SNX15

protein-coding

sorting nexin 15, the group of Sorting nexins

Gene summary

This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. Overexpression of this gene results in a decrease in the processing of insulin and hepatocyte growth factor receptors to their mature subunits. This decrease is caused by the mislocalization of furin, the endoprotease responsible for cleavage of insulin and hepatocyte growth factor receptors. This protein is involved in endosomal trafficking from the plasma membrane to recycling endosomes or the trans-Golgi network. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the upstream ADP-ribosylation factor-like 2 (ARL2) gene. [provided by RefSeq, Dec 2010]

MANE transcript

NM_013306.5

Inheritance

—

ClinVar variants

U:59B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.64

Max pathogenic AF

—

Genomic locus

chr11:65,027,439-65,040,572

External References & Databases

Ensembl (ENSG00000110025)

Transcript & Mutation Effects

hg38 • Region Span ~13.1 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 SNX15 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 61

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_013306.5. 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			59 clinvar	2 clinvar		61
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	59	2	0	61

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_013306.5	RefSeq	NP_037438.2	8	MANE Select
ENST00000377244.8	Ensembl	ENSP00000366452.3	8	MANE Select
NM_147777.4	RefSeq	NP_680086.2	7	Standard
ENST00000352068.5	Ensembl	ENSP00000316410.5	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

miR-targeted genes in lymphocytes - TarBase
miR-targeted genes in muscle cell - TarBase

Biological Process

intracellular protein transport

Molecular Function

protein binding
phosphatidylinositol binding

Cellular Component

nucleolus
cytosol
membrane
cytoplasmic vesicle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377244
Coding exons: 8
Length: 13165
Individuals with no LoFs: 125695
Homozygous LoFs: 0
Heterozygous LoFs: 53
Defined: 125748
p: 0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.874	170	205	0.828	0.0000124	2165
Missense (PolyPhen)		75	86.022	0.87187		825
Synonymous	1.20	70	84.0	0.833	0.00000473	710
Loss of Function	1.40	11	17.3	0.637	0.00000105	180

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.000065	0.000058	rare
Ashkenazi Jewish	0.00035	0.00030	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00067	0.00065	rare
European (Non-Finnish)	0.00025	0.00023	rare
South Asian	0.00011	0.000098	rare
Other	0.00018	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in several stages of intracellular trafficking. Overexpression of SNX15 disrupts the normal trafficking of proteins from the plasma membrane to recycling endosomes or the TGN. {ECO:0000269|PubMed:11085978}.;

Recessive Scores

pRec: 0.154

Intolerance Scores

LoFtool: 0.828
RVIS EVS: 0.2
RVIS percentile EVS: 67.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.688

Gene Damage Prediction

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