Free for academic non-profit institutions. Other users need a Commercial license

Aliases for FREM2 Gene

Aliases for FREM2 Gene

  • FRAS1 Related Extracellular Matrix Protein 2 2 3 5
  • ECM3 Homolog 3 4
  • FRAS1-Related Extracellular Matrix Protein 2 3
  • FRASRS2 3

External Ids for FREM2 Gene

Previous GeneCards Identifiers for FREM2 Gene

  • GC13P038159
  • GC13P039261
  • GC13P020059

Summaries for FREM2 Gene

Entrez Gene Summary for FREM2 Gene

  • This gene encodes an integral membrane protein containing numerous CSPG (chondroitin sulfate proteoglycan element) repeats and Calx-beta domains. The encoded protein localizes to the basement membrane, forming a ternary complex that plays a role in epidermal-dermal interactions. This protein is important for the integrity of skin and renal epithelia. Mutations in this gene are associated with Fraser syndrome. [provided by RefSeq, Apr 2014]

GeneCards Summary for FREM2 Gene

FREM2 (FRAS1 Related Extracellular Matrix Protein 2) is a Protein Coding gene. Diseases associated with FREM2 include Fraser Syndrome 2 and Renal Hypodysplasia/Aplasia 3. Gene Ontology (GO) annotations related to this gene include calcium ion binding. An important paralog of this gene is FREM3.

UniProtKB/Swiss-Prot for FREM2 Gene

  • Extracellular matrix protein required for maintenance of the integrity of the skin epithelium and for maintenance of renal epithelia. May be required for epidermal adhesion.

Gene Wiki entry for FREM2 Gene

Additional gene information for FREM2 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for FREM2 Gene

Genomics for FREM2 Gene

GeneHancer (GH) Regulatory Elements for FREM2 Gene

Promoters and enhancers for FREM2 Gene
GeneHancer (GH) Identifier GH Type GH
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH13J038685 Promoter/Enhancer 1.9 EPDnew Ensembl ENCODE 650.7 -0.4 -372 2.8 PKNOX1 SIN3A FEZF1 GLI4 YY1 ETS1 GLIS2 SP3 ZNF610 WT1 FREM2 LINC00437 GC13M038666 PRDX3P3
GH13J038763 Enhancer 0.6 ENCODE 14.3 +76.8 76810 0.6 CTCF ZNF654 ZNF362 ZNF189 ELF1 FEZF1 RAD21 PRDM6 SMC3 WT1 FREM2 RNU6-56P GC13M038666
GH13J038636 Enhancer 0.5 ENCODE 11.3 -50.0 -50047 0.2 SMARCE1 ZNF217 CTBP1 CUX1 RFX5 FREM2 PRDX3P3 LINC00437
GH13J038785 Enhancer 0.3 ENCODE 5.4 +98.4 98432 0.3 SP1 FREM2 RNU6-56P FREM2-AS1
GH13J038735 Enhancer 0.3 ENCODE 0.2 +48.8 48783 0.2 GATA3 FREM2-AS1 GC13M038666 FREM2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around FREM2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the FREM2 gene promoter:
  • GATA-1
  • Nkx2-5
  • p53
  • NRSF form 1
  • RSRFC4
  • SRY
  • NRSF form 2
  • GCNF
  • GCNF-1
  • GCNF-2

Genomic Locations for FREM2 Gene

Genomic Locations for FREM2 Gene
200,096 bases
Plus strand
200,096 bases
Plus strand

Genomic View for FREM2 Gene

Genes around FREM2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FREM2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FREM2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for FREM2 Gene

Proteins for FREM2 Gene

  • Protein details for FREM2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    FRAS1-related extracellular matrix protein 2
    Protein Accession:
    Secondary Accessions:
    • Q4QQG1
    • Q5H9N8
    • Q5T6Q1
    • Q6N057
    • Q6ZSB4
    • Q7Z305
    • Q7Z341

    Protein attributes for FREM2 Gene

    3169 amino acids
    Molecular mass:
    351157 Da
    Quaternary structure:
    No Data Available
    • Sequence=BAC87040.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Alternative splice isoforms for FREM2 Gene


neXtProt entry for FREM2 Gene

Post-translational modifications for FREM2 Gene

  • Glycosylation at Asn2121, Asn1741, isoforms=21584, Asn1369, Asn1244, and isoforms=2358
  • Modification sites at PhosphoSitePlus

Other Protein References for FREM2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for FREM2 Gene

Domains & Families for FREM2 Gene

Gene Families for FREM2 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Predicted membrane proteins

Protein Domains for FREM2 Gene


Suggested Antigen Peptide Sequences for FREM2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry



  • The Calx-beta domains bind calcium with high affinity and undergo a major conformational shift upon binding.
  • Belongs to the FRAS1 family.
  • The Calx-beta domains bind calcium with high affinity and undergo a major conformational shift upon binding.
  • Belongs to the FRAS1 family.
genes like me logo Genes that share domains with FREM2: view

Function for FREM2 Gene

Molecular function for FREM2 Gene

UniProtKB/Swiss-Prot Function:
Extracellular matrix protein required for maintenance of the integrity of the skin epithelium and for maintenance of renal epithelia. May be required for epidermal adhesion.

Phenotypes From GWAS Catalog for FREM2 Gene

Gene Ontology (GO) - Molecular Function for FREM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with FREM2: view
genes like me logo Genes that share phenotypes with FREM2: view

Human Phenotype Ontology for FREM2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for FREM2 Gene

Localization for FREM2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for FREM2 Gene

Cell membrane; Single-pass type I membrane protein; Extracellular side.

Subcellular locations from

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 FREM2 gene
Compartment Confidence
extracellular 5
plasma membrane 4
cytosol 2
endoplasmic reticulum 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for FREM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005604 basement membrane IEA --
GO:0005886 plasma membrane IEA --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0070062 extracellular exosome HDA 23533145
genes like me logo Genes that share ontologies with FREM2: view

Pathways & Interactions for FREM2 Gene

SuperPathways for FREM2 Gene

No Data Available

Gene Ontology (GO) - Biological Process for FREM2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001654 eye development IEA --
GO:0002009 morphogenesis of an epithelium IEA --
GO:0007154 cell communication IEA --
GO:0007155 cell adhesion IEA --
GO:0007275 multicellular organism development IEA --
genes like me logo Genes that share ontologies with FREM2: view

No data available for Pathways by source and SIGNOR curated interactions for FREM2 Gene

Drugs & Compounds for FREM2 Gene

(1) Drugs for FREM2 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
calcium Approved Nutra 0
genes like me logo Genes that share compounds with FREM2: view

Transcripts for FREM2 Gene

mRNA/cDNA for FREM2 Gene

(2) REFSEQ mRNAs :
(5) Additional mRNA sequences :
(30) Selected AceView cDNA sequences:
(2) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for FREM2 Gene

FRAS1 related extracellular matrix protein 2:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for FREM2 Gene

No ASD Table

Relevant External Links for FREM2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for FREM2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for FREM2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for FREM2 Gene

This gene is overexpressed in Kidney - Cortex (x7.7), Thyroid (x6.7), Pancreas (x5.2), and Muscle - Skeletal (x4.3).

Protein differential expression in normal tissues from HIPED for FREM2 Gene

This gene is overexpressed in Fetal heart (16.0), Serum (14.7), Fetal testis (14.1), and Urine (11.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for FREM2 Gene

NURSA nuclear receptor signaling pathways regulating expression of FREM2 Gene:


SOURCE GeneReport for Unigene cluster for FREM2 Gene:


Evidence on tissue expression from TISSUES for FREM2 Gene

  • Bone marrow(4.1)
  • Heart(2.2)
  • Kidney(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for FREM2 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
  • cardiovascular
  • digestive
  • immune
  • integumentary
  • lymphatic
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
  • skeleton
  • urinary
Head and neck:
  • brain
  • cerebellum
  • cerebrospinal fluid
  • cranial nerve
  • ear
  • epiglottis
  • eye
  • eyelid
  • face
  • forehead
  • head
  • inner ear
  • jaw
  • lacrimal apparatus
  • larynx
  • lip
  • mandible
  • maxilla
  • meninges
  • middle ear
  • mouth
  • neck
  • nose
  • outer ear
  • pharynx
  • skull
  • tongue
  • tooth
  • vocal cord
  • breast
  • chest wall
  • heart
  • heart valve
  • lung
  • rib
  • rib cage
  • sternum
  • thymus
  • trachea
  • abdominal wall
  • intestine
  • kidney
  • small intestine
  • anus
  • pelvis
  • penis
  • testicle
  • ureter
  • urethra
  • urinary bladder
  • uterus
  • vagina
  • vulva
  • digit
  • finger
  • foot
  • hand
  • lower limb
  • nail
  • toe
  • upper limb
  • blood
  • bone marrow
  • hair
  • peripheral nervous system
  • skin
  • spinal column
  • spinal cord
  • vertebrae
  • white blood cell
genes like me logo Genes that share expression patterns with FREM2: view

No data available for Protein tissue co-expression partners and mRNA Expression by UniProt/SwissProt for FREM2 Gene

Orthologs for FREM2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for FREM2 Gene

Organism Taxonomy Gene Similarity Type Details
(Pan troglodytes)
Mammalia FREM2 34 33
  • 99.37 (n)
(Canis familiaris)
Mammalia FREM2 34 33
  • 87.4 (n)
(Bos Taurus)
Mammalia FREM2 34 33
  • 86.98 (n)
(Rattus norvegicus)
Mammalia Frem2 33
  • 84.11 (n)
(Monodelphis domestica)
Mammalia FREM2 34
  • 84 (a)
(Mus musculus)
Mammalia Frem2 16 34 33
  • 83.6 (n)
(Ornithorhynchus anatinus)
Mammalia FREM2 34
  • 76 (a)
(Gallus gallus)
Aves FREM2 34 33
  • 73.75 (n)
(Anolis carolinensis)
Reptilia -- 34
  • 31 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100496696 33
  • 70.78 (n)
(Danio rerio)
Actinopterygii frem2a 34
  • 67 (a)
frem2b 34 33
  • 66.47 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 54 (a)
Cin.10028 33
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.10028 33
Species where no ortholog for FREM2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya 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)
  • fruit fly (Drosophila melanogaster)
  • 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 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)
  • worm (Caenorhabditis elegans)

