SPRY2

protein-coding

sprouty RTK signaling antagonist 2

Gene summary

This gene encodes a protein belonging to the sprouty family. The encoded protein contains a carboxyl-terminal cysteine-rich domain essential for the inhibitory activity on receptor tyrosine kinase signaling proteins and is required for growth factor stimulated translocation of the protein to membrane ruffles. In primary dermal endothelial cells this gene is transiently upregulated in response to fibroblast growth factor two. This protein is indirectly involved in the non-cell autonomous inhibitory effect on fibroblast growth factor two signaling. The protein interacts with Cas-Br-M (murine) ectropic retroviral transforming sequence, and can function as a bimodal regulator of epidermal growth factor receptor/mitogen-activated protein kinase signaling. This protein may play a role in alveoli branching during lung development as shown by a similar mouse protein. [provided by RefSeq, Jul 2008]

MANE transcript

NM_005842.4

Inheritance

ClinVar variants

U:41B:3

Top phenotype

IgA nephropathy, susceptibility to, 3

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr13:80,335,976-80,341,126

External References & Databases

Ensembl (ENSG00000136158)

Transcript & Mutation Effects

hg38 • Region Span ~5.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Tourette syndromeLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0007661

Submitter: Labcorp Genetics (formerly Invitae)

IgA nephropathy, susceptibility to, 3LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0014786

Submitter: Labcorp Genetics (formerly Invitae)

IgA nephropathy, susceptibility to, 3LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014786

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

IgA nephropathy, susceptibility to, 3AD

Manifestation: Renal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 25782674

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SPRY2 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 33

SPRY2-related disorderTotal: 5

IgA nephropathy, susceptibility to, 3Total: 3

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005842.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar	1 clinvar	2
missense			38 clinvar		1 clinvar	39
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	0	0	41	1	2	44

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 43 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005842.4	RefSeq	NP_005833.1	1	MANE Select
ENST00000377104.4	Ensembl	ENSP00000366308.3	1	MANE Select
NM_001318536.1	RefSeq	NP_001305465.1	1	Standard
NM_001318537.1	RefSeq	NP_001305466.1	1	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
spry2	Danio rerio	Structure: neural plate Quality: increased width abnormal

Gene / Model

Organism

Observed Phenotype

spry2

Danio rerio

Structure: neural plate

Quality: increased width

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

MicroRNAs in cancer - Homo sapiens (human)
Signaling Pathways in Glioblastoma
Androgen Receptor Network in Prostate Cancer
Ectoderm Differentiation
EGF-EGFR Signaling Pathway

Biological Process

establishment of mitotic spindle orientation
sensory perception of sound
negative regulation of cell population proliferation
positive regulation of gene expression
negative regulation of peptidyl-threonine phosphorylation

Molecular Function

protein binding
protein kinase binding
protein serine/threonine kinase inhibitor activity
protein serine/threonine kinase activator activity

Cellular Component

nucleus
cytosol
cytoskeleton
microtubule
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377102
Coding exons: 1
Length: 4976
Individuals with no LoFs: 125711
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125712
p: 0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.974	139	175	0.793	0.0000101	2039
Missense (PolyPhen)		42	69.913	0.60075		897
Synonymous	-1.37	87	72.2	1.21	0.00000443	649
Loss of Function	3.07	0	11.0	0.00	7.20e-7	124

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May function as an antagonist of fibroblast growth factor (FGF) pathways and may negatively modulate respiratory organogenesis. {ECO:0000269|PubMed:10887178}.;
Disease: DISEASE: IgA nephropathy 3 (IGAN3) [MIM:616818]: A form of IgA nephropathy, a common primary glomerulonephritis characterized by glomerular sclerosis, interstitial fibrosis, and mesangial glomerular deposits of immunoglobulin A and immunoglobulin G visible on renal biopsies. IgA nephropathy is associated with renal insufficiency that can progress to end-stage renal disease. Proteinuria and hematuria are characteristic clinical presentations. {ECO:0000269|PubMed:25782674}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool: 0.0887
RVIS EVS: 0.08
RVIS percentile EVS: 60.09

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.801

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium