SMOC2

Summary

SMOC2 (SPARC related modular calcium binding 2, HGNC:20323) is a protein-coding gene on chromosome 6q27, encoding SPARC-related modular calcium-binding protein 2 (Q9H3U7). Promotes matrix assembly and cell adhesiveness.

This gene encodes a member of the SPARC family (secreted protein acidic and rich in cysteine/osteonectin/BM-40), which are highly expressed during embryogenesis and wound healing. The gene product is a matricellular protein which promotes matrix assembly and can stimulate endothelial cell proliferation and migration, as well as angiogenic activity. Associated with pulmonary function, this secretory gene product contains a Kazal domain, two thymoglobulin type-1 domains, and two EF-hand calcium-binding domains. The encoded protein may serve as a target for controlling angiogenesis in tumor growth and myocardial ischemia. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 64094 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dentin dysplasia type I (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 24
• Clinical variants (ClinVar): 198 total — 3 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 8
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001166412

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20323
Approved symbol	SMOC2
Name	SPARC related modular calcium binding 2
Location	6q27
Locus type	gene with protein product
Status	Approved
Aliases	SMAP2
Ensembl gene	ENSG00000112562
Ensembl biotype	protein_coding
OMIM	607223
Entrez	64094

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 15 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000354536, ENST00000356284, ENST00000392100, ENST00000417208, ENST00000477998, ENST00000908186, ENST00000908187, ENST00000908188, ENST00000908189, ENST00000908190, ENST00000908191, ENST00000908192, ENST00000908193, ENST00000960301, ENST00000960302, ENST00000960303, ENST00000960304

RefSeq mRNA: 2 — MANE Select: NM_001166412 NM_001166412, NM_022138

CCDS: CCDS5307, CCDS55076

Canonical transcript exons

ENST00000356284 — 13 exons

Exon	Start	End
ENSE00000000348	168441184	168441454
ENSE00000000349	168666421	168667992
ENSE00001010108	168543625	168543672
ENSE00001010111	168509915	168510086
ENSE00001010116	168526346	168526452
ENSE00001010118	168527628	168527727
ENSE00001010120	168652954	168653228
ENSE00001429100	168547119	168547169
ENSE00002431221	168549129	168549203
ENSE00002442742	168598818	168599004
ENSE00002445453	168608157	168608239
ENSE00002449814	168650681	168650783
ENSE00003614213	168664074	168664111

Expression profiles

Bgee: expression breadth ubiquitous, 228 present calls, max score 99.51.

FANTOM5 (CAGE): breadth broad, TPM avg 4.4658 / max 366.3765, expressed in 411 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71245	3.1482	347
71244	1.0001	269
71246	0.3174	117

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
descending thoracic aorta	UBERON:0002345	99.51	gold quality
thoracic aorta	UBERON:0001515	99.31	gold quality
ascending aorta	UBERON:0001496	99.29	gold quality
right coronary artery	UBERON:0001625	98.75	gold quality
left uterine tube	UBERON:0001303	98.53	gold quality
mucosa of stomach	UBERON:0001199	98.36	gold quality
gall bladder	UBERON:0002110	98.19	gold quality
body of uterus	UBERON:0009853	97.99	gold quality
aorta	UBERON:0000947	97.98	gold quality
left coronary artery	UBERON:0001626	97.86	gold quality
coronary artery	UBERON:0001621	97.74	gold quality
tibia	UBERON:0000979	97.53	gold quality
myometrium	UBERON:0001296	97.44	gold quality
right ovary	UBERON:0002118	97.31	gold quality
left ovary	UBERON:0002119	97.23	gold quality
popliteal artery	UBERON:0002250	97.02	gold quality
tibial artery	UBERON:0007610	97.01	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.62	gold quality
smooth muscle tissue	UBERON:0001135	96.37	gold quality
decidua	UBERON:0002450	96.29	gold quality
saphenous vein	UBERON:0007318	96.15	gold quality
fundus of stomach	UBERON:0001160	96.03	gold quality
pigmented layer of retina	UBERON:0001782	95.99	gold quality
parietal pleura	UBERON:0002400	95.95	gold quality
cauda epididymis	UBERON:0004360	95.80	gold quality
corpus epididymis	UBERON:0004359	95.48	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.40	gold quality
lower esophagus	UBERON:0013473	95.38	gold quality
right uterine tube	UBERON:0001302	95.24	gold quality
caput epididymis	UBERON:0004358	95.04	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-124263	yes	1014.21
E-GEOD-134144	yes	849.00
E-GEOD-125970	yes	208.17
E-GEOD-135922	yes	46.96
E-HCAD-11	yes	19.42
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, GLI1

miRNA regulators (miRDB)

136 targeting SMOC2, 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-513A-5P	100.00	69.77	2465
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 23)

• Although this study specifies rat, the authors studied and discussed the human gene in this study as well. (PMID:12031507)
• identification of gene, chromosome mapping (PMID:12741954)
• SMOC-2 is a novel angiogenic factor that potentiates angiogenic effects of growth factors (PMID:16774925)
• We tested association between SMOC2 polymorphisms and FEV(1) and FVC. SMOC2 might play an important role in the determination of FEV(1) and FVC (PMID:17204727)
• SMOC2 is a risk locus for generalized vitiligo and perhaps other autoimmune diseases (PMID:19890347)
• The variant rs13208776 in SMOC2 gene does not play a major role in increasing the risk of vitiligo in Jordanian Arab patients. (PMID:20965805)
• Homozygosity mapping and candidate prioritization identify mutations, missed by whole-exome sequencing, in SMOC2, causing major dental developmental defects (PMID:22152679)
• could not detect an association between SMOC2 gene and AMD. This study tests the candidacy of SMOC2 gene to the etiology of AMD (PMID:22964816)
• mutation in exon 8 of the SMOC2 gene linked to oligodontia (PMID:23317772)
• SMOC2 SNP may play a role in autoimmune thyroid disease susceptibility as a dominant polymorphism. (PMID:23463390)
• L1-mediated CRC progression involves the acquisition of a stem cell-like phenotype, and that SMOC-2 elevation is necessary for L1-mediated induction of more aggressive/invasive CRC properties. (PMID:25915847)
• The expression of Smoc2 was significantly higher in hepatocellular carcinoma (HCC) tissues compared with corresponding non-tumor liver tissues. Smoc2 promotes the proliferation of HCC cells through accelerating cell cycle progression. (PMID:28018113)
• SMOC2 was highly expressed in both peritoneal and endometrioma lesions. Considering that the genes studied participate either directly or indirectly in cellular processes that can lead to cell migration, angiogenesis, and inappropriate invasion, it is possible that the deregulation of these genes caused the development and maintenance of ectopic tissue. (PMID:28678915)
• SMOC2 can act as an inhibitor of mineralization; there is a possible role for SMOC2 to prevent calcification disorders. (PMID:29897942)
• SMOC2 expression was markedly up-regulated in human liver samples with non-alcoholic fatty liver disease. (PMID:30581002)
• we conclude that SMOC-2 might be a novel endometrial cancer stem cell signature gene and therapeutic target for endometrial cancer. (PMID:30594556)
• Downregulation of SMOC2 expression in papillary thyroid carcinoma and its prognostic significance. (PMID:32184420)
• SMOC2, an intestinal stem cell marker, is an independent prognostic marker associated with better survival in colorectal cancers. (PMID:32884102)
• The Intestinal Stem Cell Marker SMOC2 Is an Independent Prognostic Marker Associated With Better Survival in Gastric Cancer. (PMID:34230168)
• Prognostic and clinicopathological significance of TMEFF2, SMOC-2, and SOX17 expression in endometrial carcinoma. (PMID:34339705)
• MicroRNA-19a-3p Acts as an Oncogene in Gastric Cancer and Exerts the Effect by Targeting SMOC2. (PMID:35543855)
• SMOC2 promotes an epithelial-mesenchymal transition and a pro-metastatic phenotype in epithelial cells of renal cell carcinoma origin. (PMID:35869056)
• FTO Positively Regulates Odontoblastic Differentiation via SMOC2 in Human Stem Cells from the Apical Papilla under Inflammatory Microenvironment. (PMID:38612855)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	smoc2	ENSDARG00000088157
mus_musculus	Smoc2	ENSMUSG00000023886
rattus_norvegicus	Smoc2	ENSRNOG00000014166
drosophila_melanogaster	magu	FBGN0262169
caenorhabditis_elegans		WBGENE00011437

Paralogs (1): SMOC1 (ENSG00000198732)

Protein

Protein identifiers

SPARC-related modular calcium-binding protein 2 — Q9H3U7 (reviewed: Q9H3U7)

Alternative names: Secreted modular calcium-binding protein 2, Smooth muscle-associated protein 2

All UniProt accessions (3): Q9H3U7, H0Y3J4, H0Y5I1

UniProt curated annotations — full annotation on UniProt →

Function. Promotes matrix assembly and cell adhesiveness. Can stimulate endothelial cell proliferation, migration, as well as angiogenesis.

Subunit / interactions. Binds various proteins from the extracellular matrix.

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Basement membrane.

Disease relevance. Dentin dysplasia 1 (DTDP1) [MIM:125400] A dental defect in which both primary and secondary dentitions are affected. The clinical crowns of both permanent and deciduous teeth are of normal shape, form and color in most cases, although they may be slightly opalescent and blue or brown. Teeth may be very mobile and exfoliate spontaneously because of inadequate root formation. On radiographs, the roots are short and may be more pointed than normal. Pulp chambers are usually absent except for a chevron-shaped remnant in the crown. Root canals are usually absent. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H3U7-1	1, Smap2	yes
Q9H3U7-2	2, Smap2b

RefSeq proteins (2): NP_001159884, NP_071421 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000716	Thyroglobulin_1	Domain
IPR002048	EF_hand_dom	Domain
IPR002350	Kazal_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR019577	SPARC/Testican_Ca-bd-dom	Domain
IPR036058	Kazal_dom_sf	Homologous_superfamily
IPR036857	Thyroglobulin_1_sf	Homologous_superfamily
IPR037640	SMOC2_EC	Domain
IPR051950	Dev_reg/Prot_inhib	Family

Pfam: PF00086, PF07648, PF10591, PF16597

UniProt features (38 total): binding site 10, disulfide bond 9, domain 5, sequence conflict 4, compositionally biased region 3, glycosylation site 2, region of interest 2, signal peptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H3U7-F1	73.88	0.17

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 (10): 360; 362; 364; 366; 371; 397; 399; 401; 403; 408

Disulfide bonds (9): 40–71, 44–64, 53–84, 90–113, 124–131, 133–153, 216–240, 251–258, 260–281

Glycosylation sites (2): 206, 362

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 468 (showing top): GCACCTT_MIR18A_MIR18B, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, YAATNRNNNYNATT_UNKNOWN, BENPORATH_ES_WITH_H3K27ME3, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, MYOGENIN_Q6, ZHAN_MULTIPLE_MYELOMA_PR_DN, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_ENDOTHELIAL_CELL_CHEMOTAXIS, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_CELL_CHEMOTAXIS, TGCACTT_MIR519C_MIR519B_MIR519A, GCANCTGNY_MYOD_Q6, TTTGTAG_MIR520D, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN

GO Biological Process (9): positive regulation of endothelial cell migration (GO:0010595), extracellular matrix organization (GO:0030198), positive regulation of vascular wound healing (GO:0035470), positive regulation of fibroblast growth factor receptor signaling pathway (GO:0045743), positive regulation of angiogenesis (GO:0045766), positive regulation of mitotic cell cycle (GO:0045931), positive regulation of vascular endothelial growth factor signaling pathway (GO:1900748), positive regulation of DNA biosynthetic process (GO:2000573), positive regulation of endothelial cell chemotaxis (GO:2001028)

