SNX10

Summary

SNX10 (sorting nexin 10, HGNC:14974) is a protein-coding gene on chromosome 7p15.2, encoding Sorting nexin-10 (Q9Y5X0). Probable phosphoinositide-binding protein involved in protein sorting and membrane trafficking in endosomes.

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 some family members. This gene may play a role in regulating endosome homeostasis. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 29887 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive osteopetrosis 8 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 67
• Clinical variants (ClinVar): 168 total — 12 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 54
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_013322

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14974
Approved symbol	SNX10
Name	sorting nexin 10
Location	7p15.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000086300
Ensembl biotype	protein_coding
OMIM	614780
Entrez	29887

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 27 protein_coding, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000338523, ENST00000396376, ENST00000409367, ENST00000409838, ENST00000412416, ENST00000416246, ENST00000446848, ENST00000462993, ENST00000698074, ENST00000698075, ENST00000698076, ENST00000698077, ENST00000698078, ENST00000698079, ENST00000698080, ENST00000698081, ENST00000698082, ENST00000698083, ENST00000698084, ENST00000698085, ENST00000698086, ENST00000698087, ENST00000698088, ENST00000698089, ENST00000698090, ENST00000698091, ENST00000698092, ENST00000905668, ENST00000905669, ENST00000905670, ENST00000905671, ENST00000905672, ENST00000905673, ENST00000911860, ENST00000911861, ENST00000967692

RefSeq mRNA: 8 — MANE Select: NM_013322 NM_001199835, NM_001199837, NM_001199838, NM_001318198, NM_001318199, NM_001362753, NM_001362754, NM_013322

CCDS: CCDS5399, CCDS56470

Canonical transcript exons

ENST00000338523 — 7 exons

Exon	Start	End
ENSE00001373675	26291862	26292086
ENSE00001946833	26372491	26374383
ENSE00003554944	26365047	26365145
ENSE00003574118	26346420	26346466
ENSE00003595142	26360975	26361061
ENSE00003643995	26371821	26372033
ENSE00003672342	26364535	26364635

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 99.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.5160 / max 1594.9718, expressed in 1219 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
77765	13.3862	207
77758	7.9250	1081
77766	7.1052	197
77757	6.3417	1003
204392	0.9698	424
77761	0.3634	124
77759	0.2144	119
77760	0.2104	100

Top tissues by expression

277 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	99.36	gold quality
substantia nigra pars compacta	UBERON:0001965	99.08	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.64	gold quality
pons	UBERON:0000988	98.60	gold quality
monocyte	CL:0000576	98.05	gold quality
mononuclear cell	CL:0000842	97.89	gold quality
leukocyte	CL:0000738	97.62	gold quality
superior vestibular nucleus	UBERON:0007227	97.36	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.27	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.02	gold quality
dorsal root ganglion	UBERON:0000044	95.89	gold quality
prefrontal cortex	UBERON:0000451	95.67	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.30	gold quality
anterior cingulate cortex	UBERON:0009835	95.26	gold quality
cingulate cortex	UBERON:0003027	95.20	gold quality
lateral globus pallidus	UBERON:0002476	95.09	gold quality
hypothalamus	UBERON:0001898	94.83	gold quality
superior frontal gyrus	UBERON:0002661	94.82	gold quality
middle temporal gyrus	UBERON:0002771	94.71	gold quality
frontal cortex	UBERON:0001870	94.30	gold quality
orbitofrontal cortex	UBERON:0004167	94.20	gold quality
medulla oblongata	UBERON:0001896	94.11	gold quality
neocortex	UBERON:0001950	94.02	gold quality
cerebral cortex	UBERON:0000956	93.90	gold quality
midbrain	UBERON:0001891	93.67	gold quality
substantia nigra	UBERON:0002038	93.58	gold quality
parietal lobe	UBERON:0001872	93.48	gold quality
blood	UBERON:0000178	93.37	gold quality
ventral tegmental area	UBERON:0002691	93.31	gold quality
entorhinal cortex	UBERON:0002728	93.25	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-81383	yes	415.56
E-MTAB-10553	yes	20.88
E-ANND-3	yes	15.26
E-CURD-112	yes	14.81
E-HCAD-25	yes	8.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

107 targeting SNX10, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-627-3P	99.90	71.42	3316

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 24)

• SNX10 activity may be involved in the regulation of endosome homeostasis (PMID:17012226)
• SNX10 regulates the ciliary trafficking of Rab8a, which is a critical regulator of ciliary membrane extension. (PMID:21844891)
• Since inhibition of vesicular trafficking is essential for osteoclast formation and activity and SNX10 is involved in vesicular trafficking, these studies may identify a new gene involved in the development of bone diseases including osteoporosis. (PMID:22174188)
• Identification of SNX10 as a new osteopetrosis associated gene in consanguineous families of Palestinian origin. (PMID:22499339)
• results confirm the involvement of the SNX10 gene in human ARO and identify a new subset with a relatively favorable prognosis as compared to TCIRG1-dependent cases (PMID:23280965)
• Structure of sorting nexin 11 (SNX11) reveals a novel extended phox homology (PX) domain critical for inhibition of SNX10-induced vacuolation. (PMID:23615901)
• Data suggest Tyr32 and Arg51 in SNX10 are important for protein stability and play critical roles in vacuolation in osteoclasts; mutation Arg16Leu (seen in autosomal recessive osteopetrosis patients) affects protein-protein interactions of SNX10. (PMID:25212774)
• supplementation with calcium gluconate rescued mice from the rachitic phenotype and extended life span in global Snx10-deficient mice, suggesting that this may be a life-saving component of the clinical approach to Snx10-dependent human osteopetrosis (PMID:25811986)
• In this study, whole exome sequencing (WES) was successfully used in six patients with malignant infantile osteopetrosis (MIOP) and identified mutations in four MIOP-related genes (CLCN7, TCIRG1, SNX10, and TNFRSF11A). (PMID:27187610)
• Sequence analysis of the SNX10 transcript in patients with autosomal recessive osteopetrosis revealed activation of a cryptic splice site in intron 4 resulting in a frame shift and a premature stop (p.S66Nfs * 15). (PMID:28592808)
• Sorting nexin 10 (SNX10) was remarkably down-regulated in colorectal cancer (CRC) tissues which showed the increased activity of chaperone-mediated autophagy (CMA) and decreased expression of cyclin-dependent kinase inhibitor p21(Cip1/WAF1). (PMID:29355659)
• this work revealed that SNX10 controls mTOR activation through regulating chaperone-mediated autophagy-dependent amino-acid metabolism. (PMID:29867114)
• Weak expression of SNX10 is linked to poor prognosis, and is a suitable prognostic biomarker of stomach adenocarcinoma. (PMID:30487700)
• SNX10 (sorting nexin 10) inhibits colorectal cancer initiation and progression by controlling autophagic degradation of SRC. (PMID:31208298)
• Sorting Nexin 10 Mediates Metabolic Reprogramming of Macrophages in Atherosclerosis Through the Lyn-Dependent TFEB Signaling Pathway. (PMID:32316875)
• Does Decreased SNX10 Serve as a Novel Risk Factor in Atrial Fibrillation of the Valvular Heart Disease? - A Case-Control Study. (PMID:33594863)
• SNX10 gene mutation in infantile malignant osteopetrosis: A case report and literature review.", trans “SNX101. (PMID:33678645)
• SNX10 and PTGDS are associated with the progression and prognosis of cervical squamous cell carcinoma. (PMID:34116656)
• SNX10-mediated LPS sensing causes intestinal barrier dysfunction via a caspase-5-dependent signaling cascade. (PMID:34747049)
• Identification of Key Amino Acid Residues Involved in the Localization of Sorting Nexin 10 and Induction of Vacuole Formation. (PMID:34906048)
• Overexpression Pattern of miR-301b in Osteosarcoma and Its Relevance with Osteosarcoma Cellular Behaviors via Modulating SNX10. (PMID:35732962)
• Osteopetrosis associated with PLEKHM1 and SNX10 genes, both involved in osteoclast vesicular trafficking. (PMID:35981699)
• Inhibiting sorting nexin 10 promotes mucosal healing through SREBP2-mediated stemness restoration of intestinal stem cells. (PMID:37647408)
• SNX10 promoted liver IR injury by facilitating macrophage M1 polarization via NLRP3 inflammasome activation. (PMID:38271879)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	snx10a	ENSDARG00000004405
danio_rerio	snx10b	ENSDARG00000040474
mus_musculus	Snx10	ENSMUSG00000038301
rattus_norvegicus	Snx10	ENSRNOG00000011944

Paralogs (15): SNX11 (ENSG00000002919), SNX1 (ENSG00000028528), SNX5 (ENSG00000089006), SNX8 (ENSG00000106266), SNX3 (ENSG00000112335), SNX4 (ENSG00000114520), SNX6 (ENSG00000129515), SNX9 (ENSG00000130340), SNX12 (ENSG00000147164), SNX30 (ENSG00000148158), SNX7 (ENSG00000162627), SNX32 (ENSG00000172803), SNX33 (ENSG00000173548), SNX18 (ENSG00000178996), SNX2 (ENSG00000205302)

Protein

Protein identifiers

Sorting nexin-10 — Q9Y5X0 (reviewed: Q9Y5X0)

All UniProt accessions (7): Q9Y5X0, A0A8V8TLE1, A0A8V8TLE4, A0A8V8TLG7, A0A8V8TMW7, A0A8V8TN62, G5E9H5

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Interacts with ATP6V1D; may play a role in ciliogenesis.

Subcellular location. Cytoplasm. Endosome membrane. Cytoskeleton. Microtubule organizing center. Centrosome.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3-phosphate.

Similarity. Belongs to the sorting nexin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y5X0-1	1	yes
Q9Y5X0-2	2

RefSeq proteins (8): NP_001186764, NP_001186766, NP_001186767, NP_001305127, NP_001305128, NP_001349682, NP_001349683, NP_037454* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001683	PX_dom	Domain
IPR036871	PX_dom_sf	Homologous_superfamily
IPR043544	SNX10/11	Family

Pfam: PF00787

UniProt features (28 total): helix 7, sequence variant 5, strand 5, mutagenesis site 3, binding site 3, region of interest 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6KOK	X-RAY DIFFRACTION	2
4ON3	X-RAY DIFFRACTION	2.6
4PZG	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5X0-F1	85.90	0.66

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 53; 79; 94

Mutagenesis-validated functional residues (3):

Position	Phenotype
53	abolishes vacuolization induced by overexpression.
79	slightly reduced vacuolization induced by overexpression.
94	reduced vacuolization induced by overexpression.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 506 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_DIGESTION, AP1_01, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_ACID_SECRETION, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOBP_ENDOSOME_ORGANIZATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_RESPONSE_TO_PEPTIDE, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (20): gastric acid secretion (GO:0001696), intracellular protein transport (GO:0006886), endocytosis (GO:0006897), endosome organization (GO:0007032), vesicle organization (GO:0016050), cellular homeostasis (GO:0019725), osteoclast differentiation (GO:0030316), bone mineralization involved in bone maturation (GO:0035630), tooth eruption (GO:0044691), bone resorption (GO:0045453), calcium ion homeostasis (GO:0055074), cilium assembly (GO:0060271), protein localization to cilium (GO:0061512), protein localization to centrosome (GO:0071539), ruffle assembly (GO:0097178), cellular response to leukemia inhibitory factor (GO:1990830), protein transport (GO:0015031), cell projection organization (GO:0030030), bone remodeling (GO:0046849), establishment of localization in cell (GO:0051649)

GO Molecular Function (6): 1-phosphatidylinositol binding (GO:0005545), ATPase binding (GO:0051117), phosphatidylinositol phosphate binding (GO:1901981), protein binding (GO:0005515), lipid binding (GO:0008289), phosphatidylinositol binding (GO:0035091)

GO Cellular Component (12): nucleus (GO:0005634), endosome (GO:0005768), endoplasmic reticulum (GO:0005783), centrosome (GO:0005813), secretory granule (GO:0030141), extrinsic component of endosome membrane (GO:0031313), apical cytoplasm (GO:0090651), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), endosome membrane (GO:0010008), endomembrane system (GO:0012505), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
endomembrane system	3
intracellular protein localization	2
plasma membrane bounded cell projection assembly	2
phospholipid binding	2
binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
digestive system process	1
acid secretion	1
protein transport	1
intracellular transport	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
endomembrane system organization	1
vesicle organization	1
organelle organization	1
homeostatic process	1
myeloid leukocyte differentiation	1
bone mineralization	1
ossification involved in bone maturation	1
odontogenesis	1
anatomical structure development	1
tissue homeostasis	1
bone remodeling	1
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
axoneme assembly	1
intraciliary transport involved in cilium assembly	1
cilium organization	1
protein localization to cilium	1
organelle assembly	1
trans-Golgi to periciliary membrane compartment transport	1
ciliary transition zone assembly	1
protein localization to organelle	1
protein localization to microtubule organizing center	1
ruffle organization	1
cellular response to cytokine stimulus	1

Protein interactions and networks

STRING

784 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNX10	OSTM1	Q86WC4	772
SNX10	PLEKHM1	Q9Y4G2	730
SNX10	CLCN7	P51798	719
SNX10	TCIRG1	Q13488	696
SNX10	SNX24	Q9Y343	519
SNX10	TNFRSF11A	Q9Y6Q6	514
SNX10	ATP12A	P54707	496
SNX10	ATP4A	P20648	496
SNX10	LAMP1	P11279	493
SNX10	SNX22	Q96L94	481
SNX10	SNX20	Q7Z614	478
SNX10	PRKCA	P17252	466
SNX10	HS1BP3	Q53T59	462
SNX10	ATG5	Q9H1Y0	461
SNX10	SNX16	P57768	446

IntAct

27 interactions, top by confidence:

A	B	Type	Score
ARL6IP1	SNX10	psi-mi:“MI:0915”(physical association)	0.720
SNX10	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.720
RABAC1	SNX10	psi-mi:“MI:0915”(physical association)	0.560
YIF1A	SNX10	psi-mi:“MI:0915”(physical association)	0.560
SNX10	PRKCA	psi-mi:“MI:0915”(physical association)	0.560
SNX10	YWHAG	psi-mi:“MI:0915”(physical association)	0.560
SNX10	SETDB1	psi-mi:“MI:0915”(physical association)	0.560
SNX10	KAT5	psi-mi:“MI:0915”(physical association)	0.560
LMO3	SNX10	psi-mi:“MI:0915”(physical association)	0.560
SNX10	RABAC1	psi-mi:“MI:0915”(physical association)	0.000
SNX10	ARL6IP1	psi-mi:“MI:0915”(physical association)	0.000
SNX10	YIF1A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): SNX10 (Two-hybrid), SNX10 (Two-hybrid), SNX10 (Synthetic Lethality), RABAC1 (Two-hybrid), ARL6IP1 (Two-hybrid), YIF1A (Two-hybrid), SNX10 (Proximity Label-MS), SNX10 (Affinity Capture-RNA), SNX10 (Affinity Capture-RNA)

