COL17A1

Summary

COL17A1 (collagen type XVII alpha 1 chain, HGNC:2194) is a protein-coding gene on chromosome 10q25.1, encoding Collagen alpha-1(XVII) chain (Q9UMD9). May play a role in the integrity of hemidesmosome and the attachment of basal keratinocytes to the underlying basement membrane.

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.

Source: NCBI Gene 1308 — RefSeq curated summary.

At a glance

• Gene–disease (curated): epidermolysis bullosa, junctional 4, intermediate (Definitive, GenCC) — +6 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 1,697 total — 102 pathogenic, 63 likely-pathogenic
• Phenotypes (HPO): 68
• MANE Select transcript: NM_000494

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2194
Approved symbol	COL17A1
Name	collagen type XVII alpha 1 chain
Location	10q25.1
Locus type	gene with protein product
Status	Approved
Aliases	BP180
Ensembl gene	ENSG00000065618
Ensembl biotype	protein_coding
OMIM	113811
Entrez	1308

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 13 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000369733, ENST00000393211, ENST00000433822, ENST00000480127, ENST00000483876, ENST00000488320, ENST00000647647, ENST00000648076, ENST00000649118, ENST00000650263, ENST00000859460, ENST00000859461, ENST00000859462, ENST00000859463, ENST00000859464, ENST00000859465, ENST00000859466, ENST00000961906

RefSeq mRNA: 1 — MANE Select: NM_000494 NM_000494

CCDS: CCDS7554

Canonical transcript exons

ENST00000648076 — 56 exons

Exon	Start	End
ENSE00000723546	104053920	104053982
ENSE00000723548	104055372	104055401
ENSE00000723549	104055782	104056003
ENSE00000723550	104056975	104057172
ENSE00000723552	104058146	104058190
ENSE00000723554	104059638	104059718
ENSE00000723564	104064438	104064596
ENSE00000723566	104070426	104070569
ENSE00000811676	104054092	104054118
ENSE00001026079	104054981	104055007
ENSE00001375370	104031286	104032290
ENSE00001450783	104080622	104080684
ENSE00002431212	104032906	104032968
ENSE00002431374	104033238	104033375
ENSE00002432092	104032674	104032754
ENSE00002432907	104041065	104041118
ENSE00002434437	104035263	104035373
ENSE00002434721	104039973	104039999
ENSE00002437368	104039445	104039519
ENSE00002440380	104037045	104037113
ENSE00002455258	104038406	104038528
ENSE00002462723	104048069	104048104
ENSE00002470637	104042420	104042455
ENSE00002470827	104043825	104043860
ENSE00002475582	104045758	104045793
ENSE00002481363	104046747	104046773
ENSE00002481471	104039071	104039121
ENSE00002483564	104047739	104047810
ENSE00002484497	104040351	104040410
ENSE00002484893	104050848	104050901
ENSE00002484935	104034621	104034767
ENSE00002486026	104051481	104051516
ENSE00002493479	104043501	104043581
ENSE00002505887	104050621	104050656
ENSE00002507990	104052155	104052217
ENSE00002515798	104035474	104035563
ENSE00002517268	104041303	104041344
ENSE00002521979	104039608	104039640
ENSE00002522096	104036492	104036632
ENSE00002525137	104049409	104049471
ENSE00002525449	104050089	104050124
ENSE00002529524	104041485	104041538
ENSE00002530287	104037636	104037773
ENSE00002532267	104033945	104034334
ENSE00002716720	104053031	104053135
ENSE00003473783	104062258	104062329
ENSE00003475822	104078542	104078586
ENSE00003523587	104063747	104063818
ENSE00003540910	104074184	104074231
ENSE00003602342	104077422	104077526
ENSE00003617843	104073210	104073245
ENSE00003624180	104072032	104072079
ENSE00003624672	104061405	104061473
ENSE00003669893	104060119	104060280
ENSE00003678360	104076301	104076429
ENSE00003839226	104085723	104085880

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 99.19.

FANTOM5 (CAGE): breadth broad, TPM avg 18.7294 / max 1845.5215, expressed in 238 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111284	9.6321	173
111283	5.3451	135
111285	3.1180	193
111287	0.1677	70
205981	0.1461	59
111272	0.0975	46
111286	0.0920	38
111288	0.0805	19
111277	0.0504	27

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	99.19	gold quality
skin of leg	UBERON:0001511	98.89	gold quality
zone of skin	UBERON:0000014	97.24	gold quality
upper arm skin	UBERON:0004263	96.58	gold quality
mucosa of transverse colon	UBERON:0004991	95.97	gold quality
lower esophagus mucosa	UBERON:0035834	95.87	gold quality
esophagus mucosa	UBERON:0002469	94.89	gold quality
minor salivary gland	UBERON:0001830	94.76	gold quality
rectum	UBERON:0001052	93.41	gold quality
mouth mucosa	UBERON:0003729	93.31	gold quality
upper leg skin	UBERON:0004262	92.53	gold quality
skin of hip	UBERON:0001554	91.99	gold quality
saliva-secreting gland	UBERON:0001044	89.96	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.94	gold quality
right testis	UBERON:0004534	86.88	gold quality
left testis	UBERON:0004533	86.60	gold quality
transverse colon	UBERON:0001157	86.10	gold quality
bone marrow	UBERON:0002371	86.06	gold quality
vagina	UBERON:0000996	85.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.02	silver quality
mammalian vulva	UBERON:0000997	84.89	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.89	gold quality
penis	UBERON:0000989	84.37	gold quality
tongue squamous epithelium	UBERON:0006919	84.22	gold quality
ileal mucosa	UBERON:0000331	83.98	gold quality
nipple	UBERON:0002030	82.62	gold quality
testis	UBERON:0000473	82.38	gold quality
tonsil	UBERON:0002372	82.05	gold quality
small intestine	UBERON:0002108	81.87	gold quality
gingiva	UBERON:0001828	81.56	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	2012.12
E-MTAB-8142	yes	1325.13
E-GEOD-86618	yes	728.26
E-ENAD-21	yes	618.65
E-CURD-7	yes	618.22
E-CURD-114	yes	214.34
E-GEOD-125970	yes	22.06
E-MTAB-9801	yes	6.86
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting COL17A1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-6758-3P	99.57	67.55	1078
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-140-5P	99.44	67.20	792
HSA-MIR-4506	99.34	67.47	526
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-4796-3P	99.08	68.38	1681
HSA-MIR-3136-5P	98.53	67.68	793
HSA-MIR-4439	98.53	67.53	793
HSA-MIR-7158-3P	98.46	66.45	728
HSA-MIR-3689A-5P	98.35	70.12	1049
HSA-MIR-3689B-5P	98.35	70.12	1049
HSA-MIR-3689E	98.35	70.12	1049
HSA-MIR-3689F	98.35	70.08	1052
HSA-MIR-499B-5P	98.35	68.39	988
HSA-MIR-6867-3P	98.12	66.07	1305
HSA-MIR-6502-3P	97.86	65.43	569
HSA-MIR-4494	97.86	64.93	850
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-1227-3P	97.36	66.94	834
HSA-MIR-4535	97.27	65.17	469
HSA-MIR-1306-5P	97.11	64.04	755

Literature-anchored findings (GeneRIF, showing 40)

• We describe a Chinese family with generalized atrophic benign epidermolysis bullosa (GABEB). serine to cysteine at position 265. novel polymorphic substitution of C-to-G at nucleotide position 798 in exon 10 of the COL17A1 gene, an I233M change in BPAG2 (PMID:11912005)
• this protein, an epithelial adhesion protein, is shed from the cell surface by ADAMs (PMID:12356719)
• Mutations in the coding sequence of the human collagen XVII (COL17A1) gene are not the cause of Thiel-Behnke Corneal Dystrophy. (PMID:14562173)
• truncation of the intracellular domain of BP180 impairs the organization of hemidesmosomes, affecting both the mechanical stability of basal keratinocytes and dermoepidermal cohesion. (PMID:14962091)
• bullous pemphigoid sera reacted with at least an additional antigenic site other than the NC16A, within the extracellular (37%) and intracellular (28%) domains of BP180. (PMID:14962097)
• genetic variation in COL17A1 shows no association with susceptibility to bullous pemphigoid. (PMID:14987253)
• Dimished, but correctly localised expression of BP180 in epidermolysis bullosa; COL15 mutated BP180 is still partly functional. (PMID:15009107)
• the conformation of the NC16A domain and steric availability of the cleavage site influence shedding and is important for folding of collagen XVII (PMID:15047704)
• C-terminus of collagen XVII binds to laminin 5, revealing the role of collagen XVII in the regulation of keratinocyte migration. (PMID:15161638)
• Data show that the expression of laminin gamma2 chain and collagen type XVII is altered in endometrial adenocarcinomas. (PMID:15609083)
• expression of BP180 is related to clinical severity of bullous pemphigoid (PMID:15734283)
• Epitooe mapping of anti-BP180 immunoglobulin E autoantibodies in bullous pemphigoid. (PMID:16117787)
• Deletions in recombinant proteins affect thermal stability. (PMID:16354180)
• Mutations associated with epidermolysis bullosa affect thermal stability, and affect the secondary structure of collagen XVII. (PMID:16354180)
• Results suggest that collagen XVII may be involved in the pathogenesis of various disorders affecting neuronal migration or synaptic plasticity. (PMID:16387484)
• Three epidermolysis bullosa associated mutations affecting NC4 domain do not grossly affect structure or stability of BP180. (PMID:16417243)
• Together, these data demonstrate a novel interaction between collagen XVII and alphaIIb integrin and also suggest a possibility to use tirofiban to inhibit the invasion and progression of alphaIIb expressing SCC tumors. (PMID:16487966)
• presence of six different 5’UTRs for the type XVII collagen mRNA. The start points of these six transcripts differ but no alternative exons are used. (PMID:16580182)
• Deletion mutation truncated the distal ectodomain and positioned the only N-glycosylation site 34 amino acids from the newly formed C terminus, which impaired efficient N-glycosylation. (PMID:16899459)
• 14-3-3sigma isoform interacts with BP180 in keratinocytes. (PMID:17443672)
• extracellular phosphorylation of collagen XVII by ecto-CK2 inhibits its shedding by TACE and represents novel mechanism to regulate adhesion and motility of epithelial cells (PMID:17545155)
• This study found collagen XVII to be expressed widely in the brain and to be located primarily in the soma and proximal axons of neurons. (PMID:17555727)
• bullous pemphigoid antigen 2 has a role in eliciting specific IgG and the immune responses arising in epidermolysis bullosa (PMID:17657247)
• IgE autoantibodies to BP180 and BP230 are detected at high frequencies in bullous pemphigoid. (PMID:17920818)
• transmembrane collagen XVII, pemphigoid gestationis autoantigen, promotes the migration of cytotrophoblastic cells of placenta and is a structural component of fetal membranes (PMID:18055190)
• Bullous Pemphigoid disease severity and activity correlated with levels of IgG against the BP180-NC16A domain, but also against a COOH-terminal epitope of BP180 (PMID:18571472)
• Neuronal collagen XVII expression in motor neuron disease remains similar to that seen in the normal human brain and thus a change in collagen XVII expression is not an immunohistochemically detectable feature of motor neuron disease. (PMID:18992722)
• bullous pemphigoid relevant collagen XVII fragment can also arise in an ADAM-independent manner through direct action by plasmin (PMID:19158842)
• glycine substitutions in the Col15 domain interfere with the triple-helix formation, transmembrane targeting, and ectodomain shedding of collagen XVII, and that these disturbances lead to skin blistering (PMID:19340010)
• A novel ELISA reveals high frequencies of BP180-specific IgE production in bullous pemphigoid. (PMID:19422829)
• anti-hBPAG2 IgG was initially directed against extracelllar domain epitopes;humoral responses subsequently targeted additional extra and intracellular domain BPAG2 epitopes (PMID:19812601)
• The role of collagen XVII in both autoimmune and genetic blistering disorders demonstrates its relevance to dermal-epidermal adhesion (PMID:19945617)
• Depletion of CD4-positive T cells as well as CD45R-positive B cells in an immunodeficient transgenic mouse model of bullous pemphigoid inhibits production of anti-human COL17 IgG antibodies in the recipients, resulting in no apparent clinical phenotype. (PMID:20089696)
• small proportion of pregnant women produce protein-specific IgE autoantibodies (PMID:20471095)
• Cell surface COL17 can interact with laminin 332 and, together, participate in the adherence of a cell to the extracellular matrix. (PMID:21034821)
• Alterations in type I hemidesmosome components (BP180 and BP230) are suggestive of epigenetic control in the salivary glands of patients with Sjogren’s syndrome. (PMID:21305504)
• presence of minor amounts of collagen XVII protein in JEB skin is associated with mild phenotypic manifestations. (PMID:21357940)
• migrating keratinocytes shed the Ecto-ColXVII, and this dynamically binds via its C-terminal domain to distinct partners in the ECM (PMID:21801871)
• Collagen XVII has a function in the attachment of podocyte foot processes to the glomerular basement membrane. (PMID:22457199)
• found the full-length collagen XVII protein in proliferating tissue melanocytes, basal keratinocytes and squamous cell carcinoma whereas resting melanocytes were negative (PMID:22688676)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	col19a1	ENSDARG00000096073
mus_musculus	Col17a1	ENSMUSG00000025064
rattus_norvegicus	Col17a1	ENSRNOG00000012110

Paralogs (37): COL9A2 (ENSG00000049089), COL23A1 (ENSG00000050767), COL11A1 (ENSG00000060718), COL5A3 (ENSG00000080573), COL4A4 (ENSG00000081052), COL16A1 (ENSG00000084636), COL9A3 (ENSG00000092758), COL20A1 (ENSG00000101203), COL1A1 (ENSG00000108821), COL9A1 (ENSG00000112280), COL7A1 (ENSG00000114270), COL21A1 (ENSG00000124749), COL5A1 (ENSG00000130635), COL4A2 (ENSG00000134871), COL2A1 (ENSG00000139219), COL6A1 (ENSG00000142156), COL6A2 (ENSG00000142173), EDA (ENSG00000158813), COL26A1 (ENSG00000160963), COL1A2 (ENSG00000164692), COL3A1 (ENSG00000168542), COL4A3 (ENSG00000169031), COL22A1 (ENSG00000169436), COL24A1 (ENSG00000171502), COL18A1 (ENSG00000182871), EMID1 (ENSG00000186998), COL4A1 (ENSG00000187498), COL4A5 (ENSG00000188153), COL25A1 (ENSG00000188517), COL27A1 (ENSG00000196739), COL13A1 (ENSG00000197467), COL4A6 (ENSG00000197565), COL11A2 (ENSG00000204248), COL5A2 (ENSG00000204262), COL15A1 (ENSG00000204291), COLQ (ENSG00000206561), COL28A1 (ENSG00000215018)

Protein

Protein identifiers

Collagen alpha-1(XVII) chain — Q9UMD9 (reviewed: Q9UMD9)

Alternative names: 180 kDa bullous pemphigoid antigen 2, Bullous pemphigoid antigen 2

All UniProt accessions (7): Q9UMD9, A0A3B3ISI7, A0A3B3ITM2, A0A3B3ITP5, A0A3B3IUC2, A2A2Y8, H0Y420

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in the integrity of hemidesmosome and the attachment of basal keratinocytes to the underlying basement membrane. The 120 kDa linear IgA disease antigen is an anchoring filament component involved in dermal-epidermal cohesion. Is the target of linear IgA bullous dermatosis autoantibodies.

Subunit / interactions. Homotrimers of alpha 1(XVII)chains. Interacts (via cytoplasmic region) with ITGB4 (via cytoplasmic region). Interacts (via cytoplasmic region) with DST isoform 3 (via N-terminus). Interacts (via N-terminus) with PLEC. Interacts (via cytoplasmic region) with DSP.

Subcellular location. Cell junction. Hemidesmosome. Membrane Secreted. Extracellular space. Extracellular matrix. Basement membrane Secreted. Basement membrane.

Tissue specificity. Detected in skin. In the cornea, it is detected in the epithelial basement membrane, the epithelial cells, and at a lower level in stromal cells (at protein level). Stratified squamous epithelia. Found in hemidesmosomes. Expressed in cornea, oral mucosa, esophagus, intestine, kidney collecting ducts, ureter, bladder, urethra and thymus but is absent in lung, blood vessels, skeletal muscle and nerves.

Post-translational modifications. The intracellular/endo domain is disulfide-linked. Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains. The ectodomain is shedded from the surface of keratinocytes resulting in a 120-kDa soluble form, also named as 120 kDa linear IgA disease antigen. The shedding is mediated by membrane-bound metalloproteases. This cleavage is inhibited by phosphorylation at Ser-544.

Disease relevance. Epidermolysis bullosa, junctional 4, intermediate (JEB4) [MIM:619787] A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. JEB4 is an autosomal recessive, intermediate form in which blistering lesions occur between the epidermis and the dermis at the lamina lucida level of the basement membrane zone. In intermediate forms of junctional epidermolysis bullosa, blistering does not lead to the formation of chronic granulation tissue and does not affect the lifespan of affected individuals. Nail dystrophy and dental enamel defects are present. Scarring or non-scarring alopecia and diffuse hair loss may occur. JEB4 patients manifest blisters at birth or shortly afterward. Blisters may heal with atrophic scarring and variable hypo- or hyperpigmentation. Oral mucosa may be involved. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Both the 120 kDa linear IgA disease antigen and the 97 kDa linear IgA disease antigen of COL17A1, represent major antigenic targets of autoantibodies in patients with linear IgA disease (LAD). LAD is a subepidermal blistering disorder characterized by tissue-bound and circulating IgA autoantibodies to the dermal-epidermal junction. These IgA autoantibodies preferentially react with 97 and the 120 kDa forms, but not with the full-length COL17A1, suggesting that the cleavage of the ectodomain generates novel autoantigenic epitopes.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UMD9-1	1	yes
Q9UMD9-2	2

RefSeq proteins (1): NP_000485* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008160	Collagen	Repeat
IPR050149	Collagen_superfamily	Family

Pfam: PF01391

UniProt features (54 total): compositionally biased region 20, sequence variant 12, region of interest 10, chain 3, topological domain 2, splice variant 2, sequence conflict 2, modified residue 1, glycosylation site 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8IZS	X-RAY DIFFRACTION	1.53

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UMD9-F1	47.55	0.02

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 544

Glycosylation sites (1): 1421

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1442490	Collagen degradation
R-HSA-1650814	Collagen biosynthesis and modifying enzymes
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-2022090	Assembly of collagen fibrils and other multimeric structures
R-HSA-446107	Type I hemidesmosome assembly
R-HSA-8948216	Collagen chain trimerization

MSigDB gene sets: 273 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, JAEGER_METASTASIS_DN, GOCC_COLLAGEN_TRIMER, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GGGTGGRR_PAX4_03, GOBP_HEMIDESMOSOME_ASSEMBLY, GOBP_CELL_JUNCTION_ORGANIZATION, CATTTCA_MIR203, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, GATA1_04, GOBP_EPIDERMIS_DEVELOPMENT, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, GOBP_CELL_JUNCTION_ASSEMBLY, GOCC_BASEMENT_MEMBRANE, LEE_AGING_CEREBELLUM_DN

GO Biological Process (3): cell-matrix adhesion (GO:0007160), epidermis development (GO:0008544), hemidesmosome assembly (GO:0031581)

GO Molecular Function (2): extracellular matrix structural constituent conferring tensile strength (GO:0030020), protein binding (GO:0005515)

GO Cellular Component (10): extracellular region (GO:0005576), collagen trimer (GO:0005581), basement membrane (GO:0005604), endoplasmic reticulum lumen (GO:0005788), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), hemidesmosome (GO:0030056), extracellular matrix (GO:0031012), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Collagen formation	2
Degradation of the extracellular matrix	1
Adaptive Immune System	1
Cell junction organization	1
Collagen biosynthesis and modifying enzymes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell-substrate adhesion	1
tissue development	1
cell-substrate junction assembly	1
extracellular matrix structural constituent	1
binding	1
protein-containing complex	1
extracellular matrix	1
endoplasmic reticulum	1
intracellular organelle lumen	1
membrane	1
cell periphery	1
anchoring junction	1
cell-substrate junction	1
external encapsulating structure	1
cell junction	1

Protein interactions and networks

STRING

1692 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COL17A1	DST	Q03001	999
COL17A1	PLEC	Q15149	996
COL17A1	ITGB4	P16144	986
COL17A1	CD151	P48509	985
COL17A1	LAMA3	Q16787	936
COL17A1	LAMB3	Q13751	900
COL17A1	ITGA6	P23229	888
COL17A1	LAMC2	Q13753	863
COL17A1	LAMA4	Q16363	853
COL17A1	DSG3	P32926	773
COL17A1	DSG1	Q02413	770
COL17A1	KRT14	P02533	765
COL17A1	PPL	O60437	733
COL17A1	AMTN	Q6UX39	650
COL17A1	KRT5	P13647	638

IntAct

29 interactions, top by confidence:

A	B	Type	Score
EGFR	CTNND1	psi-mi:“MI:0914”(association)	0.750
WHRN	COL17A1	psi-mi:“MI:0915”(physical association)	0.560
PNKP	COL17A1	psi-mi:“MI:0915”(physical association)	0.560
UBQLN2	COL17A1	psi-mi:“MI:0915”(physical association)	0.560
PLOD3	COL17A1	psi-mi:“MI:0915”(physical association)	0.560
COL17A1	PPIL1	psi-mi:“MI:0915”(physical association)	0.560
CSTF2T	COL17A1	psi-mi:“MI:0915”(physical association)	0.560
M		psi-mi:“MI:0914”(association)	0.350
MAPK13	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
PIK3CA	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
	GTPBP10	psi-mi:“MI:0914”(association)	0.350
LAIR2	AGRN	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
CDH1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
WHRN	COL17A1	psi-mi:“MI:0915”(physical association)	0.000
UBQLN2	COL17A1	psi-mi:“MI:0915”(physical association)	0.000
PLOD3	COL17A1	psi-mi:“MI:0915”(physical association)	0.000
PPIL1	COL17A1	psi-mi:“MI:0915”(physical association)	0.000
CSTF2T	COL17A1	psi-mi:“MI:0915”(physical association)	0.000
PNKP	COL17A1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (48): COL17A1 (Affinity Capture-MS), COL17A1 (Proximity Label-MS), COL17A1 (Affinity Capture-MS), COL17A1 (Proximity Label-MS), COL17A1 (Two-hybrid), DFNB31 (Two-hybrid), PLOD3 (Two-hybrid), PPIL1 (Two-hybrid), CSTF2T (Two-hybrid), UBQLN2 (Two-hybrid), DST (Co-localization), DST (Two-hybrid), ACTN4 (Two-hybrid), ACTN1 (Two-hybrid), ACTN4 (Affinity Capture-Western)

ESM2 similar proteins: A0A060WQA3, A0MSJ1, A5PN28, A6NHN0, A8WGB1, A8WR59, B2RNN3, B7Z0K8, C7DZK3, O35167, O35348, O76368, O88207, P0C862, P12107, P13942, P20908, P20909, P23805, P25067, P25318, P25940, P42916, P83371, P98085, Q03637, Q07092, Q07563, Q0II24, Q0VF58, Q17RW2, Q30D77, Q32S24, Q3MI99, Q4ZJM7, Q4ZJN1, Q60467, Q61245, Q64739, Q6UXH8

Diamond homologs: A6QPB3, Q07563, Q90584, Q9JMH4, Q9N281, Q9UMD9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

1697 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	102
Likely pathogenic	63
Uncertain significance	378
Likely benign	882
Benign	162

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1029877	NM_000494.4(COL17A1):c.505C>T (p.Arg169Ter)	Pathogenic
1047963	NM_000494.4(COL17A1):c.1571_1572dup (p.Gln525fs)	Pathogenic
1047964	NM_000494.4(COL17A1):c.2576dup (p.Gly860fs)	Pathogenic
1047967	NM_000494.4(COL17A1):c.3827dup (p.Gly1277fs)	Pathogenic
1047993	NM_000494.4(COL17A1):c.3828_3829insC (p.Gly1277fs)	Pathogenic
1047994	NM_000494.4(COL17A1):c.4156+1G>A	Pathogenic
1174485	NM_000494.4(COL17A1):c.4041T>G (p.Tyr1347Ter)	Pathogenic
1384976	NM_000494.4(COL17A1):c.1873C>T (p.Arg625Ter)	Pathogenic
1458976	NM_000494.4(COL17A1):c.3766+1G>C	Pathogenic
1685644	NM_000494.4(COL17A1):c.2002+2T>G	Pathogenic
1691802	NM_000494.3(COL17A1):c.418_419del	Pathogenic
1704972	NM_000494.4(COL17A1):c.2468del (p.Pro823fs)	Pathogenic
1706597	NM_000494.4(COL17A1):c.3686dup (p.Val1231fs)	Pathogenic
17645	NM_000494.4(COL17A1):c.3676C>T (p.Arg1226Ter)	Pathogenic
17646	NM_000494.4(COL17A1):c.4045dup (p.Ala1349fs)	Pathogenic
17647	NM_000494.4(COL17A1):c.2840_2844del (p.Leu947fs)	Pathogenic
17648	NM_000494.4(COL17A1):c.3067C>T (p.Gln1023Ter)	Pathogenic
17649	NM_000494.4(COL17A1):c.1601del (p.Asp534fs)	Pathogenic
17652	NM_000494.4(COL17A1):c.2336-1G>T	Pathogenic
17653	NM_000494.4(COL17A1):c.3899_3900del (p.Ser1300fs)	Pathogenic
17655	NM_000494.4(COL17A1):c.2861del (p.Gly954fs)	Pathogenic
17656	NM_000494.4(COL17A1):c.2564T>G (p.Leu855Ter)	Pathogenic
17657	NM_000494.4(COL17A1):c.1898G>A (p.Gly633Asp)	Pathogenic
17658	NM_000494.4(COL17A1):c.433C>T (p.Arg145Ter)	Pathogenic
2026643	NM_000494.4(COL17A1):c.1828del (p.Ser610fs)	Pathogenic
2037431	NM_000494.4(COL17A1):c.2906dup (p.Val970fs)	Pathogenic
208977	NM_000494.4(COL17A1):c.2816C>T (p.Thr939Ile)	Pathogenic
208978	NM_000494.4(COL17A1):c.3156C>T (p.Gly1052=)	Pathogenic
2570774	NM_000494.4(COL17A1):c.1750C>T (p.Arg584Ter)	Pathogenic
2572029	NM_000494.4(COL17A1):c.3297C>A (p.Tyr1099Ter)	Pathogenic

SpliceAI

7462 predictions. Top by Δscore:

Variant	Effect	Δscore
10:104032669:CTTA:C	donor_loss	1.0000
10:104032670:TTA:T	donor_loss	1.0000
10:104032671:TA:T	donor_loss	1.0000
10:104032672:A:AC	donor_gain	1.0000
10:104032672:AC:A	donor_gain	1.0000
10:104032673:C:CT	donor_gain	1.0000
10:104032673:CC:C	donor_gain	1.0000
10:104032673:CCT:C	donor_gain	1.0000
10:104032673:CCTT:C	donor_gain	1.0000
10:104032673:CCTTT:C	donor_gain	1.0000
10:104032750:GTCAC:G	acceptor_gain	1.0000
10:104032751:TCAC:T	acceptor_gain	1.0000
10:104032752:CAC:C	acceptor_gain	1.0000
10:104032752:CACC:C	acceptor_gain	1.0000
10:104032753:AC:A	acceptor_gain	1.0000
10:104032754:CC:C	acceptor_gain	1.0000
10:104032755:C:CA	acceptor_loss	1.0000
10:104032755:C:CC	acceptor_gain	1.0000
10:104032901:CTTA:C	donor_loss	1.0000
10:104032902:TTACC:T	donor_loss	1.0000
10:104032903:TA:T	donor_loss	1.0000
10:104032904:A:AC	donor_gain	1.0000
10:104032904:AC:A	donor_gain	1.0000
10:104032904:ACCTT:A	donor_loss	1.0000
10:104032905:C:A	donor_loss	1.0000
10:104032905:C:CC	donor_gain	1.0000
10:104032905:CC:C	donor_gain	1.0000
10:104032964:ATAAG:A	acceptor_gain	1.0000
10:104032965:TAAG:T	acceptor_gain	1.0000
10:104032966:AAG:A	acceptor_gain	1.0000

AlphaMissense

9500 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:104072058:A:G	L146P	0.999
10:104072032:A:G	W155R	0.998
10:104072032:A:T	W155R	0.998
10:104072070:A:C	I142S	0.998
10:104072070:A:G	I142T	0.998
10:104034626:A:G	L1254P	0.997
10:104034638:A:G	L1250P	0.997
10:104072061:C:G	R145P	0.996
10:104072067:C:G	R143P	0.996
10:104057002:C:G	G480R	0.995
10:104057002:C:T	G480R	0.995
10:104070551:A:T	V161D	0.995
10:104070568:C:A	W155C	0.995
10:104070568:C:G	W155C	0.995
10:104072070:A:T	I142N	0.994
10:104074221:A:C	S114R	0.994
10:104074221:A:T	S114R	0.994
10:104074223:T:G	S114R	0.994
10:104057001:C:T	G480E	0.993
10:104057017:A:G	W475R	0.993
10:104057017:A:T	W475R	0.993
10:104057041:A:G	W467R	0.993
10:104057041:A:T	W467R	0.993
10:104070547:C:A	K162N	0.993
10:104070547:C:G	K162N	0.993
10:104070511:G:C	S174R	0.992
10:104070511:G:T	S174R	0.992
10:104070513:T:G	S174R	0.992
10:104070517:A:C	S172R	0.992
10:104070517:A:T	S172R	0.992

dbSNP variants (sampled 300 via entrez): RS1000042492 (10:104057316 G>A,C,T), RS1000045995 (10:104038085 G>A,C), RS1000101551 (10:104031771 A>G), RS1000142342 (10:104051328 C>T), RS1000184698 (10:104060125 C>T), RS1000193760 (10:104051740 T>TG), RS1000297444 (10:104085211 T>C), RS1000483537 (10:104082354 A>G), RS1000497539 (10:104057757 T>C), RS1000509172 (10:104039827 A>C), RS1000605833 (10:104067611 A>C), RS1000611016 (10:104075204 A>C), RS1000655069 (10:104067326 C>T), RS1000765374 (10:104067892 GAC>G), RS1000786458 (10:104061613 G>A,C)

Disease associations

OMIM: gene MIM:113811 | disease phenotypes: MIM:226650, MIM:104500, MIM:122400, MIM:619787, MIM:104530, MIM:131760

GenCC curated gene-disease

Disease	Classification	Inheritance
epithelial recurrent erosion dystrophy	Definitive	Autosomal dominant
epidermolysis bullosa, junctional 4, intermediate	Definitive	Autosomal recessive
junctional epidermolysis bullosa, non-Herlitz type	Definitive	Autosomal recessive
amelogenesis imperfecta	Moderate	Autosomal dominant
localized junctional epidermolysis bullosa, non-Herlitz type	Supportive	Autosomal recessive
generalized junctional epidermolysis bullosa non-Herlitz type	Supportive	Autosomal recessive
late-onset junctional epidermolysis bullosa	Supportive	Autosomal recessive

Mondo (12): junctional epidermolysis bullosa, non-Herlitz type (MONDO:0009180), junctional epidermolysis bullosa (MONDO:0017612), amelogenesis imperfecta type 1B (MONDO:0007092), epithelial recurrent erosion dystrophy (MONDO:0007381), epidermolysis bullosa, junctional 4, intermediate (MONDO:0030750), amelogenesis imperfecta type 1A (MONDO:0007094), corneal dystrophy (MONDO:0018102), amelogenesis imperfecta (MONDO:0019507), epidermolysis bullosa simplex 1A, generalized severe (MONDO:0007550), late-onset junctional epidermolysis bullosa (MONDO:0019309), localized junctional epidermolysis bullosa, non-Herlitz type (MONDO:0016673), generalized junctional epidermolysis bullosa non-Herlitz type (MONDO:0019307)

Orphanet (10): Localized junctional epidermolysis bullosa (Orphanet:251393), Intermediate generalized junctional epidermolysis bullosa (Orphanet:79402), Junctional epidermolysis bullosa inversa (Orphanet:79405), OBSOLETE: Junctional epidermolysis bullosa, non-Herlitz type (Orphanet:89840), Junctional epidermolysis bullosa (Orphanet:305), Amelogenesis imperfecta (Orphanet:88661), Epithelial recurrent erosion dystrophy (Orphanet:293381), Corneal dystrophy (Orphanet:34533), Autosomal dominant generalized epidermolysis bullosa simplex, severe form (Orphanet:79396), Late-onset junctional epidermolysis bullosa (Orphanet:79406)

HPO phenotypes

68 total (30 of 68 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000079	Abnormality of the urinary system
HP:0000478	Abnormality of the eye
HP:0000495	Recurrent corneal erosions
HP:0000505	Visual impairment
HP:0000529	Progressive visual loss
HP:0000559	Corneal scarring
HP:0000613	Photophobia
HP:0000622	Blurred vision
HP:0000668	Hypodontia
HP:0000670	Carious teeth
HP:0000975	Hyperhidrosis
HP:0000982	Palmoplantar keratoderma
HP:0000987	Atypical scarring of skin
HP:0001000	Abnormality of skin pigmentation
HP:0001030	Fragile skin
HP:0001056	Milia
HP:0001057	Aplasia cutis congenita
HP:0001075	Atrophic scars
HP:0001097	Keratoconjunctivitis sicca
HP:0001131	Corneal dystrophy
HP:0001510	Growth delay
HP:0001798	Anonychia
HP:0001808	Fragile nails
HP:0001810	Dystrophic toenail
HP:0001903	Anemia
HP:0001965	Abnormal scalp morphology
HP:0002215	Sparse axillary hair
HP:0002225	Sparse pubic hair

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000960_1	Cardiac hypertrophy	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0002503	cardiac hypertrophy

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D000567	Amelogenesis Imperfecta	C07.650.800.295.250; C07.793.700.295.250; C16.131.850.800.295.250
D003317	Corneal Dystrophies, Hereditary	C11.204.236; C11.270.162; C16.320.290.162
D016109	Epidermolysis Bullosa, Junctional	C16.131.831.493.170; C16.320.850.275.170; C17.800.804.493.170; C17.800.827.275.170; C17.800.865.410.170
C562879	Amelogenesis Imperfecta, Type IB (supp.)
C538240	Amelogenesis imperfecta local hypoplastic form (supp.)
C565155	Epithelial Recurrent Erosion Dystrophy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

55 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases expression, affects methylation	3
chloropicrin	decreases expression	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation, increases methylation	2
Cisplatin	affects cotreatment, increases expression, affects expression	2
Tobacco Smoke Pollution	increases expression, affects expression	2
aristolochic acid I	increases expression	1
perfluorotetradecanoic acid	decreases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression, increases expression	1
kojic acid	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
perfluorobutyric acid	decreases expression	1
methacrylaldehyde	decreases expression, increases oxidation, increases abundance, affects cotreatment	1
ML 7	affects localization	1
Y 27632	affects localization	1
nutlin 3	affects cotreatment, increases expression, increases secretion	1
abrine	increases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Decitabine	increases expression	1
Alitretinoin	decreases expression	1
Acrolein	increases oxidation, increases abundance, affects cotreatment, decreases expression	1
Ethanol	increases expression, affects cotreatment, increases abundance	1
Arbutin	decreases expression	1
Arsenic	affects methylation	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_VT57	BPKU	Transformed cell line	Female

Clinical trials (associated diseases)

44 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00587223	PHASE3	TERMINATED	Safety and Efficacy of Apligraf in Nonhealing Wounds of Subjects With Junctional or Dystrophic Epidermolysis Bullosa (EB)
NCT06917690	PHASE3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT03578029	PHASE2	TERMINATED	Evaluation of the Safety and Efficacy Study of RGN-137 Topical Gel for Junctional and Dystrophic Epidermolysis Bullosa
NCT04908215	PHASE2	COMPLETED	INM-755 (Cannabinol) Cream for Treatment of Epidermolysis Bullosa
NCT06594393	PHASE2	RECRUITING	A Phase 2 Study of TCP-25 Gel in Patients With Epidermolysis Bullosa, STEP-study
NCT05279157	PHASE2	COMPLETED	Autologous Adipose-Derived Adult Stem Cell Implantation for Corneal Diseases (ADASCs-CT-CD)
NCT03472287	PHASE1	COMPLETED	To Evaluate the Pharmacokinetic of Diacerein and Rhein After Maximum Use in Patients With Epidermolysis Bullosa (EB)
NCT06713434	PHASE1	ACTIVE_NOT_RECRUITING	Pilot Study of ELK-003 Eye Drops for Treating Ocular Manifestations of Epidermolysis Bullosa
NCT02373397	Not specified	TERMINATED	Cacicol20® in Corneal Wound Healing and Nerve Regeneration After Phototherapeutic Keratectomy
NCT01746121	Not specified	TERMINATED	Amelogenesis Imperfecta
NCT02994862	Not specified	UNKNOWN	E. Max Laminate Veneers With and Without Using Galla Chinnesis as Natural Cross Linking and Remineralizing Agent
NCT03810859	Not specified	UNKNOWN	Non-syndromic Inherited Anomalies of Mineralized Tooth Tissues: a Whole Exome Study to Identify New Pathogenic Variants
NCT04704089	Not specified	RECRUITING	Colorimetric, Ultra-structural and Elemental Comparison of Dental Enamel Defects
NCT04897724	Not specified	UNKNOWN	Clinical Performance of Composites in Patients With Amelogenesis Imperfecta
NCT04927962	Not specified	COMPLETED	Psycho-social Impact of Amelogenesis and Dentinogenesis Imperfecta
NCT05343247	Not specified	COMPLETED	Dental Age Estimation by Different Methods in Patients With Amelogenesis Imperfecta
NCT07250906	Not specified	RECRUITING	Oral Health Related Quality of Life of Children With Amelogenesis Imperfecta
NCT03490331	PHASE1/PHASE2	TERMINATED	Clinical Trial to Assess Safety and Efficacy of Autologous Cultured Epidermal Grafts Containing Epidermal Stem Cells Genetically Modified in Patients With JEB (HOLOGENE17)
NCT03526159	PHASE1/PHASE2	RECRUITING	Gentamicin for Junctional Epidermolysis Bullosa
NCT04140786	PHASE1/PHASE2	UNKNOWN	Optimizing IV Gentamicin in JEB
NCT03269474	Not specified	UNKNOWN	Computational Drug Repurposing for All EBS Cases
NCT04727268	Not specified	UNKNOWN	Genotype-phenotype Correlation in Junctional Epidermolysis Bullosa
NCT05033574	Not specified	UNKNOWN	The State of Sexual Development in Children With Inherited Epidermolysis Bullosa
NCT06007235	Not specified	UNKNOWN	CACIPLIQ20 in Wound Healing in Subjects With Epidermolysis Bullosa
NCT06423573	Not specified	RECRUITING	A Study to Assess the Incidence of Skin Cancers in Patients With Epidermolysis Bullosa Receiving Filsuvez
NCT04484402	PHASE1/PHASE2	COMPLETED	Treatment of Patients With Inflammatory-dystrophic Diseases of the Cornea Using Autologous Stem Cells
NCT02932852	EARLY_PHASE1	UNKNOWN	Autologous Adipose-Derived Adult Stem Cell Transplantation for Corneal Diseases
NCT01084850	Not specified	UNKNOWN	Corneal Endothelium Morphology and Central Thickness in Type II Diabetes Mellitus and Normal Subjects
NCT02173847	Not specified	COMPLETED	Laser Assisted Procedures in Penetrating Keratoplasty
NCT02736877	Not specified	UNKNOWN	Corneal Transplantation Guided by OCT RESCAN
NCT02746055	Not specified	UNKNOWN	Study of the Prevalence of TGFBI Corneal Dystrophies
NCT03461991	Not specified	COMPLETED	Correlation Between In-vivo Anatomy of Corneal Dystrophies as Assessed by High- Resolution Optical Coherence Tomography (OCT) Measurement and Histological Examination
NCT03504800	Not specified	RECRUITING	OCT in Diagnosis of Irregular Corneas
NCT04129021	Not specified	RECRUITING	High Resolution, High-speed Multimodal Ophthalmic Imaging
NCT04164407	Not specified	UNKNOWN	Keratoconus, Corneal Diseases and Transplant Registry
NCT04384094	Not specified	UNKNOWN	Defining the Operating Parameters for a Rebound-esthesiometer
NCT04424550	Not specified	COMPLETED	Comparative Results After DSAEK, UT-DSAEK and DMEK for Fuchs Endothelial Corneal Dystophy
NCT05742321	Not specified	RECRUITING	Analysis of the Genotype/Phenotype Relationship in the Fuchs’ Corneal Endothelial Dystrophy in France
NCT05891106	Not specified	COMPLETED	AONDA Therapeutic Indication Study I
NCT05927740	Not specified	COMPLETED	The Efficacy of Hyperemesis Gravidarum on Macular Thickness, Corneal Thickness and Intraocular Pressure in Pregnancy