SH3YL1

protein-coding

SH3 and SYLF domain containing 1

Gene summary

Enables phosphatase binding activity and phosphatidylinositol binding activity. Predicted to be involved in regulation of ruffle assembly. Predicted to act upstream of or within phosphatidylinositol biosynthetic process. Located in ruffle membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_015677.4

Inheritance

—

ClinVar variants

U:67B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.71

Max pathogenic AF

—

Genomic locus

chr2:217,730-266,398

External References & Databases

Ensembl (ENSG00000035115)

Transcript & Mutation Effects

hg38 • Region Span ~48.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SH3YL1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 60

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015677.4. 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						0
missense			62 clinvar	2 clinvar		64
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	67	2	0	69

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 49 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015677.4	RefSeq	NP_056492.2	10	MANE Select
ENST00000356150.10	Ensembl	ENSP00000348471.5	10	MANE Select
NM_001159597.3	RefSeq	NP_001153069.1	9	Standard
NM_001282682.2	RefSeq	NP_001269611.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

phosphatidylinositol biosynthetic process
regulation of ruffle assembly

Molecular Function

protein binding
phosphatase binding
phosphatidylinositol binding

Cellular Component

ruffle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000356150
Coding exons: 10
Length: 48669
Individuals with no LoFs: 124488
Homozygous LoFs: 3
Heterozygous LoFs: 303
Defined: 124794
p: 0.00123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.501	163	182	0.895	0.00000988	2190
Missense (PolyPhen)		65	69.969	0.92898		802
Synonymous	0.893	62	71.6	0.866	0.00000445	685
Loss of Function	1.19	14	19.7	0.711	0.00000107	257

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00020	0.00019	rare
Latino/Admixed American	0.0013	0.0012	notable
Ashkenazi Jewish	0.00061	0.00060	rare
East Asian	0.00089	0.00089	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00060	0.00058	rare
South Asian	0.0054	0.0052	notable
Other	0.0021	0.0020	notable

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.188

Intolerance Scores

LoFtool: 0.852
RVIS EVS: 0.13
RVIS percentile EVS: 63

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.760

Gene Damage Prediction

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