SPRY1

Summary

SPRY1 (sprouty RTK signaling antagonist 1, HGNC:11269) is a protein-coding gene on chromosome 4q28.1, encoding Protein sprouty homolog 1 (O43609). Inhibits fibroblast growth factor (FGF)-induced retinal lens fiber differentiation, probably by inhibiting FGF-mediated phosphorylation of ERK1/2.

Involved in negative regulation of fibroblast growth factor receptor signaling pathway. Located in Golgi apparatus; cytosol; and nucleoplasm.

Source: NCBI Gene 10252 — RefSeq curated summary.

At a glance

• Gene–disease (curated): craniosynostosis (Moderate, GenCC)
• GWAS associations: 12
• Clinical variants (ClinVar): 73 total — 1 likely-pathogenic
• MANE Select transcript: NM_001258038

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11269
Approved symbol	SPRY1
Name	sprouty RTK signaling antagonist 1
Location	4q28.1
Locus type	gene with protein product
Status	Approved
Aliases	hSPRY1
Ensembl gene	ENSG00000164056
Ensembl biotype	protein_coding
OMIM	602465
Entrez	10252

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 17 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000339241, ENST00000394339, ENST00000505319, ENST00000507703, ENST00000508849, ENST00000515726, ENST00000610581, ENST00000622283, ENST00000651917, ENST00000858977, ENST00000858978, ENST00000858979, ENST00000927725, ENST00000927726, ENST00000927727, ENST00000927728, ENST00000927729, ENST00000942557

RefSeq mRNA: 5 — MANE Select: NM_001258038 NM_001258038, NM_001258039, NM_001375410, NM_005841, NM_199327

CCDS: CCDS3731

Canonical transcript exons

ENST00000651917 — 3 exons

Exon	Start	End
ENSE00001942193	123401537	123403755
ENSE00002050323	123397611	123397856
ENSE00002062639	123396795	123396932

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 99.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.8297 / max 396.4847, expressed in 1274 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
49562	11.2856	1191
49563	0.5881	357
49564	0.3784	201
49565	0.3602	150
49566	0.2174	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pericardium	UBERON:0002407	99.41	gold quality
omental fat pad	UBERON:0010414	98.85	gold quality
peritoneum	UBERON:0002358	98.83	gold quality
vena cava	UBERON:0004087	98.30	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.30	gold quality
gall bladder	UBERON:0002110	97.92	gold quality
parietal pleura	UBERON:0002400	97.51	gold quality
colonic epithelium	UBERON:0000397	97.44	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.12	gold quality
endocervix	UBERON:0000458	97.11	gold quality
left uterine tube	UBERON:0001303	96.98	gold quality
skin of leg	UBERON:0001511	96.98	gold quality
left lobe of thyroid gland	UBERON:0001120	96.94	gold quality
right coronary artery	UBERON:0001625	96.70	gold quality
left coronary artery	UBERON:0001626	96.69	gold quality
thyroid gland	UBERON:0002046	96.58	gold quality
right lobe of thyroid gland	UBERON:0001119	96.55	gold quality
coronary artery	UBERON:0001621	96.37	gold quality
descending thoracic aorta	UBERON:0002345	96.24	gold quality
adipose tissue	UBERON:0001013	95.94	gold quality
pleura	UBERON:0000977	95.83	gold quality
skin of abdomen	UBERON:0001416	95.76	gold quality
lower esophagus mucosa	UBERON:0035834	95.75	gold quality
thoracic aorta	UBERON:0001515	95.67	gold quality
tibial nerve	UBERON:0001323	95.63	gold quality
ascending aorta	UBERON:0001496	95.62	gold quality
germinal epithelium of ovary	UBERON:0001304	95.56	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.42	gold quality
lower esophagus	UBERON:0013473	95.41	gold quality
aorta	UBERON:0000947	95.36	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	130.13
E-HCAD-1	yes	31.22
E-MTAB-8410	yes	30.99
E-CURD-46	yes	30.67
E-CURD-88	yes	21.10
E-CURD-122	yes	17.09
E-MTAB-6701	yes	11.79
E-MTAB-10553	yes	8.15
E-MTAB-4850	no	139.35
E-MTAB-10137	no	7.62
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, EGR3, WT1, ZBTB7A

miRNA regulators (miRDB)

87 targeting SPRY1, 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-1277-5P	100.00	73.95	5056
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-5692A	100.00	74.40	6850
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4803	99.98	71.99	3117
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-10527-5P	99.91	72.28	3754

Literature-anchored findings (GeneRIF, showing 40)

• The bimodal regulation of epidermal growth factor signaling by human Sprouty proteins (PMID:11983899)
• Expression analysis of SPRY1a and SPRY1b shows that they are hardly expressed in adult human, but have different expression patterns in fetus, which confirmed that SPRY1 is an important gene during fetal development (PMID:14533010)
• Spry 1, 2 and 3 expression was observed in placental tissue from all three trimesters (PMID:15950061)
• the Sprouty/Caveolin-1 interaction modulates signaling in a growth factor- and Sprouty isoform-specific manner (PMID:16877379)
• Expression of an SPRY1 alternative transcript is presumed to be specific for fetal tissues and and is moderately expressd in prostate csncer tissues and cell lines. (PMID:16954433)
• DNA methylation in the Sprouty1 promoter region is responsible for downregulating Sprouty1 expression in prostate cancer (PMID:19164898)
• Sprouty1 induced by TCR signal negatively regulates further TCR signaling by interacting with proximal signaling molecules in immune synapse, providing a novel regulatory mechanism of T cells. (PMID:19915061)
• Data show that upregulation of Spry1 in HUVECs inhibits tube formation and is associated with decreased proliferation and increased expression of p21 and p27. (PMID:20054616)
• SPRY1 supported formation of activated ERK and mitogen-activated protein/ERK kinase and was essential for ERMS cell proliferation and survivalin rhabdomyosarcoma. (PMID:20068162)
• Sprouty1 and Sprouty2 effect cortical cell proliferation, differentiation, and the expression of genes regulating progenitor identity in the ventricular zone. (PMID:20237272)
• hSpry1 and HAX1 proteins are putative candidate proteins that interact with uPAR. (PMID:20696135)
• Results suggest that SPRY1 is an endogenous angiogenesis inhibitor. (PMID:20813052)
• Spry1 is a target for miR-21-mediated gene silencing. (PMID:21826097)
• The spatio-temporal expression of Decorin, Semaphorin6D, SPARC, Spry-1 and Tsukushi in developing prostate is described and observed similar mesenchymal expression patterns in rat and human. (PMID:22880013)
• siRNA-mediated knockdown of Spry1, Spry2, or Spry4 promotes IFN-inducible antileukemic effects in vitro and results in enhanced suppressive effects on malignant hematopoietic progenitors from patients with polycythemia vera. (PMID:23074222)
• Results suggest that the SPRY1 gene is an important genetic factor for determining the risk of both obesity and osteoporosis in humans. (PMID:23146288)
• miR-21 promotes robust fibrogenic EMT of EMCs, in part by directly targeting PDCD4 and SPRY1. (PMID:23441172)
• Feedback regulations of miR-21 and MAPKs via Pdcd4 and Spry1 are involved in arsenite-induced cell malignant transformation. (PMID:23469214)
• Re-expression of SPRY1, a repressed target of BCL11B, limits the transformation capacity of Ewing sarcoma cells. (PMID:23527175)
• Spry1 and Spry4 have opposing roles in VSMC phenotypic modulation, and Spry1 maintains the VSMC differentiation phenotype in vitro in part through an Akt/FoxO/myocardin pathway. (PMID:23554919)
• Sprouty1 expression is not connected with mitogenic signaling and cell proliferation. (PMID:23616430)
• The Spry1 acts as a sensor of mitogenic activity that not only attenuates RTK signaling but also induces a cellular senescence response to avoid uncontrolled proliferation. (PMID:24270409)
