SNX3

sorting nexin 3, the group of Sorting nexins

Basic information

Region (hg38): 6:108211222-108261246

Links

ENSG00000112335

∙ NCBI:8724 ∙ OMIM:605930 ∙ HGNC:11174 ∙ Uniprot:O60493 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

MMEP syndrome (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SNX3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SNX3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				2 clinvar		2
missense			6 clinvar			6
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	6	2	0

Variants in SNX3

This is a list of pathogenic ClinVar variants found in the SNX3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Phenotype	Significance	ClinVar
6-108212170-T-C		Likely benign (Jan 31, 2018)	722259
6-108212227-G-A	SNX3-related disorder	Likely benign (Oct 03, 2019)	3355140
6-108214563-A-C	not specified	Uncertain significance (Oct 06, 2021)	2253260
6-108222963-T-C	not specified	Uncertain significance (Jan 16, 2024)	3167266
6-108260792-C-T	not specified	Uncertain significance (May 26, 2023)	2565044
6-108260826-A-G	SNX3-related disorder	Likely benign (Jan 14, 2021)	3031721
6-108260842-T-G	not specified	Uncertain significance (Dec 22, 2023)	3167267
6-108260899-G-C	not specified	Uncertain significance (Jul 26, 2022)	2303714
6-108260911-G-C	not specified	Uncertain significance (Feb 28, 2023)	2490347

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SNX3	protein_coding	protein_coding	ENST00000230085	4	50039

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.249	0.725	125735	0	7	125742	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.73	44	90.1	0.488	0.00000476	1060
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000178	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.000165	0.000163
Other	0.00	0.00

dbNSFP

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}.;
Pathway: Endocytosis - Homo sapiens (human);Signaling by WNT;Signal Transduction;Post-translational protein modification;Metabolism of proteins;Ub-specific processing proteases;Deubiquitination;WNT ligand biogenesis and trafficking (Consensus)

Recessive Scores

pRec: 0.156

Intolerance Scores

loftool: 0.251
rvis_EVS: 0.12
rvis_percentile_EVS: 62.38

Haploinsufficiency Scores

pHI: 0.570
hipred: Y
hipred_score: 0.800
ghis: 0.566

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Snx3
Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);

Zebrafish Information Network

Gene name: snx3
Affected structure: nucleate erythrocyte
Phenotype tag: abnormal
Phenotype quality: decreased amount

Gene ontology

Biological process: response to bacterium;membrane invagination;positive regulation of neuron projection development;protein transport;Wnt signaling pathway;protein deubiquitination;protein to membrane docking;regulation of Wnt signaling pathway;negative regulation of protein catabolic process;negative regulation of viral entry into host cell;negative regulation of phagocytosis;negative regulation of protein transport;intralumenal vesicle formation;negative regulation of early endosome to late endosome transport
Cellular component: cytoplasm;early endosome;cytosol;endosome membrane;clathrin-coated vesicle;retromer complex;early endosome membrane;early phagosome;extracellular exosome
Molecular function: protein binding;phosphatidylinositol-5-phosphate binding;protein phosphatase binding;phosphatidylinositol-3-phosphate binding;phosphatidylinositol-4-phosphate binding;phosphatidylinositol-3,5-bisphosphate binding