SNX14

Summary

SNX14 (sorting nexin 14, HGNC:14977) is a protein-coding gene on chromosome 6q14.3, encoding Sorting nexin-14 (Q9Y5W7). Plays a role in maintaining normal neuronal excitability and synaptic transmission.

This gene encodes a member of the sorting nexin family. Members of this family have a phox (PX) phosphoinositide binding domain and are involved in intracellular trafficking. The encoded protein also contains a regulator of G protein signaling (RGS) domain. Regulator of G protein signaling family members are regulatory molecules that act as GTPase activating proteins for G alpha subunits of heterotrimeric G proteins. Alternate splicing results in transcript variants encoding distinct isoforms.

Source: NCBI Gene 57231 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal recessive spinocerebellar ataxia 20 (Definitive, ClinGen)
• Clinical variants (ClinVar): 425 total — 21 pathogenic, 26 likely-pathogenic
• Phenotypes (HPO): 77
• MANE Select transcript: NM_153816

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14977
Approved symbol	SNX14
Name	sorting nexin 14
Location	6q14.3
Locus type	gene with protein product
Status	Approved
Aliases	RGS-PX2
Ensembl gene	ENSG00000135317
Ensembl biotype	protein_coding
OMIM	616105
Entrez	57231

Gene structure

Transcript identifiers

Ensembl transcripts: 130 — 64 protein_coding, 46 nonsense_mediated_decay, 20 retained_intron

ENST00000314673, ENST00000346348, ENST00000369627, ENST00000369635, ENST00000418862, ENST00000474645, ENST00000503491, ENST00000503608, ENST00000504191, ENST00000505648, ENST00000506182, ENST00000508658, ENST00000508980, ENST00000509338, ENST00000513865, ENST00000513869, ENST00000514419, ENST00000514801, ENST00000515216, ENST00000681981, ENST00000682022, ENST00000682023, ENST00000682034, ENST00000682057, ENST00000682133, ENST00000682168, ENST00000682171, ENST00000682174, ENST00000682374, ENST00000682412, ENST00000682454, ENST00000682455, ENST00000682464, ENST00000682491, ENST00000682497, ENST00000682514, ENST00000682594, ENST00000682633, ENST00000682660, ENST00000682682, ENST00000682688, ENST00000682694, ENST00000682709, ENST00000682738, ENST00000682776, ENST00000682854, ENST00000682878, ENST00000682926, ENST00000682939, ENST00000682991, ENST00000682995, ENST00000683073, ENST00000683085, ENST00000683097, ENST00000683126, ENST00000683195, ENST00000683196, ENST00000683458, ENST00000683473, ENST00000683479, ENST00000683481, ENST00000683541, ENST00000683542, ENST00000683577, ENST00000683583, ENST00000683643, ENST00000683698, ENST00000683726, ENST00000683727, ENST00000683754, ENST00000683759, ENST00000683763, ENST00000683785, ENST00000683803, ENST00000683857, ENST00000683873, ENST00000683878, ENST00000683880, ENST00000683898, ENST00000683999, ENST00000684017, ENST00000684108, ENST00000684118, ENST00000684150, ENST00000684183, ENST00000684239, ENST00000684273, ENST00000684281, ENST00000684299, ENST00000684319, ENST00000684422, ENST00000684451, ENST00000684570, ENST00000684581, ENST00000684647, ENST00000684680, ENST00000684717, ENST00000903328, ENST00000903329, ENST00000903330, ENST00000903331, ENST00000903332, ENST00000903333, ENST00000903335, ENST00000903336, ENST00000903338, ENST00000903339, ENST00000903341, ENST00000903343, ENST00000903344, ENST00000903346, ENST00000939206, ENST00000939207, ENST00000939208, ENST00000939209, ENST00000939210, ENST00000949652, ENST00000949653, ENST00000949654, ENST00000949655, ENST00000949656, ENST00000949657, ENST00000949658, ENST00000949659, ENST00000949660, ENST00000949661, ENST00000949662, ENST00000949663, ENST00000949664, ENST00000949665