• A random population of LNCaP prostate cancer cells comprises a heterogeneous group of cells with different androgen-deprivation sensitivities and potential for invasiveness; expression levels of 2 genes known to be regulated by miR-21, an androgen-regulated microRNA, SPRY1 and JAG1 were lower in an androgen insensitive clone, than an androgen sensitive clone. (PMID:24604720)
• There is an inverse correlation between the expression of Spry1 and growth, proliferation, invasion and migration of ovarian cancer cells. (PMID:24932220)
• Cosuppression of Sprouty and Sprouty-related negative regulators of FGF signalling in prostate cancer (PMID:26075267)
• SPRY1 and SPRY2 mRNA transcripts were significantly upregulated in human CRC. Suppression of SPRY2 repressed AKT2 and EMT-inducing transcription factors and significantly increased E-cadherin expression. Concurrent downregulation of SPRY1 and SPRY2 also increased E-cadherin and suppressed mesenchymal markers in colon cancer cells. (PMID:26434583)
• Suppression of SPRY1 by age-associated methylation inhibits the replenishment of the muscle stem cell pool. (PMID:26526994)
• Spry1 plays a selective role in at least a subset of triple-negative breast cancer to promote the malignant phenotype via enhancing EGF-mediated mesenchymal phenotype. (PMID:26976794)
• Although the expression of SPRY1 was low when compared with other tumors, SPRY1 was variably expressed in primary Ewing sarcoma tumors and higher expression levels were significantly associated with improved outcome in a large patient cohort. (PMID:27375017)
• During adipogenesis and osteogenesis, TNF-alpha significantly increased Spry1 levels and overexpression of miR-21 dramatically decreased Spry1 levels in the presence of TNF-alpha, indicated important roles of miR-21 in modulating link between TNF-alpha and Spry1. Our findings introduce a molecular mechanism in which TNF-alpha suppresses adipogenic and osteogenic differentiation of PDLSCs by inhibiting miR-21/Spry1 func… (PMID:28946056)
• Study demonstrated that Spry1 has a role in supporting mitogen-induced vascular hyperplasia, at least in part by promoting Akt/Rb signaling and increasing mitogen-induced cyclinD1 expression and decreasing p27Kip1 expression. (PMID:29105817)
• Inhibition of miR-29b could attenuate atherosclerosis by inhibiting the SPRY1/MAPK signaling pathway and inflammation in aorta. (PMID:29398368)
• FREM2 is thus proposed as a novel GB biomarker and a putative biomarker of glioblastoma stem cells. Both FREM2 and SPRY1 are expressed on the surface of the GB cells, while SPRY1 alone was found overexpressed in the cytosol of non-malignant astrocytes. (PMID:29734672)
• SPRY1 maybe a negative feedback regulator in normal human epidermal keratinocytes. (PMID:30039569)
• Sprouty1 is induced after weight loss in adipose stem/progenitor cells of formerly obese people acting as a negative regulator of MAPK signalling, which is necessary to properly trigger adipogenesis at early stages by a C/EBP beta dependent mechanism. (PMID:31138786)
• Mechanism of SPRY1 methylation regulating natural aging of skin epidermal cells. (PMID:31483543)
• MicroRNA-421 promotes inflammatory response of fibroblast-like synoviocytes in rheumatoid arthritis by targeting SPRY1. (PMID:31646548)
• Sprouty1 Prevents Cellular Senescence Maintaining Proliferation and Differentiation Capacity of Human Adipose Stem/Progenitor Cells. (PMID:32304210)
• A SPRY1 domain cardiac ryanodine receptor variant associated with short-coupled torsade de pointes. (PMID:33664309)
• Circ_0020093 ameliorates IL-1beta-induced apoptosis and extracellular matrix degradation of human chondrocytes by upregulating SPRY1 via targeting miR-23b. (PMID:34046827)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	spry1	ENSDARG00000103985
mus_musculus	Spry1	ENSMUSG00000037211
rattus_norvegicus	Spry1	ENSRNOG00000025371
drosophila_melanogaster	sty	FBGN0014388

