FREM2

Protein identityUniProt · HPA

UniProt accession

Q5SZK8

Gene

FREM2

Ensembl

ENSG00000150893

Chromosome

13

Canonical length

3169 aa

Protein class

Disease related genes, Human disease related genes, Predicted membrane proteins

Subcellular location

Cytosol

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

3169 residues, UniProt reviewed canonical sequence.

>Q5SZK8|FREM2
     1  MHSAGTPGLS SRRTGNSTSF QPGPPPPPRL LLLLLLLLSL VSRVPAQPAA FGRALLSPGL
    61  AGAAGVPAEE AIVLANRGLR VPFGREVWLD PLHDLVLQVQ PGDRCAVSVL DNDALAQRPG
   121  RLSPKRFPCD FGPGEVRYSH LGARSPSRDR VRLQLRYDAP GGAVVLPLVL EVEVVFTQLE
   181  VVTRNLPLVV EELLGTSNAL DARSLEFAFQ PETEECRVGI LSGLGALPRY GELLHYPQVP
   241  GGAREGGAPE TLLMDCKAFQ ELGVRYRHTA ASRSPNRDWI PMVVELRSRG APVGSPALKR
   301  EHFQVLVRIR GGAENTAPKP SFVAMMMMEV DQFVLTALTP DMLAAEDAES PSDLLIFNLT
   361  SPFQPGQGYL VSTDDRSLPL SSFTQRDLRL LKIAYQPPSE DSDQERLFEL ELEVVDLEGA
   421  ASDPFAFMVV VKPMNTMAPV VTRNTGLILY EGQSRPLTGP AGSGPQNLVI SDEDDLEAVR
   481  LEVVAGLRHG HLVILGASSG SSAPKSFTVA ELAAGQVVYQ HDDRDGSLSD NLVLRMVDGG
   541  GRHQVQFLFP ITLVPVDDQP PVLNANTGLT LAEGETVPIL PLSLSATDMD SDDSLLLFVL
   601  ESPFLTTGHL LLRQTHPPHE KQELLRGLWR KEGAFYERTV TEWQQQDITE GRLFYRHSGP
   661  HSPGPVTDQF TFRVQDNHDP PNQSGLQRFV IRIHPVDRLP PELGSGCPLR MVVQESQLTP
   721  LRKKWLRYTD LDTDDRELRY TVTQPPTDTD ENHLPAPLGT LVLTDNPSVV VTHFTQAQIN
   781  HHKIAYRPPG QELGVATRVA QFQFQVEDRA GNVAPGTFTL YLHPVDNQPP EILNTGFTIQ
   841  EKGHHILSET ELHVNDVDTD VAHISFTLTQ APKHGHMRVS GQILHVGGLF HLEDIKQGRV
   901  SYAHNGDKSL TDSCSLEVSD RHHVVPITLR VNVRPVDDEV PILSHPTGTL ESYLDVLENG
   961  ATEITANVIK GTNEETDDLM LTFLLEDPPL YGEILVNGIP AEQFTQRDIL EGSVVYTHTS
  1021  GEIGLLPKAD SFNLSLSDMS QEWRIGGNTI QGVTIWVTIL PVDSQAPEIF VGEQLIVMEG
  1081  DKSVITSVHI SAEDVDSLND DILCTIVIQP TSGYVENISP APGSEKSRAG IAISAFNLKD
  1141  LRQGHINYVQ SVHKGVEPVE DRFVFRCSDG INFSERQFFP IVIIPTNDEQ PEMFMREFMV
  1201  MEGMSLVIDT PILNAADADV PLDDLTFTIT QFPTHGHIMN QLINGTVLVE SFTLDQIIES
  1261  SSIIYEHDDS ETQEDSFVIK LTDGKHSVEK TVLIIVIPVD DETPRMTINN GLEIEIGDTK
  1321  IINNKILMAT DLDSEDKSLV YIIRYGPGHG LLQRRKPTGA FENITLGMNF TQDEVDRNLI
  1381  QYVHLGQEGI RDLIKFDVTD GINPLIDRYF YVSIGSIDIV FPDVISKGVS LKEGGKVTLT
  1441  TDLLSTSDLN SPDENLVFTI TRAPMRGHLE CTDQPGVSIT SFTQLQLAGN KIYYIHTADD
  1501  EVKMDSFEFQ VTDGRNPVFR TFRISISDVD NKKPVVTIHK LVVSESENKL ITPFELTVED
  1561  RDTPDKLLKF TITQVPIHGH LLFNNTRPVM VFTKQDLNEN LISYKHDGTE SSEDSFSFTV
  1621  TDGTHTDFYV FPDTVFETRR PQVMKIQVLA VDNSVPQIAV NKGASTLRTL ATGHLGFMIT
  1681  SKILKVEDRD SLHISLRFIV TEAPQHGYLL NLDKGNHSIT QFTQADIDDM KICYVLREGA
  1741  NATSDMFYFA VEDGGGNKLT YQNFRLNWAW ISFEKEYYLV NEDSKFLDVV LKRRGYLGET
  1801  SFISIGTRDR TAEKDKDFKG KAQKQVQFNP GQTRATWRVR ILSDGEHEQS ETFQVVLSEP
  1861  VLAALEFPTV ATVEIVDPGD EPTVFIPQSK YSVEEDVGEL FIPIRRSGDV SQELMVVCYT
  1921  QQGTATGTVP TSVLSYSDYI SRPEDHTSVV RFDKDEREKL CRIVIIDDSL YEEEETFHVL
  1981  LSMPMGGRIG SEFPGAQVTI VPDKDDEPIF YFGDVEYSVD ESAGYVEVQV WRTGTDLSKS
  2041  SSVTVRSRKT DPPSADAGTD YVGISRNLDF APGVNMQPVR VVILDDLGQP ALEGIEKFEL
  2101  VLRMPMNAAL GEPSKATVSI NDSVSDLPKM QFKERIYTGS ESDGQIVTMI HRTGDVQYRS
  2161  SVRCYTRQGS AQVMMDFEER PNTDTSIITF LPGETEKPCI LELMDDVLYE EVEELRLVLG
  2221  TPQSNSPFGA AVGEQNETLI RIRDDADKTV IKFGETKFSV TEPKEPGESV VIRIPVIRQG
  2281  DTSKVSIVRV HTKDGSATSG EDYHPVSEEI EFKEGETQHV VEIEVTFDGV REMREAFTVH
  2341  LKPDENMIAE MQLTKAIVYI EEMSSMADVT FPSVPQIVSL LMYDDTSKAK ESAEPMSGYP
  2401  VICITACNPK YSDYDKTGSI CASENINDTL TRYRWLISAP AGPDGVTSPM REVDFDTFFT
  2461  SSKMVTLDSI YFQPGSRVQC AARAVNTNGD EGLELMSPIV TISREEGLCQ PRVPGVVGAE
  2521  PFSAKLRYTG PEDADYTNLI KLTVTMPHID GMLPVISTRE LSNFELTLSP DGTRVGNHKC
  2581  SNLLDYTEVK THYGFLTDAT KNPEIIGETY PYQYSLSIRG STTLRFYRNL NLEACLWEFV
  2641  SYYDMSELLA DCGGTIGTDG QVLNLVQSYV TLRVPLYVSY VFHSPVGVGG WQHFDLKSEL
  2701  RLTFVYDTAI LWNDGIGSPP EAELQGSLYP TSMRIGDEGR LAVHFKTEAQ FHGLFVLSHP
  2761  ASFTSSVIMS ADHPGLTFSL RLIRSEPTYN QPVQQWSFVS DFAVRDYSGT YTVKLVPCTA
  2821  PSHQEYRLPV TCNPREPVTF DLDIRFQQVS DPVAAEFSLN TQMYLLSKKS LWLSDGSMGF
  2881  GQESDVAFAE GDIIYGRVMV DPVQNLGDSF YCSIEKVFLC TGADGYVPKY SPMNAEYGCL
  2941  ADSPSLLYRF KIVDKAQPET QATSFGNVLF NAKLAVDDPE AILLVNQPGS DGFKVDSTPL
  3001  FQVALGREWY IHTIYTVRSK DNANRGIGKR SVEYHSLVSQ GKPQSTTKSR KKREIRSTPS
  3061  LAWEIGAENS RGTNIQHIAL DRTKRQIPHG RAPPDGILPW ELNSPSSAVS LVTVVGGTTV
  3121  GLLTICLTVI AVLMCRGKES FRGKDAPKGS SSSEPMVPPQ SHHNDSSEV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FREM2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0

Highest tissue expression

7.2 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FREM2.

Disease | AllUniProt

Conditions FREM2 is implicated in, by any mechanism.

• Fraser syndrome 2 (FRASRS2) MIM:617666
• Cryptophthalmos, unilateral or bilateral, isolated (CRYPTOP) MIM:123570

Disease | GeneticClinVar

132 pathogenic / likely-pathogenic of 2,507 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Fraser syndrome 2
• Isolated cryptophthalmia
• Fraser syndrome 1
• FREM2-related disorder
• Childhood-onset schizophrenia

Disease | ImmuneIEDB

Conditions an epitope on FREM2 was assayed in.

• rheumatoid arthritis B cell

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.48

gnomAD pLI

0

gnomAD missense Z

-0.86

DepMap mean gene effect

0.09

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• anatomical structure morphogenesis
• cell adhesion
• cell communication
• embryonic digit morphogenesis
• eye development
• heart development
• inner ear development
• kidney development
• morphogenesis of an epithelium

Molecular functions

• metal ion binding

Cellular components

• basement membrane
• extracellular exosome
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Na-Ca exchanger/integrin-beta4
• CalX-like domain superfamily
• CSPG repeat
• FRAS1-related extracellular matrix protein, N-terminal domain
• FRAS1-related extracellular matrix
• Calx-beta domain
• Cadherin-like
• Frem protein N-terminal domain

KeywordsUniProt

• Calcium
• Cell adhesion
• Cell membrane
• Developmental protein
• Glycoprotein
• Membrane
• Metal-binding
• Repeat
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of FREM2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• FREM1