SNX5

protein-coding

sorting nexin 5, the group of PX-BAR domain containing|Sorting nexins|Small nucleolar RNA protein coding host genes

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 functions in endosomal sorting, the phosphoinositide-signaling pathway, and macropinocytosis. This gene may play a role in the tumorigenesis of papillary thyroid carcinoma. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]

MANE transcript

NM_014426.4

Inheritance

—

ClinVar variants

U:62

Top phenotype

SNX5-related condition

gnomAD constraint

pLI —, LoF o/e 0.38

Max pathogenic AF

—

Genomic locus

chr20:17,941,597-17,968,980

External References & Databases

Ensembl (ENSG00000089006)

Transcript & Mutation Effects

hg38 • Region Span ~27.4 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 SNX5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 54

SNX5-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014426.4. 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			55 clinvar			55
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	62	0	0	62

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014426.4	RefSeq	NP_055241.1	13	MANE Select
ENST00000377759.9	Ensembl	ENSP00000366988.3	13	MANE Select
NM_001282454.2	RefSeq	NP_001269383.1	10	Standard
NM_152227.3	RefSeq	NP_689413.1	13	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
snx5	Danio rerio	Structure: Muller cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

snx5

Danio rerio

Structure: Muller cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)
Golgi Associated Vesicle Biogenesis
Clathrin derived vesicle budding
trans-Golgi Network Vesicle Budding
Vesicle-mediated transport

Biological Process

intracellular protein transport
pinocytosis
epidermal growth factor catabolic process
regulation of macroautophagy
positive regulation of renal sodium excretion

Molecular Function

protein binding
phosphatidylinositol-5-phosphate binding
D1 dopamine receptor binding
dynactin binding
phosphatidylinositol binding

Cellular Component

ruffle
phagocytic cup
cytosol
brush border
cytoplasmic vesicle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377768
Coding exons: 13
Length: 27383
Individuals with no LoFs: 125710
Homozygous LoFs: 0
Heterozygous LoFs: 38
Defined: 125748
p: 0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.139	204	210	0.973	0.0000108	2690
Missense (PolyPhen)		58	70.846	0.81868		961
Synonymous	-0.575	84	77.6	1.08	0.00000417	725
Loss of Function	2.81	9	23.8	0.379	0.00000132	298

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00049	0.00049	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00020	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in several stages of intracellular trafficking. Interacts with membranes containing phosphatidylinositol 3- phosphate (PtdIns(3P)) or phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) (PubMed:15561769). Acts in part as component of the retromer membrane-deforming SNX-BAR subcomplex. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC) (Probable). Does not have in vitro vesicle-to-membrane remodeling activity (PubMed:23085988). Involved in retrograde transport of lysosomal enzyme receptor IGF2R (PubMed:17148574, PubMed:18596235). May function as link between endosomal transport vesicles and dynactin (Probable). Plays a role in the internalization of EGFR after EGF stimulation (Probable). Involved in EGFR endosomal sorting and degradation; the function involves PIP5K1C isoform 3 and is retromer-independent (PubMed:23602387). Together with PIP5K1C isoform 3 facilitates HGS interaction with ubiquitinated EGFR, which initiates EGFR sorting to intraluminal vesicles (ILVs) of the multivesicular body for subsequent lysosomal degradation (Probable). Involved in E-cadherin sorting and degradation; inhibits PIP5K1C isoform 3-mediated E-cadherin degradation (PubMed:24610942). Plays a role in macropinocytosis (PubMed:18854019, PubMed:21048941). {ECO:0000269|PubMed:18854019, ECO:0000269|PubMed:21048941, ECO:0000269|PubMed:24610942, ECO:0000303|PubMed:15561769, ECO:0000303|PubMed:19619496, ECO:0000303|PubMed:23085988}.;

Recessive Scores

pRec: 0.208

Intolerance Scores

LoFtool: 0.812
RVIS EVS: -0.25
RVIS percentile EVS: 35.99

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.997

Gene Damage Prediction

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