ESM2 similar proteins: A2CEA7, A5DHC9, A6ZT13, A7TKX9, A8WG21, A8XEZ1, B4GD81, G5EFI8, O14827, P0C5E7, P27671, P28818, P32912, P38815, P70392, Q0IIL5, Q13972, Q19532, Q22070, Q22720, Q24592, Q28HD5, Q28YD9, Q2TA03, Q5AG56, Q5M956, Q6BIS2, Q6C5F1, Q6DDY6, Q6FN68, Q6FR40, Q6P073, Q719H9, Q7XPJ0, Q80ZJ7, Q86XE0, Q8BXK8, Q8N2K1, Q8R4G8, Q8WT44

Diamond homologs: A8WG21, F1Q506, O60493, O70492, O70493, P0CR60, P0CR61, Q08826, Q08DD7, Q0IIL5, Q1RMH8, Q2U4K2, Q4I1H6, Q4P1V3, Q4R5U9, Q4WWS3, Q522W5, Q566W7, Q5A748, Q5R5V1, Q5U211, Q6C2S9, Q6CY25, Q758Y7, Q7SB97, Q7SH92, Q91WL6, Q9CWT3, Q9UMY4, Q9UNH6, Q9Y5W9, Q9Y5X0, I1RXT2, O94291, P0CR62, P0CR63, Q2UB56, Q4WZF1, Q6FT03, Q9CY18

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

168 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	10
Uncertain significance	67
Likely benign	60
Benign	15

Top pathogenic / likely-pathogenic (22)

Variant ID	HGVS	Classification
1071167	NC_000007.13:g.(?26400575)(26404785_?)del	Pathogenic
1378555	NM_013322.3(SNX10):c.16C>T (p.Gln6Ter)	Pathogenic
139565	NM_013322.3(SNX10):c.46C>T (p.Arg16Ter)	Pathogenic
1448669	NM_013322.3(SNX10):c.230del (p.Pro77fs)	Pathogenic
1451825	NM_013322.3(SNX10):c.87C>A (p.Tyr29Ter)	Pathogenic
2112070	NM_013322.3(SNX10):c.85_86insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNGACCTCGTGATCCGCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCTCTGGCATTCTT (p.Tyr29fs)	Pathogenic
2789891	NM_013322.3(SNX10):c.338C>G (p.Ser113Ter)	Pathogenic
3714485	NM_013322.3(SNX10):c.249_250insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNCAGGGAGGCTGCAGTGAGCCGAGATGGCAGCAGCACCGTCCAGCCTTGGCTCGGCATCAGAGGGAGACCCTAAAAACCTGTTTTTC (p.Asn84fs)	Pathogenic
40050	NM_013322.3(SNX10):c.152G>A (p.Arg51Gln)	Pathogenic
453176	NM_013322.3(SNX10):c.162T>A (p.Tyr54Ter)	Pathogenic
4700979	NM_013322.3(SNX10):c.193C>T (p.Gln65Ter)	Pathogenic
4760112	NM_013322.3(SNX10):c.332T>A (p.Leu111Ter)	Pathogenic
1349342	NM_013322.3(SNX10):c.24+1G>A	Likely pathogenic
1810243	NM_013322.3(SNX10):c.213-2A>G	Likely pathogenic
2663932	NM_013322.3(SNX10):c.302del (p.Phe101fs)	Likely pathogenic
2714651	NM_013322.3(SNX10):c.95A>C (p.Tyr32Ser)	Likely pathogenic
2794892	NM_013322.3(SNX10):c.111+1G>T	Likely pathogenic
3245867	NC_000007.13:g.(?26400575)(26404785_?)dup	Likely pathogenic
3376537	NM_013322.3(SNX10):c.295G>T (p.Glu99Ter)	Likely pathogenic
3384115	NM_013322.3(SNX10):c.112-1G>C	Likely pathogenic
3594492	NM_013322.3(SNX10):c.86dup (p.Tyr29Ter)	Likely pathogenic
4747554	NM_013322.3(SNX10):c.311+1G>T	Likely pathogenic

SpliceAI

2035 predictions. Top by Δscore:

Variant	Effect	Δscore
7:26346463:AGAGG:A	donor_loss	1.0000
7:26346464:GAGGT:G	donor_loss	1.0000
7:26346466:GGTA:G	donor_loss	1.0000
7:26346467:G:GA	donor_loss	1.0000
7:26361062:G:GG	donor_gain	1.0000
7:26365042:CTAA:C	acceptor_loss	1.0000
7:26365044:A:AG	acceptor_gain	1.0000
7:26365044:AAG:A	acceptor_loss	1.0000
7:26365045:A:AC	acceptor_loss	1.0000
7:26365045:A:AG	acceptor_gain	1.0000
7:26365046:G:GC	acceptor_gain	1.0000
7:26365046:GA:G	acceptor_gain	1.0000
7:26365046:GAC:G	acceptor_gain	1.0000
7:26365046:GACA:G	acceptor_gain	1.0000
7:26365046:GACAA:G	acceptor_gain	1.0000
7:26365141:AGAAA:A	donor_gain	1.0000
7:26365142:GAAA:G	donor_gain	1.0000
7:26365142:GAAAG:G	donor_gain	1.0000
7:26365143:AAA:A	donor_gain	1.0000
7:26365144:AA:A	donor_gain	1.0000
7:26365144:AAGT:A	donor_loss	1.0000
7:26365145:AGTGA:A	donor_loss	1.0000
7:26365146:G:A	donor_loss	1.0000
7:26365146:G:GG	donor_gain	1.0000
7:26365147:T:G	donor_loss	1.0000
7:26365148:GA:G	donor_loss	1.0000
7:26292083:GCCC:G	donor_gain	0.9900
7:26292087:G:GG	donor_gain	0.9900
7:26346414:TTTCA:T	acceptor_loss	0.9900
7:26346415:TTCAG:T	acceptor_loss	0.9900

AlphaMissense

1353 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:26364578:G:C	R52T	1.000
7:26364579:A:C	R52S	1.000
7:26364579:A:T	R52S	1.000
7:26360994:T:A	V15D	0.999
7:26361051:T:A	I34K	0.999
7:26364536:C:T	T38I	0.999
7:26364551:T:C	F43S	0.999
7:26364577:A:G	R52G	0.999
7:26364578:G:T	R52I	0.999
7:26364593:T:C	F57S	0.999
7:26364614:T:C	L64P	0.999
7:26365127:T:C	L98P	0.999
7:26365135:T:C	F101L	0.999
7:26365137:C:A	F101L	0.999
7:26365137:C:G	F101L	0.999
7:26371868:T:C	F120S	0.999
7:26361051:T:G	I34R	0.998
7:26364550:T:C	F43L	0.998
7:26364552:T:A	F43L	0.998
7:26364552:T:G	F43L	0.998
7:26364592:T:C	F57L	0.998
7:26364594:C:A	F57L	0.998
7:26364594:C:G	F57L	0.998
7:26364602:T:C	L60P	0.998
7:26365114:C:A	R94S	0.998
7:26365139:T:C	L102P	0.998
7:26371861:C:G	H118D	0.998
7:26371865:T:C	L119P	0.998
7:26371867:T:C	F120L	0.998
7:26371869:C:A	F120L	0.998

dbSNP variants (sampled 300 via entrez): RS1000057971 (7:26304088 C>A,T), RS1000076606 (7:26359947 C>T), RS1000096746 (7:26335962 A>C,G), RS1000098079 (7:26323418 G>T), RS1000190147 (7:26297218 C>T), RS1000219813 (7:26296914 G>A,C), RS1000235413 (7:26297831 G>A,C,T), RS1000241355 (7:26339702 A>G), RS1000378283 (7:26363193 C>A,T), RS1000414272 (7:26315258 A>G), RS1000487940 (7:26314898 T>C), RS1000521315 (7:26295432 C>T), RS1000557072 (7:26295112 T>C), RS1000577274 (7:26356126 A>G,T), RS1000585661 (7:26348155 C>T)

