nephrin interactions
	Platelet degranulation
	Platelet activation, signaling and aggregation
	Cell-Cell communication

5/8 Kegg Pathways (Kegg details for ACTN4) (see all 8):

	Focal adhesion
	Adherens junction
	Tight junction
	Leukocyte transendothelial migration
	Regulation of actin cytoskeleton

ACTN4 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for ACTN4

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/156 Interacting proteins for ACTN4 (O43707^{1, 2, 3} ENSP00000252699⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 156)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
TJP1	Q07157¹^,²^,³, ENSP00000281537⁴	EBI-351526,EBI-79553 MINT-3088497 MINT-3088449 MINT-3088309 MINT-2984673 I2D: score=7 STRING: ENSP00000281537
COIL	P38432²^,³, ENSP00000240316⁴	MINT-2856455 I2D: score=3 STRING: ENSP00000240316
SACS	Q9NZJ4²^,³, ENSP00000371729⁴	MINT-2856495 I2D: score=3 STRING: ENSP00000371729
MAP3K3	Q99759²^,³	MINT-48410 I2D: score=2
RIPK3	Q9Y572²^,³	MINT-49099 I2D: score=2

About this table

Gene Ontology (GO): 5/12 biological process terms (GO ID links to tree view) (see all 12): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001666	response to hypoxia	IEA	--
GO:0002576	platelet degranulation	TAS	--
GO:0007596	blood coagulation	TAS	--
GO:0015031	protein transport	IEA	--
GO:0030168	platelet activation	TAS	--

ACTN4 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

ACTN4 for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for ACTN4
4 Novoseek chemical compound relationships for ACTN4 gene About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
tyrosine	5.23	8	19833736 (1), 19920151 (1)
calcium	0	3	15843471 (1), 19206166 (1)
threonine	0	1	12239280 (1)
serine	0	1	12239280 (1)

Search CenterWatch for drugs/clinical trials and news about ACTN4

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, Sirion Biotech, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for ACTN4 gene:

NM_004924.4

Unigene Cluster for ACTN4:

Actinin, alpha 4

Hs.270291 [show with all ESTs]

Unigene Representative Sequence: NM_004924

11 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000588618 ENST00000252699(uc010egc.2 uc002oja.2 uc021uug.1)

ENST00000390009 ENST00000589528 ENST00000495553 ENST00000586538 ENST00000489451

ENST00000440400 ENST00000497637 ENST00000477174 ENST00000424234

miRNA Products:		OriGene 3'-UTR Clone: ACTN4 Browse OriGene MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat ACTN4
		8/44 QIAGEN miScript miRNA Assays for microRNAs that regulate ACTN4 (see all 44):
		hsa-miR-142-5p hsa-miR-548j hsa-miR-4307 hsa-miR-548k hsa-miR-605 hsa-miR-374a hsa-miR-3921 hsa-miR-548l

		SwitchGear 3'UTR luciferase reporter plasmid: ACTN4 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for ACTN4 (see all 7) OriGene shRNA RFP: ACTN4 OriGene siRNA: ACTN4
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		Sirion Biotech Custom design and validation of potent shRNA sequences against ACTN4

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		GenScript: all cDNA clones in your preferred vector: ACTN4 (NM_004924)
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		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat ACTN4
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat ACTN4

Additional cDNA sequence:

AK299955.1 AK304554.1 AK309361.1 AK309363.1 AK309364.1 BC005033.1 BC015620.2 BC107062.1

BX647098.1 D89980.1 DQ431186.1 GU987085.1 Z36797.1

24/49 DOTS entries (see all 49):

DT.454297 DT.92038152 DT.95220089 DT.100857867 DT.87077774 DT.100857868 DT.100857861 DT.100857862

DT.95211807 DT.91923640 DT.95220202 DT.102839407 DT.95249964 DT.100857884 DT.121498871 DT.100034739

DT.100857877 DT.121498968 DT.92459345 DT.95339553 DT.92459310 DT.97860886 DT.100045174 DT.86850955

24/987 AceView cDNA sequences (see all 987):

AI817291 BQ222341 AW073755 AW502037 AI358422 CD369797 BU627209 BQ893844

BM564345 BP362352 BM827298 BM981136 BP375198 BM917043 D82247 AW592378

BG819773 BQ431621 BQ707093 BE271824 BE733621 AA700560 BM052851 AI911171

GeneLoc Exon Structure

5/9 Alternative Splicing Database (ASD) splice patterns (SP) for ACTN4 (see all 9) About this scheme

