SNX3

protein-coding

sorting nexin 3, 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 most family members. This protein interacts with phosphatidylinositol-3-phosphate, and is involved in protein trafficking. A pseudogene of this gene is present on the sex chromosomes. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

MANE transcript

NM_003795.6

Inheritance

ClinVar variants

U:14B:3

Top phenotype

SNX3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.27

Max pathogenic AF

—

Genomic locus

chr6:108,211,222-108,261,246

External References & Databases

Ensembl (ENSG00000112335)

Transcript & Mutation Effects

hg38 • Region Span ~50.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

MMEP syndromeLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0011045

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SNX3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 11

SNX3-related disorderTotal: 2

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003795.6. 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		3
missense			11 clinvar			11
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	14	3	0	17

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003795.6	RefSeq	NP_003786.1	4	MANE Select
ENST00000230085.13	Ensembl	ENSP00000230085.8	4	MANE Select
NM_001300928.2	RefSeq	NP_001287857.1	3	Standard
NM_001300929.2	RefSeq	NP_001287858.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
snx3	Danio rerio	Structure: nucleate erythrocyte Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

snx3

Danio rerio

Structure: nucleate erythrocyte

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Endocytosis - Homo sapiens (human)
Signaling by WNT
Signal Transduction
Post-translational protein modification
Metabolism of proteins

Biological Process

response to bacterium
membrane invagination
positive regulation of neuron projection development
protein transport
Wnt signaling pathway

Molecular Function

protein binding
phosphatidylinositol-5-phosphate binding
protein phosphatase binding
phosphatidylinositol-3-phosphate binding
phosphatidylinositol-4-phosphate binding

Cellular Component

cytoplasm
early endosome
cytosol
endosome membrane
clathrin-coated vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000230085
Coding exons: 4
Length: 50039
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125742
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.73	44	90.1	0.488	0.00000476	1060
Missense (PolyPhen)		11	35.626	0.30876		423
Synonymous	-1.13	44	35.5	1.24	0.00000191	310
Loss of Function	1.86	2	7.52	0.266	3.99e-7	87

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0.00017	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Phosphoinositide-binding protein required for multivesicular body formation. Specifically binds phosphatidylinositol 3-phosphate (PtdIns(P3)). Also can bind phosphatidylinositol 4-phosphate (PtdIns(P4)), phosphatidylinositol 5-phosphate (PtdIns(P5)) and phosphatidylinositol 3,5-biphosphate (PtdIns(3,5)P2) (By similarity). Plays a role in protein transport between cellular compartments. Together with RAB7A facilitates endosome membrane association of the retromer cargo-selective subcomplex (CSC/VPS). May in part act as component of the SNX3-retromer complex which mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway (PubMed:21725319, PubMed:24344282). Promotes stability and cell surface expression of epithelial sodium channel (ENAC) subunits SCNN1A and SCNN1G (By similarity). Not involved in EGFR degradation. Involved in the regulation of phagocytosis in dendritic cells possibly by regulating EEA1 recruitment to the nascent phagosomes (PubMed:23237080). Involved in iron homeostasis through regulation of endocytic recycling of the transferrin receptor TFRC presumably by delivering the transferrin:transferrin receptor complex to recycling endosomes; the function may involve the CSC retromer subcomplex (By similarity). In the case of Salmonella enterica infection plays arole in maturation of the Salmonella-containing vacuole (SCV) and promotes recruitment of LAMP1 to SCVs (PubMed:20482551). {ECO:0000250|UniProtKB:O70492, ECO:0000269|PubMed:11433298, ECO:0000269|PubMed:18767904, ECO:0000269|PubMed:21725319, ECO:0000269|PubMed:23237080, ECO:0000269|PubMed:24344282, ECO:0000305|PubMed:21725319}.;
Disease: DISEASE: Note=A chromosomal aberration involving SNX3 has been found in patients with syndromic microphthalmia. Translocation t(6;13)(q21;q12). {ECO:0000269|PubMed:12471201}.;

Recessive Scores

pRec: 0.156

Intolerance Scores

LoFtool: 0.251
RVIS EVS: 0.12
RVIS percentile EVS: 62.38

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.801

Gene Damage Prediction

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