Disease associations

OMIM: gene MIM:614780 | disease phenotypes: MIM:615085

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive osteopetrosis 8	Strong	Autosomal recessive
autosomal recessive osteopetrosis	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
autosomal recessive osteopetrosis 8	Definitive	AR

Mondo (3): autosomal recessive osteopetrosis 8 (MONDO:0014040), osteopetrosis (MONDO:0017198), autosomal recessive osteopetrosis (MONDO:0019026)

Orphanet (2): Autosomal recessive malignant osteopetrosis (Orphanet:667), Osteopetrosis and related disorders (Orphanet:2781)

HPO phenotypes

54 total (30 of 54 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000365	Hearing impairment
HP:0000388	Otitis media
HP:0000505	Visual impairment
HP:0000572	Visual loss
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000649	Abnormality of visual evoked potentials
HP:0000684	Delayed eruption of teeth
HP:0000772	Abnormal rib morphology
HP:0000774	Narrow chest
HP:0000944	Abnormal metaphysis morphology
HP:0000978	Bruising susceptibility
HP:0000980	Pallor
HP:0001337	Tremor
HP:0001363	Craniosynostosis
HP:0001508	Failure to thrive
HP:0001510	Growth delay
HP:0001641	Abnormal pulmonary valve morphology
HP:0001744	Splenomegaly
HP:0001873	Thrombocytopenia
HP:0001903	Anemia
HP:0001939	Abnormality of metabolism/homeostasis
HP:0002007	Frontal bossing
HP:0002092	Pulmonary arterial hypertension
HP:0002104	Apnea
HP:0002148	Hypophosphatemia
HP:0002205	Recurrent respiratory infections

GWAS associations

67 associations (top):

Study	Trait	p-value
GCST001524_20	Visceral adipose tissue/subcutaneous adipose tissue ratio	3.000000e-06
GCST002782_234	Waist-to-hip ratio adjusted for body mass index	5.000000e-08
GCST002782_235	Waist-to-hip ratio adjusted for body mass index	2.000000e-08
GCST004505_106	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	1.000000e-10
GCST004505_107	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	3.000000e-06
GCST004578_97	Waist-to-hip ratio adjusted for BMI in active individuals	6.000000e-06
GCST005956_35	Waist-to-hip ratio adjusted for BMI	8.000000e-14
GCST005958_8	Waist-to-hip ratio adjusted for BMI (age >50)	5.000000e-07
GCST005962_19	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	8.000000e-14
GCST006611_124	HDL cholesterol	4.000000e-11
GCST009267_10	Dental caries (decayed, missing and filled teeth)	2.000000e-07
GCST009391_1964	Metabolite levels	4.000000e-06
GCST009602_17	Metabolic syndrome	9.000000e-11
GCST010242_25	HDL cholesterol levels	3.000000e-18
GCST010244_251	Triglyceride levels	2.000000e-23
GCST011386_1	Vaginal microbiome composition (G. vaginalis)	5.000000e-06
GCST90002396_380	Mean reticulocyte volume	1.000000e-09
GCST90020024_79	A body shape index	1.000000e-09
GCST90020024_80	A body shape index	2.000000e-08
GCST90020024_81	A body shape index	5.000000e-13
GCST90020024_82	A body shape index	1.000000e-13
GCST90020024_83	A body shape index	4.000000e-13
GCST90020024_84	A body shape index	9.000000e-16
GCST90020024_85	A body shape index	6.000000e-32
GCST90020024_86	A body shape index	7.000000e-10
GCST90020024_87	A body shape index	2.000000e-17
GCST90020025_1854	Waist-to-hip ratio adjusted for BMI	8.000000e-10
GCST90020025_1855	Waist-to-hip ratio adjusted for BMI	5.000000e-17
GCST90020025_1856	Waist-to-hip ratio adjusted for BMI	2.000000e-14
GCST90020025_1857	Waist-to-hip ratio adjusted for BMI	5.000000e-20

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004767	visceral:subcutaneous adipose tissue ratio
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0004318	smoking behavior
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0008392	triiodothyronine measurement
EFO:0000195	metabolic syndrome
EFO:0004530	triglyceride measurement
EFO:0011013	vaginal microbiome measurement
EFO:0010701	mean reticulocyte volume
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D010022	Osteopetrosis	C05.116.099.708.702.678

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

47 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	5
sodium arsenite	increases expression, increases abundance	2
apilimod	affects response to substance	2
Resveratrol	affects cotreatment, increases expression	2
Doxorubicin	decreases expression, affects response to substance	2
Tretinoin	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation, decreases methylation, affects cotreatment	1
kojic acid	decreases expression	1
trichostatin A	increases expression	1
cobaltous chloride	increases expression	1
potassium chromate(VI)	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
entinostat	increases expression	1
K 7174	decreases expression	1
belinostat	decreases expression	1
abrine	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
Temozolomide	increases expression	1
Decitabine	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	decreases expression	1

Cellosaurus cell lines

5 cell lines: 4 cancer cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_QX90	NUIGi001-A	Induced pluripotent stem cell	Female
CVCL_TP85	HAP1 SNX10 (-) 1	Cancer cell line	Male
CVCL_TP86	HAP1 SNX10 (-) 2	Cancer cell line	Male
CVCL_XT61	HAP1 SNX10 (-) 3	Cancer cell line	Male
CVCL_XT62	HAP1 SNX10 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

19 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00004402	PHASE3	COMPLETED	Phase III Randomized Study of Interferon Gamma in Children With Severe, Congenital Osteopetrosis
NCT00638820	PHASE2	TERMINATED	Reduced Intensity AlloTransplant For Osteopetrosis
NCT00968864	PHASE2	TERMINATED	T-cell Depleted Alternative Donor Transplantation
NCT02171104	PHASE2	ACTIVE_NOT_RECRUITING	MT2013-31: Allo HCT for Metabolic Disorders and Severe Osteopetrosis
NCT02666768	PHASE2	COMPLETED	ACTIMMUNE in Intermediate Osteopetrosis
NCT04525352	PHASE1	TERMINATED	A Trial to Evaluate Safety and Efficacy of RP-L401-0120 in Subjects With Infantile Malignant Osteopetrosis
NCT00145886	PHASE1	TERMINATED	rhPTH Therapy for Low Turnover Bone Fragility
NCT00775931	PHASE2/PHASE3	COMPLETED	Allogeneic Transplantation For Severe Osteopetrosis
NCT01019876	PHASE2/PHASE3	COMPLETED	Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases
NCT01087398	PHASE2/PHASE3	UNKNOWN	Hematopoietic Stem Cell Transplantation for Malignant Infantile Osteopetrosis
NCT00730314	PHASE1/PHASE2	COMPLETED	Unrelated Hematopoietic Stem Cell Transplantation(HSCT) for Genetic Diseases of Blood Cells
NCT02065869	PHASE1/PHASE2	TERMINATED	Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant
NCT03301168	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Study of Gene Modified Donor T-cells Following TCR Alpha Beta Positive Depleted Stem Cell Transplant
NCT00043329	Not specified	COMPLETED	Post Marketing Surveillance Study of Actimmune in Patients With Severe, Malignant Osteopetrosis
NCT00145587	Not specified	TERMINATED	Stem Cell Transplantation for Children Affected With Osteopetrosis
NCT01199094	Not specified	COMPLETED	Clinical Assessment of Patients With High Bone Mass Due to Mutation in Lrp5
NCT01200017	Not specified	NO_LONGER_AVAILABLE	Expanded Access Protocol (EAP) Using the CliniMACS® Device for Pediatric Haplocompatible Donor Stem Cell Transplant
NCT03333200	Not specified	RECRUITING	Longitudinal Study of Neurodegenerative Disorders
NCT06521580	Not specified	COMPLETED	Outcomes of Patients With Osteopetrosis Weight-bearing Bone Fractures