GeneBe

ITGA6

protein-coding

integrin subunit alpha 6, the group of CD molecules|Integrin alpha subunits

Gene summary

The gene encodes a member of the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 6 subunit. This subunit may associate with a beta 1 or beta 4 subunit to form an integrin that interacts with extracellular matrix proteins including members of the laminin family. The alpha 6 beta 4 integrin may promote tumorigenesis, while the alpha 6 beta 1 integrin may negatively regulate erbB2/HER2 signaling. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2015]

MANE transcript

NM_000210.4

Inheritance

AR

ClinVar variants

P:53U:240B:244

Top phenotype

Epidermolysis bullosa, junctional 6, with pyloric atresia

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr2:172,234,216-172,506,459

External References & Databases

Ensembl (ENSG00000091409)OMIM (147556)HGNC:6142GenCCUniProt (P23229)AlphaFoldClinVar (ITGA6)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~272.2 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

junctional epidermolysis bullosa with pyloric atresiaDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009183

Submitter: Natera

epidermolysis bullosa, junctional 6, with pyloric atresiaLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859233

Submitter: G2P

junctional epidermolysis bullosa with pyloric atresiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009183

Submitter: Genomics England PanelApp

junctional epidermolysis bullosa with pyloric atresiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009183

Submitter: PanelApp Australia

junctional epidermolysis bullosa with pyloric atresiaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009183

Submitter: Orphanet

junctional epidermolysis bullosa with pyloric atresiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009183

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Epidermolysis bullosa, junctional 6, with pyloric atresiaAR

Manifestation: Dermatologic; Gastrointestinal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 9185503; 9158140; 11251584; 20301336Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ITGA6 variants in ClinVar

9 Conditions Cataloged
not providedTotal: 533
Epidermolysis bullosa, junctional 6, with pyloric atresiaTotal: 149
Inborn genetic diseasesTotal: 120
Junctional epidermolysis bullosa with pyloric atresiaTotal: 53
ITGA6-related disorderTotal: 22
not specifiedTotal: 9
ITGA6-related disordersTotal: 2
Junctional epidermolysis bullosaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000210.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
1
clinvar
8
clinvar
228
clinvar
1
clinvar
 238
missense
1
clinvar
220
clinvar
11
clinvar
4
clinvar
 236
nonsense
8
clinvar
5
clinvar
1
clinvar
 14
start loss
0
frameshift
19
clinvar
8
clinvar
1
clinvar
 28
splice donor/acceptor (+/-2bp)
2
clinvar
9
clinvar
10
clinvar
 21
Total30232402395537

Highest pathogenic variant AF is 0.0000074364557

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 40 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000210.4RefSeqNP_000201.225MANE Select
ENST00000684293.1EnsemblENSP00000508249.125MANE Select
NM_001079818.3RefSeqNP_001073286.125Standard
NM_001316306.2RefSeqNP_001303235.123Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
itga6aDanio rerio

Structure: whole organism

Quality: decreased length

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • PI3K-Akt signaling pathway - Homo sapiens (human)
  • Cell adhesion molecules (CAMs) - Homo sapiens (human)
  • ECM-receptor interaction - Homo sapiens (human)
  • Focal adhesion - Homo sapiens (human)
  • Dilated cardiomyopathy (DCM) - Homo sapiens (human)

Biological Process

  • cell-substrate junction assembly
  • cell-matrix adhesion
  • integrin-mediated signaling pathway
  • ectodermal cell differentiation
  • positive regulation of cell-substrate adhesion

Molecular Function

  • protein binding
  • insulin-like growth factor I binding
  • neuregulin binding
  • laminin binding
  • protein-containing complex binding

Cellular Component

  • basement membrane
  • plasma membrane
  • cell-cell adherens junction
  • focal adhesion
  • external side of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000409080
Coding exons
25
Length
79100
Individuals with no LoFs
125685
Homozygous LoFs
0
Heterozygous LoFs
63
Defined
125748
p
0.000251
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.654635740.8070.00003187108
Missense (PolyPhen)121196.920.614452445
Synonymous0.9452022200.9190.00001312088
Loss of Function4.562361.60.3730.00000360731

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000400.00031rare
Latino/Admixed American0.000230.00023rare
Ashkenazi Jewish0.0000990.000099rare
East Asian0.000280.00027rare
Finnish0.0000460.000046rare
European (Non-Finnish)0.000300.00029rare
South Asian0.000340.00033rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Integrin alpha-6/beta-1 is a receptor for laminin on platelets. Integrin alpha-6/beta-4 is a receptor for laminin in epithelial cells and it plays a critical structural role in the hemidesmosome (By similarity). ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:22351760). ITGA6:ITGB4 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464). {ECO:0000250|UniProtKB:Q61739, ECO:0000269|PubMed:20682778, ECO:0000269|PubMed:22351760, ECO:0000269|PubMed:28873464}.;
Disease
DISEASE: Epidermolysis bullosa letalis, with pyloric atresia (EB- PA) [MIM:226730]: An autosomal recessive, frequently lethal, epidermolysis bullosa with variable involvement of skin, nails, mucosa, and with variable effects on the digestive system. It is characterized by mucocutaneous fragility, aplasia cutis congenita, and gastrointestinal atresia, which most commonly affects the pylorus. Pyloric atresia is a primary manifestation rather than a scarring process secondary to epidermolysis bullosa. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.490

Intolerance Scores

LoFtool
0.608
RVIS EVS
0.25
RVIS percentile EVS
69.66

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.776

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium
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