RefSeq mRNA: 26 — MANE Select: NM_153816 NM_001297614, NM_001304479, NM_001350532, NM_001350533, NM_001350534, NM_001350535, NM_001350536, NM_001350537, NM_001350538, NM_001350539, NM_001350540, NM_001350541, NM_001350542, NM_001350543, NM_001350544, NM_001350545, NM_001350546, NM_001350547, NM_001350548, NM_001350549, NM_001350550, NM_001350551, NM_001350552, NM_001350553, NM_020468, NM_153816

CCDS: CCDS5003, CCDS5004, CCDS75490, CCDS78163, CCDS93955, CCDS93956, CCDS93957, CCDS93958, CCDS93959, CCDS93960, CCDS93961, CCDS93962, CCDS93963, CCDS93964

Canonical transcript exons

ENST00000314673 — 29 exons

Exon	Start	End
ENSE00001253010	85505496	85506005
ENSE00002068092	85593579	85593858
ENSE00003468178	85518008	85518048
ENSE00003475712	85567534	85567577
ENSE00003477557	85557976	85558060
ENSE00003494720	85543182	85543306
ENSE00003515920	85528262	85528362
ENSE00003521582	85572298	85572374
ENSE00003521880	85565332	85565419
ENSE00003530812	85543605	85543760
ENSE00003542969	85574258	85574378
ENSE00003545093	85507233	85507289
ENSE00003552532	85517756	85517875
ENSE00003555180	85541985	85542043
ENSE00003558374	85514506	85514629
ENSE00003561589	85536792	85536924
ENSE00003566395	85548301	85548376
ENSE00003579405	85533599	85533800
ENSE00003581922	85514070	85514234
ENSE00003591185	85530192	85530275
ENSE00003607386	85526126	85526237
ENSE00003612726	85513800	85513895
ENSE00003614280	85547112	85547226
ENSE00003624156	85547317	85547397
ENSE00003631671	85549723	85549879
ENSE00003635923	85572137	85572215
ENSE00003639221	85547506	85547550
ENSE00003639871	85538838	85538864
ENSE00003785186	85507968	85508059

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 98.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.2899 / max 146.6726, expressed in 1823 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74597	26.3607	1820
74598	1.0782	786
74596	0.6440	400
74600	0.5468	256
74595	0.3517	130
74599	0.3084	173

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.27	gold quality
right testis	UBERON:0004534	98.22	gold quality
calcaneal tendon	UBERON:0003701	97.87	gold quality
adrenal tissue	UBERON:0018303	97.75	gold quality
right uterine tube	UBERON:0001302	97.52	gold quality
body of pancreas	UBERON:0001150	97.25	gold quality
secondary oocyte	CL:0000655	97.06	gold quality
right lobe of thyroid gland	UBERON:0001119	97.01	gold quality
metanephros cortex	UBERON:0010533	96.86	gold quality
left lobe of thyroid gland	UBERON:0001120	96.80	gold quality
adenohypophysis	UBERON:0002196	96.67	gold quality
testis	UBERON:0000473	96.59	gold quality
mucosa of transverse colon	UBERON:0004991	96.45	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.45	gold quality
granulocyte	CL:0000094	96.40	gold quality
colonic epithelium	UBERON:0000397	96.27	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.22	gold quality
thyroid gland	UBERON:0002046	96.13	gold quality
monocyte	CL:0000576	96.10	gold quality
mucosa of stomach	UBERON:0001199	96.08	gold quality
right adrenal gland cortex	UBERON:0035827	96.06	gold quality
leukocyte	CL:0000738	96.04	gold quality
cerebellar hemisphere	UBERON:0002245	95.97	gold quality
tibial nerve	UBERON:0001323	95.96	gold quality
right lung	UBERON:0002167	95.93	gold quality
cerebellar cortex	UBERON:0002129	95.81	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.79	gold quality
right lobe of liver	UBERON:0001114	95.75	gold quality
right adrenal gland	UBERON:0001233	95.69	gold quality
islet of Langerhans	UBERON:0000006	95.65	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

49 targeting SNX14, 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-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3613-3P	100.00	76.36	7965
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-4282	99.99	75.36	6408
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-1284	99.67	73.56	1353

Literature-anchored findings (GeneRIF, showing 8)

• SNX19 and SNX14 PX domains reveal key differences in spatial control of RGS-PX proteins in cell signaling and trafficking. (PMID:25148684)
• Mutations in SNX14 cause a distinctive autosomal-recessive cerebellar ataxia and intellectual disability syndrome. (PMID:25439728)
• A unique ataxia syndrome due to biallelic SNX14 mutations leading to lysosome-autophagosome dysfunction. (PMID:25848753)
• Here we report on a child with a novel missense mutation in the SNX14 gene that appears to be debilitating for protein conformation, function and review the previously reported cases from 15 families (PMID:27913285)
• We therefore identify an important role for SNX14 in neutral lipid homeostasis between the endoplasmic reticulum , lysosomes and lipid droplets that may provide an early intervention target to alleviate the clinical symptoms of autosomal recessive cerebellar ataxia 20 (SCAR20). (PMID:29635513)
• Snx14, an endoplasmic reticulum-resident protein associated with the cerebellar ataxia SCAR20, localizes to ER-LD contacts following fatty acid treatment, where it promotes lipid droplet maturation. (PMID:30765438)
• The circSNX14 functions as a tumor suppressor via the miR-562/ LATS2 pathway in hepatocellular carcinoma cells. (PMID:37861952)
• SNX14 inhibits autophagy via the PI3K/AKT/mTOR signaling cascade in breast cancer cells. (PMID:38869753)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	snx14	ENSDARG00000006332
mus_musculus	Snx14	ENSMUSG00000032422
rattus_norvegicus	Snx14	ENSRNOG00000011348
caenorhabditis_elegans		WBGENE00013011

Paralogs (3): SNX13 (ENSG00000071189), SNX25 (ENSG00000109762), SNX19 (ENSG00000120451)

Protein

Protein identifiers

Sorting nexin-14 — Q9Y5W7 (reviewed: Q9Y5W7)

All UniProt accessions (65): A0A804HHR7, A0A804HHX8, A0A804HHZ6, A0A804HI30, A0A804HI47, Q9Y5W7, A0A804HI51, A0A804HIA1, A0A804HIC5, A0A804HIC6, A0A804HID3, A0A804HID8, A0A804HIJ3, A0A804HIK6, A0A804HIM9, A0A804HIR3, A0A804HIV6, A0A804HIW9, A0A804HIX9, A0A804HIZ9, A0A804HJ02, A0A804HJ61, A0A804HJ76, A0A804HJ79, A0A804HJ91, A0A804HJA7, A0A804HJC6, A0A804HJD1, A0A804HJF4, A0A804HJG1, A0A804HJH5, A0A804HJI4, A0A804HJK3, A0A804HJL8, A0A804HJS3, A0A804HJT4, A0A804HJW4, A0A804HJZ4, A0A804HK22, A0A804HK24, A0A804HK55, A0A804HKA3, A0A804HKC6, A0A804HKD6, A0A804HKH6, A0A804HKJ3, A0A804HKN0, A0A804HKN4, A0A804HKP6, A0A804HKT4, A0A804HKY3, A0A804HKZ1, A0A804HL41, A0A804HL44, A0A804HL53, A0A804HLC7, A0A804HLH9, D6RBA7, D6RDA6, D6RDH9, D6REK1, D6RJG9, E2QRM8, H0Y926, Q5JRQ0

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in maintaining normal neuronal excitability and synaptic transmission. May be involved in several stages of intracellular trafficking. Required for autophagosome clearance, possibly by mediating the fusion of lysosomes with autophagosomes. Binds phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2), a key component of late endosomes/lysosomes. Does not bind phosphatidylinositol 3-phosphate (PtdIns(3P)).

Subcellular location. Lysosome membrane. Late endosome membrane. Cell projection. Dendrite.

Tissue specificity. Widely expressed both in fetal and adult tissues.