Evolution for FREM2 Gene

Gene Tree for FREM2 (if available)
Gene Tree for FREM2 (if available)
Evolutionary constrained regions (ECRs) for FREM2: view image

Paralogs for FREM2 Gene

Paralogs for FREM2 Gene

(2) SIMAP similar genes for FREM2 Gene using alignment to 1 proteins:

  • FREM2_HUMAN Pseudogenes for FREM2 Gene

genes like me logo Genes that share paralogs with FREM2: view

Variants for FREM2 Gene

Sequence variations from dbSNP and Humsavar for FREM2 Gene

SNP ID Clin Chr 13 pos Variation AA Info Type
rs1028448309 uncertain-significance, Cryptophthalmos syndrome 38,880,795(+) A/G 3_prime_UTR_variant, genic_downstream_transcript_variant
rs112083916 uncertain-significance, Cryptophthalmos syndrome 38,848,621(+) T/G coding_sequence_variant, genic_downstream_transcript_variant, synonymous_variant
rs113097228 uncertain-significance, Cryptophthalmos syndrome 38,886,970(+) C/T 3_prime_UTR_variant, genic_downstream_transcript_variant
rs114333791 uncertain-significance, Cryptophthalmos syndrome 38,851,035(+) A/G coding_sequence_variant, genic_downstream_transcript_variant, synonymous_variant
rs114341997 uncertain-significance, Cryptophthalmos syndrome 38,688,991(+) C/A coding_sequence_variant, missense_variant, non_coding_transcript_variant

Structural Variations from Database of Genomic Variants (DGV) for FREM2 Gene

Variant ID Type Subtype PubMed ID
esv2660903 CNV deletion 23128226
esv2665365 CNV deletion 23128226
esv2747282 CNV deletion 23290073
esv2747283 CNV deletion 23290073
esv3307062 CNV mobile element insertion 20981092
esv3308401 CNV mobile element insertion 20981092
esv3341689 CNV insertion 20981092
esv3350637 CNV insertion 20981092
esv3381963 CNV insertion 20981092
esv3550338 CNV deletion 23714750
esv3580611 CNV loss 25503493
esv3631823 CNV loss 21293372
esv3631824 CNV loss 21293372
esv4433 CNV loss 18987735
nsv1008 CNV deletion 18451855
nsv507692 OTHER sequence alteration 20534489
nsv64239 CNV deletion 16902084
nsv819985 CNV loss 19587683
nsv826623 CNV loss 20364138
nsv832584 CNV gain 17160897
nsv832585 CNV gain 17160897

Variation tolerance for FREM2 Gene

Residual Variation Intolerance Score: 81% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 22.54; 99.44% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for FREM2 Gene

Human Gene Mutation Database (HGMD)
SNPedia medical, phenotypic, and genealogical associations of SNPs for

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for FREM2 Gene

Disorders for FREM2 Gene

MalaCards: The human disease database

(11) MalaCards diseases for FREM2 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
fraser syndrome 2
  • frasrs2
renal hypodysplasia/aplasia 3
  • rhda3
anus disease
  • anal disease
fraser syndrome 1
  • frasrs1
- elite association - COSMIC cancer census association via MalaCards
Search FREM2 in MalaCards View complete list of genes associated with diseases


  • Fraser syndrome 2 (FRASRS2) [MIM:617666]: A form of Fraser syndrome, an autosomal recessive disorder characterized by cryptophthalmos, cutaneous syndactyly, and urogenital abnormalities including renal agenesis or hypoplasia. Additional features include abnormalities of the larynx, ear malformations, and facial abnormalities. {ECO:0000269 PubMed:15838507}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for FREM2

genes like me logo Genes that share disorders with FREM2: view

No data available for Genatlas for FREM2 Gene

Publications for FREM2 Gene

  1. Genome-wide association study does not reveal major genetic determinants for anti-cytomegalovirus antibody response. (PMID: 21993531) Kuparinen T … Hurme M (Genes and immunity 2012) 3 44 58
  2. Molecular study of 33 families with Fraser syndrome new data and mutation review. (PMID: 18671281) van Haelst MM … Scambler PJ (American journal of medical genetics. Part A 2008) 3 22 58
  3. Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. (PMID: 16335952) Liu T … Smith RD (Journal of proteome research 2005) 3 4 58
  4. Identification of a new gene mutated in Fraser syndrome and mouse myelencephalic blebs. (PMID: 15838507) Jadeja S … Scambler PJ (Nature genetics 2005) 3 4 58
  5. Complete sequencing and characterization of 21,243 full-length human cDNAs. (PMID: 14702039) Ota T … Sugano S (Nature genetics 2004) 3 4 58

Products for FREM2 Gene

Sources for FREM2 Gene

Loading form....