SFRP5

Summary

SFRP5 (secreted frizzled related protein 5, HGNC:10779) is a protein-coding gene on chromosome 10q24.2, encoding Secreted frizzled-related protein 5 (Q5T4F7). Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts.

Secreted frizzled-related protein 5 (SFRP5) is a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs act as soluble modulators of Wnt signaling. SFRP5 and SFRP1 may be involved in determining the polarity of photoreceptor cells in the retina. SFRP5 is highly expressed in the retinal pigment epithelium, and moderately expressed in the pancreas.

Source: NCBI Gene 6425 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 67 total
• MANE Select transcript: NM_003015

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10779
Approved symbol	SFRP5
Name	secreted frizzled related protein 5
Location	10q24.2
Locus type	gene with protein product
Status	Approved
Aliases	SARP3
Ensembl gene	ENSG00000120057
Ensembl biotype	protein_coding
OMIM	604158
Entrez	6425

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000266066

RefSeq mRNA: 1 — MANE Select: NM_003015 NM_003015

CCDS: CCDS7472

Canonical transcript exons

ENST00000266066 — 3 exons

Exon	Start	End
ENSE00000987201	97769668	97769745
ENSE00001097768	97766751	97767860
ENSE00001097769	97771305	97771999

Expression profiles

Bgee: expression breadth ubiquitous, 188 present calls, max score 98.95.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3403 / max 208.0431, expressed in 239 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
110951	0.9939	200
110950	0.3463	116

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	98.95	gold quality
tibial nerve	UBERON:0001323	97.87	gold quality
body of pancreas	UBERON:0001150	96.41	gold quality
sural nerve	UBERON:0015488	93.98	gold quality
right atrium auricular region	UBERON:0006631	93.47	gold quality
cardiac atrium	UBERON:0002081	92.66	gold quality
pancreas	UBERON:0001264	88.82	gold quality
cardiac muscle of right atrium	UBERON:0003379	87.55	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.20	gold quality
olfactory bulb	UBERON:0002264	86.90	gold quality
cartilage tissue	UBERON:0002418	86.19	gold quality
duodenum	UBERON:0002114	85.91	gold quality
myocardium	UBERON:0002349	85.74	gold quality
triceps brachii	UBERON:0001509	85.14	gold quality
trigeminal ganglion	UBERON:0001675	84.84	gold quality
gluteal muscle	UBERON:0002000	83.37	gold quality
lower esophagus muscularis layer	UBERON:0035833	82.27	gold quality
lower esophagus	UBERON:0013473	82.16	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.77	gold quality
small intestine	UBERON:0002108	81.54	gold quality
dorsal root ganglion	UBERON:0000044	80.85	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	80.57	silver quality
esophagogastric junction muscularis propria	UBERON:0035841	80.19	gold quality
choroid plexus epithelium	UBERON:0003911	80.10	gold quality
tibia	UBERON:0000979	79.92	gold quality
tongue squamous epithelium	UBERON:0006919	79.25	gold quality
inferior olivary complex	UBERON:0002127	78.93	silver quality
diaphragm	UBERON:0001103	77.45	gold quality
intestine	UBERON:0000160	77.42	gold quality
jejunal mucosa	UBERON:0000399	77.41	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	815.18
E-MTAB-10553	yes	19.70
E-GEOD-135922	yes	18.78
E-HCAD-9	yes	8.12
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CLDN19, CLDN3, DNMT1, DNMT3A, DNMT3B

miRNA regulators (miRDB)

38 targeting SFRP5, 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-196A-1-3P	99.99	72.15	2772
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-6513-5P	99.43	67.81	1071
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-4703-5P	98.53	70.13	1645
HSA-MIR-3942-5P	98.52	69.51	1517
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-6728-5P	97.79	66.33	891
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-450B-3P	97.56	66.12	512
HSA-MIR-6865-3P	97.54	64.67	684

Literature-anchored findings (GeneRIF, showing 40)

