Secreted frizzled-related protein 4 (SFRP4) is a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs act as soluble modulators of Wnt signaling. The expression of SFRP4 in ventricular myocardium correlates with apoptosis related gene expression. [provided by RefSeq, Jul 2008] See more...

Aliases for SFRP4 Gene

Aliases for SFRP4 Gene

  • Secreted Frizzled Related Protein 4 2 3 5
  • Secreted Frizzled-Related Protein 4 2 3 4
  • FRPHE 2 3 4
  • Frizzled Protein, Human Endometrium 3 4
  • FRZB-2 2 3
  • SFRP-4 3 4
  • FRP-4 2 3
  • FrpHE 2 4
  • Secreted Frizzled-Related Protein 4; Secreted Frizzled-Related Protein 4 3
  • SFRP4 5
  • PYL 3

External Ids for SFRP4 Gene

Previous GeneCards Identifiers for SFRP4 Gene

  • GC07M037591
  • GC07M037686
  • GC07M037652
  • GC07M037718

Summaries for SFRP4 Gene

Entrez Gene Summary for SFRP4 Gene

  • Secreted frizzled-related protein 4 (SFRP4) is a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs act as soluble modulators of Wnt signaling. The expression of SFRP4 in ventricular myocardium correlates with apoptosis related gene expression. [provided by RefSeq, Jul 2008]

GeneCards Summary for SFRP4 Gene

SFRP4 (Secreted Frizzled Related Protein 4) is a Protein Coding gene. Diseases associated with SFRP4 include Pyle Disease and Metaphyseal Dysplasia. Among its related pathways are Wnt Signaling Pathway and Pluripotency and Adipogenesis. Gene Ontology (GO) annotations related to this gene include G protein-coupled receptor activity and Wnt-protein binding. An important paralog of this gene is FRZB.

UniProtKB/Swiss-Prot Summary for SFRP4 Gene

  • Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types (By similarity). SFRP4 plays a role in bone morphogenesis. May also act as a regulator of adult uterine morphology and function. May also increase apoptosis during ovulation possibly through modulation of FZ1/FZ4/WNT4 signaling (By similarity). Has phosphaturic effects by specifically inhibiting sodium-dependent phosphate uptake (PubMed:12952927).

Gene Wiki entry for SFRP4 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for SFRP4 Gene

Genomics for SFRP4 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for SFRP4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH07J037916 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE CraniofacialAtlas 257.8 +109.2 109181 2.6 ZNF654 ZNF600 ATF2 NFIC ZBTB10 TRIM22 ZNF341 CTCF KMT2B KLF9 SFRP4 EPDR1 lnc-ELMO1-2 HSALNG0057307 NME8
GH07J037901 Enhancer 0.9 Ensembl ENCODE 19.4 +123.6 123639 1.7 ZNF654 JUND NFIC YY1 REST TRIM22 CTCF MAFF RXRA RAD21 HSALNG0057305 SFRP4 EPDR1 lnc-ELMO1-2 NME8
GH07J037941 Enhancer 1 ENCODE 15.6 +82.1 82053 4.3 SSRP1 ATF2 CEBPA ATF3 CHD4 YY1 MXD4 KLF11 TRIM22 CHD2 SFRP4 EPDR1 TRGC1 HSALNG0057307 lnc-ELMO1-2 NME8
GH07J038215 Enhancer 1.2 Ensembl ENCODE dbSUPER 10 -194.1 -194113 9.2 ZNF654 IKZF1 MYC CTCF REST TRIM22 ARNT ELF1 FOXA2 RAD21 NONHSAG047369.2 STARD3NL TRGC2 SFRP4
GH07J037986 Enhancer 0.9 Ensembl ENCODE dbSUPER 11.3 +38.3 38287 2.6 ZIC2 NFE2 BHLHE40 BATF IKZF1 BMI1 NANOG IKZF2 MTA2 DPF2 SFRP4 EPDR1 lnc-EPDR1-2 lnc-EPDR1-1 NME8
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around SFRP4 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for SFRP4

Top Transcription factor binding sites by QIAGEN in the SFRP4 gene promoter:
  • AP-2alpha
  • AREB6
  • ATF-2
  • CRE-BP1
  • Nkx2-5
  • p53

Genomic Locations for SFRP4 Gene

Latest Assembly
chr7:37,905,932-38,025,695
(GRCh38/hg38)
Size:
119,764 bases
Orientation:
Minus strand

Previous Assembly
chr7:37,945,534-37,956,419
(GRCh37/hg19 by Entrez Gene)
Size:
10,886 bases
Orientation:
Minus strand

chr7:37,945,543-38,065,297
(GRCh37/hg19 by Ensembl)
Size:
119,755 bases
Orientation:
Minus strand

Genomic View for SFRP4 Gene

Genes around SFRP4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
SFRP4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for SFRP4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for SFRP4 Gene

Proteins for SFRP4 Gene

  • Protein details for SFRP4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q6FHJ7-SFRP4_HUMAN
    Recommended name:
    Secreted frizzled-related protein 4
    Protein Accession:
    Q6FHJ7
    Secondary Accessions:
    • B4DYC1
    • O14877
    • Q05BG7
    • Q1ZYW2
    • Q4G124
    • Q6FHM0
    • Q6PD64

    Protein attributes for SFRP4 Gene

    Size:
    346 amino acids
    Molecular mass:
    39827 Da
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=BAG63683.1; Type=Erroneous initiation; Evidence={ECO:0000305};

neXtProt entry for SFRP4 Gene

Post-translational modifications for SFRP4 Gene

  • Glycosylation at Asn38, Asn68, Asn116, Asn194, and Asn240
  • Modification sites at PhosphoSitePlus
  • Glycosylation from GlyConnect
    • SFRP4_HUMAN (1726)

Other Protein References for SFRP4 Gene

ENSEMBL proteins:
REFSEQ proteins:

Protein products for research

  • Abcam proteins for SFRP4

No data available for DME Specific Peptides for SFRP4 Gene

Domains & Families for SFRP4 Gene

Gene Families for SFRP4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Predicted intracellular proteins
  • Predicted secreted proteins

Suggested Antigen Peptide Sequences for SFRP4 Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ53955, highly similar to Secreted frizzled-related protein 4 (B4E1T4_HUMAN)
  • Frizzled protein, human endometrium (SFRP4_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q6FHJ7

UniProtKB/Swiss-Prot:

SFRP4_HUMAN :
  • The FZ domain is involved in binding with Wnt ligands.
  • Belongs to the secreted frizzled-related protein (sFRP) family.
Domain:
  • The FZ domain is involved in binding with Wnt ligands.
Family:
  • Belongs to the secreted frizzled-related protein (sFRP) family.
genes like me logo Genes that share domains with SFRP4: view

Function for SFRP4 Gene

Molecular function for SFRP4 Gene

UniProtKB/Swiss-Prot Function:
Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types (By similarity). SFRP4 plays a role in bone morphogenesis. May also act as a regulator of adult uterine morphology and function. May also increase apoptosis during ovulation possibly through modulation of FZ1/FZ4/WNT4 signaling (By similarity). Has phosphaturic effects by specifically inhibiting sodium-dependent phosphate uptake (PubMed:12952927).
UniProtKB/Swiss-Prot Induction:
Increased levels in failing myocardium. Up-regulated in several tumor types including ostomalacia-associated tumors and endometrial and breast carcinomas.
GENATLAS Biochemistry:
Drosophila frizzled polarity homolog,secreted related protein 4,mouse sfrp 4 homolog,likely involved in WNT binding and signal transduction

Phenotypes From GWAS Catalog for SFRP4 Gene

Gene Ontology (GO) - Molecular Function for SFRP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IEA,IPI 15607035
GO:0017147 Wnt-protein binding IDA,NAS 24431302
genes like me logo Genes that share ontologies with SFRP4: view
genes like me logo Genes that share phenotypes with SFRP4: view

Human Phenotype Ontology for SFRP4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for SFRP4 Gene

MGI Knock Outs for SFRP4:

Animal Models for research

  • Taconic Biosciences Mouse Models for SFRP4

miRNA for SFRP4 Gene

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SFRP4

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for SFRP4 Gene

Localization for SFRP4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for SFRP4 Gene

Secreted. Note=Cytoplasmic in ovarian tumor cells.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for SFRP4 gene
Compartment Confidence
extracellular 5
nucleus 4
plasma membrane 3
cytoskeleton 2
mitochondrion 2
endoplasmic reticulum 2
cytosol 2
golgi apparatus 2
peroxisome 1
endosome 1
lysosome 1

Gene Ontology (GO) - Cellular Components for SFRP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IBA,IDA 14760084
GO:0005634 nucleus IDA 18938133
GO:0005737 cytoplasm IBA,IDA 11793365
GO:0009986 cell surface IDA 14760084
genes like me logo Genes that share ontologies with SFRP4: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for SFRP4 Gene

Pathways & Interactions for SFRP4 Gene

genes like me logo Genes that share pathways with SFRP4: view

Pathways by source for SFRP4 Gene

Gene Ontology (GO) - Biological Process for SFRP4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002092 positive regulation of receptor internalization IDA 16151791
GO:0007275 multicellular organism development IEA --
GO:0008285 negative regulation of cell proliferation IMP 14760084
GO:0009725 response to hormone NAS 10211996
GO:0010628 positive regulation of gene expression IDA 18938133
genes like me logo Genes that share ontologies with SFRP4: view

No data available for SIGNOR curated interactions for SFRP4 Gene

Drugs & Compounds for SFRP4 Gene

(5) Drugs for SFRP4 Gene - From: DrugBank and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Cyclothiazide Approved Pharma Target, inhibitor 0
Perindopril Approved Pharma Target, inhibitor ACE inhibitor, Angiotensin-converting enzyme (ACE) inhibitor 72

(2) Additional Compounds for SFRP4 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
sodium
  • Na(+)
  • Na+
  • SODIUM ion
  • Sodium(1+)
7440-23-5
genes like me logo Genes that share compounds with SFRP4: view

Transcripts for SFRP4 Gene

mRNA/cDNA for SFRP4 Gene

1 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for SFRP4

Alternative Splicing Database (ASD) splice patterns (SP) for SFRP4 Gene

No ASD Table

Relevant External Links for SFRP4 Gene

GeneLoc Exon Structure for
SFRP4

Expression for SFRP4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for SFRP4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for SFRP4 Gene

This gene is overexpressed in Cervix - Endocervix (x10.8), Nerve - Tibial (x6.4), Uterus (x5.8), and Cervix - Ectocervix (x5.3).

Protein differential expression in normal tissues from HIPED for SFRP4 Gene

This gene is overexpressed in Cervix (32.2), Pancreas (18.8), and Breast (12.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for SFRP4 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for SFRP4

SOURCE GeneReport for Unigene cluster for SFRP4 Gene:

Hs.658169

mRNA Expression by UniProt/SwissProt for SFRP4 Gene:

Q6FHJ7-SFRP4_HUMAN
Tissue specificity: Expressed in mesenchymal cells. Highly expressed in the stroma of proliferative endometrium. Expressed in cardiomyocytes. Shows moderate to strong expression in ovarian tumors with expression increasing as the tumor stage increases. In ovarian tumors, expression levels are inversely correlated with expression of CTNNB1 (at protein level).

Evidence on tissue expression from TISSUES for SFRP4 Gene

  • Nervous system(4.7)
  • Muscle(2.9)
  • Lung(2.7)
  • Intestine(2.6)
  • Pancreas(2.4)
  • Heart(2.3)
  • Eye(2.2)
  • Skin(2.1)
  • Kidney(2.1)
  • Bone(2)
genes like me logo Genes that share expression patterns with SFRP4: view

Primer products for research

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for SFRP4 Gene

Orthologs for SFRP4 Gene

This gene was present in the common ancestor of animals.

Orthologs for SFRP4 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia SFRP4 29 30
  • 99.71 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia SFRP4 29 30
  • 91.81 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia SFRP4 29 30
  • 91.71 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Sfrp4 29
  • 88.41 (n)
Mouse
(Mus musculus)
Mammalia Sfrp4 29 16 30
  • 88.31 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia SFRP4 30
  • 83 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia SFRP4 30
  • 74 (a)
OneToOne
Chicken
(Gallus gallus)
Aves SFRP4 29 30
  • 73.23 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia SFRP4 30
  • 63 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia sfrp4 29
  • 69.04 (n)
Zebrafish
(Danio rerio)
Actinopterygii FP102169.1 30
  • 19 (a)
ManyToMany
Fruit Fly
(Drosophila melanogaster)
Insecta fz4 30
  • 11 (a)
OneToMany
Worm
(Caenorhabditis elegans)
Secernentea mig-1 30
  • 12 (a)
OneToMany
Species where no ortholog for SFRP4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for SFRP4 Gene

ENSEMBL:
Gene Tree for SFRP4 (if available)
TreeFam:
Gene Tree for SFRP4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for SFRP4: view image
Alliance of Genome Resources:
Additional Orthologs for SFRP4

Paralogs for SFRP4 Gene

Paralogs for SFRP4 Gene

(1) SIMAP similar genes for SFRP4 Gene using alignment to 2 proteins:

  • SFRP4_HUMAN
  • C9JMJ2_HUMAN
genes like me logo Genes that share paralogs with SFRP4: view

Variants for SFRP4 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for SFRP4 Gene

SNP ID Clinical significance and condition Chr 07 pos Variation AA Info Type
989454 Likely Pathogenic: Pyle metaphyseal dysplasia 37,916,377(-) G/T
NM_003014.4(SFRP4):c.161C>A (p.Ala54Asp)
MISSENSE
989455 Likely Pathogenic: Pyle metaphyseal dysplasia 37,916,165(-) A/T
NM_003014.4(SFRP4):c.373T>A (p.Cys125Ser)
MISSENSE
rs112343199 Benign: not provided 37,916,436(-) G/A
NM_003014.4(SFRP4):c.102C>T (p.His34=)
SYNONYMOUS
rs1384911388 Likely Benign: not provided 37,912,292(-) C/T
NM_003014.4(SFRP4):c.618G>A (p.Val206=)
SYNONYMOUS
rs35937440 Benign: not provided 37,907,482(-) C/G
NM_003014.4(SFRP4):c.1038G>C (p.Val346=)
SYNONYMOUS

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for SFRP4 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for SFRP4 Gene

Variant ID Type Subtype PubMed ID
nsv8074 CNV loss 18304495

Variation tolerance for SFRP4 Gene

Residual Variation Intolerance Score: 25% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.04; 68.68% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for SFRP4 Gene

Human Gene Mutation Database (HGMD)
SFRP4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
SFRP4
Leiden Open Variation Database (LOVD)
SFRP4

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for SFRP4 Gene

Disorders for SFRP4 Gene

MalaCards: The human disease database

(14) MalaCards diseases for SFRP4 Gene - From: OMI, CVR, ORP, COP, and GCD

Disorder Aliases PubMed IDs
pyle disease
  • pyl
metaphyseal dysplasia
  • bakwin-krida syndrome
osteomalacia
  • adult rickets
hypophosphatemic rickets, autosomal dominant
  • adhr
hypophosphatemia
- elite association - COSMIC cancer census association via MalaCards
Search SFRP4 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

SFRP4_HUMAN
  • Pyle disease (PYL) [MIM:265900]: A disorder characterized by cortical-bone thinning, limb deformity, bone fragility and fractures. {ECO:0000269 PubMed:27355534}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for SFRP4

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with SFRP4: view

No data available for Genatlas for SFRP4 Gene

Publications for SFRP4 Gene

  1. Differential expression of frpHE: a novel human stromal protein of the secreted frizzled gene family, during the endometrial cycle and malignancy. (PMID: 10211996) Abu-Jawdeh G … Kocher O (Laboratory investigation; a journal of technical methods and pathology 1999) 2 3 4 22
  2. Cortical-Bone Fragility--Insights from sFRP4 Deficiency in Pyle's Disease. (PMID: 27355534) Kiper POS … Baron R (The New England journal of medicine 2016) 3 4 72
  3. Expression of secreted frizzled-related protein 4 (SFRP4) in primary serous ovarian tumours. (PMID: 19480240) Drake J … Dharmarajan A (European journal of gynaecological oncology 2009) 3 4 22
  4. Wnt antagonist gene polymorphisms and renal cancer. (PMID: 19562778) Hirata H … Dahiya R (Cancer 2009) 3 22 40
  5. Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent. (PMID: 12952927) Berndt T … Kumar R (The Journal of clinical investigation 2003) 3 4 22

Products for SFRP4 Gene

Sources for SFRP4 Gene