FRMD4A FERM domain containing 4A [Homo sapiens (human)] - Gene

Summary

Official Symbol: FRMD4Aprovided by HGNC
Official Full Name: FERM domain containing 4Aprovided by HGNC
Primary source: HGNC:HGNC:25491
See related: Ensembl:ENSG00000151474 MIM:616305; AllianceGenome:HGNC:25491
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: FRMD4; CCAFCA; bA295P9.4
Summary: 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]
Expression: Ubiquitous expression in fat (RPKM 10.5), skin (RPKM 7.3) and 25 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 10p13

Exon count:: 30

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	10	NC_000010.11 (13643706..14330924, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	10	NC_060934.1 (13656726..14343958, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (13685706..14372923, complement)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

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

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Polymorphisms in the FRMD4A Gene Are Associated With Chronic Obstructive Pulmonary Disease Susceptibility in a Latin American Population.", trans "Polimorfismos en el gen FRMD4A se asocian a riesgo de enfermedad pulmonar obstructiva cronica en poblacion latinoamericana.
Title: Polymorphisms in the FRMD4A Gene Are Associated With Chronic Obstructive Pulmonary Disease Susceptibility in a Latin American Population.
FRMD4A RNAi or inhibition of cytohesins strongly upregulated secretion of endogenous tau. These results suggest that FRMD4A, a genetic risk factor for late-onset Alzheimer's disease, regulates tau secretion by activating cytohesin-Arf6 signaling.
Title: FRMD4A-cytohesin signaling modulates the cellular release of tau.
Findings suggest that FRMD4A expression correlates with the development of tongue squamous cell carcinoma.
Title: FRMD4A: A potential therapeutic target for the treatment of tongue squamous cell carcinoma.
novel microcephaly, intellectual disability and dysmorphism syndrome is associated with a mutation in FRMD4A.
Title: A syndrome of congenital microcephaly, intellectual disability and dysmorphism with a homozygous mutation in FRMD4A.
data suggest that FRMD4A could be a relevant candidate gene for AD risk.
Title: Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease.
findings suggest FRMD4A as a novel candidate therapeutic target in HNSCC based on the key role in metastatic growth we have identified
Title: FRMD4A upregulation in human squamous cell carcinoma promotes tumor growth and metastasis and is associated with poor prognosis.
A single nucleotide polymorphism in the FERM domain containing 4A protein is associated with nicotine dependence.
Title: Large-scale genome-wide association study of Asian population reveals genetic factors in FRMD4A and other loci influencing smoking initiation and nicotine dependence.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
Observational study of gene-disease association. (HuGE Navigator)
Title: A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease.

Submit: New GeneRIF Correction

Phenotypes

Go to the top of the page Help

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
Severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome MedGen: C4225193 OMIM: 616819 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide association scan of RR and QT interval duration in 3 European genetically isolated populations: the EUROSPAN project. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome wide association study (GWAS) of Chagas cardiomyopathy in Trypanosoma cruzi seropositive subjects. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide haplotype association study identifies the FRMD4A gene as a risk locus for Alzheimer's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis identifies new susceptibility loci for migraine. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

RH46504 (e-PCR)
- UniSTS:42260

STS-R39119 (e-PCR)
- UniSTS:76576

D11S2977 (e-PCR)
- UniSTS:152096

RH65818 (e-PCR)
- UniSTS:24112

D8S2279 (e-PCR)
- UniSTS:473907

SHGC-147648 (e-PCR)
- UniSTS:172852

D10S1332E (e-PCR)
- UniSTS:151352

D11S3020 (e-PCR)
- UniSTS:152124

RH76384 (e-PCR)
- UniSTS:87359

NIB1705 (e-PCR)
- UniSTS:75841

D10S1864 (e-PCR)
- UniSTS:14404

D10S1361E (e-PCR)
- UniSTS:151366

D10S223 (e-PCR), detects polymorphism
- UniSTS:18247

RH70373 (e-PCR)
- UniSTS:67403

D10S1382E (e-PCR)
- UniSTS:151378

SHGC-79195 (e-PCR)
- UniSTS:102738

SHGC-83769 (e-PCR)
- UniSTS:104281

SHGC-149575 (e-PCR)
- UniSTS:184924

G62020 (e-PCR)
- UniSTS:139101

SHGC-78712 (e-PCR)
- UniSTS:95585

RH45517 (e-PCR)
- UniSTS:32359

RH45365 (e-PCR)
- UniSTS:14699

D1S1423 (e-PCR)
- UniSTS:149619

D10S1707 (e-PCR), detects polymorphism
- UniSTS:35187

SHGC-153502 (e-PCR)
- UniSTS:177789

AFMa111yb9 (e-PCR)
- UniSTS:66686

SHGC-154294 (e-PCR)
- UniSTS:178058

SHGC-132597 (e-PCR)
- UniSTS:173963

SHGC-36407 (e-PCR)
- UniSTS:6541

A008J08 (e-PCR)
- UniSTS:30875

A008T01 (e-PCR)
- UniSTS:16284

STS-N70116 (e-PCR)
- UniSTS:8353

D10S223 (e-PCR), detects polymorphism
- UniSTS:6570

D10S1545E (e-PCR)
- UniSTS:153772

SHGC-147850 (e-PCR)
- UniSTS:176049

D10S2275 (e-PCR)
- UniSTS:58805

D10S1369E (e-PCR)
- UniSTS:9143

SHGC-33538 (e-PCR)
- UniSTS:54979

SHGC-152835 (e-PCR)
- UniSTS:177609

HSC13H072 (e-PCR)
- UniSTS:50381

RH78375 (e-PCR)
- UniSTS:73422

RH94371 (e-PCR)
- UniSTS:91360

SHGC-149858 (e-PCR)
- UniSTS:182240

D10S1664 (e-PCR), detects polymorphism
- UniSTS:3041

SHGC-146212 (e-PCR)
- UniSTS:175084

WI-21574 (e-PCR)
- UniSTS:1005

SHGC-148669 (e-PCR)
- UniSTS:173037

SHGC-153952 (e-PCR)
- UniSTS:182258

D10S506 (e-PCR)
- UniSTS:2549

SHGC-12991 (e-PCR)
- UniSTS:77821

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables protein-macromolecule adaptor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in establishment of epithelial cell polarity	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of protein secretion	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein secretion	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in adherens junction	IBA Inferred from Biological aspect of Ancestor more info
is_active_in bicellular tight junction	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IMP Inferred from Mutant Phenotype more info	PubMed
located_in cytoskeleton	IEA Inferred from Electronic Annotation more info

General protein information

Go to the top of the page Help

Preferred Names: FERM domain-containing protein 4A

Names: FERM domain containing 4

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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_047164.1 RefSeqGene

Range

4944..692162

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001318336.2 → NP_001305265.1 FERM domain-containing protein 4A isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks two 5' exons but instead contains an alternate 5' terminal exon, and it thus differs in the 5' UTR and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (b) has a distinct N-terminus and is longer than isoform a.

Source sequence(s)

AC044781, AK001072, AK289693, AL157392, BC151244, BU073361

UniProtKB/Swiss-Prot

Q9P2Q2

UniProtKB/TrEMBL

Q9NW91

Conserved Domains (5) summary

smart00295
Location:37 → 237

B41; Band 4.1 homologues

cd13191
Location:233 → 343

FERM_C_FRMD4A_FRMD4B; FERM domain C-lobe of FERM domain-containing protein 4A and 4B (FRMD4A and 4B)

pfam00373
Location:123 → 237

FERM_M; FERM central domain

pfam09379
Location:40 → 101

FERM_N; FERM N-terminal domain

pfam11819
Location:400 → 507

DUF3338; Domain of unknown function (DUF3338)
NM_001318337.2 → NP_001305266.1 FERM domain-containing protein 4A isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks two 5' exons but instead contains an alternate 5' terminal exon, and it thus differs in the 5' UTR and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (c) has a distinct N-terminus and is longer than isoform a.

Source sequence(s)

AK094045, AK289693, AL157392, BU073361

UniProtKB/Swiss-Prot

Q9P2Q2

Conserved Domains (5) summary

smart00295
Location:54 → 254

B41; Band 4.1 homologues

cd13191
Location:250 → 360

FERM_C_FRMD4A_FRMD4B; FERM domain C-lobe of FERM domain-containing protein 4A and 4B (FRMD4A and 4B)

pfam00373
Location:140 → 254

FERM_M; FERM central domain

pfam09379
Location:57 → 118

FERM_N; FERM N-terminal domain

pfam11819
Location:417 → 524

DUF3338; Domain of unknown function (DUF3338)
NM_001318338.2 → NP_001305267.1 FERM domain-containing protein 4A isoform d

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks several 5' exons but instead contains an alternate 5' terminal exon, and it thus differs in the 5' UTR and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (d) is shorter at the N-terminus, compared to isoform a.

Source sequence(s)

AK289693, AL157392, BP278325, BU073361

UniProtKB/Swiss-Prot

Q9P2Q2

Conserved Domains (2) summary

pfam11819
Location:47 → 181

DUF3338; Domain of unknown function (DUF3338)

cl17171
Location:1 → 18

PH-like; Pleckstrin homology-like domain
NM_018027.5 → NP_060497.3 FERM domain-containing protein 4A isoform a

See identical proteins and their annotated locations for NP_060497.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes isoform a.

Source sequence(s)

AC069025, AK289693, AL157392, BC151244, BU073361

Consensus CDS

CCDS7101.1

UniProtKB/Swiss-Prot

A7E2Y3, Q5T377, Q9P2Q2

Related

ENSP00000350032.2, ENST00000357447.7

Conserved Domains (4) summary

smart00295
Location:21 → 221

B41; Band 4.1 homologues

cd13191
Location:217 → 327

FERM_C_FRMD4A_FRMD4B; FERM domain C-lobe of FERM domain-containing protein 4A and 4B (FRMD4A and 4B)

cd17200
Location:18 → 106

FERM_F1_FRMD4B; FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in FERM domain-containing protein 4B (FRMD4B)

pfam11819
Location:356 → 490

DUF3338; Domain of unknown function (DUF3338)

RNA

NR_134578.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) shares the first two exons with variant 1 but lacks the remaining exons, and instead contains alternate 3' exon structure. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.

Source sequence(s)

AC069025, AL157896, BC018891, BC151244