ASPN

Summary

ASPN (asporin, HGNC:14872) is a protein-coding gene on chromosome 9q22.31, encoding Asporin (Q9BXN1). 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.

This gene encodes a cartilage extracellular protein that is member of the small leucine-rich proteoglycan family. The encoded protein may regulate chondrogenesis by inhibiting transforming growth factor-beta 1-induced gene expression in cartilage. This protein also binds collagen and calcium and may induce collagen mineralization. Polymorphisms in the aspartic acid repeat region of this gene are associated with a susceptibility to osteoarthritis, and also with intervertebral disc disease. Alternative splicing of this gene results in multiple transcript variants.

Source: NCBI Gene 54829 — RefSeq curated summary.

At a glance

• Gene–disease (curated): osteoarthritis susceptibility 3 (Limited, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 42 total — 2 pathogenic
• Phenotypes (HPO): 6
• MANE Select transcript: NM_017680

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14872
Approved symbol	ASPN
Name	asporin
Location	9q22.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20129, SLRR1C, PLAP-1
Ensembl gene	ENSG00000106819
Ensembl biotype	protein_coding
OMIM	608135
Entrez	54829

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 nonsense_mediated_decay

ENST00000375543, ENST00000375544, ENST00000650794, ENST00000651738, ENST00000907468, ENST00000907469, ENST00000907470

RefSeq mRNA: 2 — MANE Select: NM_017680 NM_001193335, NM_017680

Canonical transcript exons

ENST00000375544 — 8 exons

Exon	Start	End
ENSE00000711478	92459632	92459770
ENSE00000711479	92460474	92460567
ENSE00000711481	92464919	92465029
ENSE00000869933	92470669	92470781
ENSE00000869936	92466358	92466571
ENSE00001031659	92482293	92482506
ENSE00001467400	92474624	92474927
ENSE00003647036	92456205	92457485

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 99.71.

FANTOM5 (CAGE): breadth broad, TPM avg 6.9316 / max 412.0078, expressed in 427 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
101432	3.4884	362
101431	3.1477	303
101429	0.1382	71
101430	0.0902	50
101428	0.0672	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	99.71	gold quality
synovial joint	UBERON:0002217	99.70	gold quality
periodontal ligament	UBERON:0008266	99.64	gold quality
calcaneal tendon	UBERON:0003701	99.63	gold quality
tendon	UBERON:0000043	99.14	gold quality
saphenous vein	UBERON:0007318	99.06	gold quality
blood vessel layer	UBERON:0004797	98.97	gold quality
visceral pleura	UBERON:0002401	98.73	gold quality
right coronary artery	UBERON:0001625	98.71	gold quality
ascending aorta	UBERON:0001496	97.34	gold quality
thoracic aorta	UBERON:0001515	97.33	gold quality
vena cava	UBERON:0004087	97.03	gold quality
skin of hip	UBERON:0001554	97.02	gold quality
descending thoracic aorta	UBERON:0002345	96.95	gold quality
gall bladder	UBERON:0002110	96.92	gold quality
coronary artery	UBERON:0001621	96.16	gold quality
cartilage tissue	UBERON:0002418	96.14	gold quality
left coronary artery	UBERON:0001626	95.79	gold quality
nipple	UBERON:0002030	95.67	gold quality
layer of synovial tissue	UBERON:0007616	95.60	gold quality
aorta	UBERON:0000947	95.38	gold quality
pleura	UBERON:0000977	95.31	gold quality
pylorus	UBERON:0001166	95.29	gold quality
decidua	UBERON:0002450	94.95	gold quality
myometrium	UBERON:0001296	94.86	gold quality
parietal pleura	UBERON:0002400	93.94	gold quality
popliteal artery	UBERON:0002250	93.88	gold quality
tibial artery	UBERON:0007610	93.86	gold quality
superficial temporal artery	UBERON:0001614	93.76	gold quality
urethra	UBERON:0000057	92.71	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-8322	yes	2937.61
E-CURD-126	yes	1732.07
E-HCAD-10	yes	32.64
E-MTAB-10287	yes	26.47
E-MTAB-8410	yes	17.55
E-MTAB-10042	yes	9.00
E-MTAB-10553	yes	6.33
E-GEOD-124858	no	78.88
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SMAD3, SP1

miRNA regulators (miRDB)

64 targeting ASPN, 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-3120-5P	100.00	65.56	965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-200A-5P	99.76	69.10	949

Literature-anchored findings (GeneRIF, showing 40)

• these findings provide another functional link between extracellular matrix proteins, TGF-beta activity and disease, suggesting new therapeutic strategies for osteoarthritis. (PMID:15640800)
• No significant differences were observed in any of the multiple comparisons performed in osteoarthritis and controls (PMID:16542493)
• expression may be associated with the process of cytodifferentiation of periodontal ligament cells (PMID:16632759)
• Association of the D14 allele with knee osteoarthritis susceptibility in Han Chinese. (PMID:17024313)
• the association of the ASPN D14 allele and knee OA has global relevance [meta-analysis] (PMID:17517696)
• This study further highlighted the significance of asporin in osteoarthritis. (PMID:17603749)
• Characterization of the human ASPN promoter region revealed a region from -126 to -82 that is sufficient for full promoter activity; however, TGF-beta1 failed to increase activity through the ASPN promoter. (PMID:17804408)
• describe mechanisms for asporin function and regulation in human articular cartilage; asporin blocks chondrogenesis and inhibits TGF-beta1-induced expression of matrix genes and the resulting chondrocyte phenotypes. (PMID:17827158)
• The frequency of the aspartic acid repeat polymorphism was examined. These results suggest that asporin may play a role in OA susceptibility of the knee in the Korean female population. (PMID:18178444)
• ASPN is a lumbar-disc degeneration (LDD) gene in Asians, and common risk factors may be considered for osteoarthritis and LDD. (PMID:18304494)
• Asporin is up-regulated in disease states. It binds to various growth factors, including TGF-beta and BMP-2, and negatively regulates their activity. By inhibiting binding of TGF-beta1 to its type II receptor, asporin forms a functional feedback loop. (PMID:18336287)
• These data suggest that polymorphisms within ASPN are not a major influence in susceptibility to hand or knee OA in US Caucasians. (PMID:18434216)
• In the discs of Caucasian subjects there was greatest expression of asporin in the more degenerate human discs in vivo. (PMID:19327154)
• Asporin has a role in osteoblast-driven collagen biomineralization activity. (PMID:19589127)
• The ratio of Asporin to TGF-beta1 (transforming growth factor-beta1) mRNA in patients with severe cartilage damage was higher than that in osteoartritis patients with mild cartilage damage (PMID:19997821)
• Association of an asporin repeat polymorphism with ankylosing spondylitis in Han Chinese population: a case-control study, is reported. (PMID:20144272)
• Our results show an obvious association between the D repeat polymorphism of ASPN and Developmental dysplasia of the hip (PMID:21329514)
• ASPN plays positive roles in the mineralization of dental pulp stem cells and predentin to dentin. (PMID:21413025)
• Data indicate that the expression of ASPN gene is finely regulated in cartilage and suggest a major role of Sp1. (PMID:21528154)
• mir-101 and mir-21 target PLAP-1 to regulate its expression during osteogenic differentiation of PDLCs. (PMID:22367347)
• Asporin is associated with hand osteoarthritis progression. (PMID:23357225)
• polymorphisms within the ASPN gene could influence knee osteoarthritis susceptibility (PMID:23733110)
• A meta-analysis suggest that the D-repeat of asporin gene (ASPN) may not be a major susceptibility locus in the Caucasian and Asian populations with knee osteoarthritis. (PMID:23942062)
• The asporin-encoding gene is a promising candidate as a susceptibility gene for osteoarthritis and degenerative disc disease. [Review] (PMID:24003854)
• Our data suggest that the D15 asporin allele could be considered a knee osteoarthritis risk allele significant only for women in the Iranian population. (PMID:24078942)
• This meta-analysis shows that the ASPN D14, D13, and D15 alleles are not associated with the development of osteoarthritis in Europeans and Asians. [Meta-Analysis] (PMID:24306268)
• Asporin may represent a new therapeutic target molecule for the development of drugs aimed at manipulating the cancer microenvironment. (PMID:24441039)
• D14-PLAP-1 suppressed BMP-2 signal transduction more efficiently than D13-PLAP-1; stronger affinity of D14-PLAP-1 protein to BMP-2 compared with D13-PLAP-1 protein. D repeat polymorphism of PLAP-1/asporin has influence on functions of PDL cells. (PMID:24453179)
• Our results showed that ASPN rs13301537 T to C change and variant C genotype may contribute to knee OA risk in a Chinese Han population. (PMID:25030405)
• Osteomodulin, osteoglycin, and asporin appear to be distinctly regulated in osteoarthritis labrum compared to OA cartilage. (PMID:25371314)
• Collectively, our findings indicate that ASPN is upregulated and plays an oncogenic role in gastric cancer progression and metastasis by influencing the EGFR signaling pathway. (PMID:25673058)
• this is the first case-control study in Mexican women that suggests that menopause and the D-repeat polymorphism in the ASPN gene are associated with knee OA (PMID:26016288)
• To test the associations of ASPN variations with risk of subsequent oncologic outcomes. (PMID:26446945)
• Suggest that the D14 allele of the ASPN polymorphism could exert an influence on primary osteoarthritis of the knee etiology in a Mexican Mestizo population. (PMID:26620055)
• we found that asporin can be downregulated by bone morphogenetic protein 4 in Hs578T cells and its upregulation may be facilited by serum-free cultivation or by three dimensional growth (PMID:27409832)
• higher expression of asporin was noticed in CRC tissues and it was correlated with later clinical stage of the patients. Asporin promoted the migration and invasion of the tumor cells partially through an EGFR/Src/cortactin- signaling pathway. (PMID:27705916)
• High ASPN expression in stroma is associated with prostate cancer progression. (PMID:28152543)
• Asporin promotes epithelial mesenchymal transformation, invasion, and migration of pancreatic cancer cellss by activating CD44-AKT/ERK-NF-kappaB pathway in paracrine and autocrine manner. (PMID:28400334)
• our study provides evidence that asporin is an important risk factor in intervertebral disc degeneration. The identification of the intrinsic expression mechanisms of asporin provides further understanding of disc degeneration. (PMID:28646230)
• ASPN D-repeat polymorphism is not associated with an increased Knee Osteoarthritis risk. (PMID:28889984)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	aspn	ENSDARG00000002192
mus_musculus	Aspn	ENSMUSG00000021388
rattus_norvegicus	Aspn	ENSRNOG00000015410

Paralogs (22): DCN (ENSG00000011465), RTN4R (ENSG00000040608), FLRT3 (ENSG00000125848), FLRT1 (ENSG00000126500), LRRC4 (ENSG00000128594), LRRC4B (ENSG00000131409), PODNL1 (ENSG00000132000), LRTM1 (ENSG00000144771), LRRC4C (ENSG00000148948), LRRTM1 (ENSG00000162951), LRRC15 (ENSG00000172061), PODN (ENSG00000174348), LRRTM4 (ENSG00000176204), BGN (ENSG00000182492), LRRC19 (ENSG00000184434), FLRT2 (ENSG00000185070), GP1BA (ENSG00000185245), RTN4RL1 (ENSG00000185924), RTN4RL2 (ENSG00000186907), NYX (ENSG00000188937), LRRC66 (ENSG00000188993), LRRTM3 (ENSG00000198739)

Protein

Protein identifiers

Asporin — Q9BXN1 (reviewed: Q9BXN1)

Alternative names: Periodontal ligament-associated protein 1

All UniProt accessions (4): Q9BXN1, A0A494C084, A0A494C1J0, Q5TBF2

UniProt curated annotations — full annotation on UniProt →

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. 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.

Subunit / interactions. Interacts with TGFB1, TGFB2 and TGFB3. DCN, BGN, and FMOD inhibit binding to TGFB1. Interacts with BMP2. Interacts in vitro with type II collagen. Interacts with type I collagen. DCN can inhibit collagen binding.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Higher levels in osteoarthritic articular cartilage, aorta, uterus. Moderate expression in small intestine, heart, liver, bladder, ovary, stomach, and in the adrenal, thyroid, and mammary glands. Low expression in trachea, bone marrow, and lung. Colocalizes with TGFB1 in chondrocytes within osteoarthritic (OA) lesions of articular cartilage.

Post-translational modifications. There is no serine/glycine dipeptide sequence expected for the attachment of O-linked glycosaminoglycans and this is probably not a proteoglycan. The O-linked polysaccharide on 54-Ser is probably the mucin type linked to GalNAc. The N-linked glycan at Asn-282 is composed of variable structures of GlcNAc, mannose, fucose, HexNAc and hexose.

Disease relevance. 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. Disease susceptibility is associated with variants 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. 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. Disease susceptibility is associated with variants 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.

Domain organisation. The LRR 5 repeat can inhibit BMP2-induced cytodifferentiation and may be involved in the interaction with BMP2. The repeats LRR 10, LRR 11 and LRR 12 are involved in binding type I collagen. The poly-Asp region is involved in binding calcium.

Induction. By TGFB1.

Polymorphism. The poly-Asp region of ASPN is polymorphic and ranges at least from 11 to 17 Asp.

Similarity. Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class I subfamily.

RefSeq proteins (2): NP_001180264, NP_060150* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000372	LRRNT	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR016352	SLRP_I_decor/aspor/byglycan	Family
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR050333	SLRP	Family

Pfam: PF01462, PF13855

UniProt features (24 total): repeat 11, disulfide bond 3, region of interest 2, glycosylation site 2, signal peptide 1, propeptide 1, compositionally biased region 1, chain 1, sequence conflict 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXN1-F1	85.71	0.77

Functional residue map

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

Disulfide bonds (3): 75–81, 79–88, 333–366

Glycosylation sites (2): 55, 282

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-3000178	ECM proteoglycans
R-HSA-1474244	Extracellular matrix organization

MSigDB gene sets: 173 (showing top): TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, MODULE_418, SMID_BREAST_CANCER_RELAPSE_IN_LUNG_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP, GOBP_TOOTH_MINERALIZATION, TURASHVILI_BREAST_CARCINOMA_DUCTAL_VS_LOBULAR_DN, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_BONE_MINERALIZATION, GOBP_REGULATION_OF_TRANSMEMBRANE_RECEPTOR_PROTEIN_SERINE_THREONINE_KINASE_SIGNALING_PATHWAY, NF1_Q6_01, GOBP_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_UP

GO Biological Process (5): bone mineralization (GO:0030282), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), negative regulation of tooth mineralization (GO:0070171), response to fluoride (GO:1902617), biomineral tissue development (GO:0031214)

GO Molecular Function (3): calcium ion binding (GO:0005509), protein binding (GO:0005515), extracellular matrix structural constituent conferring compression resistance (GO:0030021)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012), cell projection (GO:0042995), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Extracellular matrix organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
ossification	1
biomineral tissue development	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
tooth mineralization	1
negative regulation of biomineral tissue development	1
regulation of tooth mineralization	1
response to chemical	1
tissue development	1
animal organ development	1
metal ion binding	1
binding	1
extracellular matrix structural constituent	1
external encapsulating structure	1

Protein interactions and networks

STRING

2066 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ASPN	MATN3	O15232	934
ASPN	FRZB	Q92765	890
ASPN	CILP	O75339	843
ASPN	CTDSP2	O14595	840
ASPN	TGFB1	P01137	830
ASPN	HDAC11	Q96DB2	807
ASPN	GDF5	P43026	786
ASPN	GBA1	P04062	784
ASPN	COL11A1	P12107	739
ASPN	POSTN	Q15063	733
ASPN	CTRB2	Q6GPI1	726
ASPN	CTRB1	P17538	724
ASPN	COL9A3	Q14050	684
ASPN	THBS2	P35442	672
ASPN	COL2A1	P02458	658

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ASPN	ITIH2	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): ASPN (Positive Genetic), PSMD2 (Affinity Capture-Western), ASPN (Affinity Capture-Western), SELM (Affinity Capture-MS), ITIH2 (Affinity Capture-MS), ASPN (PCA), RPL37A (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: C0STK7, G5EFX6, G5EG78, O15455, O35103, O35367, O42235, O60938, O62702, O73798, O75094, O77742, O88280, O94813, P08953, P24014, P24348, P46023, Q04833, Q0PV50, Q3ZBN5, Q58A48, Q5RI43, Q5TJ59, Q65YW8, Q65Z91, Q6AXL3, Q6R5N8, Q6X0I2, Q8C031, Q8SXT3, Q965M2, Q99983, Q99MB1, Q99MQ4, Q9BXN1, Q9CQ76, Q9DE66, Q9HCJ2, Q9JI18

Diamond homologs: A3KNN3, A4IIW9, A6H789, A6H793, A6NJW4, A8WHP9, C3YZ59, E5DHB5, G5EFX6, O02678, O14498, O35367, O42235, O46542, O60938, O62702, O75093, O75094, O88186, O88279, O88280, O94813, P02750, P07585, P14770, P21793, P24014, P28654, P28675, P35379, P59034, P59035, P70193, P79763, Q01129, Q28888, Q29393, Q3SXY7, Q3UY51, Q3ZBN5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	22
Likely benign	4
Benign	7

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1073961	NC_000009.11:g.(?95007241)(95237179_?)del	Pathogenic
2425154	NC_000009.11:g.(?94485944)(95527026_?)del	Pathogenic

SpliceAI

1355 predictions. Top by Δscore:

Variant	Effect	Δscore
9:92470637:AAAT:A	donor_gain	1.0000
9:92470667:A:AC	donor_gain	1.0000
9:92470668:C:CC	donor_gain	1.0000
9:92482288:CATA:C	donor_loss	1.0000
9:92482289:ATAC:A	donor_loss	1.0000
9:92482290:TA:T	donor_loss	1.0000
9:92482291:ACC:A	donor_loss	1.0000
9:92459766:CCAGC:C	acceptor_gain	0.9900
9:92459767:CAGC:C	acceptor_gain	0.9900
9:92459767:CAGCC:C	acceptor_gain	0.9900
9:92459771:C:CA	acceptor_loss	0.9900
9:92459771:C:CC	acceptor_gain	0.9900
9:92459772:T:G	acceptor_loss	0.9900
9:92459780:A:C	acceptor_loss	0.9900
9:92460565:AGCC:A	acceptor_loss	0.9900
9:92460566:GCC:G	acceptor_loss	0.9900
9:92460567:CCTAA:C	acceptor_loss	0.9900
9:92460568:C:CC	acceptor_gain	0.9900
9:92460569:T:C	acceptor_loss	0.9900
9:92466475:G:C	donor_gain	0.9900
9:92466570:CC:C	acceptor_gain	0.9900
9:92466571:CC:C	acceptor_gain	0.9900
9:92466572:C:T	acceptor_gain	0.9900
9:92466573:T:C	acceptor_gain	0.9900
9:92466578:C:CT	acceptor_gain	0.9900
9:92466582:C:CT	acceptor_gain	0.9900
9:92466583:A:C	acceptor_gain	0.9900
9:92470638:A:C	donor_gain	0.9900
9:92470663:TCTTA:T	donor_loss	0.9900
9:92470664:CTTAC:C	donor_loss	0.9900

AlphaMissense

2534 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:92470730:A:G	L109P	1.000
9:92474634:G:C	C88W	1.000
9:92460543:A:G	L246P	0.999
9:92466416:A:C	N181K	0.999
9:92466416:A:T	N181K	0.999
9:92466432:A:G	L176P	0.999
9:92466495:A:G	L155P	0.999
9:92470720:A:C	N112K	0.999
9:92470720:A:T	N112K	0.999
9:92470721:T:A	N112I	0.999
9:92474635:C:G	C88S	0.999
9:92474635:C:T	C88Y	0.999
9:92474636:A:G	C88R	0.999
9:92474636:A:T	C88S	0.999
9:92474662:C:G	C79S	0.999
9:92474663:A:G	C79R	0.999
9:92474663:A:T	C79S	0.999
9:92466417:T:A	N181I	0.998
9:92466479:A:C	N160K	0.998
9:92466479:A:T	N160K	0.998
9:92466551:G:C	N136K	0.998
9:92466551:G:T	N136K	0.998
9:92466553:T:A	N136Y	0.998
9:92466561:A:G	L133P	0.998
9:92466567:A:G	L131P	0.998
9:92470722:T:A	N112Y	0.998
9:92470730:A:T	L109H	0.998
9:92474635:C:A	C88F	0.998
9:92474662:C:T	C79Y	0.998
9:92457335:A:G	C366R	0.997

dbSNP variants (sampled 300 via entrez): RS1000031047 (9:92479716 T>G), RS1000034795 (9:92480031 T>C), RS1000208110 (9:92479130 A>G), RS1000293279 (9:92464688 T>C), RS1000408994 (9:92465128 G>A,T), RS1000548718 (9:92474042 G>A), RS1000692010 (9:92467723 G>A), RS1001097233 (9:92481830 T>C), RS1001105763 (9:92477587 C>A), RS1001299956 (9:92470603 T>C), RS1001319110 (9:92473181 TG>T), RS1001351311 (9:92462817 C>T), RS1001372600 (9:92473543 C>G), RS1001400361 (9:92463656 G>A,C), RS1001425022 (9:92463210 T>C)

Disease associations

OMIM: gene MIM:608135 | disease phenotypes: MIM:615290, MIM:607850

GenCC curated gene-disease

Disease	Classification	Inheritance
osteoarthritis susceptibility 3	Limited	Autosomal dominant

Mondo (5): autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures (MONDO:0014121), hereditary sensory and autonomic neuropathy type 1 (MONDO:0018213), breast ductal adenocarcinoma (MONDO:0005590), osteoarthritis susceptibility 3 (MONDO:0011923), lumbar disk degeneration, susceptibility to (MONDO:0100206)

Orphanet (3): Autosomal dominant childhood-onset proximal spinal muscular atrophy (Orphanet:363447), BICD2-related autosomal dominant childhood-onset proximal spinal muscular atrophy (Orphanet:363454), Hereditary sensory and autonomic neuropathy type 1 (Orphanet:36386)

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001387	Joint stiffness
HP:0002758	Osteoarthritis
HP:0002829	Arthralgia
HP:0006226	Osteoarthritis of the first carpometacarpal joint
HP:0006233	Osteoarthritis of the distal interphalangeal joint

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010725_16	Malaria	9.000000e-06
GCST010725_28	Malaria	6.000000e-06
GCST010725_95	Malaria	6.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression	2
Estradiol	affects expression, affects cotreatment, decreases expression	2
Progesterone	affects cotreatment, decreases expression, increases expression	2
testosterone enanthate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
triadimefon	decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
incobotulinumtoxinA	increases expression	1
Calcitriol	decreases expression	1
Dexamethasone	affects cotreatment, increases expression, decreases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression, decreases expression	1
Valproic Acid	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT06113055	PHASE2	UNKNOWN	Hereditary Sensory Neuropathy Serine Trial
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT02134496	Not specified	COMPLETED	PACU Discharge Without Motorfunction Assessment After Spinal Anaesthesia
NCT01733407	PHASE1/PHASE2	COMPLETED	L-Serine Supplementation in Hereditary Sensory Neuropathy Type 1
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery