COL12A1

collagen type XII alpha 1 chain, the group of Fibronectin type III domain containing|Collagen proteoglycans|Collagens

Basic information

Region (hg38): 6:75084326-75206267

Previous symbols: [ "COL12A1L" ]

Links

ENSG00000111799

∙ NCBI:1303 ∙ OMIM:120320 ∙ HGNC:2188 ∙ Uniprot:Q99715 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Bethlem myopathy 2 (Strong), mode of inheritance: AD
Bethlem myopathy 2 (Strong), mode of inheritance: AD
Bethlem myopathy (Supportive), mode of inheritance: AD
Ullrich congenital muscular dystrophy (Supportive), mode of inheritance: AD
Bethlem myopathy 2 (Supportive), mode of inheritance: AD
Bethlem myopathy 2 (Limited), mode of inheritance: AD
Bethlem myopathy 2 (Strong), mode of inheritance: AD
Ullrich congenital muscular dystrophy 2 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bethlem myopathy 2; Ullrich congenital muscular dystrophy 2	AD/AR	General	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	Musculoskeletal	24334604; 24334769

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COL12A1 gene.

Bethlem_myopathy_2 (3061 variants)
Ullrich_congenital_muscular_dystrophy_2 (3031 variants)
not_provided (948 variants)
Inborn_genetic_diseases (335 variants)
not_specified (160 variants)
COL12A1-related_disorder (94 variants)
Ullrich_congenital_muscular_dystrophy (7 variants)
Bethlem_myopathy (3 variants)
See_cases (3 variants)
Ehlers-Danlos_syndrome (3 variants)
Ullrich_congenital_muscular_dystrophy_1A (2 variants)
Myopathic_Ehlers-Danlos_syndrome (2 variants)
Charcot-Marie-Tooth_disease_type_2 (1 variants)
Cataract_16_multiple_types (1 variants)
Neurodevelopmental_disorder (1 variants)
Global_developmental_delay (1 variants)
Abnormality_of_connective_tissue (1 variants)
EMG:_myotonic_runs (1 variants)
Bethlem_myopathy_1A (1 variants)
Bartter_disease_type_4B (1 variants)
EMG_abnormality (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL12A1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004370.6. 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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	27 clinvar	656 clinvar	44 clinvar	728
missense	2 clinvar	13 clinvar	1602 clinvar	345 clinvar	11 clinvar	1973
nonsense	17 clinvar	14 clinvar	13 clinvar	1 clinvar	1 clinvar	46
start loss			1			1
frameshift	27 clinvar	17 clinvar	12 clinvar			56
splice donor/acceptor (+/-2bp)	7 clinvar	33 clinvar	12 clinvar	1 clinvar		53
Total	53	78	1667	1003	56

Highest pathogenic variant AF is 0.000017970277

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COL12A1	protein_coding	protein_coding	ENST00000322507	65	121726

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.974	0.0264	124752	0	52	124804	0.000208

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.11	1423	1.66e+3	0.855	0.0000889	19725
Missense in Polyphen		656	850.06	0.77171		10050
Synonymous	-0.336	609	599	1.02	0.0000334	6190
Loss of Function	9.16	33	157	0.211	0.00000858	1944

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000410	0.000399
Ashkenazi Jewish	0.0000993	0.0000993
East Asian	0.000502	0.000501
Finnish	0.0000471	0.0000464
European (Non-Finnish)	0.000179	0.000177
Middle Eastern	0.000502	0.000501
South Asian	0.000365	0.000360
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Type XII collagen interacts with type I collagen- containing fibrils, the COL1 domain could be associated with the surface of the fibrils, and the COL2 and NC3 domains may be localized in the perifibrillar matrix. {ECO:0000250}.;
Disease: DISEASE: Ullrich congenital muscular dystrophy 2 (UCMD2) [MIM:616470]: A form of Ullrich muscular dystrophy, a congenital myopathy characterized by muscle weakness and multiple joint contractures, generally noted at birth or early infancy. The clinical course is more severe than in Bethlem myopathy. {ECO:0000269|PubMed:24334604}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Bethlem myopathy 2 (BTHLM2) [MIM:616471]: A form of Bethlem myopathy, a benign proximal myopathy characterized by early childhood onset and joint contractures most frequently affecting the elbows and ankles. BTHLM2 inheritance is autosomal dominant. {ECO:0000269|PubMed:24334604, ECO:0000269|PubMed:24334769}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Protein digestion and absorption - Homo sapiens (human);Collagen chain trimerization;Collagen biosynthesis and modifying enzymes;Collagen degradation;Collagen formation;Extracellular matrix organization;Integrin;Degradation of the extracellular matrix (Consensus)

Recessive Scores

pRec: 0.144

Intolerance Scores

loftool: 0.0488
rvis_EVS: -1.63
rvis_percentile_EVS: 2.88

Haploinsufficiency Scores

pHI: 0.925
hipred: Y
hipred_score: 0.650
ghis: 0.591

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.602

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Col12a1
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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; muscle phenotype; limbs/digits/tail phenotype; growth/size/body region phenotype; cellular phenotype;

Gene ontology

Biological process: skeletal system development;growth plate cartilage chondrocyte morphogenesis;cell adhesion;collagen fibril organization;endodermal cell differentiation
Cellular component: extracellular region;collagen type XII trimer;extracellular space;endoplasmic reticulum lumen;extracellular matrix;collagen-containing extracellular matrix;extracellular exosome;extracellular vesicle
Molecular function: extracellular matrix structural constituent conferring tensile strength