ExUns:	1a	·	1b	^	2	^	3a	·	3b	^	4a	·	4b	^	5	^	6	^	7a	·	7b	^	8	^	9	^	10	^	11	^	12a	·	12b	^	13a	·	13b	^	14	^	15	^	16	^	17	^	18a	·	18b	^	19	^
SP1:																									-
SP2:																							-
SP3:
SP4:									-		-		-		-		-		-		-		-		-		-		-
SP5:																							-

ExUns:	20a	·	20b	^	21a	·	21b	^	22a	·	22b	^	23a	·	23b	·	23c	·	23d	^	24
SP1:	-				-		-
SP2:
SP3:	-		-		-
SP4:
SP5:

ECgene alternative splicing isoforms for ACTN4

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

ACTN4 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: CGAGGGGCCA

About this image

ACTN4 expression in embryonic tissues and stem cells
Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

1 LifeMap In Vivo Development Anatomical Compartment/Cell

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Kidney

Podocyte Layer

Podocytes

Kidney

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See ACTN4 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for ACTN4

SOURCE GeneReport for Unigene cluster: Hs.270291

UniProtKB/Swiss-Prot: ACTN4_HUMAN, O43707

Tissue specificity: Widely expressed

SABiosciences Expression via Pathway-Focused PCR Arrays including ACTN4:

Adherens Junctions in human mouse rat

Tight Junctions in human mouse rat

Focal Adhesions in human mouse rat

Cell Motility in human mouse rat

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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for ACTN4 gene from 5/21 species (see all 21) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	ACTN4¹	actinin, alpha 4	87.02(n) 93.14(a)		396024 NM_205126.1 NP_990457.1
lizard (Anolis carolinensis)	Reptilia	ACTN4⁶	--	95(a)	1 ↔ 1	GL343665.1(143759-206512)
zebrafish (Danio rerio)	Actinopterygii	wufb53f05²	wufb53f05	79.58(n)		322221 BC054901.1
fruit fly (Drosophila melanogaster)	Insecta	Actn³	cytoskeletal anchoring actin binding	67(a)		--
worm (Caenorhabditis elegans)	Secernentea	atn-1⁶	AcTiniN family member (atn-1)	59(a)	1 → many	V(12478394-12484433)

ENSEMBL Gene Tree for ACTN4 (if available)
TreeFam Gene Tree for ACTN4 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for ACTN4 gene

SPTBN2² SPTA1² SYNE2² SPTBN4² SPTBN1² SPTB² SPTBN5² ACTN2²

SPTAN1² ACTN1² SYNE1² CLMN²

17 SIMAP similar genes for ACTN4 using alignment to 8 protein entries: ACTN4_HUMAN (see all proteins):

MLL-ACTN4 ACTN2 ACTN1 ACTN3 MACF1 HSpTB1

SPTBN2 SPNB4 SPTBN4 SPTBN1 SPTB CALM3

CALM1 CALM2 SPTAN1 CETN3 CLMN

ACTN4 for paralogs About GeneDecksing

2 Pseudogenes.org Pseudogenes for ACTN4
PGOHUM00000244677 PGOHUM00000246045

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 19 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs62121764^1,2	C,F	--	35582934(+)	`GATCTT/CGGCTT`	1	--	us2k¹		3		NA	6
rs17523223^1,2	C,F,H	--	35584718(+)	`CGGGAC/TTCTGC`	1	--	us2k¹		13		EA MN NS NA CSA	1734
rs73933037^1,2	C	--	35585460(+)	`AGGCGG/TGCTTG`	1	--	int¹		2		WA	120
rs2194132^1,2	C	--	35586903(-)	`CCACTC/TTGCCA`	1	--	int¹		2		NA	4
rs79226268^1,2	F	--	35587492(+)	`CCTCCC/TGAGAG`	1	--	int¹		1		WA	118
rs55761044^1,2		--	35587577(+)	`GGGTGA/GAAACC`	1	--	int¹		0	--	--	--	--
rs78871891^1,2	C,F	--	35588777(+)	`TTTTCG/ATGTTC`	1	--	int¹		1		NA	120
rs113293049^1,2	C	--	35588959(+)	`GTTTTC/TTTTGA`	1	--	int¹		1		NA	2
rs73032668^1,2	C	--	35589256(+)	`TTGAAG/ATAGAT`	1	--	int¹		3		NA WA	240
rs73552655^1,2	C	--	35589258(+)	`GAAGTA/GGATCT`	1	--	int¹		2		WA	120

HapMap Linkage Disequilibrium report for ACTN4 (39138289 - 39222223 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 7 variations for ACTN4
2 CNVs: 9794 73365
5 Indels: 89218 89221 89220 78181 89219
Human Gene Mutation Database (HGMD): ACTN4

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

ACTN4 for disorders           About GeneDecksing

OMIM gene information: 604638
OMIM disorders: 603278
UniProtKB/Swiss-Prot: ACTN4_HUMAN, O43707

Defects in ACTN4 are the cause of focal segmental glomerulosclerosis type 1 (FSGS1) [MIM:603278]. A renal

pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular

filtration rate and edema. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state

requiring either dialysis therapy or kidney transplantation

20/40 diseases for ACTN4 (see all 40): About MalaCards

focal segmental glomerulosclerosis glomerulosclerosis focal segmental glomerulosclerosis 1 steroid-resistant nephrotic syndrome

crescentic glomerulonephritis nephrotic syndrome nephrosis frasier syndrome

sickle cell anemia oral squamous cell carcinoma systemic lupus erythematosus wilms tumor

squamous cell carcinoma lupus erythematosus macular degeneration proteinuria

glomerulopathy glomerulonephritis protein s deficiency endocarditis

3 diseases from the University of Copenhagen DISEASES database for ACTN4:

Nephrotic syndrome Glomerulonephritis Proteinuria

10/14 Novoseek disease relationships for ACTN4 gene (see all 14) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
nphs1	90.9	7	15780077 (1), 18443213 (1), 16186681 (1), 16752799 (1) (see all 7)
glomerulosclerosis, focal segmental	90.5	30	19666657 (2), 16251236 (2), 18436095 (2), 19142020 (2) (see all 17)
nephrotic syndrome	78.9	13	15031339 (2), 15780077 (1), 11793093 (1), 19956976 (1) (see all 9)
glomerulosclerosis	73.4	5	17082197 (1), 12782671 (1), 19956976 (1), 15627790 (1)
proteinuria	71	9	11730159 (1), 11793093 (1), 17082197 (1), 12761234 (1) (see all 7)
nephrosis	52.7	2	15031339 (1)
renal disease	52.5	4	16841182 (1), 18164029 (1), 19652713 (1)
renal failure chronic	41.1	3	12617336 (2)
wilms tumor	31.7	2	14569107 (2)
renal failure	31.4	2	17082197 (1), 19838113 (1)

Human Genome Epidemiology (HuGE) Navigator: ACTN4 (8 documents)

Export disorders for ACTN4 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for ACTN4 gene, integrated from 9 sources (see all 198):
(articles sorted by number of sources associating them with ACTN4)

Utopia: connect your pdf to the dynamic
world of online information

Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. (PubMed id 10700177)^{1, 2, 3, 9} Kaplan J.M.... Pollak M.R. (2000)
The human non-muscle alpha-actinin protein encoded by the ACTN4 gene suppresses tumorigenicity of human neuroblastoma cells. (PubMed id 10656685)^{1, 2, 9} Nikolopoulos S.N.... Ross R.A. (2000)
Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry. (PubMed id 17370265)^{1, 2} Denis N.J.... Figeys D. (2007)
Molecular composition of IMP1 ribonucleoprotein granules. (PubMed id 17289661)^{1, 2} Joeson L.... Nielsen F.C. (2007)
Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. (PubMed id 16344560)^{1, 2} Kimura K.... Sugano S. (2006)
CART: an Hrs/actinin-4/BERP/myosin V protein complex required for efficient receptor recycling. (PubMed id 15772161)^{1, 2} Yan Q....Bean A.J. (2005)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)^{1, 2} Gerhard D.S....Malek J. (2004)
Interaction of two actin-binding proteins, synaptopodin and alpha- actinin-4, with the tight junction protein MAGI-1. (PubMed id 12042308)^{1, 2} Patrie K.M.... Margolis B. (2002)
Actinin-4, a novel actin-bundling protein associated with cell motility and cancer invasion. (PubMed id 9508771)^{1, 2} Honda K.... Hirohashi S. (1998)
A locus for inherited focal segmental glomerulosclerosis maps to chromosome 19q13. (PubMed id 9461087)^{1, 3} Mathis B.J....Pollak M.R. (1998)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 81	HGNC: 166	AceView: ACTN4	Ensembl:ENSG00000130402	euGenes: HUgn81
ECgene: ACTN4	Kegg: 81	H-InvDB: ACTN4

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for ACTN4	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for ACTN4	Genetics and Cytogenetics in Oncology and Haematology
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ACTN4

Intellectual Property for ACTN4 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for ACTN4 gene:
Search GeneIP for patents involving ACTN4

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

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actinin, alpha 4

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actinin, alpha 4

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