SNX17

protein-coding

sorting nexin 17, 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. This protein does not contain a coiled coil region, like some family members, but contains a B41 domain. This protein interacts with the cytoplasmic domain of P-selectin, and may function in the intracellular trafficking of P-selectin. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2012]

MANE transcript

NM_014748.4

Inheritance

—

ClinVar variants

U:67B:3

Top phenotype

SNX17-related disorder

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr2:27,370,496-27,377,535

External References & Databases

Ensembl (ENSG00000115234)

Transcript & Mutation Effects

hg38 • Region Span ~7.0 kb

Loading mutation effect viewer...

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 SNX17 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 52

SNX17-related disorderTotal: 3

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014748.4. 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			3 clinvar	2 clinvar		5
missense			57 clinvar	1 clinvar		58
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	67	3	0	70

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 69 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014748.4	RefSeq	NP_055563.1	15	MANE Select
ENST00000233575.7	Ensembl	ENSP00000233575.2	15	MANE Select
NM_001267059.2	RefSeq	NP_001253988.1	15	Standard
NM_001267060.2	RefSeq	NP_001253989.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cardiac septum development
cholesterol catabolic process
intracellular protein transport
receptor-mediated endocytosis
signal transduction

Molecular Function

signaling receptor binding
protein binding
protein C-terminus binding
phosphatidylinositol binding
low-density lipoprotein particle receptor binding

Cellular Component

endosome
early endosome
Golgi apparatus
cytosol
endosome membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000233575
Coding exons: 15
Length: 6607
Individuals with no LoFs: 125726
Homozygous LoFs: 0
Heterozygous LoFs: 22
Defined: 125748
p: 0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.778	250	287	0.871	0.0000180	3043
Missense (PolyPhen)		44	77.135	0.57043		940
Synonymous	-1.55	128	108	1.19	0.00000587	941
Loss of Function	3.30	10	29.3	0.341	0.00000149	326

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Critical regulator of endosomal recycling of numerous receptors, channels, and other transmembrane proteins. Binds to NPxY sequences in the cytoplasmic tails of target cargos. Plays a role in the sorting of endocytosed LRP1 and APP, and prevents their degradation. Required for maintenance of normal cell surface levels of APP and LRP1. Recycles internalized integrins ITGB1, ITGB5 and their associated alpha subunits, preventing them from lysosomal degradation. Interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)). {ECO:0000269|PubMed:15121882, ECO:0000269|PubMed:15769472, ECO:0000269|PubMed:16712798, ECO:0000269|PubMed:19005208, ECO:0000269|PubMed:21512128, ECO:0000269|PubMed:22492727}.;

Recessive Scores

pRec: 0.117

Intolerance Scores

LoFtool: 0.460
RVIS EVS: 0.04
RVIS percentile EVS: 57.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.957

Gene Damage Prediction

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