Disease relevance. Spinocerebellar ataxia, autosomal recessive, 20 (SCAR20) [MIM:616354] A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR20 is characterized by cerebellar atrophy, ataxia, coarsened facial features, severely delayed psychomotor development with poor or absent speech, and intellectual disability. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the sorting nexin family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9Y5W7-1	1	yes
Q9Y5W7-2	2
Q9Y5W7-3	3
Q9Y5W7-4	4

RefSeq proteins (26): NP_001284543, NP_001291408, NP_001337461, NP_001337462, NP_001337463, NP_001337464, NP_001337465, NP_001337466, NP_001337467, NP_001337468, NP_001337469, NP_001337470, NP_001337471, NP_001337472, NP_001337473, NP_001337474, NP_001337475, NP_001337476, NP_001337477, NP_001337478, NP_001337479, NP_001337480, NP_001337481, NP_001337482, NP_065201, NP_722523* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001683	PX_dom	Domain
IPR003114	Phox_assoc	Domain
IPR013937	Sorting_nexin_C	Domain
IPR016137	RGS	Domain
IPR036305	RGS_sf	Homologous_superfamily
IPR036871	PX_dom_sf	Homologous_superfamily
IPR037436	SNX14_PX	Domain
IPR037892	SNX14_RGS	Domain
IPR044926	RGS_subdomain_2	Homologous_superfamily

Pfam: PF00615, PF00787, PF02194, PF08628

UniProt features (26 total): sequence conflict 6, helix 5, strand 4, domain 3, splice variant 3, transmembrane region 2, chain 1, sequence variant 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4BGJ	X-RAY DIFFRACTION	2.55
4PQO	X-RAY DIFFRACTION	2.55
4PQP	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5W7-F1	73.75	0.22

Functional residue map

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

Post-translational modifications (1): 548

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 274 (showing top): GOCC_VACUOLAR_MEMBRANE, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MACROAUTOPHAGY, GOBP_CELL_CELL_SIGNALING, TGACATY_UNKNOWN, GOBP_SYNAPTIC_SIGNALING, GOCC_NEURON_PROJECTION, MILI_PSEUDOPODIA_CHEMOTAXIS_DN, GOCC_LATE_ENDOSOME_MEMBRANE, GOCC_POSTSYNAPSE, GAVIN_FOXP3_TARGETS_CLUSTER_T4, AHR_Q5, GOCC_SYNAPSE, ZHENG_BOUND_BY_FOXP3, ZHENG_FOXP3_TARGETS_UP

GO Biological Process (3): protein transport (GO:0015031), autophagosome maturation (GO:0097352), postsynaptic modulation of chemical synaptic transmission (GO:0099170)

GO Molecular Function (2): phosphatidylinositol binding (GO:0035091), phosphatidylinositol-3,5-bisphosphate binding (GO:0080025)

GO Cellular Component (11): lysosome (GO:0005764), lysosomal membrane (GO:0005765), late endosome (GO:0005770), cytosol (GO:0005829), dendrite (GO:0030425), late endosome membrane (GO:0031902), postsynapse (GO:0098794), endosome (GO:0005768), membrane (GO:0016020), cell projection (GO:0042995), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
transport	1
intracellular protein localization	1
establishment of protein localization	1
macroautophagy	1
protein-containing complex disassembly	1
modulation of chemical synaptic transmission	1
postsynapse	1
anion binding	1
phosphatidylinositol phosphate binding	1
phosphatidylinositol bisphosphate binding	1
lytic vacuole	1
lysosome	1
lytic vacuole membrane	1
endosome	1
cytoplasm	1
neuron projection	1
dendritic tree	1
late endosome	1
endosome membrane	1
synapse	1
endomembrane system	1
cytoplasmic vesicle	1
cell junction	1

Protein interactions and networks

STRING

1154 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNX14	SAXO6	Q8TC05	694
SNX14	SNX17	Q15036	584
SNX14	ZNF529	Q6P280	578
SNX14	EPG5	Q9HCE0	555
SNX14	RAB18	Q9NP72	549
SNX14	SNX13	Q9Y5W8	539
SNX14	SNX25	Q9H3E2	532
SNX14	SNX27	Q96L92	520
SNX14	SNX11	Q9Y5W9	519
SNX14	ACSL3	O95573	513
SNX14	WDR45	Q9Y484	513
SNX14	SNX1	Q13596	503
SNX14	SNX6	Q9UNH7	495
SNX14	SNX2	P82862	480
SNX14	RGS8	P57771	472

IntAct

62 interactions, top by confidence:

A	B	Type	Score
IPPK	TMEM223	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530
MCOLN3	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
CNGA3	C2CD2L	psi-mi:“MI:0914”(association)	0.530
CHRNA9	CHEK1	psi-mi:“MI:0914”(association)	0.530
TEX264	PER1	psi-mi:“MI:0914”(association)	0.530
TLR5	MAN1A2	psi-mi:“MI:0914”(association)	0.530
TSPAN2	TSPAN3	psi-mi:“MI:0914”(association)	0.530
SNX14	SNX13	psi-mi:“MI:0915”(physical association)	0.400
	SNX14	psi-mi:“MI:0915”(physical association)	0.370
	ESYT2	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
	HLA-C	psi-mi:“MI:0914”(association)	0.350
CYP51A1	PGRMC1	psi-mi:“MI:0914”(association)	0.350
KCNA2	TMEM129	psi-mi:“MI:0914”(association)	0.350
ATP1A3	TMEM223	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
CMTM5	TMEM120B	psi-mi:“MI:0914”(association)	0.350
OR1M1	NBAS	psi-mi:“MI:0914”(association)	0.350
ZDHHC12	NBAS	psi-mi:“MI:0914”(association)	0.350
AVPR1B	KLRG2	psi-mi:“MI:0914”(association)	0.350
SIGLECL1	RBFOX3	psi-mi:“MI:0914”(association)	0.350
EDAR	UPK3BL1	psi-mi:“MI:0914”(association)	0.350

BioGRID (108): SNX14 (Affinity Capture-RNA), SNX14 (Affinity Capture-RNA), SNX14 (Affinity Capture-MS), SNX14 (Affinity Capture-MS), SNX14 (Affinity Capture-MS), SNX14 (Affinity Capture-MS), SNX14 (Affinity Capture-MS), SNX14 (Affinity Capture-MS), SNX14 (Affinity Capture-MS), SNX14 (Affinity Capture-MS), SNX14 (Affinity Capture-MS), SNX14 (Affinity Capture-MS), SNX14 (Affinity Capture-MS), SNX14 (Affinity Capture-MS), SNX14 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IES7, A0JN62, A0JNW5, A2AAE1, A2AGL3, A2RSJ4, A2RT67, A2RUS2, A2RV80, B0LPN4, B1H2P5, E7F240, E9Q401, O00507, O94967, P30957, P48553, P51593, Q14161, Q2LD37, Q3TLI0, Q3UHE1, Q3UVG3, Q3UX43, Q5F361, Q5M7Q1, Q5RAQ5, Q5ZJK1, Q658Y4, Q68CL5, Q6BDS2, Q6P6Y1, Q6TEP1, Q6VNB8, Q7TMY8, Q7TSG1, Q7Z6Z7, Q8BHY8, Q8CB44, Q8CGF6

Diamond homologs: P40959, P57768, P57769, Q08DX0, Q3MPQ4, Q4FZZ1, Q559T8, Q5AG56, Q5PNP1, Q5R6Q7, Q5R7A7, Q5R903, Q7Z7A4, Q8BHY8, Q8BX57, Q8C080, Q8R4V0, Q8TEQ0, Q96BR1, Q9D3S3, Q9ERE3, Q9FG38, Q9Y5W7, Q9Y5W8, B1AVY7, P83099, Q54TC3, Q54WZ5, Q6CUC4, Q6PHS6, Q75CC3, Q8CFD4, Q8IPH9, Q96L93, Q9Y5X2, Q05B62, Q13596, Q4R503, Q5RFP8, Q6FNH2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transport of small molecules	11	5.0×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytosolic calcium ion concentration	6	9.5×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	21
Likely pathogenic	26
Uncertain significance	164
Likely benign	106
Benign	52

