SNX10

sorting nexin 10, the group of Sorting nexins

Basic information

Region (hg38): 7:26291862-26374383

Links

ENSG00000086300 ∙ NCBI:29887 ∙ OMIM:614780 ∙ HGNC:14974 ∙ Uniprot:Q9Y5X0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive osteopetrosis 8 (Strong), mode of inheritance: AR
• autosomal recessive osteopetrosis 8 (Strong), mode of inheritance: AR
• autosomal recessive osteopetrosis (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Osteopetrosis, autosomal recessive 8	AR	Musculoskeletal	The condition has been described as manifesting with sequelae of osteopetrosis, including failure to thrive related to upper airway issues, as well as complications affecting multiple organ systems, and successful BMT in early childhood has been described	Audiologic/Otolaryngologic; Craniofacial; Dental; Hematologic; Musculoskeletal; Ophthalmologic	22499339; 23123320

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SNX10 gene.

• not_provided (130 variants)
• Inborn_genetic_diseases (14 variants)
• Autosomal_recessive_osteopetrosis_8 (9 variants)
• SNX10-related_disorder (7 variants)
• Osteopetrosis (1 variants)
• Infantile_osteopetrosis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SNX10 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000013322.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				24	3	27
missense	1	1	55	1		58
nonsense	5	3	1			9
start loss						0
frameshift	3	2				5
splice donor/acceptor (+/-2bp)		4	1			5
Total	9	10	57	25	3

Highest pathogenic variant AF is 0.0000129994

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SNX10	protein_coding	protein_coding	ENST00000338523	6	82409

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.39e-10	0.0492	125699	0	47	125746	0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.547	95	111	0.854	0.00000588	1346
Missense in Polyphen		29	39.989	0.72519		436
Synonymous	0.541	35	39.3	0.890	0.00000219	340
Loss of Function	-0.249	14	13.0	1.07	7.16e-7	143

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000910	0.0000905
Ashkenazi Jewish	0.00	0.00
East Asian	0.000272	0.000272
Finnish	0.000140	0.0000924
European (Non-Finnish)	0.000318	0.000316
Middle Eastern	0.000272	0.000272
South Asian	0.00	0.00
Other	0.000331	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable phosphoinositide-binding protein involved in protein sorting and membrane trafficking in endosomes. Plays a role in cilium biogenesis through regulation of the transport and the localization of proteins to the cilium. Required for the localization to the cilium of V-ATPase subunit ATP6V1D and ATP6V0D1, and RAB8A. Involved in osteoclast differentiation and therefore bone resorption. {ECO:0000269|PubMed:17012226, ECO:0000269|PubMed:21844891, ECO:0000269|PubMed:22499339}.
• Disease: DISEASE: Osteopetrosis, autosomal recessive 8 (OPTB8) [MIM:615085]: A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. OPTB8 is clinically characterized by dense bones with no distinction between outer and inner plates, due to extensive encroachment of cortical bone into the medullary space, increased head circumference, broad open fontanelle, frontal bossing, and hepatosplenomegaly. Osteoclasts number is low and their bone resorptive capacity is impaired. {ECO:0000269|PubMed:22499339, ECO:0000269|PubMed:23123320, ECO:0000269|PubMed:23280965}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.113

Intolerance Scores

• loftool: 0.579
• rvis_EVS: -0.1
• rvis_percentile_EVS: 46.2

Haploinsufficiency Scores

• pHI: 0.209
• hipred: N
• hipred_score: 0.350
• ghis: 0.604

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.209

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Snx10
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; digestive/alimentary phenotype; hematopoietic system 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); skeleton phenotype; immune system phenotype

Zebrafish Information Network

• Gene name: snx10a
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: gastric acid secretion;endocytosis;endosome organization;protein transport;bone mineralization;osteoclast differentiation;tooth eruption;bone resorption;calcium ion homeostasis;cilium assembly;protein localization to cilium;protein localization to centrosome;ruffle assembly;cellular response to leukemia inhibitory factor
• Cellular component: nucleus;endoplasmic reticulum;centrosome;secretory granule;extrinsic component of endosome membrane;apical cytoplasm
• Molecular function: protein binding;1-phosphatidylinositol binding;ATPase binding