SPRY1

protein-coding

sprouty RTK signaling antagonist 1

Gene summary

Predicted to enable protein kinase inhibitor activity. Involved in negative regulation of fibroblast growth factor receptor signaling pathway. Predicted to be located in plasma membrane. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001258038.2

Inheritance

ClinVar variants

P:1U:56B:5

Top phenotype

SPRY1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.58

Max pathogenic AF

—

Genomic locus

chr4:123,396,795-123,403,760

External References & Databases

Ensembl (ENSG00000164056)

Transcript & Mutation Effects

hg38 • Region Span ~7.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

craniosynostosisMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0015469

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SPRY1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 55

SPRY1-related disorderTotal: 5

Inborn genetic diseasesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001258038.2. 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				2 clinvar	1 clinvar	3
missense			55 clinvar	2 clinvar		57
nonsense						0
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	1	56	4	1	62

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001258038.2	RefSeq	NP_001244967.1	1	MANE Select
ENST00000651917.1	Ensembl	ENSP00000498292.1	1	MANE Select
NM_001258039.1	RefSeq	NP_001244968.1	1	Standard
NM_001375410.1	RefSeq	NP_001362339.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Androgen Receptor Network in Prostate Cancer
Glucocorticoid Receptor Pathway
Nuclear Receptors Meta-Pathway
Signal Transduction
sprouty regulation of tyrosine kinase signals

Biological Process

establishment of mitotic spindle orientation
metanephros development
ureteric bud development
organ induction
negative regulation of cell population proliferation

Molecular Function

protein binding

Cellular Component

nucleoplasm
Golgi apparatus
cytosol
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000394339
Coding exons: 1
Length: 6961
Individuals with no LoFs: 125737
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125748
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.950	200	166	1.21	0.00000879	2081
Missense (PolyPhen)		60	58.901	1.0187		768
Synonymous	-0.719	71	63.7	1.11	0.00000340	626
Loss of Function	1.14	5	8.60	0.581	3.82e-7	140

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May function as an antagonist of fibroblast growth factor (FGF) pathways and may negatively modulate respiratory organogenesis.;

Recessive Scores

pRec: 0.175

Intolerance Scores

LoFtool: 0.587
RVIS EVS: -0.16
RVIS percentile EVS: 41.91

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.774

Gene Damage Prediction

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