FRMD4A

Protein identityUniProt · HPA

UniProt accession

Q9P2Q2

Gene

FRMD4A

Ensembl

ENSG00000151474

Chromosome

10

Canonical length

1039 aa

Protein class

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

Subcellular location

Nucleoplasm,Golgi apparatus

OverviewNCBI Gene

This gene encodes a FERM domain-containing protein that regulates epithelial cell polarity. It connects ADP ribosylation factor 6 (ARF6) with the Par protein complex, which regulates the remodeling of adherens junctions and linear actin cable formation during epithelial cell polarization. Polymorphisms in this gene are associated with Alzheimer's disease, and also with nicotine dependence. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

Canonical amino-acid sequenceUniProt

1039 residues, UniProt reviewed canonical sequence.

>Q9P2Q2|FRMD4A
     1  MAVQLVPDSA LGLLMMTEGR RCQVHLLDDR KLELLVQPKL LAKELLDLVA SHFNLKEKEY
    61  FGIAFTDETG HLNWLQLDRR VLEHDFPKKS GPVVLYFCVR FYIESISYLK DNATIELFFL
   121  NAKSCIYKEL IDVDSEVVFE LASYILQEAK GDFSSNEVVR SDLKKLPALP TQALKEHPSL
   181  AYCEDRVIEH YKKLNGQTRG QAIVNYMSIV ESLPTYGVHY YAVKDKQGIP WWLGLSYKGI
   241  FQYDYHDKVK PRKIFQWRQL ENLYFREKKF SVEVHDPRRA SVTRRTFGHS GIAVHTWYAC
   301  PALIKSIWAM AISQHQFYLD RKQSKSKIHA ARSLSEIAID LTETGTLKTS KLANMGSKGK
   361  IISGSSGSLL SSGSQESDSS QSAKKDMLAA LKSRQEALEE TLRQRLEELK KLCLREAELT
   421  GKLPVEYPLD PGEEPPIVRR RIGTAFKLDE QKILPKGEEA ELERLEREFA IQSQITEAAR
   481  RLASDPNVSK KLKKQRKTSY LNALKKLQEI ENAINENRIK SGKKPTQRAS LIIDDGNIAS
   541  EDSSLSDALV LEDEDSQVTS TISPLHSPHK GLPPRPPSHN RPPPPQSLEG LRQMHYHRND
   601  YDKSPIKPKM WSESSLDEPY EKVKKRSSHS HSSSHKRFPS TGSCAEAGGG SNSLQNSPIR
   661  GLPHWNSQSS MPSTPDLRVR SPHYVHSTRS VDISPTRLHS LALHFRHRSS SLESQGKLLG
   721  SENDTGSPDF YTPRTRSSNG SDPMDDCSSC TSHSSSEHYY PAQMNANYST LAEDSPSKAR
   781  QRQRQRQRAA GALGSASSGS MPNLAARGGA GGAGGAGGGV YLHSQSQPSS QYRIKEYPLY
   841  IEGGATPVVV RSLESDQEGH YSVKAQFKTS NSYTAGGLFK ESWRGGGGDE GDTGRLTPSR
   901  SQILRTPSLG REGAHDKGAG RAAVSDELRQ WYQRSTASHK EHSRLSHTSS TSSDSGSQYS
   961  TSSQSTFVAH SRVTRMPQMC KATSAALPQS QRSSTPSSEI GATPPSSPHH ILTWQTGEAT
  1021  ENSPILDGSE SPPHQSTDE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FRMD4A 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

0

Mean surface accessibility (rSASA)

0.5

Highest tissue expression

53 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FRMD4A.

Disease | AllUniProt

Conditions FRMD4A is implicated in, by any mechanism.

• Agenesis of the corpus callosum, with facial anomalies and cerebellar ataxia (CCAFCA) MIM:616819

Disease | GeneticClinVar

3 pathogenic / likely-pathogenic of 266 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome

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)

0.14

gnomAD pLI

1

gnomAD missense Z

2.46

DepMap mean gene effect

0.02

DepMap dependency class

selective

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

• establishment of epithelial cell polarity
• negative regulation of protein secretion
• positive regulation of protein secretion

Molecular functions

• protein-macromolecule adaptor activity

Cellular components

• adherens junction
• bicellular tight junction
• cytoplasm
• cytoskeleton

Protein domainsUniProt · Pfam · InterPro

• FERM domain
• PH-like domain superfamily
• FERM/acyl-CoA-binding protein superfamily
• FERM, N-terminal
• FERM, C-terminal PH-like domain
• FERM conserved site
• FERM central domain
• Band 4.1 domain
• Cytohesin Ubiquitin Protein Inducing Domain
• Ubiquitin-like domain superfamily
• FERM superfamily, second domain
• FRMD4A/B, FERM domain C-lobe
• FERM domain-containing protein 4A/B
• FERM central domain
• FERM N-terminal domain
• FERM C-terminal PH-like domain
• Cytohesin Ubiquitin Protein Inducing Domain

KeywordsUniProt

• Cell junction
• Coiled coil
• Cytoplasm
• Cytoskeleton
• Intellectual disability
• Phosphoprotein
• Tight junction

InteractionsUniProt · HPA

Protein binding partners of FRMD4A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CYTH2
• CYTH3
• PARD3