COL7A1
collagen type VII alpha 1 chain, the group of Fibronectin type III domain containing|Collagens|MicroRNA protein coding host genes
Basic information
Region (hg38): 3:48564073-48595329
Previous symbols: [ "EBDCT", "EBD1", "EBR1" ]
Links
Phenotypes
GenCC
Source:
- generalized dominant dystrophic epidermolysis bullosa (Strong), mode of inheritance: AD
- pretibial dystrophic epidermolysis bullosa (Strong), mode of inheritance: AD
- epidermolysis bullosa with congenital localized absence of skin and deformity of nails (Strong), mode of inheritance: AD
- dystrophic epidermolysis bullosa pruriginosa (Strong), mode of inheritance: AD
- transient bullous dermolysis of the newborn (Strong), mode of inheritance: AD
- pretibial dystrophic epidermolysis bullosa (Strong), mode of inheritance: AR
- recessive dystrophic epidermolysis bullosa (Strong), mode of inheritance: AR
- dystrophic epidermolysis bullosa pruriginosa (Strong), mode of inheritance: AR
- transient bullous dermolysis of the newborn (Strong), mode of inheritance: AR
- epidermolysis bullosa with congenital localized absence of skin and deformity of nails (Strong), mode of inheritance: AD
- recessive dystrophic epidermolysis bullosa (Strong), mode of inheritance: AR
- generalized dominant dystrophic epidermolysis bullosa (Strong), mode of inheritance: AD
- recessive dystrophic epidermolysis bullosa (Supportive), mode of inheritance: AR
- recessive dystrophic epidermolysis bullosa inversa (Supportive), mode of inheritance: AR
- pretibial dystrophic epidermolysis bullosa (Supportive), mode of inheritance: AD
- transient bullous dermolysis of the newborn (Supportive), mode of inheritance: AD
- recessive dystrophic epidermolysis bullosa-generalized other (Supportive), mode of inheritance: AR
- dystrophic epidermolysis bullosa pruriginosa (Supportive), mode of inheritance: AD
- acral dystrophic epidermolysis bullosa (Supportive), mode of inheritance: AD
- dystrophic epidermolysis bullosa, nails only (Supportive), mode of inheritance: AD
- generalized dominant dystrophic epidermolysis bullosa (Supportive), mode of inheritance: AD
- generalized dominant dystrophic epidermolysis bullosa (Strong), mode of inheritance: AD
- epidermolysis bullosa with congenital localized absence of skin and deformity of nails (Strong), mode of inheritance: AR
- recessive dystrophic epidermolysis bullosa (Definitive), mode of inheritance: AR
- recessive dystrophic epidermolysis bullosa (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Epidermolysis bullosa dystrophica, autosomal dominant; Epidermolysis bullosa dystrophica, autosomal recessive; Epidermolysis bullosa dystrophica inversia; Epidermolysis bullosa pruriginosa; Nail disorder, nonsyndromic congenital, 8; Epidermolysis bullosa dystrophica, with congenital localized absence of skin and deformity of nails; Epidermolysis bullosa, pretibial; Transient bullous dermolysis of the newborn | AD/AR | Dermatologic | A topical gene therapy has been approved for treatment of forms of dystrophic epidermolysis bullosa | Dermatologic | 1347297; 1680286; 8513326; 8345225; 8245264; 8170945; 8037207; 8541842; 7577595; 8644729; 9406826; 9347800; 9182828; 9856844; 9892921; 10583163; 10383749; 10469344; 12485454; 11874498; 11843659; 12787275; 16225626; 16965329; 17434045; 16971478; 20574443; 20920254; 21113014; 21182502; 21196708; 21352278; 21382783; 21574979; 21629976; 21849769; 21967228; 22058051; 22266148; 22515571; 22854212; 22909362; 22974128; 23013315; 35347281; 36516090 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (443 variants)
- Epidermolysis bullosa dystrophica (135 variants)
- Recessive dystrophic epidermolysis bullosa (77 variants)
- COL7A1-related disorder (25 variants)
- 7 conditions (17 variants)
- Generalized dominant dystrophic epidermolysis bullosa (17 variants)
- Epidermolysis bullosa dystrophica inversa, autosomal recessive (13 variants)
- Transient bullous dermolysis of the newborn (8 variants)
- Generalized dominant dystrophic epidermolysis bullosa;Recessive dystrophic epidermolysis bullosa (6 variants)
- Epidermolysis bullosa pruriginosa (6 variants)
- Epidermolysis bullosa pruriginosa, autosomal recessive (4 variants)
- Inborn genetic diseases (4 variants)
- Epidermolysis bullosa dystrophica, autosomal recessive, localisata variant (3 variants)
- Pretibial dystrophic epidermolysis bullosa (3 variants)
- Epidermolysis bullosa pruriginosa, autosomal dominant (2 variants)
- Anonychia (2 variants)
- Abnormality of the skin (2 variants)
- See cases (2 variants)
- Nail dystrophy;Abnormality of the skin;Skin erosion (1 variants)
- Short stature;Toe syndactyly;Finger syndactyly;Palmoplantar blistering (1 variants)
- 14 conditions (1 variants)
- Dominant dystrophic epidermolysis bullosa with absence of skin (1 variants)
- Abnormal blistering of the skin (1 variants)
- Recessive dystrophic epidermolysis bullosa;Generalized dominant dystrophic epidermolysis bullosa (1 variants)
- Epidermolysis bullosa (1 variants)
- Abnormality of the skin;Skin erosion;Nail dystrophy (1 variants)
- Nonsyndromic congenital nail disorder 8 (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL7A1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 24 | 1193 | 1232 | |||
| missense | 130 | 83 | 819 | 235 | 27 | 1294 |
| nonsense | 114 | 122 | ||||
| start loss | 3 | |||||
| frameshift | 211 | 16 | 228 | |||
| inframe indel | 16 | 22 | ||||
| splice donor/acceptor (+/-2bp) | 64 | 151 | 217 | |||
| splice region | 10 | 4 | 92 | 403 | 13 | 522 |
| non coding | 31 | 1062 | 52 | 1149 | ||
| Total | 534 | 265 | 892 | 2491 | 85 |
Highest pathogenic variant AF is 0.0000854
Variants in COL7A1
This is a list of pathogenic ClinVar variants found in the COL7A1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 3-48564136-C-A | Epidermolysis bullosa dystrophica | Uncertain significance (Jan 13, 2018) | ||
| 3-48564190-C-G | Epidermolysis bullosa dystrophica | Benign (Jan 12, 2018) | ||
| 3-48564244-G-A | Epidermolysis bullosa dystrophica | Likely benign (Jan 13, 2018) | ||
| 3-48564244-G-T | Epidermolysis bullosa dystrophica | Uncertain significance (Jan 12, 2018) | ||
| 3-48564301-G-A | Epidermolysis bullosa dystrophica | Uncertain significance (Jan 12, 2018) | ||
| 3-48564319-C-T | Epidermolysis bullosa dystrophica | Uncertain significance (Apr 27, 2017) | ||
| 3-48564341-A-G | Epidermolysis bullosa dystrophica | Benign (Jan 13, 2018) | ||
| 3-48564366-T-A | Epidermolysis bullosa dystrophica | Uncertain significance (Jan 13, 2018) | ||
| 3-48564407-C-T | Likely benign (Sep 09, 2023) | |||
| 3-48564417-C-A | Uncertain significance (Oct 28, 2021) | |||
| 3-48564425-G-A | Epidermolysis bullosa dystrophica inversa, autosomal recessive | Likely benign (Jan 31, 2024) | ||
| 3-48564428-G-A | Likely benign (Sep 09, 2023) | |||
| 3-48564430-G-C | Likely benign (Oct 05, 2023) | |||
| 3-48564431-G-A | Likely benign (Jul 10, 2023) | |||
| 3-48564440-G-T | Likely benign (Oct 14, 2023) | |||
| 3-48564763-G-A | Likely benign (Feb 25, 2023) | |||
| 3-48564766-G-C | Likely benign (Jan 19, 2024) | |||
| 3-48564769-G-T | Likely benign (Jan 04, 2024) | |||
| 3-48564773-C-A | Likely benign (Dec 09, 2023) | |||
| 3-48564774-A-G | Likely benign (Feb 20, 2022) | |||
| 3-48564779-A-C | COL7A1-related disorder | Uncertain significance (Aug 24, 2022) | ||
| 3-48564781-A-T | 7 conditions | Conflicting classifications of pathogenicity (May 06, 2024) | ||
| 3-48564784-T-C | Epidermolysis bullosa dystrophica inversa, autosomal recessive | Uncertain significance (Nov 14, 2020) | ||
| 3-48564787-C-T | Likely benign (Apr 28, 2023) | |||
| 3-48564792-G-C | Uncertain significance (Aug 29, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| COL7A1 | protein_coding | protein_coding | ENST00000328333 | 118 | 31195 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 2.44e-40 | 1.00 | 124974 | 2 | 772 | 125748 | 0.00308 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.59 | 1594 | 1.78e+3 | 0.894 | 0.000123 | 18151 |
| Missense in Polyphen | 195 | 260.01 | 0.74996 | 2620 | ||
| Synonymous | 0.407 | 658 | 671 | 0.980 | 0.0000440 | 6645 |
| Loss of Function | 6.48 | 100 | 199 | 0.504 | 0.0000119 | 2205 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00214 | 0.00212 |
| Ashkenazi Jewish | 0.00180 | 0.00179 |
| East Asian | 0.00131 | 0.00131 |
| Finnish | 0.0138 | 0.0123 |
| European (Non-Finnish) | 0.00228 | 0.00216 |
| Middle Eastern | 0.00131 | 0.00131 |
| South Asian | 0.00455 | 0.00455 |
| Other | 0.00339 | 0.00326 |
dbNSFP
Source:
- Function
- FUNCTION: Stratified squamous epithelial basement membrane protein that forms anchoring fibrils which may contribute to epithelial basement membrane organization and adherence by interacting with extracellular matrix (ECM) proteins such as type IV collagen.;
- Disease
- DISEASE: Note=Epidermolysis bullosa acquisita (EBA) is an autoimmune acquired blistering skin disease resulting from autoantibodies to type VII collagen.; DISEASE: Epidermolysis bullosa dystrophica, autosomal dominant (DDEB) [MIM:131750]: A group of autosomal dominant blistering skin diseases characterized by tissue separation which occurs below the dermal-epidermal basement membrane at the level of the anchoring fibrils. Various clinical types with different severity are recognized, ranging from severe mutilating forms to mild forms with limited and localized scarring, and less frequent extracutaneous manifestations. {ECO:0000269|PubMed:10084325, ECO:0000269|PubMed:10232406, ECO:0000269|PubMed:10232407, ECO:0000269|PubMed:10232408, ECO:0000269|PubMed:10233777, ECO:0000269|PubMed:10836608, ECO:0000269|PubMed:11142768, ECO:0000269|PubMed:20598510, ECO:0000269|PubMed:7861014, ECO:0000269|PubMed:8170945, ECO:0000269|PubMed:9215684, ECO:0000269|PubMed:9668111, ECO:0000269|PubMed:9740253, ECO:0000269|PubMed:9856843}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epidermolysis bullosa dystrophica, autosomal recessive (RDEB) [MIM:226600]: A group of autosomal recessive blistering skin diseases characterized by tissue separation which occurs below the dermal-epidermal basement membrane at the level of the anchoring fibrils. Various clinical types with different severity are recognized, ranging from severe mutilating forms, such as epidermolysis bullosa dystrophica Hallopeau-Siemens type, to mild forms with limited localized scarring and less frequent extracutaneous manifestations. Mild forms include epidermolysis bullosa mitis and epidermolysis bullosa localisata. {ECO:0000269|PubMed:10084325, ECO:0000269|PubMed:10620140, ECO:0000269|PubMed:11167698, ECO:0000269|PubMed:12787275, ECO:0000269|PubMed:20598510, ECO:0000269|PubMed:8513326, ECO:0000269|PubMed:8592061, ECO:0000269|PubMed:8618018, ECO:0000269|PubMed:8757758, ECO:0000269|PubMed:9215684, ECO:0000269|PubMed:9326325, ECO:0000269|PubMed:9444387, ECO:0000269|PubMed:9740253, ECO:0000269|PubMed:9804332}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Transient bullous dermolysis of the newborn (TBDN) [MIM:131705]: TBDN is a neonatal form of dystrophic epidermolysis bullosa characterized by sub-epidermal blisters, reduced or abnormal anchoring fibrils at the dermo-epidermal junction, and electron-dense inclusions in keratinocytes. TBDN heals spontaneously or strongly improves within the first months and years of life. {ECO:0000269|PubMed:9856844}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epidermolysis bullosa dystrophica, pretibial type (PR- DEB) [MIM:131850]: A form of dystrophic epidermolysis bullosa characterized by pretibial blisters that develop into prurigo-like hyperkeratotic lesions. It predominantly affects the pretibial areas, sparing the knees and other parts of the skin. Other clinical features include nail dystrophy, albopapuloid skin lesions, and hypertrophic scars without pretibial predominance. The phenotype shows considerable interindividual variability. Inheritance is autosomal dominant. {ECO:0000269|PubMed:8541842}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epidermolysis bullosa dystrophica, Bart type (B-DEB) [MIM:132000]: An autosomal dominant form of dystrophic epidermolysis bullosa characterized by congenital localized absence of skin, skin fragility and deformity of nails. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epidermolysis bullosa pruriginosa (EBP) [MIM:604129]: A distinct clinical subtype of epidermolysis bullosa dystrophica. It is characterized by skin fragility, blistering, scar formation, intense pruritus and excoriated prurigo nodules. Onset is in early childhood, but in some cases is delayed until the second or third decade of life. Inheritance can be autosomal dominant or recessive. {ECO:0000269|PubMed:10383749, ECO:0000269|PubMed:11142768}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Nail disorder, non-syndromic congenital, 8 (NDNC8) [MIM:607523]: A nail disorder characterized by isolated toenail dystrophy. The nail changes are most severe in the great toes and consist of the nail plate being buried in the nail bed with a deformed and narrow free edge. {ECO:0000269|PubMed:11843659}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epidermolysis bullosa dystrophica, with subcorneal cleavage (EBDSC) [MIM:131750]: A bullous skin disorder with variable sized clefts just beneath the level of the stratum corneum. Clinical features include blisters, milia, atrophic scarring, nail dystrophy, and oral and conjunctival involvement, as seen in dystrophic epidermolysis bullosa. {ECO:0000269|PubMed:11874498, ECO:0000269|PubMed:2653224}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Protein digestion and absorption - Homo sapiens (human);Assembly of collagen fibrils and other multimeric structures;Vesicle-mediated transport;Membrane Trafficking;Collagen chain trimerization;Collagen biosynthesis and modifying enzymes;Post-translational protein modification;Metabolism of proteins;Collagen formation;Extracellular matrix organization;Anchoring fibril formation;Cargo concentration in the ER;Integrin;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;COPII-mediated vesicle transport;ER to Golgi Anterograde Transport;Beta1 integrin cell surface interactions;Syndecan-1-mediated signaling events;Integrins in angiogenesis
(Consensus)
Recessive Scores
- pRec
- 0.253
Intolerance Scores
- loftool
- 0.0371
- rvis_EVS
- -4.24
- rvis_percentile_EVS
- 0.13
Haploinsufficiency Scores
- pHI
- 0.146
- hipred
- Y
- hipred_score
- 0.637
- ghis
- 0.534
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.790
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Col7a1
- Phenotype
- craniofacial phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); skeleton phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype;
Gene ontology
- Biological process
- growth plate cartilage chondrocyte morphogenesis;endoplasmic reticulum to Golgi vesicle-mediated transport;cell adhesion;epidermis development;negative regulation of endopeptidase activity;extracellular matrix organization;endodermal cell differentiation;COPII vesicle coating
- Cellular component
- Golgi membrane;extracellular region;collagen type VII trimer;basement membrane;extracellular space;endoplasmic reticulum lumen;COPII-coated ER to Golgi transport vesicle;extracellular matrix;endoplasmic reticulum-Golgi intermediate compartment membrane;collagen-containing extracellular matrix
- Molecular function
- serine-type endopeptidase inhibitor activity;protein binding;extracellular matrix structural constituent conferring tensile strength