COL10A1

Chr 6AD

collagen type X alpha 1 chain

NCBI Gene: 1300ENSG00000123500UniProt: Q03692

Type X collagen is a product of hypertrophic chondrocytes and has been localized to presumptive mineralization zones of hyaline cartilage

Primary Disease Associations & Inheritance

Metaphyseal chondrodysplasia, Schmid typeMIM #156500
AD
UniProtSchmid type metaphyseal chondrodysplasia
579
ClinVar variants
105
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— COL10A1
🧬
Gene-Disease Validity (ClinGen)
Schmid metaphyseal chondrodysplasia · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
105 Pathogenic / Likely Pathogenic· 327 VUS of 579 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.94LOEUF
pLI 0.000
Z-score 1.74
OE 0.56 (0.34–0.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-1.15Z-score
OE missense 1.17 (1.08–1.26)
436 obs / 373.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.56 (0.34–0.94)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.17 (1.08–1.26)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02
0≤1.21.6
LoF obs/exp: 10 / 17.9Missense obs/exp: 436 / 373.5Syn Z: -0.19

ClinVar Variant Classifications

579 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic56
Likely Pathogenic49
VUS327
Likely Benign85
Benign33
Conflicting29
56
Pathogenic
49
Likely Pathogenic
327
VUS
85
Likely Benign
33
Benign
29
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
8
36
0
56
Likely Pathogenic
18
16
15
0
49
VUS
13
275
36
3
327
Likely Benign
1
14
8
62
85
Benign
0
10
17
6
33
Conflicting
—29
Total4432311271579

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

COL10A1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

COL10A1-related metaphyseal chondrodysplasia, Schmid type

definitive
ADDominant NegativeAltered Gene Product Structure
Dev. DisordersSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Metaphyseal chondrodysplasia, Schmid type

MIM #156500

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — COL10A1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical Characteristics of Short-Stature Patients With Collagen Gene Mutation and the Therapeutic Response to rhGH.
Chen M et al.·Front Endocrinol (Lausanne)
2022Cohort
Oncogenic mechanisms of COL10A1 in cancer and clinical challenges (Review).
Yi Q et al.·Oncol Rep
2024Review
Characterization of a novel COL10A1 variant associated with Schmid-type metaphyseal chondrodysplasia and a literature review.
Wu H et al.·Mol Genet Genomic Med
2021Review
Shared biomarkers and mechanisms in idiopathic pulmonary fibrosis and non-small cell lung cancer.
Ding X et al.·Int Immunopharmacol
2024Functional
OX40 and Regulatory Marker Alterations in Lesional and Non-Lesional Keloid Tissues.
Bar J et al.·Allergy
2025
Undercarboxylated OCN Inhibits Chondrocyte Hypertrophy and Osteoarthritis Development through GPRC6A/HIF-1α Cascade.
Du Z et al.·Int J Biol Sci
2025
COL10A1 as a Prognostic Biomarker in Association with Immune Infiltration in Prostate Cancer.
Wang C et al.·Curr Cancer Drug Targets
2024
The regulatory effect of CoL10A1 to the intracranial vascular invasion and cell proliferation in breast cancer via EMT pathway.
Wang X et al.·Sci Rep
2025
Promising protein biomarkers for early gastric cancer: clinical performance of combined detection.
Shen W et al.·Clin Chem Lab Med
2025
Prognostic value of COL10A1 and its correlation with tumor-infiltrating immune cells in urothelial bladder cancer: A comprehensive study based on bioinformatics and clinical analysis validation.
Wang X et al.·Front Immunol
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Cloning and Expression of Col10a1 Gene and Its Response to Wnt/TGF-β Signaling Inhibitors in the Chinese Three-Keeled Pond Turtle (Mauremys reevesii).
Li Y et al.·Animals (Basel)
2025🔓 Open Access
COL10A1 Overexpression Promotes Gastric Cancer Aggressiveness Through EMT and Major Oncogenic Pathways.
Necula LG et al.·Int J Mol Sci
2025🔓 Open Access
COL10A1+ fibroblasts promote colorectal cancer metastasis and M2 macrophage polarization with pan-cancer relevance.
Hu S et al.·J Exp Clin Cancer Res
2025🔓 Open Access
The p.W651fsX666 mutation on COL10A1 results in impaired trimerization of normal collagen X to induce Schmid type Metaphyseal chondrodysplasia.
Yang J et al.·Hum Mol Genet
2025
Resident CD24 +LCN2 + LPCs aggravate fibrosis and inflammatory progression via the recruitment of TPPP3 +COL10A1 + macrophages in NASH.
Ding M et al.·Acta Biochim Biophys Sin (Shanghai)
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools