COL10A1

Summary

COL10A1 (collagen type X alpha 1 chain, HGNC:2185) is a protein-coding gene on chromosome 6q22.1, encoding Collagen alpha-1(X) chain (Q03692). Type X collagen is a product of hypertrophic chondrocytes and has been localized to presumptive mineralization zones of hyaline cartilage.

This gene encodes the alpha chain of type X collagen, a short chain collagen expressed by hypertrophic chondrocytes during endochondral ossification. Unlike type VIII collagen, the other short chain collagen, type X collagen is a homotrimer. Mutations in this gene are associated with Schmid type metaphyseal chondrodysplasia (SMCD) and Japanese type spondylometaphyseal dysplasia (SMD).

Source: NCBI Gene 1300 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Schmid metaphyseal chondrodysplasia (Definitive, ClinGen)
• GWAS associations: 6
• Clinical variants (ClinVar): 521 total — 30 pathogenic, 42 likely-pathogenic
• Phenotypes (HPO): 50
• MANE Select transcript: NM_000493

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2185
Approved symbol	COL10A1
Name	collagen type X alpha 1 chain
Location	6q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000123500
Ensembl biotype	protein_coding
OMIM	120110
Entrez	1300

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000243222, ENST00000327673, ENST00000418500, ENST00000452729, ENST00000651968

RefSeq mRNA: 3 — MANE Select: NM_000493 NM_000493, NM_001424106, NM_001424107

CCDS: CCDS5105

Canonical transcript exons

ENST00000651968 — 3 exons

Exon	Start	End
ENSE00003849057	116118909	116121961
ENSE00003849278	116126053	116126132
ENSE00003894379	116125339	116125507

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 99.91.

FANTOM5 (CAGE): breadth broad, TPM avg 4.4781 / max 1044.0527, expressed in 211 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75239	4.1582	94
75240	0.3199	127

Top tissues by expression

267 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	99.91	gold quality
periodontal ligament	UBERON:0008266	94.21	gold quality
buccal mucosa cell	CL:0002336	88.98	gold quality
cartilage tissue	UBERON:0002418	85.85	gold quality
mucosa of paranasal sinus	UBERON:0005030	81.57	gold quality
trabecular bone tissue	UBERON:0002483	81.15	gold quality
visceral pleura	UBERON:0002401	79.55	gold quality
gall bladder	UBERON:0002110	77.28	gold quality
calcaneal tendon	UBERON:0003701	76.19	gold quality
epithelial cell of pancreas	CL:0000083	75.51	silver quality
corpus callosum	UBERON:0002336	75.25	gold quality
choroid plexus epithelium	UBERON:0003911	73.55	silver quality
colonic epithelium	UBERON:0000397	72.73	gold quality
diaphragm	UBERON:0001103	72.20	gold quality
germinal epithelium of ovary	UBERON:0001304	71.69	gold quality
hair follicle	UBERON:0002073	71.13	silver quality
cervix squamous epithelium	UBERON:0006922	70.76	gold quality
trachea	UBERON:0003126	70.74	gold quality
stromal cell of endometrium	CL:0002255	69.69	gold quality
tendon	UBERON:0000043	69.08	gold quality
bone marrow cell	CL:0002092	68.55	silver quality
mucosa of urinary bladder	UBERON:0001259	68.39	gold quality
tongue squamous epithelium	UBERON:0006919	67.81	gold quality
monocyte	CL:0000576	67.33	gold quality
mononuclear cell	CL:0000842	66.91	gold quality
adrenal tissue	UBERON:0018303	66.39	gold quality
pleura	UBERON:0000977	65.44	gold quality
olfactory bulb	UBERON:0002264	65.43	gold quality
leukocyte	CL:0000738	65.39	gold quality
bone element	UBERON:0001474	65.30	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	33.79
E-ANND-3	yes	3.72
E-CURD-53	no	122.89

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BHLHE40, CEBPZ, DLX5, E2F1, EGR1, EPAS1, FOS, GLI2, GLI3, LEF1, MSX2, NFKB1, NKX3-2, PPARG, RUNX2, SIRT1, SMAD6, SOX9, SP1, SP3, TCF3, TFAP2A

miRNA regulators (miRDB)

67 targeting COL10A1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-4762-5P	99.57	68.54	1424

Literature-anchored findings (GeneRIF, showing 40)

• chains harboring Schmid metaphyseal chondrodysplasia NC1 domain mutations are selectively retained and degraded in stably transfected cells (PMID:11805116)
• The crystal structure at 2.0 A resolution of the human collagen X NC1 domain reveals an intimate trimeric assembly strengthened by a buried cluster of calcium ions. (PMID:11839302)
• The 4.6 kb promoter is able to drive specific expression of Col10a1 in hypertrophic cartilage. (PMID:15464363)
• exposure of the NC1 thiol may trigger the recognition and degradation of mutant collagen X chains (PMID:15695517)
• The effect of COL10A1 nonsense mutations in cartilage tissue has been examined in two patients, demonstrating that the mutant mRNA is completely removed by nonsense mediated mRNA decay (PMID:15880705)
• retinoids stimulate collagen X transcription IN chondrocytes (PMID:16598786)
• the triple-helical region of collagen X contains a specific DDR2 binding site that is capable of receptor activation (PMID:16806867)
• Premature induction of hypertrophy-related molecules (type X collagen and matrix metalloproteinase 13) occurred before production of type II collagen and was followed by up-regulation of alkaline phosphatase activity. (PMID:17009260)
• Chondrogenesis in mesenchymal stem cells on the other hand resulted in up-regulation of collagen types I, IIA, IIB, and X, demonstrating differentiation towards cartilage of a mixed phenotype. (PMID:17072841)
• Type X collagen was not detected in any of atehrosclerotic plaques investigated in crural arteries. (PMID:17335825)
• Investigated a family affected with the Spahr type of metaphyseal chondrodysplasia. Sequencing of RMRP, and a haplotype analysis using highly informative markers around the COL10A1 excluded both genes from being pathogenic in this family. (PMID:18553549)
• methylation-based COL10A1 gene silencing is established in cartilage tissue and human articular chondrocytes during chondrogenesis. (PMID:18759285)
• HY(hypertrophy) box is the core element responsive to RUNX-2 in human COL10A1 promoter (PMID:19116917)
• The total expression of type X collagen in the concave side growth plates of the lower end vertebrae was higher than that in the same side growth plates of apex. (PMID:20073986)
• These results indicate that nitrogen-rich plasma polymerized surfaces inhibit COL10A1 expression via the suppression of COX-1. (PMID:20225218)
• The effect of parathyroid hormone on expression of COL10 and COL2 in mesenchymal stem cells from osteoarthritic patients and analyzed the potential mechanisms related to its effect, was investigated. (PMID:20569194)
• speculate that complete loss of mutant transcripts yields COL10A1 haploinsufficiency and late clinical presentation while incomplete loss of mutant transcripts yields dominant-negative effects with early clinical presentation (PMID:20872587)
• MCDS is a rare genetic skeletal disorder caused by a collagen type X defect. Though much is known about the molecular pathology of the causative COL10A1 mutations, causal therapy of the disease is not yet available (PMID:21360259)
• a frameshift mutation leading to elongation of the deduced alpha1(X) chain associated with Metaphyseal Chondrodysplasia type Schmid (PMID:21447328)
• Genetic variation near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration. (PMID:21665990)
• Yiqi Huayu Bushen Recipe increased the expression of aggrecan, decreased the expression of type X collagen, and promoted cell proliferation in cells from degenerated human intervertebral discs. (PMID:22015197)
• The results show that COL10A1 is a tumor biomarker upregulated in a wide variety of tumors including those of the breast, colon, bladder, stomach, esophagus, lung, testis, ovary and pancreas. (PMID:22894674)
• Concentration of serum collagen type X levels correlated with cartilage degradation in osteoarthritis patients. (PMID:25245039)
• a novel sequence variation involving an unusual mutational site of the COL10A1 gene can cause mild metaphyseal chondrodysplasia (PMID:25542771)
• COL10A1 mutation 2005delC in a Chinese pedigree with Schmid type metaphyseal chondrodysplasia is close to the C-terminus of the protein sequence and may result in genetic heterogeneity of the Chinese population (PMID:25974987)
• increased expression of stromal colXalpha1 and low TILs correlate with poor pathologic response in ER+/HER2+ breast tumors. Further studies are needed to confirm their predictive value and impact on long-term outcomes, and to determine whether this collagen exerts a protective effect on the cancer cells or simply reflects other factors within the tumor microenvironment (PMID:27090210)
• This first report of individuals with a homozygous variant in COL10A1 defines a new type of autosomal recessive skeletal dysplasia. The observations in COL10A1 variant carriers suggest a phenotypic overlap between the mildest forms of metaphyseal chondrodysplasia, Schmid type (MCDS) and idiopathic short stature (PMID:28830906)
• All affected individuals are heterozygous for the missense mutation collagen type X alpha 1 chain (COL10A1) rs111033552. (PMID:29234170)
• biomarkers suitable for the assessment of chronological ageing were identified, and extrapolated to the context of photo-damaged skin. In particular, KANK4, ACAN, Col XI alpha1, and PSG1, were expressed at an increased level in both chronologically-aged and photo-damaged skin. (PMID:29913199)
• the disease mechanism involves the misfolding of the mutant protein causing increased endoplasmic reticulum (ER) stress and an unfolded protein response (UPR). However, in an iliac crest biopsy, the COL10A1 p.Y632X mutation was found to produce instability of the mutant mRNA such that little mutant protein may be produced. (PMID:30010889)
• Schmid type metaphyseal chondrodysplasia (SMCD) is a rare skeletal dysplasia, characterized by short stature, short limbs, bowing of the legs, and radiographic features of metaphyseal irregularities with fraying and splaying, more severe at the knee. It is caused by mutations of the COL10A1 gene. (PMID:30209734)
• Plasma samples from lung cancer patients and healthy heavy-smokers controls were tested for levels of COL11A1 and COL10A1 (n = 57 each) and SPARC (n = 90 each). Higher plasma levels of COL10A1 were detected in patients (p </= 0.001), a difference that was driven specifically by females (p < 0.001). No difference in COL11A1 levels between patients and controls was found (PMID:30227835)
• three polymorphisms located in COL6A5, COL8A1, and COL10A1 were investigated as potential susceptibility biomarkers for atopic eczema. (PMID:31275967)
• Two novel mutations were identified in the present study, which will facilitate diagnosis of Schmid-type metaphyseal chondrodysplasia and further expand the spectrum of the COL10A1 mutations associated with MCDS patients (PMID:31856751)
• Bioinformatics analysis of prognostic significance of COL10A1 in breast cancer. (PMID:32043519)
• Effect of miR-26a-5p on gastric cancer cell proliferation, migration and invasion by targeting COL10A1. (PMID:32096148)
• RNAseq-Based Prioritization Revealed COL6A5, COL8A1, COL10A1 and MIR146A as Common and Differential Susceptibility Biomarkers for Psoriasis and Psoriatic Arthritis: Confirmation from Genotyping Analysis of 1417 Italian Subjects. (PMID:32326527)
• Genome-Scale Analysis Identifies Novel Transcript-Variants in Esophageal Adenocarcinoma. (PMID:32344180)
• MiR-218 affects hypertrophic differentiation of human mesenchymal stromal cells during chondrogenesis via targeting RUNX2, MEF2C, and COL10A1. (PMID:33303006)
• Analysis of Collagen type X alpha 1 (COL10A1) expression and prognostic significance in gastric cancer based on bioinformatics. (PMID:33371777)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
danio_rerio	col10a1a	ENSDARG00000054753
danio_rerio	col10a1b	ENSDARG00000101535

Paralogs (23): C1QTNF3 (ENSG00000082196), COL19A1 (ENSG00000082293), PDCD7 (ENSG00000090470), C1QL1 (ENSG00000131094), C1QTNF6 (ENSG00000133466), C1QL2 (ENSG00000144119), COL8A1 (ENSG00000144810), C1QTNF2 (ENSG00000145861), C1QC (ENSG00000159189), C1QTNF7 (ENSG00000163145), C1QL3 (ENSG00000165985), COL8A2 (ENSG00000171812), C1QTNF4 (ENSG00000172247), C1QB (ENSG00000173369), C1QA (ENSG00000173372), C1QTNF1 (ENSG00000173918), ADIPOQ (ENSG00000181092), OTOL1 (ENSG00000182447), C1QTNF8 (ENSG00000184471), C1QL4 (ENSG00000186897), C1QTNF9B (ENSG00000205863), C1QTNF5 (ENSG00000223953), C1QTNF9 (ENSG00000240654)

Protein

Protein identifiers

Collagen alpha-1(X) chain — Q03692 (reviewed: Q03692)

All UniProt accessions (4): A0A650AXN9, Q03692, Q5QPC7, Q5QPC8

UniProt curated annotations — full annotation on UniProt →

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

Subunit / interactions. Homotrimer.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Post-translational modifications. Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (3): NP_000484, NP_001411035, NP_001411036 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001073	C1q_dom	Domain
IPR008160	Collagen	Repeat
IPR008983	Tumour_necrosis_fac-like_dom	Homologous_superfamily
IPR050392	Collagen/C1q_domain	Family

Pfam: PF00386, PF01391

UniProt features (56 total): sequence variant 23, strand 10, compositionally biased region 9, binding site 5, region of interest 4, signal peptide 1, chain 1, domain 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1GR3	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q03692-F1	58.80	0.22

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 626; 627; 633; 634; 634

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-1442490	Collagen degradation
R-HSA-1650814	Collagen biosynthesis and modifying enzymes
R-HSA-2022090	Assembly of collagen fibrils and other multimeric structures
R-HSA-216083	Integrin cell surface interactions
R-HSA-3000171	Non-integrin membrane-ECM interactions
R-HSA-8948216	Collagen chain trimerization

MSigDB gene sets: 246 (showing top): YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOCC_COLLAGEN_TRIMER, MODULE_118, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, RIGGI_EWING_SARCOMA_PROGENITOR_DN, HFH4_01, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_LOBULAR_NORMAL_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, AFFAR_YY1_TARGETS_UP, FOXJ2_02, PID_AVB3_INTEGRIN_PATHWAY, MCCLUNG_COCAIN_REWARD_4WK, CTAWWWATA_RSRFC4_Q2, KAYO_AGING_MUSCLE_UP

GO Biological Process (1): skeletal system development (GO:0001501)

GO Molecular Function (3): extracellular matrix structural constituent conferring tensile strength (GO:0030020), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), collagen trimer (GO:0005581), collagen type X trimer (GO:0005599), endoplasmic reticulum lumen (GO:0005788), extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Collagen formation	2
Extracellular matrix organization	2
Degradation of the extracellular matrix	1
Collagen biosynthesis and modifying enzymes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
system development	1
extracellular matrix structural constituent	1
cation binding	1
binding	1
cellular anatomical structure	1
protein-containing complex	1
network-forming collagen trimer	1
hexagonal collagen network	1
endoplasmic reticulum	1
intracellular organelle lumen	1
external encapsulating structure	1

Protein interactions and networks

STRING

1860 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
COL10A1	MMP13	P45452	903
COL10A1	RUNX2	Q13950	867
COL10A1	ACAN	P16112	849
COL10A1	ADAMTS4	O75173	838
COL10A1	SOX9	P48436	794
COL10A1	IHH	Q14623	745
COL10A1	IBSP	P21815	732
COL10A1	ADAMTS3	O15072	730
COL10A1	ADAMTS5	Q9UNA0	647
COL10A1	ALPL	P05186	644
COL10A1	BGN	P13247	636
COL10A1	DLX3	O60479	632
COL10A1	MMP11	P24347	618
COL10A1	PTHLH	P12272	616
COL10A1	CCN6	O95389	615

IntAct

46 interactions, top by confidence:

A	B	Type	Score
UBQLN1	COL10A1	psi-mi:“MI:0915”(physical association)	0.720
COL10A1	UBQLN1	psi-mi:“MI:0915”(physical association)	0.720
BANP	COL10A1	psi-mi:“MI:0915”(physical association)	0.560
UBQLN1	COL10A1	psi-mi:“MI:0915”(physical association)	0.560
COL10A1	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
ZNF410	COL10A1	psi-mi:“MI:0915”(physical association)	0.560
COL10A1	CIDEB	psi-mi:“MI:0915”(physical association)	0.560
COL10A1	ZNF410	psi-mi:“MI:0915”(physical association)	0.560
COL10A1	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
COL10A1	BANP	psi-mi:“MI:0915”(physical association)	0.560
COL10A1	NRF1	psi-mi:“MI:0915”(physical association)	0.560
COL10A1	SGTB	psi-mi:“MI:0915”(physical association)	0.560
VSNL1	COL10A1	psi-mi:“MI:0915”(physical association)	0.560
COL10A1	MESD	psi-mi:“MI:0915”(physical association)	0.560
COL10A1	C1QL1	psi-mi:“MI:0914”(association)	0.530
COL10A1	COL10A1	psi-mi:“MI:0407”(direct interaction)	0.440
COL10A1	P4HB	psi-mi:“MI:0915”(physical association)	0.400
COL10A1	CRTAP	psi-mi:“MI:0914”(association)	0.350
COL10A1	PLOD2	psi-mi:“MI:0914”(association)	0.350
COL10A1	P4HA2	psi-mi:“MI:0914”(association)	0.350
COL10A1	UBQLN1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (43): UBQLN1 (Two-hybrid), BANP (Two-hybrid), COL10A1 (Proximity Label-MS), C1QL4 (Affinity Capture-MS), C1QL1 (Affinity Capture-MS), TOMM34 (Affinity Capture-MS), COLGALT2 (Affinity Capture-MS), NUMB (Affinity Capture-MS), COL4A2 (Affinity Capture-MS), MPP1 (Affinity Capture-MS), COL10A1 (Two-hybrid), COL10A1 (Two-hybrid), UBQLN1 (Two-hybrid), CIDEB (Two-hybrid), VSNL1 (Two-hybrid)

ESM2 similar proteins: A0A060WQA3, A0MSJ1, A5PN28, A6NHN0, A8WGB1, A8WR59, B2RNN3, C7DZK3, O35167, O35348, O76368, O88207, P08125, P0C862, P12106, P12107, P13942, P20849, P20908, P20909, P23206, P25067, P25318, P83371, P98085, Q03637, Q03692, Q05306, Q05722, Q07092, Q0II24, Q0VF58, Q14993, Q17RW2, Q30D77, Q32S24, Q4ZJM7, Q4ZJN1, Q60467, Q61245

Diamond homologs: A0A060WQA3, A5PN28, A6NHN0, B2RNN3, O75973, O88992, P02745, P02746, P08125, P0C862, P14106, P14282, P23206, P25067, P25318, P27658, P31720, P31721, P83371, P98085, P98086, Q00780, Q02105, Q03692, Q05306, Q05A80, Q06575, Q06576, Q06577, Q0II24, Q15848, Q2KIU3, Q2KIX7, Q3Y5Z3, Q4ZJM7, Q4ZJM9, Q4ZJN1, Q5E9E3, Q5FVH0, Q5RJ80

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
EGR1	“up-regulates quantity by expression”	COL10A1	“transcriptional regulation”
SIRT1	“down-regulates quantity by repression”	COL10A1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

521 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	30
Likely pathogenic	42
Uncertain significance	306
Likely benign	72
Benign	31

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1008255	NM_000493.4(COL10A1):c.1725del (p.Leu575fs)	Pathogenic
1047790	NM_000493.4(COL10A1):c.1994_1995del (p.Ser664_Ser665insTer)	Pathogenic
1062777	NM_000493.4(COL10A1):c.1989C>A (p.Tyr663Ter)	Pathogenic
1067305	NM_000493.4(COL10A1):c.1853G>T (p.Gly618Val)	Pathogenic
1224366	NM_000493.4(COL10A1):c.1896C>G (p.Tyr632Ter)	Pathogenic
1381713	NM_000493.4(COL10A1):c.1869C>A (p.Tyr623Ter)	Pathogenic
1395717	NM_000493.4(COL10A1):c.1897del (p.Leu633fs)	Pathogenic
1405298	NM_000493.4(COL10A1):c.1957C>T (p.Gln653Ter)	Pathogenic
1427331	NM_000493.4(COL10A1):c.1867_1876del (p.Tyr623fs)	Pathogenic
1679893	NM_000493.4(COL10A1):c.1951_1952dup (p.Trp651fs)	Pathogenic
1683460	NM_000493.4(COL10A1):c.1853_1866del (p.Gly618fs)	Pathogenic
1683461	NM_000493.4(COL10A1):c.1772G>T (p.Cys591Phe)	Pathogenic
1704250	NM_000493.4(COL10A1):c.1900del (p.Asp634fs)	Pathogenic
1723872	NM_000493.4(COL10A1):c.1833G>A (p.Trp611Ter)	Pathogenic
17464	NM_000493.4(COL10A1):c.1857_1869del (p.Val621fs)	Pathogenic
17468	NM_000493.4(COL10A1):c.1859del (p.Pro620fs)	Pathogenic
17472	NM_000493.4(COL10A1):c.1884C>G (p.Tyr628Ter)	Pathogenic
17474	NM_000493.4(COL10A1):c.1951T>C (p.Trp651Arg)	Pathogenic
17475	NM_000493.4(COL10A1):c.52G>A (p.Gly18Arg)	Pathogenic
17476	NM_000493.4(COL10A1):c.53G>A (p.Gly18Glu)	Pathogenic
17480	NM_000493.4(COL10A1):c.1790A>G (p.Tyr597Cys)	Pathogenic
17482	NM_000493.4(COL10A1):c.1832G>A (p.Trp611Ter)	Pathogenic
2769683	NM_000493.4(COL10A1):c.1844dup (p.Tyr615Ter)	Pathogenic
29632	NM_000493.4(COL10A1):c.1989C>G (p.Tyr663Ter)	Pathogenic
3235752	NM_000493.4(COL10A1):c.1945C>T (p.Gln649Ter)	Pathogenic
3362910	NM_000493.4(COL10A1):c.1952_1953insA (p.Trp651Ter)	Pathogenic
3366892	NM_000493.4(COL10A1):c.1293_1296dup (p.Pro433fs)	Pathogenic
4723714	NM_000493.4(COL10A1):c.1861_1873del (p.Val621fs)	Pathogenic
4755432	Single allele	Pathogenic
817837	NM_000493.4(COL10A1):c.1914del (p.Ser639fs)	Pathogenic

SpliceAI

720 predictions. Top by Δscore:

Variant	Effect	Δscore
6:116125335:TTAC:T	donor_loss	1.0000
6:116125336:TA:T	donor_loss	1.0000
6:116125337:A:AC	donor_gain	1.0000
6:116125338:C:CA	donor_loss	1.0000
6:116125338:C:CC	donor_gain	1.0000
6:116125503:GGATT:G	acceptor_gain	1.0000
6:116125504:GATT:G	acceptor_gain	1.0000
6:116125505:ATT:A	acceptor_gain	1.0000
6:116125506:TT:T	acceptor_gain	1.0000
6:116125508:C:CC	acceptor_gain	1.0000
6:116125508:CTGA:C	acceptor_loss	1.0000
6:116126049:TTAC:T	donor_loss	1.0000
6:116126050:TAC:T	donor_loss	1.0000
6:116126051:A:AC	donor_gain	1.0000
6:116126052:C:CC	donor_gain	1.0000
6:116126052:CCTG:C	donor_gain	1.0000
6:116121266:G:GT	donor_gain	0.9900
6:116121353:G:GT	donor_gain	0.9900
6:116121962:CTAA:C	acceptor_loss	0.9900
6:116121963:T:C	acceptor_loss	0.9900
6:116125343:A:AC	donor_gain	0.9900
6:116125344:C:CC	donor_gain	0.9900
6:116125344:CT:C	donor_gain	0.9900
6:116126048:CTTA:C	donor_loss	0.9900
6:116126051:ACCTG:A	donor_gain	0.9900
6:116126052:CCTGC:C	donor_gain	0.9900
6:116121959:TAC:T	acceptor_gain	0.9800
6:116121962:C:CC	acceptor_gain	0.9800
6:116125338:CCT:C	donor_gain	0.9800
6:116125339:CTT:C	donor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000033516 (6:116155885 G>A), RS1000043820 (6:116216754 ATTTATCTCT>A), RS1000049843 (6:116206990 T>C), RS1000068351 (6:116137384 G>T), RS1000113914 (6:116200180 G>A,T), RS1000149318 (6:116155568 A>G), RS1000195940 (6:116189728 A>G), RS1000202309 (6:116174839 A>T), RS1000215489 (6:116178374 G>A), RS1000219478 (6:116129799 G>A,T), RS1000247169 (6:116178102 C>A,T), RS1000248518 (6:116187837 T>C), RS1000251361 (6:116172523 T>C), RS1000267999 (6:116148900 A>C,G), RS1000361868 (6:116142492 T>C)

Disease associations

OMIM: gene MIM:120110 | disease phenotypes: MIM:156500, MIM:154400, MIM:612650

GenCC curated gene-disease

Disease	Classification	Inheritance
Schmid metaphyseal chondrodysplasia	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Schmid metaphyseal chondrodysplasia	Definitive	AD

Mondo (3): Schmid metaphyseal chondrodysplasia (MONDO:0007983), Nager acrofacial dysostosis (MONDO:0007943), primary ciliary dyskinesia 12 (MONDO:0012979)

Orphanet (3): Metaphyseal chondrodysplasia, Schmid type (Orphanet:174), Nager syndrome (Orphanet:245), Primary ciliary dyskinesia (Orphanet:244)

HPO phenotypes

50 total (30 of 50 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000907	Anterior rib cupping
HP:0000926	Platyspondyly
HP:0001248	Short tubular bones of the hand
HP:0001385	Hip dysplasia
HP:0001513	Obesity
HP:0002515	Waddling gait
HP:0002650	Scoliosis
HP:0002812	Coxa vara
HP:0002829	Arthralgia
HP:0002857	Genu valgum
HP:0002938	Lumbar hyperlordosis
HP:0002970	Genu varum
HP:0002979	Bowing of the legs
HP:0002980	Femoral bowing
HP:0003015	Flared metaphysis
HP:0003016	Metaphyseal widening
HP:0003021	Metaphyseal cupping
HP:0003025	Metaphyseal irregularity
HP:0003026	Short long bone
HP:0003301	Irregular vertebral endplates
HP:0003371	Enlargement of the proximal femoral epiphysis
HP:0003411	Proximal femoral metaphyseal irregularity
HP:0003468	Abnormal vertebral morphology
HP:0003502	Mild short stature
HP:0003508	Proportionate short stature
HP:0004019	Radial metaphyseal irregularity
HP:0004042	Ulnar metaphyseal irregularity
HP:0004322	Short stature
HP:0004979	Metaphyseal sclerosis

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001100_6	Age-related macular degeneration	1.000000e-08
GCST001884_5	Age-related macular degeneration	2.000000e-08
GCST003997_6	Myopia	2.000000e-13
GCST006291_58	Spherical equivalent or myopia (age of diagnosis)	7.000000e-11
GCST007643_3	Gemcitabine-induced early high-grade neutropenia in pancreatic cancer	3.000000e-06
GCST010002_333	Refractive error	2.000000e-36

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
C538184	Acrofacial dysostosis, Nager type (supp.)
C567211	Ciliary Dyskinesia, Primary, 12 (supp.)
C537352	Metaphyseal chondrodysplasia Schmid type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, decreases expression	2
2,4,6-tribromophenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
tetrabromobisphenol A	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
2-palmitoylglycerol	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Fulvestrant	affects cotreatment, decreases methylation	1
Alginic Acid	increases expression	1
Aluminum Oxide	increases expression	1
Berberine	increases expression	1
Dexamethasone	increases expression, decreases reaction	1
Estradiol	increases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression, affects response to substance, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
T-2 Toxin	increases expression	1
Okadaic Acid	decreases expression	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

1 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04931056	Not specified	COMPLETED	A Post Market Clinical Follow-up Study on Biomet Microfixation HTR PEKK (Midface), Facial & Mandibular Plates.