SNX14

sorting nexin 14, the group of Sorting nexins

Basic information

Region (hg38): 6:85504775-85594156

Links

ENSG00000135317 ∙ NCBI:57231 ∙ OMIM:616105 ∙ HGNC:14977 ∙ Uniprot:Q9Y5W7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive spinocerebellar ataxia 20 (Strong), mode of inheritance: AR
• autosomal recessive spinocerebellar ataxia 20 (Supportive), mode of inheritance: AR
• autosomal recessive spinocerebellar ataxia 20 (Strong), mode of inheritance: AR
• autosomal recessive spinocerebellar ataxia 20 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia, autosomal recessive 20	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Neurologic	24501761; 25439728; 25848753

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SNX14 gene.

• not provided (195 variants)
• Autosomal recessive spinocerebellar ataxia 20 (27 variants)
• Inborn genetic diseases (24 variants)
• not specified (4 variants)
• SNX14-related condition (2 variants)
• Neurodevelopmental disorder (2 variants)
• Abnormal brain morphology (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SNX14 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			1	26	1	28
missense			69	1	2	72
nonsense	3	4				7
start loss						0
frameshift	4	3				7
inframe indel			2			2
splice donor/acceptor (+/-2bp)	2	5				7
splice region			6	6	5	17
non coding		1	6	40	43	90
Total	9	13	78	67	46

Highest pathogenic variant AF is 0.0000395

Variants in SNX14

This is a list of pathogenic ClinVar variants found in the SNX14 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-85505665-C-T			Likely benign (Sep 26, 2018)
6-85505711-TTC-T			Likely benign (Nov 08, 2018)
6-85505762-G-A			Likely benign (Jan 12, 2020)
6-85505953-C-A		not specified	Uncertain significance (Aug 24, 2023)
6-85506008-A-C			Uncertain significance (Jun 10, 2022)
6-85506179-C-T			Benign (Jul 21, 2018)
6-85507215-T-G			Likely benign (Jul 10, 2023)
6-85507264-ACAATGTC-A		Autosomal recessive spinocerebellar ataxia 20	Conflicting classifications of pathogenicity (May 02, 2023)
6-85507291-T-C		Autosomal recessive spinocerebellar ataxia 20	Likely pathogenic (May 08, 2023)
6-85507303-AAAT-A			Likely benign (Jan 25, 2023)
6-85507361-A-G			Benign (Jan 20, 2019)
6-85507372-T-C			Benign (Jan 20, 2019)
6-85507730-G-T			Benign (Jul 06, 2018)
6-85507915-C-A			Likely benign (Sep 23, 2019)
6-85507915-C-T			Likely benign (Jul 05, 2018)
6-85507948-C-T			Benign (Mar 19, 2023)
6-85507949-G-C			Likely benign (Jun 26, 2022)
6-85507988-G-C		Inborn genetic diseases	Uncertain significance (Jan 10, 2023)
6-85508025-C-T			Likely benign (Mar 26, 2022)
6-85508039-C-T		Autosomal recessive spinocerebellar ataxia 20	Uncertain significance (Feb 15, 2019)
6-85508042-TA-T		Autosomal recessive spinocerebellar ataxia 20	Pathogenic (May 02, 2023)
6-85508059-T-C			Uncertain significance (May 10, 2023)
6-85508320-TA-T			Likely benign (Aug 21, 2019)
6-85508320-T-TA			Benign (Sep 02, 2019)
6-85513595-G-A			Benign (Mar 16, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SNX14	protein_coding	protein_coding	ENST00000314673	29	88661

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.07e-17	0.982	125650	0	98	125748	0.000390

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.85	350	462	0.758	0.0000218	6215
Missense in Polyphen		87	141.32	0.61564		1963
Synonymous	-0.719	169	158	1.07	0.00000731	1692
Loss of Function	2.61	35	56.1	0.624	0.00000270	748

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000525	0.000516
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00122	0.00114
Finnish	0.000144	0.000139
European (Non-Finnish)	0.000437	0.000422
Middle Eastern	0.00122	0.00114
South Asian	0.000405	0.000392
Other	0.000336	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in maintaining normal neuronal excitability and synaptic transmission. May be involved in several stages of intracellular trafficking (By similarity). Required for autophagosome clearance, possibly by mediating the fusion of lysosomes with autophagosomes (Probable). Binds phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2), a key component of late endosomes/lysosomes (PubMed:25848753). Does not bind phosphatidylinositol 3-phosphate (PtdIns(3P)) (PubMed:25848753, PubMed:25148684). {ECO:0000250|UniProtKB:Q8BHY8, ECO:0000269|PubMed:25148684, ECO:0000269|PubMed:25848753, ECO:0000305|PubMed:25848753}.

Recessive Scores

• pRec: 0.108

Intolerance Scores

• loftool: 0.964
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.65

Haploinsufficiency Scores

• pHI: 0.168
• hipred: Y
• hipred_score: 0.536
• ghis: 0.619

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.508

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Snx14

Zebrafish Information Network

• Gene name: snx14
• Affected structure: neuron
• Phenotype tag: abnormal
• Phenotype quality: apoptotic

Gene ontology

• Biological process: protein transport;autophagosome maturation
• Cellular component: lysosome;lysosomal membrane;late endosome;integral component of membrane;dendrite;late endosome membrane
• Molecular function: phosphatidylinositol-3,5-bisphosphate binding