SFRP2

Summary

SFRP2 (secreted frizzled related protein 2, HGNC:10777) is a protein-coding gene on chromosome 4q31.3, encoding Secreted frizzled-related protein 2 (Q96HF1). Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts.

This gene encodes 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. Methylation of this gene is a potential marker for the presence of colorectal cancer.

Source: NCBI Gene 6423 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 35 total
• MANE Select transcript: NM_003013

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10777
Approved symbol	SFRP2
Name	secreted frizzled related protein 2
Location	4q31.3
Locus type	gene with protein product
Status	Approved
Aliases	SARP1, SDF-5, FRP-2
Ensembl gene	ENSG00000145423
Ensembl biotype	protein_coding
OMIM	604157
Entrez	6423

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000274063, ENST00000918154

RefSeq mRNA: 1 — MANE Select: NM_003013 NM_003013

CCDS: CCDS34082

Canonical transcript exons

ENST00000274063 — 3 exons

Exon	Start	End
ENSE00000970467	153788334	153789083
ENSE00000970468	153785864	153785944
ENSE00001002639	153780591	153781755

Expression profiles

Bgee: expression breadth ubiquitous, 225 present calls, max score 99.53.

FANTOM5 (CAGE): breadth broad, TPM avg 41.9574 / max 4499.1883, expressed in 668 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54443	41.9574	668

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	99.53	gold quality
parietal pleura	UBERON:0002400	99.39	gold quality
gall bladder	UBERON:0002110	99.37	gold quality
vena cava	UBERON:0004087	99.28	gold quality
upper leg skin	UBERON:0004262	99.24	gold quality
skin of hip	UBERON:0001554	99.03	gold quality
trachea	UBERON:0003126	99.03	gold quality
mammary duct	UBERON:0001765	98.96	gold quality
pericardium	UBERON:0002407	98.95	gold quality
epithelium of mammary gland	UBERON:0003244	98.69	gold quality
ventricular zone	UBERON:0003053	98.47	gold quality
thoracic mammary gland	UBERON:0005200	98.06	gold quality
visceral pleura	UBERON:0002401	98.00	gold quality
mucosa of stomach	UBERON:0001199	97.91	gold quality
mammary gland	UBERON:0001911	97.79	gold quality
mammalian vulva	UBERON:0000997	97.45	gold quality
saphenous vein	UBERON:0007318	97.36	gold quality
right coronary artery	UBERON:0001625	97.11	gold quality
calcaneal tendon	UBERON:0003701	97.06	gold quality
superficial temporal artery	UBERON:0001614	96.84	gold quality
synovial joint	UBERON:0002217	96.62	gold quality
urethra	UBERON:0000057	96.61	gold quality
pharyngeal mucosa	UBERON:0000355	96.59	gold quality
nipple	UBERON:0002030	96.56	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	96.52	gold quality
caecum	UBERON:0001153	96.32	gold quality
popliteal artery	UBERON:0002250	96.31	gold quality
tibial artery	UBERON:0007610	96.30	gold quality
left uterine tube	UBERON:0001303	96.06	gold quality
seminal vesicle	UBERON:0000998	95.79	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-MTAB-6108	yes	5652.53
E-GEOD-124472	yes	3235.65
E-MTAB-8142	yes	3147.69
E-MTAB-7407	yes	2724.00
E-HCAD-10	yes	1998.66
E-GEOD-98556	yes	1558.31
E-MTAB-7008	yes	995.74
E-MTAB-9388	yes	399.77
E-MTAB-8410	yes	51.90
E-HCAD-31	yes	28.02
E-HCAD-1	yes	20.46
E-GEOD-93593	yes	14.86
E-MTAB-5061	yes	11.33
E-ENAD-27	yes	6.51
E-MTAB-11121	no	3045.42

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXO1, FOXO3, GLI1, MEF2C, MYC, PAX6, POU2F1, POU2F2, THRA

miRNA regulators (miRDB)

82 targeting SFRP2, 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-3163	100.00	77.23	8605
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-1323	99.83	69.89	2471

Literature-anchored findings (GeneRIF, showing 40)

• SFRP2 is a target of the Pax2 transcription factor (PMID:14561758)
• secreted Frizzled-related protein 2 induces cellular resistance to apoptosis (PMID:14709558)
• identified SFRP2 methylation as a sensitive single DNA-based marker for identification of colorectal cancer in stool samples (PMID:15094274)
• SFRP2 was methylated in 73% of the normal squamous esophageal mucosa samples. (PMID:16407829)
• The SFRP2 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)
• Methylation testing of fecal DNA using a panel of epigenetic markers (methylated SFRP2, HPP1 and MGMT) may be a simple and promising non-invasive screening method for colorectal carcinoma and precancerous lesions. (PMID:17352030)
• Aberrant methylated SFRP2 could be detected frequently in stools from patients with CRC and precancerous lesions. Methylation testing of fecal DNA may be a simple, promising, and noninvasive screening tool for colorectal neoplasia. (PMID:17410438)
• SFRP2 methylation may serve as a marker for molecular stool-based adenoma and colorectal cancer screening. (PMID:17639423)
• Epigenetic inactivation of SFRP2 is associated with gastric carcinogenesis (PMID:17848950)
• Reduced tumor expression of Wnt inhibitory factor-1 (WIF1), sFRP2, and sFRP4 mRNA was confirmed in all pituitary tumors. (PMID:18079202)
• Aberrant DNA methylation and histone modifications work together to silence the sFRP2 gene in renal cell carcinoma (RCC) cells. (PMID:18404682)
• Loss of SFRP2 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/lymphocyte enhancer factor (TCF/LEF) transcriptional activity in liver cancer cells. (PMID:18592156)
• SFRP2 promoter hypermethylation was more frequent in microsatellite unstable colorectal neoplasms. (PMID:18795670)
• SFRP2 gene is a high-frequent target of epigenetic inactivation in human breast cancer; its methylation leads to abrogation of SFRP2 expression, conferring a growth advantage to epithelial mammary cells; this supports a tumor suppressive function of SFRP2 (PMID:18990230)
• Restoration of the expression of SFRP1 and SFRP2 attenuated Wnt signaling in CaSki cells, decreased abnormal accumulation of free beta-catenin in the nucleus, and suppressed ovarian cancer cell growth. (PMID:19095296)
• In multiple myeloma cell lines, aberrant promoter hypermethylation of the secreted Frizzled-related protein genes was a common event, and hypermethylation of SFRP2 was associated with transcriptional silencing. (PMID:19299079)
• SFRP2 is a novel stimulator of angiogenesis that stimulates angiogenesis via a calcineurin/NFAT pathway and may be a favorable target for the inhibition of angiogenesis in solid tumors. (PMID:19458075)
• SDF-2, SDF-4 and SDF-5 are expressed in mammary tissues and cells and that a reduced level of SDF-2 and SDF-4 are associated with a poor clinical outcome. (PMID:19513569)
• Hypermethylation of SFRP1 and 2 was present in nine malignant hematopoietic cell lines. (PMID:20030932)
• Loss of WNT pathway inhibition due to SFRP2 gene silencing is associated with medulloblastoma. (PMID:20208569)
• This is the first report documenting that sFRP2 activates the canonical Wnt pathway and promotes cell growth by evoking diverse signaling cascades in renal cancer cells. (PMID:20501806)
• SFRP2 promoter methylation is aberrant in mesothelioma. (PMID:20596629)
• induces transient rise of intracellular Ca2+ via emptying of intracellular calcium stores in neutrophils (PMID:20602801)
• Investigated the methylation of the SFRP2, P16, DAPK1, HIC1, and MGMT genes, as well as the mutation of amino acid codons 12 and 13 of the KRAS gene in normal and tumor tissue DNA of patients diagnosed with sporadic colorectal cancer. (PMID:20682398)
• Combined effects of epigenetic alterations in SFRP2 and point mutations in K-ras protein play a role in development of mucinous type anal adenocarcinoma. (PMID:20686305)
• Recombinant sFRP2 enhanced Wnt3a-dependent phosphorylation of LRP6 as well as both cytosolic beta-catenin levels and its nuclear translocation. sFRP2 enhanced the Wnt3a-mediated transcription of several genes including DKK1 and NKD1. (PMID:20723538)
• These results support sFRP2’s role as an enhancer of Wnt3A/beta-catenin signaling, a result with biological impact for both normal development and diverse pathologies such as tumorigenesis. (PMID:20723538)
• Promoter hypermethylation of SFRP2 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)
• SFRP2 may play an important role in the development of earlobe keloid, especially at the keloid edge. (PMID:21174795)
• Hypermethylation of SFRP2 gene is associated with advanced gastric cancer. (PMID:21409489)
• serum SFRP2 methylation status represents a promising, non-invasive marker for colorectal carcinoma detection and staging (PMID:21463549)
• Among the extracellular regulators that suppress the Wnt pathway, secreted frizzled-related protein 2 (SFRP2), was up-regulated 4.3-fold in healthy smokers and 4.9-fold in COPD smokers. (PMID:21490961)
• A study evaluating the pattern of SFRP2 methylation throughout the promoter during progressive tumorigenesis. (PMID:21709714)
• Promoter hypermethylation of tumor suppressor SFRP2 is associated with prostate carcinoma. (PMID:22136354)
• there is a loss of SFRP-2 expression from benign to malignant prostate glands and differential SFRP-2 expression among two possible subgroups of Gleason grade 5 tumours (PMID:22175903)
• Sodium butyrate may modulate the SFRP1/2 expression through histone modification and promoter demethylation causing anti-tumor effects in gastric neoplasms. (PMID:22246241)
• Data suggest that silencing of secreted frizzled-related protein 2 expression through promoter hypermethylation may be a factor in ESCC carcinogenesis through loss of its tumor-suppressive activity. (PMID:22363119)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	sfrp2	ENSDARG00000070050
mus_musculus	Sfrp2	ENSMUSG00000027996
rattus_norvegicus	Sfrp2	ENSRNOG00000009465
drosophila_melanogaster	fz3	FBGN0027343

Paralogs (15): FZD3 (ENSG00000104290), SFRP1 (ENSG00000104332), SFRP4 (ENSG00000106483), FZD10 (ENSG00000111432), SFRP5 (ENSG00000120057), SMO (ENSG00000128602), 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 2 — Q96HF1 (reviewed: Q96HF1)

Alternative names: Secreted apoptosis-related protein 1

All UniProt accessions (2): Q96HF1, A0A140VJU3

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. SFRP2 may be important for eye retinal development and for myogenesis.

Subcellular location. Secreted.

Tissue specificity. Expressed in adipose tissue, heart, brain, skeletal muscle, pancreas, thymus, prostate, testis, ovary, small intestine and colon. Highest levels in adipose tissue, small intestine and colon.

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_003004* (*=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
IPR041764	SFRP2_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-Q96HF1-F1	82.34	0.47

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): 175–247, 190–295, 40–103, 50–96, 87–125, 114–152, 118–142, 172–245

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-201681	TCF dependent signaling in response to WNT
R-HSA-3772470	Negative regulation of TCF-dependent signaling by WNT ligand antagonists
R-HSA-162582	Signal Transduction
R-HSA-195721	Signaling by WNT

MSigDB gene sets: 433 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_PEPTIDYL_TYROSINE_PHOSPHORYLATION, GOBP_COLLAGEN_FIBRIL_ORGANIZATION, GOBP_CARTILAGE_DEVELOPMENT, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_CARDIAC_LEFT_VENTRICLE_MORPHOGENESIS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT

GO Biological Process (65): branching involved in blood vessel morphogenesis (GO:0001569), neural tube closure (GO:0001843), chondrocyte development (GO:0002063), outflow tract morphogenesis (GO:0003151), cardiac left ventricle morphogenesis (GO:0003214), cell-cell signaling (GO:0007267), mesodermal cell fate specification (GO:0007501), response to nutrient (GO:0007584), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), male gonad development (GO:0008584), response to xenobiotic stimulus (GO:0009410), negative regulation of gene expression (GO:0010629), cardiac muscle cell apoptotic process (GO:0010659), negative regulation of cardiac muscle cell apoptotic process (GO:0010667), negative regulation of epithelial to mesenchymal transition (GO:0010719), regulation of neuron projection development (GO:0010975), negative regulation of Wnt signaling pathway (GO:0030178), collagen fibril organization (GO:0030199), positive regulation of cell growth (GO:0030307), negative regulation of cell growth (GO:0030308), negative regulation of cell migration (GO:0030336), BMP signaling pathway (GO:0030509), negative regulation of BMP signaling pathway (GO:0030514), positive regulation of cell adhesion mediated by integrin (GO:0033630), non-canonical Wnt signaling pathway (GO:0035567), post-anal tail morphogenesis (GO:0036342), negative regulation of mesodermal cell fate specification (GO:0042662), embryonic digit morphogenesis (GO:0042733), positive regulation of apoptotic process (GO:0043065), positive regulation of fat cell differentiation (GO:0045600), positive regulation of osteoblast differentiation (GO:0045669), positive regulation of angiogenesis (GO:0045766), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), digestive tract morphogenesis (GO:0048546), stem cell fate specification (GO:0048866), negative regulation of epithelial cell proliferation (GO:0050680), negative regulation of peptidyl-tyrosine phosphorylation (GO:0050732), convergent extension involved in axis elongation (GO:0060028)

GO Molecular Function (7): fibronectin binding (GO:0001968), integrin binding (GO:0005178), Wnt-protein binding (GO:0017147), receptor ligand activity (GO:0048018), endopeptidase activator activity (GO:0061133), protein binding (GO:0005515), enzyme activator activity (GO:0008047)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012), extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Signaling by WNT	1
TCF dependent signaling in response to WNT	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to chemical	2
cell population proliferation	2
regulation of cell population proliferation	2
positive regulation of cellular process	2
protein binding	2
signaling receptor binding	2
angiogenesis	1
blood vessel morphogenesis	1
branching morphogenesis of an epithelial tube	1
primary neural tube formation	1
tube closure	1
chondrocyte differentiation	1
cell development	1
heart morphogenesis	1
anatomical structure morphogenesis	1
cardiac ventricle morphogenesis	1
cell communication	1
signaling	1
cell fate specification	1
mesodermal cell fate commitment	1
response to nutrient levels	1
negative regulation of cellular process	1
gonad development	1
development of primary male sexual characteristics	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
striated muscle cell apoptotic process	1
cardiac muscle cell apoptotic process	1
negative regulation of striated muscle cell apoptotic process	1
regulation of cardiac muscle cell apoptotic process	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
negative regulation of cell differentiation	1
negative regulation of multicellular organismal process	1
neuron projection development	1
regulation of plasma membrane bounded cell projection organization	1
negative regulation of signal transduction	1
Wnt signaling pathway	1
regulation of Wnt signaling pathway	1

Protein interactions and networks

STRING

2532 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SFRP2	CTNNB1	P35222	834
SFRP2	DKK1	O94907	831
SFRP2	LRP5	O75197	808
SFRP2	ANKRD42	Q8N9B4	785
SFRP2	BMP1	P13497	757
SFRP2	WNT3A	P56704	746
SFRP2	WIF1	Q9Y5W5	736
SFRP2	AXIN2	Q9Y2T1	728
SFRP2	DKK3	Q9UBP4	725
SFRP2	DKK2	Q9UBU2	725
SFRP2	WNT5A	P41221	694
SFRP2	WNT7B	P56706	694
SFRP2	WNT2	P09544	665
SFRP2	BARX1	Q9HBU1	664
SFRP2	LRP6	O75581	658

IntAct

17 interactions, top by confidence:

A	B	Type	Score
SFRP2	MAEA	psi-mi:“MI:0914”(association)	0.530
SFRP2	CCAR1	psi-mi:“MI:0915”(physical association)	0.400
DBNDD2	SFRP2	psi-mi:“MI:0915”(physical association)	0.370
EEF1G	SFRP2	psi-mi:“MI:0915”(physical association)	0.370
SFRP2	PFKM	psi-mi:“MI:0915”(physical association)	0.370
SFRP2	BMPR1A	psi-mi:“MI:0915”(physical association)	0.370
BUB1	SFRP2	psi-mi:“MI:0915”(physical association)	0.370
SFRP2	CDH1	psi-mi:“MI:0915”(physical association)	0.370
SFRP2	CTNNA1	psi-mi:“MI:0915”(physical association)	0.370
SFRP2	DCC	psi-mi:“MI:0915”(physical association)	0.370
MLH3	SFRP2	psi-mi:“MI:0915”(physical association)	0.370
SFRP2	RAD54B	psi-mi:“MI:0915”(physical association)	0.370
SFRP2	SMAD4	psi-mi:“MI:0915”(physical association)	0.370
SFRP2	ARMC8	psi-mi:“MI:0914”(association)	0.350

BioGRID (33): ARMC8 (Affinity Capture-MS), MAEA (Affinity Capture-MS), MKLN1 (Affinity Capture-MS), RMND5A (Affinity Capture-MS), RANBP9 (Affinity Capture-MS), ARMC8 (Affinity Capture-MS), MKLN1 (Affinity Capture-MS), SFRP2 (Two-hybrid), SFRP5 (Two-hybrid), SFRP2 (Reconstituted Complex), PPP1CC (Affinity Capture-Western), PPP1CA (Affinity Capture-Western), SFRP2 (Affinity Capture-Western), SFRP2 (Affinity Capture-Western), SFRP2 (Affinity Capture-Western)

ESM2 similar proteins: A0A1D5PUP4, A5YT95, O35757, O62650, O75882, O95980, P07225, P09858, P10669, P17247, P19883, P21214, P21674, P26012, P26013, P27090, P30371, P31514, P31515, P47931, P49767, P50291, P61811, P61812, P97299, P97953, Q07257, Q0VBD0, Q17QD6, Q38L25, Q5RA73, Q6NW40, Q6V9H4, Q6ZQ11, Q863H1, Q86X52, Q8BFR2, Q8CI19, Q8JG54, Q8N475

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

162 predictions. Top by Δscore:

Variant	Effect	Δscore
4:153781751:CAGTG:C	acceptor_gain	1.0000
4:153781752:AGTG:A	acceptor_gain	1.0000
4:153781753:GTG:G	acceptor_gain	1.0000
4:153781754:TG:T	acceptor_gain	1.0000
4:153781755:GC:G	acceptor_loss	1.0000
4:153781756:C:CC	acceptor_gain	1.0000
4:153781756:C:CG	acceptor_loss	1.0000
4:153781757:T:G	acceptor_loss	1.0000
4:153781758:A:C	acceptor_gain	1.0000
4:153785859:CTTA:C	donor_loss	1.0000
4:153785860:TTA:T	donor_loss	1.0000
4:153785861:TA:T	donor_loss	1.0000
4:153785862:A:AC	donor_gain	1.0000
4:153785862:A:C	donor_loss	1.0000
4:153785863:C:CC	donor_gain	1.0000
4:153785863:C:CG	donor_loss	1.0000
4:153785945:C:CC	acceptor_gain	1.0000
4:153788328:GCTTA:G	donor_loss	1.0000
4:153788329:CTTA:C	donor_loss	1.0000
4:153788330:TTAC:T	donor_loss	1.0000
4:153788331:TA:T	donor_loss	1.0000
4:153788332:A:AC	donor_gain	1.0000
4:153788332:ACCTT:A	donor_gain	1.0000
4:153788333:C:CA	donor_loss	1.0000
4:153788333:C:CC	donor_gain	1.0000
4:153788333:CCTT:C	donor_gain	1.0000
4:153788333:CCTTC:C	donor_gain	1.0000
4:153788336:T:A	donor_gain	1.0000
4:153781758:A:AC	acceptor_gain	0.9900
4:153785858:ACTT:A	donor_loss	0.9900

AlphaMissense

1962 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:153788402:A:C	F145C	1.000
4:153788428:C:A	W136C	1.000
4:153788428:C:G	W136C	1.000
4:153788430:A:G	W136R	1.000
4:153788430:A:T	W136R	1.000
4:153788599:C:A	W79C	1.000
4:153788599:C:G	W79C	1.000
4:153781511:C:A	W276C	0.999
4:153781511:C:G	W276C	0.999
4:153781563:A:T	V259D	0.999
4:153781566:A:G	L258P	0.999
4:153785866:A:C	F194C	0.999
4:153785866:A:G	F194S	0.999
4:153788380:G:C	C152W	0.999
4:153788381:C:G	C152S	0.999
4:153788382:A:G	C152R	0.999
4:153788382:A:T	C152S	0.999
4:153788402:A:G	F145S	0.999
4:153788411:C:G	C142S	0.999
4:153788412:A:G	C142R	0.999
4:153788412:A:T	C142S	0.999
4:153788440:G:C	F132L	0.999
4:153788440:G:T	F132L	0.999
4:153788442:A:G	F132L	0.999
4:153788461:G:C	C125W	0.999
4:153788462:C:G	C125S	0.999
4:153788462:C:T	C125Y	0.999
4:153788463:A:G	C125R	0.999
4:153788463:A:T	C125S	0.999
4:153788482:G:C	C118W	0.999

dbSNP variants (sampled 300 via entrez): RS1000026971 (4:153784174 T>C), RS1000230585 (4:153790140 C>A,G), RS1000842314 (4:153785893 A>G,T), RS1000868440 (4:153789104 C>T), RS10009567 (4:153790284 C>G,T), RS1001470747 (4:153790344 C>A), RS1001606684 (4:153790550 A>T), RS1002309285 (4:153788517 G>T), RS1002353783 (4:153786354 A>G,T), RS1002641518 (4:153781481 G>A), RS1002819081 (4:153788248 G>A,C), RS1002871980 (4:153781492 ACT>A), RS1003097593 (4:153788032 C>T), RS10031991 (4:153790517 A>G), RS1003314317 (4:153786761 G>C)

Disease associations

OMIM: gene MIM:604157 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (1): Microphthalmia-anophthalmia-coloboma (Orphanet:98555)

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST004125_2	Type 2 diabetes (age of onset)	4.000000e-06
GCST006110_6	Nose morphology	7.000000e-06
GCST006447_2	Bone mineral density (spine)	1.000000e-06
GCST006976_72	Macular thickness	8.000000e-10
GCST009464_1	Facial morphology	8.000000e-09
GCST009464_10	Facial morphology	4.000000e-12
GCST009464_13	Facial morphology	2.000000e-09
GCST009464_34	Facial morphology	2.000000e-10
GCST010701_3	Cortical surface area (MOSTest)	1.000000e-08
GCST010702_5	Subcortical volume (MOSTest)	3.000000e-08
GCST010703_140	Brain morphology (MOSTest)	4.000000e-08
GCST012060_1	Nose morphology	2.000000e-17

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007701	spine bone mineral density
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Decitabine	decreases methylation, increases methylation, affects methylation, affects expression, affects cotreatment (+1 more)	7
Valproic Acid	increases expression, affects cotreatment, decreases expression	6
trichostatin A	affects methylation, affects cotreatment, increases expression, decreases expression, affects expression	5
bisphenol A	affects cotreatment, decreases methylation, increases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	3
methylmercuric chloride	decreases expression	2
entinostat	decreases expression, affects cotreatment	2
LDN 193189	affects cotreatment, decreases expression, increases expression	2
Arsenic Trioxide	decreases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Dexamethasone	increases expression, decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
bisphenol F	affects cotreatment, increases expression	1
ascorbate-2-phosphate	affects binding, affects cotreatment, decreases expression	1
terbufos	increases methylation	1
arsenite	increases methylation	1
rutecarpine	increases expression	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
Chir 99021	affects cotreatment, decreases expression, affects binding	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases methylation	1
XAV939	affects binding, affects cotreatment, decreases expression	1
3-(4-pyridyl)-1H-indole	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Arsenates	affects cotreatment, increases expression	1
Arsenic	affects methylation	1

Clinical trials (associated diseases)

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