FREM2 FRAS1 related extracellular matrix 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: FREM2provided by HGNC
Official Full Name: FRAS1 related extracellular matrix 2provided by HGNC
Primary source: HGNC:HGNC:25396
See related: Ensembl:ENSG00000150893 MIM:608945; AllianceGenome:HGNC:25396
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CRYPTOP; FRASRS2
Summary: 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]
Expression: Biased expression in kidney (RPKM 4.7), thyroid (RPKM 3.2) and 11 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 13q13.3

Exon count:: 26

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	13	NC_000013.11 (38687077..38887131)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	13	NC_060937.1 (37903789..38103862)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	13	NC_000013.10 (39261214..39461268)

Chromosome 13 - NC_000013.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Targeted resequencing of the 13q13 spondyloarthritis-linked locus identifies a rare variant in FREM2 possibly associated with familial spondyloarthritis.
Title: Targeted resequencing of the 13q13 spondyloarthritis-linked locus identifies a rare variant in FREM2 possibly associated with familial spondyloarthritis.
Novel loss of function variants in FRAS1 AND FREM2 underlie renal agenesis in consanguineous families.
Title: Novel loss of function variants in FRAS1 AND FREM2 underlie renal agenesis in consanguineous families.
Our findings extend the spectrum of FREM2 mutations, and provide insights into opportunities for the prenatal diagnosis of isolated cryptophthalmos. Furthermore, our work highlights the importance of the FREM2 protein during the development of eyelids and the anterior segment of the eyeballs, establishes a suitable animal model for studying epithelial reopening during eyelid development and serves as a valuable reference
Title: Loss-of-function mutations in FREM2 disrupt eye morphogenesis.
Based on these data, we conclude that deficiency of FREM2, and possibly FRAS1, are associated with an increased risk of developing Congenital diaphragmatic hernia (CDH) and that loss of the FREM1/FREM2/FRAS1 complex, or its function, leads to anterior sac CDH development through its effects on mesothelial fold progression
Title: The role of FREM2 and FRAS1 in the development of congenital diaphragmatic hernia.
Our results showed that p.Arg2167Trp had a weaker effect in interrupting interactions between FREM2 and FREM1 than FS-associated missense mutation p.Glu1972Lys. Overall, our data demonstrate that the homozygous mutation p.Arg2167Trp in FREM2 causes isolated Cryptophthalmos(CO), which will facilitate our better understanding of the molecular mechanisms underlying the disease
Title: A homozygous mutation p.Arg2167Trp in FREM2 causes isolated cryptophthalmos.
FREM2 is thus proposed as a novel GB biomarker and a putative biomarker of glioblastoma stem cells. Both FREM2 and SPRY1 are expressed on the surface of the GB cells, while SPRY1 alone was found overexpressed in the cytosol of non-malignant astrocytes.
Title: Meta-Analysis and Experimental Validation Identified FREM2 and SPRY1 as New Glioblastoma Marker Candidates.
In 15 of 590 families, we identified recessive mutations in the genes FRAS1, FREM2, GRIP1, FREM1, ITGA8, and GREM1, all of which function in the interaction of the ureteric bud and the metanephric mesenchyme.
Title: Mild recessive mutations in six Fraser syndrome-related genes cause isolated congenital anomalies of the kidney and urinary tract.
Amplification of the FREM2 gene is associated with mesenchymal differentiation in gliosarcoma.
Title: Amplification of the STOML3, FREM2, and LHFP genes is associated with mesenchymal differentiation in gliosarcoma.
Heterozygous missense mutations in FREM2 cause non-syndromic congenital abnormalities of the kidney and urinary tract in humans.
Title: Identification of two novel CAKUT-causing genes by massively parallel exon resequencing of candidate genes in patients with unilateral renal agenesis.
1 new mutation in FREM2 was identified in families with Fraser syndrome.
Title: Molecular study of 33 families with Fraser syndrome new data and mutation review.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Fraser syndrome 2 MedGen: C4540036 OMIM: 617666 GeneReviews: Not available	not available
Isolated cryptophthalmia MedGen: C1852453 OMIM: 123570 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Genome-wide association study does not reveal major genetic determinants for anti-cytomegalovirus antibody response. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D13S1017 (e-PCR)
- UniSTS:152350

G63132 (e-PCR)
- UniSTS:140250

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in anatomical structure morphogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell communication	IEA Inferred from Electronic Annotation more info
involved_in embryonic digit morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in eye development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heart development	IEA Inferred from Electronic Annotation more info
involved_in inner ear development	IEA Inferred from Electronic Annotation more info
involved_in kidney development	IEA Inferred from Electronic Annotation more info
involved_in morphogenesis of an epithelium	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in basement membrane	IEA Inferred from Electronic Annotation more info
is_active_in collagen-containing extracellular matrix	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular exosome	HDA more info	PubMed
located_in plasma membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: FRAS1-related extracellular matrix protein 2

Names: ECM3 homolog; FRAS1 related extracellular matrix protein 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008125.2 RefSeqGene

Range

5042..205096

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_207361.6 → NP_997244.4 FRAS1-related extracellular matrix protein 2 precursor

Status: REVIEWED

Source sequence(s)

AL354819, BN000687, BX640686, CN291155, KF455770

Consensus CDS

CCDS31960.1

UniProtKB/Swiss-Prot

Q4QQG1, Q5H9N8, Q5SZK8, Q5T6Q1, Q6N057, Q6ZSB4, Q7Z305, Q7Z341

Related

ENSP00000280481.7, ENST00000280481.9

Conserved Domains (2) summary

pfam16184
Location:1482 → 1623

Cadherin_3; Cadherin-like

cl02522
Location:2249 → 2341

Calx-beta; Calx-beta domain