• The SFRP5 protein gene plays an important role in the pathogenesis of bladder tumor and can be detected using cellular DNA extracted from urine samples. (PMID:16609023)
• In its role as tumor suppressor gene. SFRP5 methylation may be a novel DNA-based biomarker potentially useful in clinical breast cancer management. (PMID:18356147)
• Loss of SFRP5 is associated with oral squamous cell carcinoma (PMID:18497987)
• Hypermethylation and aberrant expression of SFRP genes are common in pancreatic cancer, which may be involved in pancreatic carcinogenesis. (PMID:18528941)
• Ectopic expression of SFRPs downregulated T-cell factor transcriptional activity in liver cancer cells, while overexpression of a beta-catenin mutant and depletion of SFRP1 using siRNA synergistically upregulated TCF/LEF transcriptional activity. (PMID:18592156)
• SFRP5 promoter hypermethylation was significantly more frequent in microsatellite unstable colorectal neoplasms. (PMID:18795670)
• In multiple myeloma cell lines, hypermethylation of SFRP5 was associated with transcriptional silencing. SFRP5 methylation was restricted to advanced MM stages & plasma-cell leukemia and may play a role in disease progression. (PMID:19299079)
• SFRP5 is downregulated and inversely correlated with MMP-7 and MT1-MMP in gastric cancer (PMID:19586554)
• data suggested that epigenetic silencing of SFRP5 leads to oncogenic activation of the Wnt pathway and contributes to ovarian cancer progression and chemoresistance through the TWIST-mediated EMT and AKT2 signaling (PMID:19957335)
• Promoter hypermethylation of SFRP5 is associated with Acute myeloid leukemia. (PMID:20795789)
• This study suggests that a cause of catenin delocalization in oral cancer could be due to WNT pathway activation, by epigenetic alterations of SFRP-1, SFRP-2, SFRP-4, SFRP-5, WIF-1, DKK-3 genes (PMID:20811686)
• significant decrease in the expression of SFRP1 and SFRP5 was observed in gastric cancer compared with corresponding normal gastric tissues (PMID:21830441)
• Pro-inflammatory wnt5a and anti-inflammatory sFRP5 are differentially regulated by nutritional factors in obese human subjects (PMID:22384249)
• Patients with unmethylated SFRP5 are more likely to benefit from EGFR-TKI therapy. (PMID:23009178)
• findings suggest that epithelium-derived SFRP5 may play a probable defensive role in impeding gastric cancer progression, characteristically by inhibiting GEC migration induced by macrophage-derived Wnt5a via JNK signaling activation (PMID:23054609)
• Circulating Sfrp5 is likely to play a major role in insulin resistance in humans. (PMID:23185036)
• Concomitant epigenetic silencing of SOX1 and SFRPs through promoter hypermethylation is frequent in hepatocellular carcinoma, and this might contribute to abnormal activation of canonical Wnt signal pathway. (PMID:23215838)
• Plasma levels of SFRP5 were decreased in Chinese obese and T2DM subjects. SFRP5 was an independent factor affecting glucolipid metabolism, inflammation and insulin resistance. (PMID:23290274)
• Sfrp5 may play a role in the pathogenesis of T2 Diabetes mellitus. (PMID:23653377)
• We were able to show a significant association of sFRP5 with both total abdominal and subcutaneous fat. The association signal was only seen in obese males in which the minor allele of rs7072751 explains 1.8 % of variance in total abdominal fat. (PMID:24287795)
• Serum SFRP5 is regulated by weight status and seems to be correlated with metabolic disorders in children. (PMID:24330025)
• Epigenetic silencing of SFRP5 by hepatitis B virus X protein enhances hepatoma cell tumorigenicity through Wnt signaling pathway (PMID:24374650)
• Wnt5a overproduction and SFRP5 deficiency in gastric mucosa may together play an important role in gastric inflammation and carcinogenesis. (PMID:24416340)
• SFRP5 gene methylation in leukemia cells activates Wnt/ss-catenin signaling to upregulate mdr1/P-gp expression and cause multidrug resistance. (PMID:24434572)
• Therefore, cytokine release and insulin signaling were analyzed to investigate the impact of Sfrp5 on inflammation and insulin signaling in primary human adipocytes and skeletal muscle cells (hSkMC). (PMID:24465779)
• Serum SFRP5 levels significantly correlated with body mass index, the homeostasis model of assessment of insulin resistance, adiponectin levels, and CAD severity. Low SFRP5 levels may contribute to CAD. (PMID:24530778)
• SFRP5 and WNT5A comprise a balanced duo that may regulate metabolic homeostasis in prepubertal children. (PMID:24603290)
• Secreted frizzled-related protein 5 suppresses inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes through down-regulation of c-Jun N-terminal kinase. (PMID:24764263)
• This review article focuses on the effects of SFRP5 on the major systems of the body and on its association with the Wnt signaling pathways–{review} (PMID:25003224)
• Serum WISP2 correlated directly with fatty acid binding protein 4. Serum SFRP5 did not differ between obese (n=32) vs. nonobese (n=25) PCOS women, but reference women had lower SFRP5 (p<5x10(-6) as compared to both PCOS groups). (PMID:25089371)
• Aberrant methylation of APC gene was statistically significant associated with age over 50, DDK3 with male, SFRP4, WIF1, and WNT5a with increasing tumor stage SFRP4 and WIF1 with tumor differentiation and SFRP2 and SFRP5 with histological type (PMID:25107489)
• Data suggest that serum SFRP5 levels are up-regulated in subjects with newly diagnosed type 2 diabetes as compared to prediabetic or control subjects; subjects were matched for obesity/overweight/body mass index. (PMID:25139699)
• Sfrp5 represents a candidate for a mature adipocyte marker gene. (PMID:25324487)
• The wnt5a/sFRP5 system is altered in human sepsis and might therefore be of interest for future studies on molecular pathophysiology of this common human disease. (PMID:25382802)
• Decreased first trimester serum Sfrp-5 levels are significantly associated with the increased risk of gestational diabetes mellitus. (PMID:26100762)
• Report reduced hepatic SFRP5 expression in morbidly women with NAFLD. (PMID:26256895)
• The inverse association of serum Sfrp5 with beta-cell function suggests a detrimental role of Sfrp5 for insulin secretion also in humans. The severity of NAFLD does not appear to affect this relationship. The weak association between serum Sfrp5 and insulin sensitivity was partially explained by body mass. (PMID:27019073)
• Results identify several coding and non-coding variants in the sFRP5 gene region, the majority of which resulted in a non-synonymous amino acid change in the protein. One of the variants (c.-3G[A) shows a trend towards association between the variant frequency and the obese phenotype. (PMID:27497818)
• Results indicate that miR-125b can regulate SFRP5 expression and thus influence the growth and activation of cardiac fibroblasts. (PMID:27592695)
• serum concentration correlated with blood pressure in obese children and increased in response to lifestyle intervention (PMID:27882931)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	sfrp5	ENSDARG00000039041
mus_musculus	Sfrp5	ENSMUSG00000018822
rattus_norvegicus	Sfrp5	ENSRNOG00000014940
drosophila_melanogaster	fz3	FBGN0027343

Paralogs (15): FZD3 (ENSG00000104290), SFRP1 (ENSG00000104332), SFRP4 (ENSG00000106483), FZD10 (ENSG00000111432), SMO (ENSG00000128602), SFRP2 (ENSG00000145423), FZD7 (ENSG00000155760), FZD1 (ENSG00000157240), FRZB (ENSG00000162998), FZD5 (ENSG00000163251), FZD6 (ENSG00000164930), FZD4 (ENSG00000174804), FZD8 (ENSG00000177283), FZD2 (ENSG00000180340), FZD9 (ENSG00000188763)

Protein

Protein identifiers

Secreted frizzled-related protein 5 — Q5T4F7 (reviewed: Q5T4F7)

Alternative names: Frizzled-related protein 1b, Secreted apoptosis-related protein 3

All UniProt accessions (1): Q5T4F7

UniProt curated annotations — full annotation on UniProt →

Function. Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types. SFRP5 may be involved in determining the polarity of photoreceptor, and perhaps, other cells in the retina.

Subcellular location. Secreted.

Tissue specificity. Highly expressed in the retinal pigment epithelium (RPE) and pancreas. Weak expression in heart, liver and muscle.

Domain organisation. The FZ domain is involved in binding with Wnt ligands.

Similarity. Belongs to the secreted frizzled-related protein (sFRP) family.

RefSeq proteins (1): NP_003006* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001134	Netrin_domain	Domain
IPR008993	TIMP-like_OB-fold	Homologous_superfamily
IPR015526	Frizzled/SFRP	Family
IPR018933	Netrin_module_non-TIMP	Domain
IPR020067	Frizzled_dom	Domain
IPR036790	Frizzled_dom_sf	Homologous_superfamily
IPR041761	SFRP5_CRD	Domain

Pfam: PF01392, PF01759

UniProt features (14 total): disulfide bond 8, domain 2, signal peptide 1, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T4F7-F1	81.73	0.63

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 (8): 184–255, 198–303, 53–116, 63–109, 100–135, 124–162, 128–152, 181–253

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 119 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_NON_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_REGULATION_OF_NON_CANONICAL_WNT_SIGNALING_PATHWAY, SCHLESINGER_METHYLATED_DE_NOVO_IN_CANCER, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GTGCCTT_MIR506, GOBP_DIGESTIVE_SYSTEM_DEVELOPMENT, OHM_METHYLATED_IN_ADULT_CANCERS, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GATA6_01, GOBP_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION

GO Biological Process (16): regulation of transcription by RNA polymerase II (GO:0006357), apoptotic process (GO:0006915), establishment or maintenance of cell polarity (GO:0007163), signal transduction (GO:0007165), visual perception (GO:0007601), negative regulation of cell population proliferation (GO:0008285), anatomical structure morphogenesis (GO:0009653), cell differentiation (GO:0030154), negative regulation of Wnt signaling pathway (GO:0030178), non-canonical Wnt signaling pathway (GO:0035567), digestive tract morphogenesis (GO:0048546), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), canonical Wnt signaling pathway (GO:0060070), negative regulation of canonical Wnt signaling pathway (GO:0090090), negative regulation of non-canonical Wnt signaling pathway (GO:2000051), Wnt signaling pathway (GO:0016055)

GO Molecular Function (2): Wnt-protein binding (GO:0017147), protein binding (GO:0005515)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
Wnt signaling pathway	3
cellular process	2
negative regulation of Wnt signaling pathway	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
sensory perception of light stimulus	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
developmental process	1
anatomical structure development	1
cellular developmental process	1
negative regulation of signal transduction	1
regulation of Wnt signaling pathway	1
tube morphogenesis	1
digestive tract development	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
negative regulation of intracellular signal transduction	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
non-canonical Wnt signaling pathway	1
regulation of non-canonical Wnt signaling pathway	1
cell surface receptor signaling pathway	1
protein binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1044 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SFRP5	WNT11	O96014	910
SFRP5	WNT8B	Q93098	849
SFRP5	ANKRD42	Q8N9B4	834
SFRP5	WNT5A	P41221	782
SFRP5	CTNNB1	P35222	768
SFRP5	WIF1	Q9Y5W5	704
SFRP5	AXIN2	Q9Y2T1	682
SFRP5	WNT10B	O00744	676
SFRP5	WNT3A	P56704	662
SFRP5	LRP5	O75197	660
SFRP5	DKK3	Q9UBP4	659
SFRP5	WNT5B	Q9H1J7	655
SFRP5	LCN1	P31025	639
SFRP5	DKK1	O94907	614
SFRP5	WNT2	P09544	609

IntAct

0 interactions, top by confidence:

BioGRID (4): SFRP5 (Two-hybrid), SFRP5 (Affinity Capture-Western), SFRP5 (Affinity Capture-Western), SFRP5 (Affinity Capture-Western)

ESM2 similar proteins: A0A0D3QS98, A0A0D3QS99, A2A5I3, O19010, O19011, O42596, P01137, P04202, P04629, P07200, P09533, P16562, P17246, P18341, P35739, P50414, P54108, P54831, P57110, Q01974, Q38HS2, Q3KPV7, Q3UFB7, Q505J3, Q5R7Y0, Q5T4F7, Q60477, Q658N2, Q6UWX4, Q7T141, Q7TSQ1, Q80XH4, Q8BG58, Q91009, Q99JR5, Q9CXM0, Q9D2G9, Q9EQT5, Q9GZM7, Q9H3Y0

Diamond homologs: A0A0K3AWM6, B3DIG4, G5ECQ2, O00144, O19116, O42579, O57328, O57329, O60353, O70421, O75084, O93274, P18537, P58421, P97299, P97401, Q08463, Q08464, Q13467, Q14332, Q24760, Q498S8, Q5BL72, Q5RCN4, Q5RF67, Q5T4F7, Q61086, Q61088, Q61089, Q61090, Q61091, Q6FHJ7, Q7YRN1, Q80YN4, Q863H1, Q8AVJ9, Q8BKG4, Q8C4U3, Q8CHL0, Q8K4C8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

372 predictions. Top by Δscore:

Variant	Effect	Δscore
10:97767856:GACCA:G	acceptor_gain	1.0000
10:97767857:ACCA:A	acceptor_gain	1.0000
10:97767858:CCA:C	acceptor_gain	1.0000
10:97767858:CCAC:C	acceptor_gain	1.0000
10:97767859:CA:C	acceptor_gain	1.0000
10:97767859:CACTG:C	acceptor_gain	1.0000
10:97767860:AC:A	acceptor_loss	1.0000
10:97767861:C:CC	acceptor_gain	1.0000
10:97767861:CTGTG:C	acceptor_loss	1.0000
10:97767863:G:C	acceptor_gain	1.0000
10:97769664:TCA:T	donor_loss	1.0000
10:97769665:CACCA:C	donor_loss	1.0000
10:97769666:A:AC	donor_gain	1.0000
10:97769666:AC:A	donor_gain	1.0000
10:97769666:ACC:A	donor_loss	1.0000
10:97769667:C:CC	donor_gain	1.0000
10:97769667:C:G	donor_loss	1.0000
10:97769667:CC:C	donor_gain	1.0000
10:97769667:CCAA:C	donor_gain	1.0000
10:97769743:TCA:T	acceptor_gain	1.0000
10:97769743:TCAC:T	acceptor_loss	1.0000
10:97769744:CA:C	acceptor_gain	1.0000
10:97769744:CAC:C	acceptor_gain	1.0000
10:97769746:C:CC	acceptor_gain	1.0000
10:97769746:C:CG	acceptor_loss	1.0000
10:97769747:T:G	acceptor_loss	1.0000
10:97767863:G:GC	acceptor_gain	0.9900
10:97769667:CCA:C	donor_gain	0.9900
10:97769667:CCAAA:C	donor_gain	0.9900
10:97769741:GGTCA:G	acceptor_gain	0.9900

AlphaMissense

2072 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:97771370:A:C	F155C	1.000
10:97771396:C:A	W146C	1.000
10:97771396:C:G	W146C	1.000
10:97771398:A:G	W146R	1.000
10:97771398:A:T	W146R	1.000
10:97771508:C:T	C109Y	1.000
10:97771558:C:A	W92C	1.000
10:97771558:C:G	W92C	1.000
10:97771646:C:G	C63S	1.000
10:97771647:A:T	C63S	1.000
10:97767705:A:G	C255R	0.999
10:97771348:G:C	C162W	0.999
10:97771349:C:A	C162F	0.999
10:97771349:C:G	C162S	0.999
10:97771349:C:T	C162Y	0.999
10:97771350:A:G	C162R	0.999
10:97771350:A:T	C162S	0.999
10:97771370:A:G	F155S	0.999
10:97771379:C:A	C152F	0.999
10:97771379:C:T	C152Y	0.999
10:97771380:A:G	C152R	0.999
10:97771403:A:C	F144C	0.999
10:97771430:C:T	C135Y	0.999
10:97771431:A:G	C135R	0.999
10:97771450:G:C	C128W	0.999
10:97771451:C:A	C128F	0.999
10:97771451:C:G	C128S	0.999
10:97771451:C:T	C128Y	0.999
10:97771452:A:G	C128R	0.999
10:97771452:A:T	C128S	0.999

dbSNP variants (sampled 300 via entrez): RS1000049071 (10:97772266 C>G), RS1000374889 (10:97773891 G>T), RS1000579318 (10:97768168 C>T), RS1000828569 (10:97767227 C>T), RS1000954640 (10:97768464 A>G), RS1001367038 (10:97772843 G>A), RS1001456698 (10:97773568 A>G), RS1003317434 (10:97769401 G>A), RS1003389485 (10:97769116 CACTGG>C), RS1003735536 (10:97770700 G>A), RS1004107883 (10:97770964 G>A), RS1005173238 (10:97772885 T>G), RS1006911104 (10:97773726 G>A), RS1007339664 (10:97771910 G>A), RS1007635719 (10:97772221 A>G)

Disease associations

OMIM: gene MIM:604158 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002497_25	Blood pressure	3.000000e-07
GCST006192_45	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	7.000000e-06
GCST006193_2	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	3.000000e-07
GCST006195_88	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	5.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006336	diastolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11189381	Toxicity	3	Bisphosphonates	Osteonecrosis

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11189381	SFRP5	3	0.00	1	Bisphosphonates

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Decitabine	decreases methylation, affects methylation, affects expression, affects cotreatment, increases expression	6
Benzo(a)pyrene	increases expression, increases methylation, affects methylation	3
aristolochic acid I	increases expression	1
testosterone undecanoate	affects cotreatment, increases expression	1
trichostatin A	affects cotreatment, increases expression	1
beta-lapachone	decreases expression	1
pinostrobin	decreases expression, decreases reaction, increases expression, increases phosphorylation	1
tofacitinib	increases expression	1
N4-(2,2-dimethyl-3-oxo-4H-pyrid(1,4)oxazin-6-yl)-5-fluoro-N2-(3,4,5-trimethoxyphenyl)-2,4-pyrimidinediamine	increases expression	1
licochalcone B	increases expression	1
malondialdehyde-low density lipoprotein, human	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Arbutin	decreases expression	1
Arsenic	affects methylation	1
Biguanides	affects expression	1
Cadmium	decreases expression	1
Curcumin	decreases expression	1
Doxorubicin	decreases expression	1
Folic Acid	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Polyamines	affects expression	1
Tetrachlorodibenzodioxin	affects methylation	1
Triclosan	increases expression	1
Levonorgestrel	increases expression, affects cotreatment	1
Reactive Oxygen Species	decreases reaction, increases abundance	1
p-Chloromercuribenzoic Acid	increases expression	1

Clinical trials (associated diseases)

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