ASPN

asporin, the group of Small leucine rich repeat proteoglycans

Basic information

Region (hg38): 9:92456204-92482506

Links

ENSG00000106819 ∙ NCBI:54829 ∙ OMIM:608135 ∙ HGNC:14872 ∙ Uniprot:Q9BXN1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• not provided (4 variants)
• Inborn genetic diseases (2 variants)
• Osteoarthritis susceptibility 3 (1 variants)
• not specified (1 variants)
• Lumbar disk degeneration, susceptibility to (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ASPN 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						0
missense			2			2
nonsense						0
start loss						0
frameshift						0
inframe indel			1		4	5
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	3	0	4

Variants in ASPN

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

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

Position	Type	Phenotype	Significance	ClinVar
9-92457338-G-A			Uncertain significance (-)
9-92460550-A-G		ASPN-related disorder	Likely benign (Aug 20, 2019)
9-92465001-A-T		not specified	Uncertain significance (Jan 31, 2022)
9-92466381-C-T		ASPN-related disorder	Benign (May 08, 2019)
9-92470675-T-A		ASPN-related disorder	Likely benign (Sep 02, 2020)
9-92474742-CTCA-C			Benign (Oct 11, 2021)
9-92474742-C-CTCA		Osteoarthritis susceptibility 3 • Lumbar disk degeneration, susceptibility to • not specified • CENPP-related disorder	Benign (Mar 19, 2020)
9-92474742-C-CTCATCA			Benign (Mar 05, 2021)
9-92474742-C-CTCATCATCA			Uncertain significance (Jun 22, 2023)
9-92474742-C-CTCATCATCATCA		CENPP-related disorder	Benign (Oct 31, 2019)
9-92474742-C-CTCATCATCATCATCA			Benign (Mar 05, 2021)
9-92474766-A-G		ASPN-related disorder	Likely benign (Sep 17, 2019)
9-92474809-A-G		ASPN-related disorder	Likely benign (Apr 28, 2022)
9-92474836-G-T		not specified	Uncertain significance (Aug 30, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ASPN	protein_coding	protein_coding	ENST00000375544	7	26302

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.04e-7	0.550	125477	0	263	125740	0.00105

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.746	167	196	0.850	0.00000951	2529
Missense in Polyphen		54	70.562	0.76528		953
Synonymous	1.63	54	71.6	0.754	0.00000356	691
Loss of Function	0.993	13	17.5	0.744	0.00000108	223

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00111	0.00111
Ashkenazi Jewish	0.00199	0.00199
East Asian	0.000497	0.000489
Finnish	0.00130	0.00129
European (Non-Finnish)	0.00129	0.00125
Middle Eastern	0.000497	0.000489
South Asian	0.000834	0.000817
Other	0.00148	0.00147

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Negatively regulates periodontal ligament (PDL) differentiation and mineralization to ensure that the PDL is not ossified and to maintain homeostasis of the tooth-supporting system. Inhibits BMP2-induced cytodifferentiation of PDL cells by preventing its binding to BMPR1B/BMP type-1B receptor, resulting in inhibition of BMP-dependent activation of SMAD proteins (By similarity). Critical regulator of TGF-beta in articular cartilage and plays an essential role in cartilage homeostasis and osteoarthritis (OA) pathogenesis. Negatively regulates chondrogenesis in the articular cartilage by blocking the TGF- beta/receptor interaction on the cell surface and inhibiting the canonical TGF-beta/Smad signal. Binds calcium and plays a role in osteoblast-driven collagen biomineralization activity. {ECO:0000250, ECO:0000269|PubMed:17827158, ECO:0000269|PubMed:19589127}.
• Disease: DISEASE: Osteoarthritis 3 (OS3) [MIM:607850]: A degenerative disease of the joints characterized by degradation of the hyaline articular cartilage and remodeling of the subchondral bone with sclerosis. Clinical symptoms include pain and joint stiffness often leading to significant disability and joint replacement. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Susceptibility to osteoarthritis is conferred by a triplet repeat expansion polymorphism. ASPN allele having 14 aspartic acid repeats in the N-terminal region of the protein (D14), is overrepresented relative to the common allele having 13 aspartic acid repeats (D13). The frequency of the D14 allele increases with disease severity. The D14 allele is also overrepresented in individuals with hip osteoarthritis.; DISEASE: Intervertebral disc disease (IDD) [MIM:603932]: A common musculo-skeletal disorder caused by degeneration of intervertebral disks of the lumbar spine. It results in low-back pain and unilateral leg pain. {ECO:0000269|PubMed:18304494}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Susceptibility to intervertebral disk disease, particularly lumbar disk degeneration, is conferred by a triplet repeat expansion polymorphism. ASPN allele having 14 aspartic acid repeats in the N-terminal region of the protein (D14), is associated with the disorder in some populations (PubMed:18304494). {ECO:0000269|PubMed:18304494}.
• Pathway: Extracellular matrix organization;ECM proteoglycans (Consensus)

Recessive Scores

• pRec: 0.164

Haploinsufficiency Scores

• pHI: 0.779
• hipred: N
• hipred_score: 0.443
• ghis: 0.584

Essentials

• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.272

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Aspn
• Phenotype: limbs/digits/tail phenotype

Gene ontology

• Biological process: bone mineralization;negative regulation of transforming growth factor beta receptor signaling pathway;negative regulation of tooth mineralization
• Cellular component: extracellular matrix;collagen-containing extracellular matrix
• Molecular function: calcium ion binding;collagen binding;extracellular matrix structural constituent conferring compression resistance