Seroatlas · Human Serome Atlas

FREM1

FRAS1-related extracellular matrix protein 1

Also known as: C9orf143, C9orf145, C9orf154, DKFZp686M16108, FLJ25461, FREM1_HUMAN, TILRR

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: Q5H8C1
Gene: FREM1
Ensembl: ENSG00000164946
Chromosome: 9
Canonical length: 2179 aa
Protein class: Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted secreted proteins
Secretome location: Secreted to extracellular matrix

OverviewNCBI Gene

This gene encodes a basement membrane protein that may play a role in craniofacial and renal development. Mutations in this gene have been associated with bifid nose with or without anorectal and renal anomalies. Alternatively spliced transcript variants encoding different isoforms have been described. PubMed ID 19940113 describes one such variant that initiates transcription within a distinct, internal exon; the resulting shorter isoform (named Toll-like/interleukin-1 receptor regulator, TILRR) is suggested to be a co-receptor of the interleukin 1 receptor family and may regulate receptor function and Toll-like receptor/interleukin 1 receptor signal transduction, contributing to the control of inflammatory response activation. [provided by RefSeq, Apr 2011]

Canonical amino-acid sequenceUniProt

2179 residues, UniProt reviewed canonical sequence.

>Q5H8C1|FREM1
     1  MNSLSWGAAN AVLLLLLLAW ASPTFISINR GVRVMKGHSA FLSGDDLKFA IPKEKDACKV
    61  EVVMNEPITQ RVGKLTPQVF DCHFLPNEVK YVHNGCPILD EDTVKLRLYR FTERDTFIET
   121  FILWVYLLEP DCNIIHMSNN VLEVPEFNGL SQAIDKNLLR FDYDRMASLE CTVSLDTART
   181  RLPAHGQMVL GEPRPEEPRG DQPHSFFPES QLRAKLKCPG GSCTPGLKKI GSLKVSCEEF
   241  LLMGLRYQHL DPPSPNIDYI SIQLDLTDTR SKIVYKSESA WLPVYIRAGI PNQIPKAAFM
   301  AVFILEVDQF ILTSLTTSVL DCEEDETPKP LLVFNITKAP LQGYVTHLLD HTRPISSFTW
   361  KDLSDMQIAY QPPNSSHSER RHDEVELEVY DFFFERSAPM TVHISIRTAD TNAPRVSWNT
   421  GLSLLEGQSR AITWEQFQVV DNDDIGAVRL VTVGGLQHGW LTLRGGKGFL FTVADLQAGV
   481  VRYHHDDSDS TKDFVVFRIF DGHHSIRHKF PINVLPKDDS PPFLITNVVI ELEEGQTILI
   541  QGSMLRASDV DASDDYIFFN ITKPPQAGEI MKKPGPGLIG YPVHGFLQRD LFNGIIYYRH
   601  FGGEIFEDSF QFVLWDSHEP PNLSVPQVAT IHITPVDDQL PKEAPGVSRH LVVKETEVAY
   661  ITKKQLHFID SESYDRELVY TITTPPFFSF SHRHLDAGKL FMVDSIPKVV KNPTALELRS
   721  FTQHAVNYMK VAYMPPMQDI GPHCRDVQFT FSVSNQHGGT LHGICFNITI LPVDNQVPEA
   781  FTNPLKVTEG GQSIISTEHI LISDADTKLD NIDLSLRELP LHGRVELNGF PLNSGGTFSW
   841  GDLHTLKVRY QHDGTEVLQD DLLLEVTDGT NSAEFVLHVE VFPVNDEPPV LKADLMPVMN
   901  CSEGGEVVIT SEYIFATDVD SDNLKLMFVI AREPQHGVVR RAGVTVDQFS QRDVISEAVT
   961  YKHTGGEIGL MPCFDTITLV VSDGEAGPFV NGCCYNGPNP SVPLHASFPV YDLNITVYPV
  1021  DNQPPSIAIG PVFVVDEGCS TALTVNHLSA TDPDTAADDL EFVLVSPPQF GYLENILPSV
  1081  GFEKSNIGIS IDSFQWKDMN AFHINYVQSR HLRIEPTADQ FTVYVTDGKH HSLEIPFSII
  1141  INPTNDEAPD FVVQNITVCE GQMKELDSSI ISAVDLDIPQ DALLFSITQK PRHGLLIDRG
  1201  FSKDFSENKQ PANPHQKHAP VHSFSMELLK TGMRLTYMHD DSESLADDFT IQLSDGKHKI
  1261  LKTISVEVIP VNDEKPMLSK KAEIAMNMGE TRIISSAILS AIDEDSPREK IYYVFERLPQ
  1321  NGQLQLKIGR DWVPLSPGMK CTQEEVDLNL LRYTHTGAMD SQNQDSFTFY LWDGNNRSPA
  1381  LDCQITIKDM EKGDIVILTK PLVVSKGDRG FLTTTTLLAV DGTDKPEELL YVITSPPRYG
  1441  QIEYVHYPGV PITNFSQMDV VGQTVCYVHK SKVTVSSDRF RFIISNGLRT EHGVFEITLE
  1501  TVDRALPVVT RNKGLRLAQG AVGLLSPDLL QLTDPDTPAE NLTFLLVQLP QHGQLYLWGT
  1561  GLLQHNFTQQ DVDSKNVAYR HSGGDSQTDC FTFMATDGTN QGFIVNGRVW EEPVLFTIQV
  1621  DQLDKTAPRI TLLHSPSQVG LLKNGCYGIY ITSRVLKASD PDTEDDQIIF KILQGPKHGH
  1681  LENTTTGEFI HEKFSQKDLN SKTILYIINP SLEVNSDTVE FQIMDPTGNS ATPQILELKW
  1741  SHIEWSQTEY EVCENVGLLP LEIIRRGYSM DSAFVGIKVN QVSAAVGKDF TVIPSKLIQF
  1801  DPGMSTKMWN IAITYDGLEE DDEVFEVILN SPVNAVLGTK TKAAVKILDS KGGQCHPSYS
  1861  SNQSKHSTWE KGIWHLLPPG SSSSTTSGSF HLERRPLPSS MQLAVIRGDT LRGFDSTDLS
  1921  QRKLRTRGNG KTVRPSSVYR NGTDIIYNYH GIVSLKLEDD SFPTHKRKAK VSIISQPQKT
  1981  IKVAELPQAD KVESTTDSHF PRQDQLPSFP KNCTLELKGL FHFEEGIQKL YQCNGIAWKA
  2041  WSPQTKDVED KSCPAGWHQH SGYCHILITE QKGTWNAAAQ ACREQYLGNL VTVFSRQHMR
  2101  WLWDIGGRKS FWIGLNDQVH AGHWEWIGGE PVAFTNGRRG PSQRSKLGKS CVLVQRQGKW
  2161  QTKDCRRAKP HNYVCSRKL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FREM1 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: Secreted
Secreted: Yes
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.31
Highest tissue expression: 34 nTPM

Expression across tissuesHPA

Tissue

epididymis: 34 nTPM
kidney: 21 nTPM
endometrium: 18 nTPM
smooth muscle: 13 nTPM
cervix: 10 nTPM
cerebellum: 10 nTPM

Single-cell type

distal convoluted tubule cells: 529 nCPM
renal collecting duct intercalated cells: 516 nCPM
megakaryocyte-erythroid progenitors: 508 nCPM
renal connecting tubule cells: 475 nCPM
fibro-adipogenic progenitors: 262 nCPM
megakaryocyte progenitors: 213 nCPM

Immune cell

basophil: 0 nTPM
classical monocyte: 0 nTPM
eosinophil: 0 nTPM
gdT-cell: 0 nTPM
intermediate monocyte: 0 nTPM
MAIT T-cell: 0 nTPM

Brain region

cerebellum: 8.6 nTPM
white matter: 7.5 nTPM
spinal cord: 6.1 nTPM
medulla oblongata: 4.2 nTPM
choroid plexus: 4.1 nTPM
midbrain: 2.5 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FREM1.

Disease | AllUniProt

Conditions FREM1 is implicated in, by any mechanism.

Bifid nose, with or without anorectal and renal anomalies (BNAR) MIM:608980
Manitoba oculotrichoanal syndrome (MOTA) MIM:248450
Trigonocephaly 2 (TRIGNO2) MIM:614485

Disease | GeneticClinVar

77 pathogenic / likely-pathogenic of 1,500 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

BNAR syndrome
Oculotrichoanal syndrome
Trigonocephaly 2
FREM1-related disorder
Inborn genetic diseases

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): 1.12
gnomAD pLI: 0
gnomAD missense Z: -3.51
DepMap mean gene effect: 0.03
DepMap dependency class: none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of FREM1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

FREM2

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads FREM1 as an antibody target. Whether an autoantibody or antibody against FREM1 could matter depends on whether native FREM1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

FREM1 is annotated as secreted, so native FREM1 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.

Annotation status

The present source text does not explicitly label FREM1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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