GeneBe

COL17A1

protein-coding

collagen type XVII alpha 1 chain, the group of Collagens|MicroRNA protein coding host genes

Gene summary

This gene encodes the alpha chain of type XVII collagen. Unlike most collagens, collagen XVII is a transmembrane protein. Collagen XVII is a structural component of hemidesmosomes, multiprotein complexes at the dermal-epidermal basement membrane zone that mediate adhesion of keratinocytes to the underlying membrane. Mutations in this gene are associated with both generalized atrophic benign and junctional epidermolysis bullosa. Two homotrimeric forms of type XVII collagen exist. The full length form is the transmembrane protein. A soluble form, referred to as either ectodomain or LAD-1, is generated by proteolytic processing of the full length form. [provided by RefSeq, Jul 2008]

Previous symbols:
  • BPAG2

MANE transcript

NM_000494.4

Inheritance

AD, AR

ClinVar variants

P:184U:393B:470

Top phenotype

Epithelial recurrent erosion dystrophy; Epidermolysis bullosa, junctional 4, intermediate

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr10:104,031,286-104,085,880

External References & Databases

Ensembl (ENSG00000065618)NCBI Gene (1308)OMIM (113811)HGNC:2194GenCCUniProt (Q9UMD9)AlphaFoldClinVar (COL17A1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~54.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

epithelial recurrent erosion dystrophySTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007381

Submitter: Labcorp Genetics (formerly Invitae)

epithelial recurrent erosion dystrophyMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0007381

Submitter: Ambry Genetics

junctional epidermolysis bullosa, non-Herlitz typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009180

Submitter: Labcorp Genetics (formerly Invitae)

junctional epidermolysis bullosa, non-Herlitz typeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009180

Submitter: Ambry Genetics

epidermolysis bullosa, junctional 4, intermediateDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0030750

Submitter: G2P

epithelial recurrent erosion dystrophyDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007381

Submitter: G2P

amelogenesis imperfectaMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0019507

Submitter: Ambry Genetics

junctional epidermolysis bullosa, non-Herlitz typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009180

Submitter: Genomics England PanelApp

epidermolysis bullosa, junctional 4, intermediateDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0030750

Submitter: Ambry Genetics

generalized junctional epidermolysis bullosa non-Herlitz typeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019307

Submitter: Orphanet

epithelial recurrent erosion dystrophySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007381

Submitter: Orphanet

late-onset junctional epidermolysis bullosaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019309

Submitter: Orphanet

epithelial recurrent erosion dystrophyMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0007381

Submitter: Ambry Genetics

localized junctional epidermolysis bullosa, non-Herlitz typeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0016673

Submitter: Orphanet

Clinical Genomic Database (CGD)

Epithelial recurrent erosion dystrophy; Epidermolysis bullosa, junctional 4, intermediateAD/AR

Manifestation: Dermatologic; Ophthalmologic

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: 2663347; 7883981; 7550320; 9038345; 9403072; 17263807; 17596158; 19369679; 20301304; 21357940; 21466533; 22965308; 25676728Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to COL17A1 variants in ClinVar

18 Conditions Cataloged
not providedTotal: 1228
Inborn genetic diseasesTotal: 262
Junctional epidermolysis bullosa, non-Herlitz typeTotal: 151
not specifiedTotal: 86
COL17A1-related disorderTotal: 75
Epidermolysis bullosa, junctional 4, intermediateTotal: 59
Epithelial recurrent erosion dystrophyTotal: 39
Amelogenesis imperfecta type 1ATotal: 17

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000494.4. 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
2
clinvar
6
clinvar
418
clinvar
6
clinvar
 432
missense
7
clinvar
8
clinvar
375
clinvar
35
clinvar
11
clinvar
 436
nonsense
37
clinvar
8
clinvar
 45
start loss
0
frameshift
46
clinvar
18
clinvar
1
clinvar
 65
splice donor/acceptor (+/-2bp)
8
clinvar
50
clinvar
11
clinvar
 69
Total10084393453171047

Highest pathogenic variant AF is 0.00012335286

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000494.4RefSeqNP_000485.355MANE Select
ENST00000648076.2EnsemblENSP00000497653.155MANE Select
ENST00000369733.8EnsemblENSP00000358748.351Standard
ENST00000393211.3EnsemblENSP00000376905.314Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
col17a1aDanio rerio

Structure: post-vent region

Quality: distended

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Protein digestion and absorption - Homo sapiens (human)
  • Collagen chain trimerization
  • Collagen biosynthesis and modifying enzymes
  • Alpha6Beta4Integrin
  • Collagen degradation

Biological Process

  • cell-matrix adhesion
  • epidermis development
  • extracellular matrix organization
  • hemidesmosome assembly
  • regulation of immune response

Molecular Function

  • extracellular matrix structural constituent
  • protein binding
  • extracellular matrix structural constituent conferring tensile strength

Cellular Component

  • extracellular region
  • collagen trimer
  • basement membrane
  • extracellular space
  • endoplasmic reticulum lumen

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000353479
Coding exons
55
Length
54717
Individuals with no LoFs
125513
Homozygous LoFs
0
Heterozygous LoFs
235
Defined
125748
p
0.000935
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.7489208581.070.00005099419
Missense (PolyPhen)206203.541.01212033
Synonymous-0.2893383311.020.00002143217
Loss of Function3.635997.70.6040.000005861068

Population LoF Frequency

PopulationCAFp-valueStatus
African0.00180.0018notable
Latino/Admixed American0.000720.00072rare
Ashkenazi Jewish0.00440.0044notable
East Asian0.000710.00071rare
Finnish0.000650.00065rare
European (Non-Finnish)0.000670.00066rare
South Asian0.000890.00085rare
Other0.00150.0015notable

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: May play a role in the integrity of hemidesmosome and the attachment of basal keratinocytes to the underlying basement membrane.;
Disease
DISEASE: Generalized atrophic benign epidermolysis bullosa (GABEB) [MIM:226650]: A non-lethal, adult form of junctional epidermolysis bullosa characterized by life-long blistering of the skin, associated with hair and tooth abnormalities. {ECO:0000269|PubMed:10652291, ECO:0000269|PubMed:10951237, ECO:0000269|PubMed:11912005, ECO:0000269|PubMed:8669466, ECO:0000269|PubMed:9199555}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epithelial recurrent erosion dystrophy (ERED) [MIM:122400]: A corneal dystrophy characterized by recurrent episodes of epithelial erosions from childhood, with occasional impairment of vision. Most patients have attacks of redness, photophobia, epiphora, and ocular pain. Exposure to sunlight or draught, dust and smoke and lack of sleep can precipitate attacks. {ECO:0000269|PubMed:25676728}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.283

Intolerance Scores

LoFtool
0.104
RVIS EVS
-0.71
RVIS percentile EVS
14.58

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.407

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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