GO Molecular Function (5): calcium ion binding (GO:0005509), heparin binding (GO:0008201), extracellular matrix binding (GO:0050840), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): basement membrane (GO:0005604), obsolete extracellular space (GO:0005615), cell periphery (GO:0071944), extracellular region (GO:0005576), obsolete collagen-containing extracellular matrix (GO:0062023)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of signal transduction	2
binding	2
cellular anatomical structure	2
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
extracellular structure organization	1
external encapsulating structure organization	1
positive regulation of angiogenesis	1
vascular wound healing	1
regulation of vascular wound healing	1
positive regulation of wound healing	1
fibroblast growth factor receptor signaling pathway	1
regulation of fibroblast growth factor receptor signaling pathway	1
angiogenesis	1
regulation of angiogenesis	1
positive regulation of vasculature development	1
mitotic cell cycle	1
regulation of mitotic cell cycle	1
positive regulation of cell cycle	1
vascular endothelial growth factor signaling pathway	1
regulation of vascular endothelial growth factor signaling pathway	1
positive regulation of macromolecule biosynthetic process	1
positive regulation of DNA metabolic process	1
DNA biosynthetic process	1
regulation of DNA biosynthetic process	1
positive regulation of endothelial cell migration	1
endothelial cell chemotaxis	1
positive regulation of chemotaxis	1
regulation of endothelial cell chemotaxis	1
metal ion binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
cation binding	1
extracellular matrix	1

Protein interactions and networks

STRING

1436 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMOC2	OLFM4	Q6UX06	592
SMOC2	ASCL2	Q99929	585
SMOC2	LGR5	O75473	566
SMOC2	TDRP	Q86YL5	534
SMOC2	LRIG1	Q96JA1	523
SMOC2	STMND1	H3BQB6	512
SMOC2	WDR27	A2RRH5	511
SMOC2	SPARC	P09486	510
SMOC2	FRMD1	Q8N878	501
SMOC2	DYNLT2	Q8IZS6	499
SMOC2	DACT2	Q5SW24	493
SMOC2	FBXO38	Q6PIJ6	490
SMOC2	CABP2	Q9NPB3	487
SMOC2	FST	P19883	472
SMOC2	FZD6	O60353	469

IntAct

4 interactions, top by confidence:

A	B	Type	Score
KRTAP5-1	SMOC2	psi-mi:“MI:0915”(physical association)	0.560
SMOC2	KRTAP5-1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): SMOC2 (Affinity Capture-RNA), SMOC2 (Biochemical Activity), KRTAP5-1 (Two-hybrid), SMOC2 (Reconstituted Complex), SMOC2 (Proximity Label-MS), SMOC2 (Reconstituted Complex), SMOC2 (Cross-Linking-MS (XL-MS)), SMOC2 (Affinity Capture-RNA), SMOC2 (Affinity Capture-MS)

ESM2 similar proteins: A2BD09, A3KNS2, A5GFQ5, P15943, P24338, Q01580, Q06175, Q06186, Q06335, Q06481, Q08AE8, Q08DX0, Q09118, Q0P5N1, Q0VCT2, Q0VDN7, Q13438, Q2L6K8, Q3MHX6, Q3SWX1, Q58D79, Q58T08, Q5HZV5, Q5MJS3, Q5RKH6, Q68BL7, Q6GN40, Q701R2, Q86VZ4, Q8BHP7, Q8BQ47, Q8CB67, Q8CD91, Q8K2C7, Q8N129, Q8TEQ0, Q92563, Q96C34, Q96KC8, Q99075

Diamond homologs: A0A1D0C023, B3F211, B5DFC9, P04233, P04441, P10247, P10493, P31226, P81439, P84032, Q08629, Q14112, Q62288, Q8BKV0, Q8BLY1, Q8CD91, Q92563, Q9ER58, Q9H3U7, Q9H4F8, A2ASQ1, A5YT95, O00468, O62650, O93390, O95633, P07214, P09486, P10669, P13213, P16975, P19883, P20112, P21674, P23499, P24054, P25304, P31514, P31515, P31696

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	108
Likely benign	27
Benign	41

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
225685	NM_001166412.2(SMOC2):c.648T>A (p.Cys216Ter)	Pathogenic
2871699	NM_001166412.2(SMOC2):c.13C>T (p.Gln5Ter)	Pathogenic
30657	NM_001166412.2(SMOC2):c.84+1G>T	Pathogenic
432362	NM_001166412.2(SMOC2):c.1122del (p.Phe375fs)	Likely pathogenic