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
190314	NM_153816.6(SNX14):c.2596C>T (p.Gln866Ter)	Pathogenic
190315	NM_153816.2(SNX14):c.1108+1181_2108-2342del	Pathogenic
190316	NM_153816.6(SNX14):c.645dup (p.Glu216fs)	Pathogenic
190318	NM_153816.6(SNX14):c.1132C>T (p.Arg378Ter)	Pathogenic
190319	NM_153816.6(SNX14):c.428T>A (p.Leu143Ter)	Pathogenic
190320	NM_153816.6(SNX14):c.2670del (p.Lys889_Cys890insTer)	Pathogenic
2572991	NM_153816.6(SNX14):c.1878del (p.Lys626fs)	Pathogenic
2573004	NM_153816.6(SNX14):c.2148+1G>T	Pathogenic
268133	NM_153816.6(SNX14):c.1108G>A (p.Glu370Lys)	Pathogenic
3246248	NC_000006.11:g.(?86256810)(86267798_?)del	Pathogenic
3337607	NM_153816.6(SNX14):c.2148+1G>A	Pathogenic
3364549	NM_153816.6(SNX14):c.1098_1101del (p.Phe365_Cys366insTer)	Pathogenic
3726079	NM_153816.6(SNX14):c.597_598insGAGAAGGGTCGAAGGCGCCGCGGGCTGGGGTCGGTGGCTTAGGGAGCCCGTCCCGCCATGGTGGCCGCGGCTGGTNNNNNNNNNNAAAAAAAAAAAAAAAAAAAAAAAAGCAGCAATG (p.Lys200delinsGluLysGlyArgArgArgArgGlyLeuGlySerValAlaTer)	Pathogenic
373031	NM_153816.6(SNX14):c.1108G>T (p.Glu370Ter)	Pathogenic
375550	NM_153816.6(SNX14):c.1707_1708insTTTTTTTTTTT (p.Pro570fs)	Pathogenic
3897619	NM_153816.6(SNX14):c.1811-8A>G	Pathogenic
4083499	GRCh37/hg19 6q14.3(chr6:86235844-86253478)x0	Pathogenic
4292559	NM_153816.6(SNX14):c.1475+1G>A	Pathogenic
522726	NM_153816.6(SNX14):c.331C>T (p.Arg111Ter)	Pathogenic
802248	NM_153816.6(SNX14):c.1608+1G>T	Pathogenic
817573	NM_153816.6(SNX14):c.1725dup (p.Glu576Ter)	Pathogenic
1066863	NC_000006.11:g.(?86252900)(86259597_?)dup	Likely pathogenic
1321152	NM_153816.6(SNX14):c.867+1G>T	Likely pathogenic
1521366	NM_153816.6(SNX14):c.913-1G>T	Likely pathogenic
2018455	NM_153816.6(SNX14):c.1390-2A>G	Likely pathogenic
2433658	NM_153816.6(SNX14):c.44_45del (p.Arg15fs)	Likely pathogenic
2497676	NM_153816.6(SNX14):c.462-589A>G	Likely pathogenic
2573000	NM_153816.6(SNX14):c.2746-2A>G	Likely pathogenic
2580356	GRCh37/hg19 6q14.3(chr6:86281805-86351207)x1	Likely pathogenic
2627362	NC_000006.11:g.(86251762_86252899)_(86259598_86267693)dup	Likely pathogenic

SpliceAI

4766 predictions. Top by Δscore:

Variant	Effect	Δscore
6:85508183:C:CA	donor_gain	1.0000
6:85508184:C:A	donor_gain	1.0000
6:85508700:A:AC	donor_gain	1.0000
6:85513782:A:AC	donor_gain	1.0000
6:85513783:C:CC	donor_gain	1.0000
6:85513783:CTT:C	donor_gain	1.0000
6:85513785:T:TA	donor_gain	1.0000
6:85514626:AAAG:A	acceptor_gain	1.0000
6:85514629:GCTAA:G	acceptor_loss	1.0000
6:85514630:C:CA	acceptor_loss	1.0000
6:85514630:C:CC	acceptor_gain	1.0000
6:85514631:T:A	acceptor_loss	1.0000
6:85515831:A:AC	donor_gain	1.0000
6:85515832:A:C	donor_gain	1.0000
6:85517755:CCTT:C	donor_gain	1.0000
6:85517889:T:C	acceptor_gain	1.0000
6:85517889:T:TC	acceptor_gain	1.0000
6:85517892:T:C	acceptor_gain	1.0000
6:85517892:T:TC	acceptor_gain	1.0000
6:85517894:G:GC	acceptor_gain	1.0000
6:85518004:TCACC:T	donor_loss	1.0000
6:85518005:CACC:C	donor_loss	1.0000
6:85518006:A:AC	donor_gain	1.0000
6:85518006:A:AT	donor_loss	1.0000
6:85518006:AC:A	donor_gain	1.0000
6:85518006:ACCT:A	donor_gain	1.0000
6:85518007:C:CT	donor_gain	1.0000
6:85518007:CC:C	donor_gain	1.0000
6:85518007:CCT:C	donor_gain	1.0000
6:85518007:CCTC:C	donor_gain	1.0000

AlphaMissense

6258 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:85526185:A:G	L683P	1.000
6:85528266:A:G	L664P	1.000
6:85530196:A:C	F630L	1.000
6:85530196:A:T	F630L	1.000
6:85530198:A:G	F630L	1.000
6:85530206:A:G	L627P	1.000
6:85530218:A:G	L623P	1.000
6:85530241:T:A	R615S	1.000
6:85530241:T:G	R615S	1.000
6:85530242:C:G	R615T	1.000
6:85533622:A:T	V596D	1.000
6:85533716:A:G	W565R	1.000
6:85533716:A:T	W565R	1.000
6:85518030:A:T	V709D	0.999
6:85526187:A:C	F682L	0.999
6:85526187:A:T	F682L	0.999
6:85526188:A:G	F682S	0.999
6:85526189:A:G	F682L	0.999
6:85526197:A:G	L679P	0.999
6:85526200:A:G	L678P	0.999
6:85526205:A:C	S676R	0.999
6:85526205:A:T	S676R	0.999
6:85526207:T:G	S676R	0.999
6:85526215:A:G	L673P	0.999
6:85526233:A:G	L667P	0.999
6:85528331:C:A	K642N	0.999
6:85528331:C:G	K642N	0.999
6:85528341:A:T	L639H	0.999
6:85530195:G:C	H631D	0.999
6:85530197:A:G	F630S	0.999

dbSNP variants (sampled 300 via entrez): RS1000011141 (6:85582899 G>A), RS1000066106 (6:85589282 G>A), RS1000067114 (6:85512240 T>C), RS1000089812 (6:85536795 A>G), RS1000115636 (6:85546057 A>G), RS1000159033 (6:85589040 C>A,T), RS1000194598 (6:85512065 G>A), RS1000220712 (6:85589008 C>A,T), RS1000248894 (6:85552714 T>C,G), RS1000254440 (6:85508635 T>A,C), RS1000275098 (6:85518243 T>C), RS1000342493 (6:85570827 T>C), RS1000354337 (6:85559181 G>A), RS1000357859 (6:85550410 C>G), RS1000363134 (6:85514436 A>C)

Disease associations

OMIM: gene MIM:616105 | disease phenotypes: MIM:616354

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive spinocerebellar ataxia 20	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
autosomal recessive spinocerebellar ataxia 20	Definitive	AR

Mondo (3): autosomal recessive spinocerebellar ataxia 20 (MONDO:0014601), neurodevelopmental disorder (MONDO:0700092), cerebellar ataxia (MONDO:0000437)

Orphanet (2): Intellectual disability-coarse face-macrocephaly-cerebellar hypotrophy syndrome (Orphanet:397709), Rare ataxia (Orphanet:102002)

HPO phenotypes

77 total (30 of 77 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000158	Macroglossia
HP:0000218	High palate
HP:0000280	Coarse facial features
HP:0000283	Broad face
HP:0000286	Epicanthus
HP:0000289	Broad philtrum
HP:0000293	Full cheeks
HP:0000307	Pointed chin
HP:0000343	Long philtrum
HP:0000350	Small forehead
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000414	Bulbous nose
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000506	Telecanthus
HP:0000639	Nystagmus
HP:0000678	Dental crowding
HP:0000684	Delayed eruption of teeth
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0000768	Pectus carinatum
HP:0000998	Hypertrichosis
HP:0001156	Brachydactyly
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D002524	Cerebellar Ataxia	C10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
nickel sulfate	increases expression	1
1-nitropyrene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
abrine	decreases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Bilirubin	decreases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	affects expression	1
Aflatoxin B1	decreases methylation	1
Aflatoxin M1	decreases expression	1
Lactic Acid	decreases expression	1
Vitamin K 3	affects expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice