COL5A1

collagen type V alpha 1 chain, the group of Collagens

Basic information

Region (hg38): 9:134641803-134844843

Links

ENSG00000130635NCBI:1289OMIM:120215HGNC:2209Uniprot:P20908AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • Ehlers-Danlos syndrome, classic type (Strong), mode of inheritance: AD
  • Ehlers-Danlos syndrome, classic type (Strong), mode of inheritance: AD
  • Ehlers-Danlos syndrome, classic type (Definitive), mode of inheritance: AD
  • Ehlers-Danlos syndrome, classic type (Supportive), mode of inheritance: AD
  • arterial disorder (Limited), mode of inheritance: AD
  • Ehlers-Danlos syndrome, classic type, 1 (Strong), mode of inheritance: AD
  • Ehlers-Danlos syndrome (Definitive), mode of inheritance: AD
  • Ehlers-Danlos syndrome, classic type (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Ehlers-Danlos syndrome, classic type, 1ADCardiovascular; ObstetricIndividuals with Ehlers-Danlos syndrome may have aortic root dilatation, but the natural history is unclear, and may not typically progress, though yearly surveillance with echocardiogram when aortic dilatation or mitral valve prolapse is peresent has been recommended; Precautions in pregnancy may be beneficial; Individuals with Fibromuscular dysplasia may have vascular complications, including aneurysms, and early diagnosis may provide early managementAudiologic/Otolaryngologic; Cardiovascular; Dermatologic; Musculoskeletal; Obstetric; Ophthalmologic8541855; 8923000; 9042913; 10602121; 10777716; 11992482; 12180144; 15264295; 15580559; 18972565; 20635400; 20847697; 20301422; 21611149; 22696272; 32938213
Homozygous variants have been reported

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COL5A1 gene.

  • Ehlers-Danlos_syndrome,_classic_type,_1 (2744 variants)
  • not_provided (1109 variants)
  • Familial_thoracic_aortic_aneurysm_and_aortic_dissection (857 variants)
  • not_specified (463 variants)
  • Ehlers-Danlos_syndrome,_classic_type (169 variants)
  • Fibromuscular_dysplasia,_multifocal (166 variants)
  • COL5A1-related_disorder (123 variants)
  • Ehlers-Danlos_syndrome (118 variants)
  • Ehlers-Danlos_syndrome_type_7A (88 variants)
  • Connective_tissue_disorder (36 variants)
  • Ehlers-Danlos_syndrome,_classic_type,_2 (17 variants)
  • Abnormal_bleeding (6 variants)
  • Cardiovascular_phenotype (6 variants)
  • See_cases (6 variants)
  • Thrombocytopenia (4 variants)
  • Atrophic_scars (2 variants)
  • Soft_skin (2 variants)
  • Marfan_syndrome (2 variants)
  • Hyperextensible_skin (2 variants)
  • Joint_hypermobility (2 variants)
  • Bruising_susceptibility (2 variants)
  • Dural_ectasia (1 variants)
  • Neuropathic_spinal_arthropathy (1 variants)
  • Arthralgia (1 variants)
  • Mitral_valve_prolapse (1 variants)
  • Inborn_genetic_diseases (1 variants)
  • Cardiac_arrhythmia (1 variants)
  • Bilateral_talipes_equinovarus (1 variants)
  • Gastroesophageal_reflux (1 variants)
  • Clubfoot (1 variants)
  • Aortic_dilatation (1 variants)
  • Cutis_laxa (1 variants)
  • Constrictive_median_neuropathy (1 variants)
  • Scoliosis (1 variants)
  • Skeletal_dysplasia (1 variants)
  • Hyperextensible_hand_joints (1 variants)
  • Thoracic_aortic_aneurysm_or_dissection (1 variants)
  • Joint_dislocation (1 variants)
  • Brugada_syndrome (1 variants)
  • Hypertelorism (1 variants)
  • Loeys-Dietz_syndrome (1 variants)
  • COL5A1-related_disorders (1 variants)
  • Relative_macrocephaly (1 variants)
  • Pneumothorax (1 variants)
  • Shoulder_subluxation (1 variants)
  • Joint_hyperflexibility (1 variants)
  • Neurodevelopmental_disorder_with_or_without_autism_or_seizures (1 variants)
  • Difficulty_walking (1 variants)
  • Hypoparathyroidism (1 variants)
  • Inguinal_hernia (1 variants)
  • Abnormal_digit_morphology (1 variants)
  • Large_joint_dislocations (1 variants)
  • Aortic_valve_disease_1 (1 variants)
  • Confusion (1 variants)
  • Cigarette-paper_scars (1 variants)
  • Prostate_cancer (1 variants)
  • Pain (1 variants)
  • Edema_of_the_dorsum_of_feet (1 variants)
  • Venous_malformation (1 variants)
  • Patellar_dislocation (1 variants)
  • Wolff-Parkinson-White_pattern (1 variants)
  • Cataract (1 variants)
  • Narrow_chest (1 variants)
  • Congenital_hip_dislocation (1 variants)
  • Abnormally_lax_or_hyperextensible_skin (1 variants)
  • Abnormality_of_the_lower_limb (1 variants)
  • Joint_laxity (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL5A1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000093.5. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
1
clinvar
32
clinvar
737
clinvar
31
clinvar
802
missense
11
clinvar
41
clinvar
800
clinvar
381
clinvar
95
clinvar
1328
nonsense
51
clinvar
15
clinvar
66
start loss
3
3
frameshift
138
clinvar
24
clinvar
4
clinvar
166
splice donor/acceptor (+/-2bp)
8
clinvar
49
clinvar
1
clinvar
1
clinvar
59
Total 212 130 836 1119 127

Highest pathogenic variant AF is 0.00004524399

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
COL5A1protein_codingprotein_codingENST00000371817 66203067
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.001.15e-17125729031257320.0000119
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense2.079371.13e+30.8270.000074711580
Missense in Polyphen245290.030.844732969
Synonymous-1.825264761.110.00003873909
Loss of Function9.7521150.01740.000005781322

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00002890.0000289
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.000.00
European (Non-Finnish)0.00001760.0000176
Middle Eastern0.000.00
South Asian0.000.00
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Type V collagen is a member of group I collagen (fibrillar forming collagen). It is a minor connective tissue component of nearly ubiquitous distribution. Type V collagen binds to DNA, heparan sulfate, thrombospondin, heparin, and insulin.;
Disease
DISEASE: Ehlers-Danlos syndrome, classic type, 1 (EDSCL1) [MIM:130000]: A form of Ehlers-Danlos syndrome, a group of connective tissue disorders characterized by skin hyperextensibility, articular hypermobility, and tissue fragility. The main features of classic Ehlers-Danlos syndrome are joint hypermobility and dislocation, and fragile, bruisable skin. EDSCL1 inheritance is autosomal dominant. {ECO:0000269|PubMed:10602121, ECO:0000269|PubMed:11992482, ECO:0000269|PubMed:15580559, ECO:0000269|PubMed:18972565, ECO:0000269|PubMed:9042913}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Protein digestion and absorption - Homo sapiens (human);Allograft Rejection;miRNA targets in ECM and membrane receptors;Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;miR-509-3p alteration of YAP1-ECM axis;Collagen chain trimerization;Collagen biosynthesis and modifying enzymes;Collagen formation;Extracellular matrix organization;Integrin;Validated transcriptional targets of deltaNp63 isoforms;Beta1 integrin cell surface interactions;Syndecan-1-mediated signaling events;Integrins in angiogenesis (Consensus)

Intolerance Scores

loftool
0.0114
rvis_EVS
-3.01
rvis_percentile_EVS
0.52

Haploinsufficiency Scores

pHI
0.693
hipred
Y
hipred_score
0.853
ghis
0.595

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.817

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Col5a1
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); embryo phenotype; normal 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); vision/eye phenotype;

Gene ontology

Biological process
blood vessel development;heart morphogenesis;cell adhesion;cell migration;extracellular matrix organization;collagen fibril organization;collagen biosynthetic process;wound healing, spreading of epidermal cells;tendon development;skin development;integrin biosynthetic process;eye morphogenesis;regulation of cellular component organization;supramolecular fiber organization;negative regulation of endodermal cell differentiation
Cellular component
extracellular region;collagen type V trimer;basement membrane;extracellular space;endoplasmic reticulum lumen;extracellular matrix;collagen-containing extracellular matrix
Molecular function
integrin binding;extracellular matrix structural constituent;protein binding;heparin binding;extracellular matrix structural constituent conferring tensile strength;proteoglycan binding;metal ion binding;platelet-derived growth factor binding