COL10A1

collagen type X alpha 1 chain, the group of C1q domain containing|Collagens

Basic information

Region (hg38): 6:116118909-116158747

Links

ENSG00000123500 ∙ NCBI:1300 ∙ OMIM:120110 ∙ HGNC:2185 ∙ Uniprot:Q03692 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Schmid metaphyseal chondrodysplasia (Definitive), mode of inheritance: AD
• Schmid metaphyseal chondrodysplasia (Definitive), mode of inheritance: AD
• Schmid metaphyseal chondrodysplasia (Strong), mode of inheritance: AD
• Schmid metaphyseal chondrodysplasia (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Metaphyseal chondrodysplasia, Schmid type	AD	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	14279845; 3281118; 8220429; 7936797; 8782043; 9837818; 10929364; 12554676; 15578582; 14227699; 17403716; 20872587; 21360259; 21447328

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COL10A1 gene.

• not_provided (362 variants)
• Inborn_genetic_diseases (111 variants)
• Metaphyseal_chondrodysplasia,_Schmid_type (105 variants)
• not_specified (22 variants)
• COL10A1-related_disorder (18 variants)
• Nager_syndrome (1 variants)
• Metaphyseal_chondrodysplasia (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL10A1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000493.4. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	63	6	72
missense	9	17	242	37	7	312
nonsense	12	7	6			25
start loss					1	1
frameshift	14	20	9	2		45
splice donor/acceptor (+/-2bp)			1			1
Total	35	44	261	102	14

Highest pathogenic variant AF is 0.0000049576

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COL10A1	protein_coding	protein_coding	ENST00000327673	2	39825

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000298	0.941	125518	0	230	125748	0.000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.15	436	374	1.17	0.0000180	4223
Missense in Polyphen		39	39.101	0.99742		536
Synonymous	-0.189	142	139	1.02	0.00000722	1639
Loss of Function	1.74	10	17.9	0.557	0.00000103	229

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000624	0.000624
Ashkenazi Jewish	0.0116	0.0116
East Asian	0.000490	0.000489
Finnish	0.0000926	0.0000924
European (Non-Finnish)	0.000552	0.000545
Middle Eastern	0.000490	0.000489
South Asian	0.000523	0.000523
Other	0.000984	0.000978

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Type X collagen is a product of hypertrophic chondrocytes and has been localized to presumptive mineralization zones of hyaline cartilage.
• Disease: DISEASE: Schmid type metaphyseal chondrodysplasia (SMCD) [MIM:156500]: Dominantly inherited disorder of the osseous skeleton. The cardinal features of the phenotype are mild short stature, coxa vara and a waddling gait. Radiography usually shows sclerosis of the ribs, flaring of the metaphyses, and a wide irregular growth plate, especially of the knees. A variant form of SMCD is spondylometaphyseal dysplasia Japanese type. It is characterized by spinal involvement comprising mild platyspondyly, vertebral body abnormalities, and end-plate irregularity. {ECO:0000269|PubMed:15880705, ECO:0000269|PubMed:7607655, ECO:0000269|PubMed:7876225, ECO:0000269|PubMed:8004099, ECO:0000269|PubMed:8304336, ECO:0000269|PubMed:8782043, ECO:0000269|PubMed:9067753, ECO:0000269|PubMed:9852679}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Protein digestion and absorption - Homo sapiens (human);Endochondral Ossification;Senescence and Autophagy in Cancer;Assembly of collagen fibrils and other multimeric structures;Collagen chain trimerization;Collagen biosynthesis and modifying enzymes;Collagen formation;Extracellular matrix organization;Integrin (Consensus)

Recessive Scores

• pRec: 0.366

Intolerance Scores

• loftool: 0.164
• rvis_EVS: -0.02
• rvis_percentile_EVS: 52.25

Haploinsufficiency Scores

• pHI: 0.0619
• hipred: N
• hipred_score: 0.459
• ghis: 0.407

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• gene_indispensability_pred: N
• gene_indispensability_score: 0.340

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Col10a1
• Phenotype: immune system phenotype; skeleton phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); 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); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype

Gene ontology

• Biological process: skeletal system development;extracellular matrix organization
• Cellular component: extracellular region;collagen trimer;extracellular space;endoplasmic reticulum lumen;extracellular matrix;collagen-containing extracellular matrix
• Molecular function: extracellular matrix structural constituent;protein binding;extracellular matrix structural constituent conferring tensile strength;metal ion binding