SpliceAI

4210 predictions. Top by Δscore:

Variant	Effect	Δscore
6:168507611:G:GT	donor_gain	1.0000
6:168509913:A:G	acceptor_gain	1.0000
6:168510083:AAAGG:A	donor_loss	1.0000
6:168510084:AAGG:A	donor_loss	1.0000
6:168510085:AGGT:A	donor_loss	1.0000
6:168510087:GT:G	donor_loss	1.0000
6:168510088:T:G	donor_loss	1.0000
6:168526344:A:AG	acceptor_gain	1.0000
6:168526345:G:GG	acceptor_gain	1.0000
6:168526345:GAC:G	acceptor_gain	1.0000
6:168526448:G:GG	donor_gain	1.0000
6:168526471:G:T	donor_gain	1.0000
6:168527623:CGCA:C	acceptor_loss	1.0000
6:168527624:GCA:G	acceptor_loss	1.0000
6:168527625:CA:C	acceptor_loss	1.0000
6:168527626:A:AG	acceptor_gain	1.0000
6:168527626:A:G	acceptor_loss	1.0000
6:168527627:G:GG	acceptor_gain	1.0000
6:168543619:TTTTA:T	acceptor_loss	1.0000
6:168543620:TTTA:T	acceptor_loss	1.0000
6:168543621:TTA:T	acceptor_loss	1.0000
6:168543622:TAG:T	acceptor_loss	1.0000
6:168543623:A:AG	acceptor_gain	1.0000
6:168543623:AGGTT:A	acceptor_loss	1.0000
6:168543624:G:GA	acceptor_loss	1.0000
6:168543624:G:GG	acceptor_gain	1.0000
6:168547110:T:TA	acceptor_gain	1.0000
6:168547170:G:C	donor_loss	1.0000
6:168547171:T:A	donor_loss	1.0000
6:168549115:ATTTT:A	acceptor_gain	1.0000

AlphaMissense

2920 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:168509987:T:A	C53S	1.000
6:168509987:T:C	C53R	1.000
6:168509988:G:C	C53S	1.000
6:168526357:T:A	C90S	1.000
6:168526357:T:C	C90R	1.000
6:168526358:G:A	C90Y	1.000
6:168526358:G:C	C90S	1.000
6:168526359:T:G	C90W	1.000
6:168526414:T:C	F109L	1.000
6:168526415:T:G	F109C	1.000
6:168526416:C:A	F109L	1.000
6:168526416:C:G	F109L	1.000
6:168526421:C:A	P111H	1.000
6:168526426:T:A	C113S	1.000
6:168526426:T:C	C113R	1.000
6:168526427:G:A	C113Y	1.000
6:168526427:G:C	C113S	1.000
6:168526428:C:G	C113W	1.000
6:168527634:T:A	C124S	1.000
6:168527635:G:C	C124S	1.000
6:168527655:T:C	C131R	1.000
6:168527657:C:G	C131W	1.000
6:168527658:T:A	W132R	1.000
6:168527658:T:C	W132R	1.000
6:168527660:G:C	W132C	1.000
6:168527660:G:T	W132C	1.000
6:168527661:T:A	C133S	1.000
6:168527661:T:C	C133R	1.000
6:168527662:G:C	C133S	1.000
6:168527663:C:G	C133W	1.000

dbSNP variants (sampled 300 via entrez): RS1000006439 (6:168478127 A>G), RS1000031663 (6:168461394 A>G), RS1000036237 (6:168518339 G>A), RS1000061635 (6:168483298 A>T), RS1000093872 (6:168482896 A>G), RS1000125539 (6:168666719 G>A,C), RS1000128845 (6:168470275 G>A), RS1000134066 (6:168624438 A>G), RS1000136769 (6:168532295 A>G,T), RS1000138866 (6:168519073 A>G), RS1000165815 (6:168473745 T>A), RS1000172262 (6:168450673 C>G), RS1000184580 (6:168445265 G>A), RS1000207433 (6:168560263 A>C), RS1000228855 (6:168508277 C>T)

Disease associations

OMIM: gene MIM:607223 | disease phenotypes: MIM:125400, MIM:181500

GenCC curated gene-disease

Disease	Classification	Inheritance
dentin dysplasia type I	Strong	Autosomal recessive
atypical dentin dysplasia due to SMOC2 deficiency	Strong	Autosomal recessive

Mondo (3): dentin dysplasia type I (MONDO:0007436), schizophrenia (MONDO:0005090), atypical dentin dysplasia due to SMOC2 deficiency (MONDO:0017819)

Orphanet (3): Atypical dentin dysplasia due to SMOC2 deficiency (Orphanet:314721), Dentin dysplasia type I (Orphanet:99789), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

8 total (9 of 8 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000677	Oligodontia
HP:0000679	Taurodontia
HP:0000691	Microdontia
HP:0000700	Periapical bone loss
HP:0006297	Enamel hypoplasia
HP:0006336	Short dental root
HP:0006350	Pulp obliteration
HP:0100753	Schizophrenia

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST000520_2	Vitiligo	9.000000e-08
GCST002938_39	Copper levels	8.000000e-06
GCST003771_1	Loneliness	3.000000e-06
GCST006629_58	Pulse pressure	2.000000e-09
GCST006631_47	Nicotine dependence and major depression (severity of comorbidity)	6.000000e-06
GCST007096_141	Pulse pressure	1.000000e-23
GCST007097_153	Pulse pressure	3.000000e-10
GCST007097_154	Pulse pressure	8.000000e-11
GCST007157_2	Corneal astigmatism	1.000000e-06
GCST008839_603	Height	5.000000e-10
GCST009532_20	Circulating leptin levels in high cardiovascular risk	2.000000e-06
GCST010653_12	Thyroid stimulating hormone levels	1.000000e-11
GCST012226_689	Waist circumference adjusted for body mass index	5.000000e-12
GCST012226_690	Waist circumference adjusted for body mass index	6.000000e-17
GCST012226_691	Waist circumference adjusted for body mass index	6.000000e-09
GCST012226_692	Waist circumference adjusted for body mass index	4.000000e-08
GCST012226_708	Waist circumference adjusted for body mass index	2.000000e-12
GCST012226_709	Waist circumference adjusted for body mass index	3.000000e-08
GCST90007003_7	Gut microbiota relative abundance (Ruminococcus belonging to family Lachnospiraceae)	3.000000e-06
GCST90020028_114	Hip circumference adjusted for BMI	1.000000e-09
GCST90020028_115	Hip circumference adjusted for BMI	2.000000e-14
GCST90020028_116	Hip circumference adjusted for BMI	3.000000e-09
GCST90020029_1456	Waist circumference adjusted for body mass index	4.000000e-09
GCST90020029_1457	Waist circumference adjusted for body mass index	2.000000e-08

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0007865	loneliness measurement
EFO:0005763	pulse pressure measurement
EFO:0007006	depressive symptom measurement
EFO:0009262	nicotine dependence symptom count
EFO:1002040	Corneal astigmatism
EFO:0005000	leptin measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007874	gut microbiome measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C538215	Dentin dysplasia, type 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

44 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, increases methylation, affects cotreatment	7
sodium arsenite	decreases expression, increases expression, affects methylation	4
Estradiol	decreases reaction, increases expression, affects cotreatment, decreases expression	4
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases methylation	3
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
bisphenol S	increases expression, affects cotreatment, decreases methylation	2
Dexamethasone	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cadmium Chloride	increases expression	2
bisphenol F	affects cotreatment, increases expression	1
sotorasib	affects cotreatment, increases expression	1
bisphenol A	affects cotreatment, increases expression	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases abundance, increases methylation	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	affects methylation	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
trametinib	affects cotreatment, increases expression	1
NVP-BKM120	increases expression, affects cotreatment	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Vorinostat	decreases expression	1
Panobinostat	affects cotreatment, increases expression	1
Cytarabine	decreases expression	1
Dietary Carbohydrates	increases expression	1
Diethylhexyl Phthalate	increases abundance, increases methylation	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A7JF	SDUBMSi011-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety