COL12A1

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

Basic information

Region (hg38): 6:75084325-75206267

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

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.

• Ullrich congenital muscular dystrophy 2;Bethlem myopathy 2 (39 variants)
• Ullrich congenital muscular dystrophy 2 (5 variants)
• not provided (2 variants)
• Bethlem myopathy 2;Ullrich congenital muscular dystrophy 2 (2 variants)
• Bethlem myopathy 2 (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.

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			13	551	41	605
missense		8	1256	146	14	1424
nonsense	16	6	9	1	1	33
start loss						0
frameshift	22	6	11			39
inframe indel		1	12			13
splice donor/acceptor (+/-2bp)	7	24	11	1		43
splice region		1	92	95	7	195
non coding			11	363	107	481
Total	45	45	1323	1062	163

Highest pathogenic variant AF is 0.0000197

Variants in COL12A1

This is a list of pathogenic ClinVar variants found in the COL12A1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-75086337-A-C			Benign (Aug 03, 2018)
6-75086531-C-A			Likely benign (Jul 28, 2020)
6-75086541-A-G			Uncertain significance (Mar 22, 2019)
6-75086552-C-T		Ullrich congenital muscular dystrophy 2;Bethlem myopathy 2 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 07, 2023)
6-75086553-G-A		Ullrich congenital muscular dystrophy 2;Bethlem myopathy 2	Conflicting classifications of pathogenicity (Sep 23, 2023)
6-75086554-G-A		Ullrich congenital muscular dystrophy 2;Bethlem myopathy 2	Uncertain significance (Dec 11, 2021)
6-75086568-T-C		Ullrich congenital muscular dystrophy 2;Bethlem myopathy 2	Likely benign (Dec 09, 2023)
6-75086576-G-T		Ullrich congenital muscular dystrophy 2;Bethlem myopathy 2	Likely benign (Jul 25, 2022)
6-75086648-GTA-G			Benign (Aug 08, 2019)
6-75086648-G-GTA			Benign (Aug 10, 2019)
6-75086648-G-GTATA			Benign (Aug 30, 2019)
6-75086648-G-GTATATA			Likely benign (Sep 15, 2019)
6-75086758-G-T			Benign (Jul 06, 2018)
6-75087281-GA-G			Benign (Aug 10, 2019)
6-75087557-C-T		Bethlem myopathy 2;Ullrich congenital muscular dystrophy 2	Likely benign (Oct 13, 2023)
6-75087559-A-G		Ullrich congenital muscular dystrophy 2;Bethlem myopathy 2	Likely benign (Jun 04, 2022)
6-75087561-A-G		Ullrich congenital muscular dystrophy 2;Bethlem myopathy 2	Likely benign (Sep 25, 2022)
6-75087566-C-T		Ullrich congenital muscular dystrophy 2;Bethlem myopathy 2	Likely benign (May 01, 2023)
6-75087572-C-T		Ullrich congenital muscular dystrophy 2;Bethlem myopathy 2	Uncertain significance (Sep 15, 2022)
6-75087573-G-C		Ullrich congenital muscular dystrophy 2;Bethlem myopathy 2	Uncertain significance (Oct 17, 2023)
6-75087580-G-A		Ullrich congenital muscular dystrophy 2;Bethlem myopathy 2	Uncertain significance (Apr 01, 2022)
6-75087582-T-C		Ullrich congenital muscular dystrophy 2;Bethlem myopathy 2	Uncertain significance (Jan 25, 2024)
6-75087585-CC-TT			Uncertain significance (Apr 11, 2019)
6-75087586-C-T		not specified • Ullrich congenital muscular dystrophy 2;Bethlem myopathy 2 • Bethlem myopathy 2 • Ullrich congenital muscular dystrophy 2	Benign (Feb 01, 2024)
6-75087589-G-A		Ullrich congenital muscular dystrophy 2;Bethlem myopathy 2	Benign (Jan 12, 2024)

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