Paralogs (3): SPRY2 (ENSG00000136158), SPRY3 (ENSG00000168939), SPRY4 (ENSG00000187678)

Protein

Protein identifiers

Protein sprouty homolog 1 — O43609 (reviewed: O43609)

All UniProt accessions (4): O43609, D6REX7, D6RHD2, D6RIE6

UniProt curated annotations — full annotation on UniProt →

Function. Inhibits fibroblast growth factor (FGF)-induced retinal lens fiber differentiation, probably by inhibiting FGF-mediated phosphorylation of ERK1/2. Inhibits TGFB-induced epithelial-to-mesenchymal transition in lens epithelial cells.

Subunit / interactions. Forms heterodimers with SPRY2. Interacts with TESK1. Interacts with CAV1 (via C-terminus).

Subcellular location. Cytoplasm. Membrane.

Domain organisation. The Cys-rich domain is responsible for the localization of the protein to the membrane ruffles.

Similarity. Belongs to the sprouty family.

RefSeq proteins (5): NP_001244967, NP_001244968, NP_001362339, NP_005832, NP_955359 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007875	Sprouty	Family
IPR051192	Sprouty_domain	Family

Pfam: PF05210

UniProt features (7 total): region of interest 2, compositionally biased region 2, chain 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43609-F1	61.99	0.14

Functional residue map

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

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-182971	EGFR downregulation
R-HSA-162582	Signal Transduction
R-HSA-177929	Signaling by EGFR
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 407 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, TGGTGCT_MIR29A_MIR29B_MIR29C, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, GOBP_LENS_FIBER_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_METANEPHROS_DEVELOPMENT

GO Biological Process (18): establishment of mitotic spindle orientation (GO:0000132), metanephros development (GO:0001656), ureteric bud development (GO:0001657), organ induction (GO:0001759), negative regulation of cell population proliferation (GO:0008285), negative regulation of epithelial to mesenchymal transition (GO:0010719), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), negative regulation of fibroblast growth factor receptor signaling pathway (GO:0040037), negative regulation of Ras protein signal transduction (GO:0046580), animal organ development (GO:0048513), negative regulation of neurotrophin TRK receptor signaling pathway (GO:0051387), bud elongation involved in lung branching (GO:0060449), epithelial to mesenchymal transition involved in cardiac fibroblast development (GO:0060940), ERK1 and ERK2 cascade (GO:0070371), negative regulation of ERK1 and ERK2 cascade (GO:0070373), negative regulation of lens fiber cell differentiation (GO:1902747), multicellular organism development (GO:0007275), regulation of signal transduction (GO:0009966)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (6): nucleoplasm (GO:0005654), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Signaling by EGFR	1
Signaling by Receptor Tyrosine Kinases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
negative regulation of multicellular organismal process	2
negative regulation of signal transduction	2
negative regulation of cellular response to growth factor stimulus	2
anatomical structure development	2
cytoplasm	2
mitotic cell cycle	1
establishment of mitotic spindle localization	1
establishment of spindle orientation	1
kidney development	1
mesonephric tubule development	1
regulation of animal organ formation	1
specification of animal organ identity	1
developmental induction	1
positive regulation of animal organ morphogenesis	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
negative regulation of cell differentiation	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
fibroblast growth factor receptor signaling pathway	1
regulation of fibroblast growth factor receptor signaling pathway	1
Ras protein signal transduction	1
regulation of Ras protein signal transduction	1
negative regulation of small GTPase mediated signal transduction	1
neurotrophin TRK receptor signaling pathway	1
regulation of neurotrophin TRK receptor signaling pathway	1
epithelial tube branching involved in lung morphogenesis	1
branch elongation of an epithelium	1
cardiac epithelial to mesenchymal transition	1
epicardium-derived cardiac fibroblast cell development	1
MAPK cascade	1
negative regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
negative regulation of epithelial cell differentiation	1

Protein interactions and networks

STRING

1119 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPRY1	GRB2	P29354	968
SPRY1	RAF1	P04049	847
SPRY1	SOS1	Q07889	839
SPRY1	FRS2	Q8WU20	758
SPRY1	FGF8	P55075	701
SPRY1	PDCD4	Q53EL6	650
SPRY1	TRIM36	Q9NQ86	649
SPRY1	FKBP1B	P68106	633
SPRY1	FGF6	P10767	622
SPRY1	SPARC	P09486	594
SPRY1	FGF3	P11487	567
SPRY1	TMLHE	Q9NVH6	548
SPRY1	FGF16	O43320	544
SPRY1	GDNF	P39905	536
SPRY1	ETV5	P41161	534

IntAct

294 interactions, top by confidence:

A	B	Type	Score
SPRY1	LCE2D	psi-mi:“MI:0915”(physical association)	0.780
LCE2D	SPRY1	psi-mi:“MI:0915”(physical association)	0.780
SPRY1	MDFI	psi-mi:“MI:0915”(physical association)	0.740
MDFI	SPRY1	psi-mi:“MI:0915”(physical association)	0.740
SPRY1	HOXA1	psi-mi:“MI:0915”(physical association)	0.720
SPRY1	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.720
SPRY1	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-9	SPRY1	psi-mi:“MI:0915”(physical association)	0.720
CREB5	SPRY1	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-7	SPRY1	psi-mi:“MI:0915”(physical association)	0.720
SPRY1	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.720
HOXA1	SPRY1	psi-mi:“MI:0915”(physical association)	0.720
SPRY1	CREB5	psi-mi:“MI:0915”(physical association)	0.720
MEOX2	SPRY1	psi-mi:“MI:0915”(physical association)	0.670
SPRY1	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (136): SPRY1 (Two-hybrid), SPRY1 (Two-hybrid), SPRY1 (Two-hybrid), SPRY1 (Two-hybrid), SPRY1 (Two-hybrid), SPRY2 (Two-hybrid), R3HDM2 (Two-hybrid), KRTAP4-2 (Two-hybrid), HEXIM2 (Two-hybrid), LCE1B (Two-hybrid), LCE2D (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-1 (Two-hybrid), KRTAP10-5 (Two-hybrid)

ESM2 similar proteins: A0A1B0GRQ0, A0A1B0GSZ0, A0A1B0GVT2, A0A590UK83, A0PK05, A2VDU1, A2VE22, A4QNL6, A5D7B5, A5D992, O43609, O75324, P0DKX4, P29414, P61807, P61808, Q0VFM5, Q15053, Q16655, Q17Q87, Q1L0X2, Q2KIK3, Q2TBG9, Q3MHM8, Q498C7, Q4V921, Q58CU5, Q5RBD8, Q5RF07, Q5RGQ8, Q64448, Q6UWT2, Q80ZU4, Q8BGN6, Q8BUM6, Q8C3K5, Q8C817, Q8K1D8, Q8N6S5, Q91VT8

Diamond homologs: A2VDU1, A5D992, O43597, O43609, O43610, O44783, Q08E39, Q1L0X2, Q2MJR0, Q2PFN5, Q3C2P8, Q3UUD2, Q5R959, Q5RDN2, Q5Y171, Q6NYK3, Q6P6N5, Q7Z698, Q7Z699, Q866R9, Q924S7, Q924S8, Q9C004, Q9PTL1, Q9PTL2, Q9QXV8, Q9QXV9, Q9WTP2, Q66JG9, P50551

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SPRY1	down-regulates	SOS1	binding
PTPN11	down-regulates	SPRY1	dephosphorylation
hsa-mir-132-3p	“down-regulates quantity by repression”	SPRY1	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 76 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Keratinization	30	31.5×	2e-37
Formation of the cornified envelope	14	23.2×	2e-14

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	13	53.4×	2e-17

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	56
Likely benign	4
Benign	6

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
985257	NM_001258038.2(SPRY1):c.173_174insAG (p.Val59fs)	Likely pathogenic

SpliceAI

332 predictions. Top by Δscore:

Variant	Effect	Δscore
4:123396930:TAGG:T	donor_loss	1.0000
4:123396929:TTAG:T	donor_gain	0.9900
4:123396933:G:GG	donor_gain	0.9900
4:123396934:T:A	donor_loss	0.9900
4:123397501:G:GT	donor_gain	0.9900
4:123396928:ATTAG:A	donor_gain	0.9800
4:123396930:TAG:T	donor_gain	0.9800
4:123396931:AG:A	donor_gain	0.9800
4:123396932:GG:G	donor_gain	0.9800
4:123401535:AG:A	acceptor_gain	0.9700
4:123401536:GG:G	acceptor_gain	0.9700
4:123402710:AT:A	acceptor_gain	0.9700
4:123402711:T:G	acceptor_gain	0.9700
4:123401533:TTAG:T	acceptor_loss	0.9600
4:123401535:AGGAT:A	acceptor_loss	0.9600
4:123401536:G:GA	acceptor_loss	0.9600
4:123401536:GGA:G	acceptor_gain	0.9600
4:123402711:T:TA	acceptor_gain	0.9600
4:123398509:CCTAG:C	donor_loss	0.9400
4:123398510:CTAGG:C	donor_loss	0.9400
4:123398512:AG:A	donor_loss	0.9400
4:123398513:GG:G	donor_loss	0.9400
4:123398514:G:GC	donor_loss	0.9400
4:123398515:T:A	donor_loss	0.9400
4:123398516:G:GG	donor_loss	0.9400
4:123401535:A:AG	acceptor_gain	0.9400
4:123401536:G:GG	acceptor_gain	0.9400
4:123396935:AA:A	donor_loss	0.9300
4:123401529:C:A	acceptor_loss	0.9300
4:123402710:ATG:A	acceptor_gain	0.9200

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000475492 (4:123399887 A>C), RS1000789776 (4:123398904 G>A), RS1001285453 (4:123399506 C>G,T), RS1002110121 (4:123403377 C>T), RS1002197646 (4:123397351 C>T), RS1002544590 (4:123403707 G>A,C), RS1003281697 (4:123400736 G>A,C), RS1004309842 (4:123395454 A>G), RS1004583075 (4:123402668 C>G,T), RS1004736493 (4:123400455 A>G), RS1005093087 (4:123396793 G>A), RS1005292008 (4:123402935 T>A), RS1005472316 (4:123398478 C>G,T), RS1005866891 (4:123398603 G>A,C), RS1006185043 (4:123400325 A>G)

Disease associations

OMIM: gene MIM:602465 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
craniosynostosis	Moderate	Autosomal recessive

Mondo (1): craniosynostosis (MONDO:0015469)

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST002436_2	Irritable bowel syndrome	8.000000e-08
GCST003226_11	Pelvic organ prolapse	2.000000e-06
GCST004865_78	Itch intensity from mosquito bite adjusted by bite size	6.000000e-07
GCST006186_5	Systolic blood pressure x smoking status (current vs non-current) interaction (1df test)	6.000000e-06
GCST006193_93	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	4.000000e-08
GCST006194_2	Diastolic blood pressure x smoking status (current vs non-current) interaction (1df test)	3.000000e-08
GCST008079_135	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	3.000000e-06
GCST008079_80	LDL cholesterol levels x alcohol consumption (drinkers vs non-drinkers) interaction (2df)	6.000000e-09
GCST009391_1260	Metabolite levels	6.000000e-06
GCST010243_84	Apolipoprotein B levels	1.000000e-10
GCST010244_72	Triglyceride levels	2.000000e-09
GCST90020024_687	A body shape index	8.000000e-09

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0006335	systolic blood pressure
EFO:0006527	smoking status measurement
EFO:0006336	diastolic blood pressure
EFO:0004329	alcohol drinking
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004761	uric acid measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004530	triglyceride measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, decreases expression, affects cotreatment, increases abundance	5
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression	5
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	5
trichostatin A	affects cotreatment, decreases expression	3
(+)-JQ1 compound	decreases expression	3
Tetrachlorodibenzodioxin	decreases expression, increases expression	3
Aflatoxin B1	increases expression, affects expression, decreases methylation	3
Resveratrol	decreases reaction, increases expression, decreases expression	2
Vorinostat	affects cotreatment, decreases expression	2
Ethanol	increases abundance, affects cotreatment, increases expression, decreases expression	2
Cisplatin	affects cotreatment, increases expression	2
Doxorubicin	decreases expression, increases expression	2
Estradiol	affects expression, affects cotreatment, decreases expression	2
Oxygen	decreases reaction, increases expression, affects expression	2
Silver	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment	2
aristolochic acid I	decreases expression	1
1-cyclopropyl-4-(4-((5-methyl-3-(3-(4-(trifluoromethoxy)phenyl)-1,2,4-oxadiazol-5-yl)-1H-pyrazol-1-yl)methyl)pyridin-2-yl)piperazine	decreases reaction, increases expression	1
GSK-J4	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
chloroacetaldehyde	decreases expression	1
baicalein	decreases expression, decreases reaction, affects reaction, increases expression	1
bisphenol A	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
beta-lapachone	decreases expression	1
arsenite	decreases expression, decreases reaction	1
methylparaben	decreases expression	1
nickel chloride	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00722436	PHASE4	TERMINATED	Tranexamic Acid for Craniofacial Surgery
NCT02188576	PHASE4	COMPLETED	The Efficacy and Population Pharmacokinetics of Tranexamic Acid for Craniosynostosis Surgery
NCT02229968	PHASE2	ACTIVE_NOT_RECRUITING	Efficacy of Amicar for Children Having Craniofacial Surgery
NCT00912119	PHASE1	COMPLETED	Amicar Pharmacokinetics of Children Having Craniofacial Surgery
NCT00077831	Not specified	COMPLETED	Child and Infant Learning Project
NCT00106977	Not specified	COMPLETED	Clinical Study of Muenke Syndrome (FGFR3-Related Craniosynostosis)
NCT00367796	Not specified	COMPLETED	Genetic Analysis of Craniosynostosis, Philadelphia Type
NCT00769847	Not specified	WITHDRAWN	Endoscopic Treatment for Isolated, Single Suture Craniosynostosis
NCT00773643	Not specified	COMPLETED	Osteogenic Profiling of Tissue From Children With Craniosynostosis
NCT01898650	Not specified	COMPLETED	MRI for Non-invasive Evaluation of Brain Stress
NCT02287805	Not specified	COMPLETED	Qualitative and Quantitative Study Which Aims to Determine the Specifics of the Announcement for the Diagnosis of Patients With Craniosynostosis and Their Parents to Better Support Them in Their Care
NCT02561728	Not specified	WITHDRAWN	Hanger Helmet Study
NCT03025763	Not specified	ACTIVE_NOT_RECRUITING	Network Of Clinical Research Studies On Craniosynostosis, Skull Malformations With Premature Fusion Of Skull Bones
NCT03231085	Not specified	COMPLETED	Comparison of the Rate of Preoperative Haemoglobin After Administration of Epoetin Alpha Associated With an Oral Medical Supplementation Versus Intravenous Before Surgery of Craniosynostosis at the Child
NCT04704284	Not specified	COMPLETED	Comparing MRI to CT on Pediatric Craniosynostosis.
NCT05911139	Not specified	ENROLLING_BY_INVITATION	Influence of General Anesthesia on the Dynamic Changes in Brain Damage Markers During and After Craniosynostosis Operations in Infancy
NCT06928727	Not specified	RECRUITING	Ocular Characteristics in Patients With Craniosynostosis