CLEC16A

Summary

CLEC16A (C-type lectin domain containing 16A, HGNC:29013) is a protein-coding gene on chromosome 16p13.13, encoding Protein CLEC16A (Q2KHT3). Regulator of mitophagy through the upstream regulation of the RNF41/NRDP1-PRKN pathway.

This gene encodes a member of the C-type lectin domain containing family. Single nucleotide polymorphisms in introns of this gene have been associated with diabetes mellitus, multiple sclerosis and rheumatoid arthritis. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 23274 — RefSeq curated summary.

At a glance

• Gene–disease (curated): schizophrenia (No Known Disease Relationship, GenCC)
• GWAS associations: 107
• Clinical variants (ClinVar): 206 total
• MANE Select transcript: NM_015226

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29013
Approved symbol	CLEC16A
Name	C-type lectin domain containing 16A
Location	16p13.13
Locus type	gene with protein product
Status	Approved
Aliases	Gop-1
Ensembl gene	ENSG00000038532
Ensembl biotype	protein_coding
OMIM	611303
Entrez	23274

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 4 protein_coding_CDS_not_defined, 3 retained_intron

ENST00000261657, ENST00000409552, ENST00000409790, ENST00000428742, ENST00000436973, ENST00000459723, ENST00000463459, ENST00000463896, ENST00000465491, ENST00000476025, ENST00000487189, ENST00000494853, ENST00000646363, ENST00000703130, ENST00000904404, ENST00000904405, ENST00000923410, ENST00000923411

RefSeq mRNA: 3 — MANE Select: NM_015226 NM_001243403, NM_001410905, NM_015226

CCDS: CCDS45409, CCDS58423, CCDS92106

Canonical transcript exons

ENST00000409790 — 24 exons

Exon	Start	End
ENSE00000829668	11125979	11126146
ENSE00000829669	11123742	11123946
ENSE00000829674	10971125	10971230
ENSE00000829675	10969161	10969309
ENSE00000829676	10962455	10962588
ENSE00001237012	10957782	10957910
ENSE00001779937	10972554	10972559
ENSE00003467641	11047292	11047342
ENSE00003496961	11020193	11020325
ENSE00003514355	10979329	10979382
ENSE00003517264	11039754	11039876
ENSE00003527519	11044028	11044072
ENSE00003528687	11166388	11166552
ENSE00003532020	11060902	11061022
ENSE00003541189	10977225	10977399
ENSE00003551876	11051513	11051641
ENSE00003559926	11024821	11024921
ENSE00003562888	10982878	10982991
ENSE00003581546	11042254	11042363
ENSE00003595097	11120615	11120766
ENSE00003676155	11003074	11003305
ENSE00003988038	10944564	10944797
ENSE00003988039	10972938	10973061
ENSE00003988040	11178335	11182186

Expression profiles

Bgee: expression breadth ubiquitous, 225 present calls, max score 94.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.2798 / max 312.3710, expressed in 1810 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152736	19.1111	1810
152735	1.0798	638
152738	0.0429	18
152734	0.0396	8
152744	0.0064	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	94.50	gold quality
right testis	UBERON:0004534	94.24	gold quality
testis	UBERON:0000473	90.99	gold quality
sural nerve	UBERON:0015488	88.38	gold quality
lower esophagus mucosa	UBERON:0035834	88.21	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.28	gold quality
colonic epithelium	UBERON:0000397	85.72	gold quality
apex of heart	UBERON:0002098	85.55	gold quality
cerebellar hemisphere	UBERON:0002245	85.40	gold quality
right frontal lobe	UBERON:0002810	85.38	gold quality
Brodmann (1909) area 10	UBERON:0013541	85.34	gold quality
cerebellar cortex	UBERON:0002129	85.30	gold quality
adrenal tissue	UBERON:0018303	85.28	gold quality
adenohypophysis	UBERON:0002196	85.11	gold quality
gastrocnemius	UBERON:0001388	84.83	gold quality
cortical plate	UBERON:0005343	84.50	gold quality
metanephros cortex	UBERON:0010533	84.36	gold quality
muscle of leg	UBERON:0001383	84.35	gold quality
pituitary gland	UBERON:0000007	83.67	gold quality
cerebellum	UBERON:0002037	83.64	gold quality
prefrontal cortex	UBERON:0000451	83.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.43	gold quality
stromal cell of endometrium	CL:0002255	83.27	gold quality
mucosa of transverse colon	UBERON:0004991	83.27	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.24	gold quality
skin of leg	UBERON:0001511	83.18	gold quality
tibial nerve	UBERON:0001323	83.11	gold quality
bone marrow cell	CL:0002092	82.92	gold quality
right lobe of liver	UBERON:0001114	82.92	gold quality
granulocyte	CL:0000094	82.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

116 targeting CLEC16A, 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-8485	100.00	77.57	4731
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-149-3P	99.72	68.22	3963

Literature-anchored findings (GeneRIF, showing 40)

• results indicate that KIAA0350 might be involved in the pathogenesis of type 1 diabetes and demonstrate the utility of the genome-wide association approach in the identification of previously unsuspected genetic determinants of complex traits (PMID:17632545)
• Two alleles at 16p13 are independently associated with the risk of Addison’s disease in the Norwegian population, suggesting this chromosomal region to harbor common autoimmunity gene(s), CLEC16A and CIITA being possible independent candidates. (PMID:18593762)
• There is evidence of a genome-wide significant association between KIAA0350 and risk of multiple sclerosis in Australians. (PMID:18650830)
• Variation within the CLEC16A gene shows consistent disease association with both multiple sclerosis and type 1 diabetes in Italy. (PMID:18946483)
• CLEC16A is a multiple sclerosis susceptibility gene. (PMID:18987646)
• The intron polymorphism rs725613 in the KIAA0350 gene is associated with susceptibility to type 1 diabetes in the Chinese population. (PMID:19178520)
• Autoimmune disease association signals in KIAA0350 are not involved in celiac disease susceptibility (PMID:19317741)
• a CLEC16A/KIAA0350 polymorphism may have a role in NOD2/CARD15(-) Crohn’s disease patients (PMID:19337309)
• A CLEC16A variant confers risk for juvenile idiopathic arthritis and anti-cyclic citrullinated peptide antibody negative rheumatoid arthritis (PMID:19734133)
• Studies indicate that five SNPs showed genome-wide significant association with MS: HLA-DRA, IL7R, IL2RA, CD58 and CLEC16A. (PMID:19834503)
• SEMA3F, CLEC16A, LAMA3, and PCSK2 variants have roles in myocardial infarction in Japanese individuals (PMID:20036365)
• The initial chi-square test revealed that the Cright curved arrow T polymorphism of CLEC16A and the Aright curved arrow G polymorphism of SPTBN5 were significantly ssociated with ischemic stroke among individuals with metabolic syndrome. (PMID:20043139)
• Results show that CLEC16A does not have a prominent function in susceptibility to anti-cyclic citrullinated peptide (CCP)-positive rheumatoid arthritis. (PMID:20220768)
• Studies indicate that SNP in IL7RA, IL2RA, CD58 and CLEC16A genes has been consistently associated with MS. (PMID:20450971)
• A significant association with multiple sclerosis is found for four single nucleotide polymorphisms within the CLEC16A gene, all located in the same linkage disequilibrium (LD) block. (PMID:20849399)
• Expression analysis revealed that rs12708716 genotype was significantly associated with the relative expression levels of two different CLEC16A transcripts in thymus (P=0.004) (PMID:21179112)
• Data show independent genetic signals in the CIITA-CLEC16A-SOCS1 gene complex in multiple sclerosis susceptibility. (PMID:21653641)
• Fine mapping identified 26 single-nucleotide polymorphisms (SNPs) across the CLEC16A-SOCS1 and 11 SNPs across the SPIB locus with significant association to primary biliary cirrhosis. (PMID:22257840)
• Genome-wide significant association was found for rs20541 and rs998592, thus establishing IL-13 and KIAA0350/CLEC16A as susceptibility loci for alopecia areata. IL-13 and KIAA0350/CLEC16A are also susceptibility loci for other autoimmune diseases. (PMID:22534877)
• Polymorphisms in the inflammatory genes CIITA, CLEC16A and IFNG influence BMD, bone loss and fracture in elderly women (PMID:23133532)
• The data indicates a possible regulatory role for multiple sclerosis-associated non-coding CLEC16A SNPs and a common control mechanism for the expression of CLEC16A, SOCS1 and DEXI. (PMID:23151489)
• Our results suggest that polymorphisms rs6498169 of CLEC16A gene confers susceptibility to AITDs. We therefore disclose for the first time the association of rs6498169 SNP with AITDs. (PMID:24646814)
• Study demonstrates that a diabetogenic SNP in the CLEC16A locus correlates with islet CLEC16A expression, beta cell function, and glycemic control in human subjects. Clec16a controls beta cell function and prevents diabetes by controlling mitophagy. (PMID:24949970)
• Forty-eight SNPs, all located in CLEC16A, provided a statistically significant association with type 1 diabetes mellitus, with rs34306440 being most significantly associated. The mechanisim is likely through reduced expression of DEXI transcripts. (PMID:25008175)
• data suggests that two polymorphisms of the CLEC16A gene play an important role in the developing of ACS in men. (PMID:25447402)
• The study suggested that a CLEC16A polymorphism may be protective against Vogt-Koyanagi-Harada syndrome syndrome in a Chinese Han population. (PMID:25576669)
• identify CLEC16A as a pivotal gene in multiple sclerosis that serves as a direct regulator of the human leukocyte antigen class II pathway in antigen-presenting cells. (PMID:25823473)
• Clec16a knockdown mice showed reduced number of B cells and elevated IgM levels compared with controls. (PMID:25891430)
• This study demonstrated that the Polymorphism, Single Nucleotide of CLEC16A is associated with multiple sclerosis in Russia. (PMID:25903733)
• CLEC16A was found to be a susceptibility factor for SLE, with possible contribution to the development of the disease. (PMID:26121298)
• A possible regulatory role for the multiple sclerosis-associated rs12927355 in CLEC16A. (PMID:26203907)
• Study provides evidence that Clec16a plays a key role in the survival of Purkinje cells and in the degradative function or clearance of autolysosomes. (PMID:26987296)
• Golgi-associated CLEC16A negatively regulates autophagy via modulation of mTOR activity. (PMID:28223137)
• The genotypes of IL-4 (rs2243250)*C/C and CLEC16A (rs6498169)*G/G were associated with primary progressive multiple sclerosis in Russians. The association between the HLA-DRB1*15 and PPMS found out in other populations was confirmed in Russians. (PMID:28617357)
• Data (including data from studies using knockout and transgenic mice/cells) suggest that CLEC16A, NRDP1, and USP8 form tripartite complex; CLEC16A-NRDP1-USP8 complex appears to rely on ubiquitin signals to promote mitophagy and maintain mitochondrial function necessary for beta-cell function. (CLEC16A = C-type lectin domain family 16 member A; NRDP1 = ubiquitin-protein ligase NRDP1; USP8 = ubiquitin specific peptidase 8) (PMID:29180353)
• CLEC16A restrains secretory functions including cytokine release and cytotoxicity, and a delicate balance of CLEC16A is needed for NK cell function and homeostasis. (PMID:30774629)
• CLEC16A rs12708716 is associated with insulin-triggered type 1 diabetes. (PMID:30970177)
• The Role of Autoimmunity-Related Gene CLEC16A in the B Cell Receptor-Mediated HLA Class II Pathway. (PMID:32641384)
• Mitophagy protects beta cells from inflammatory damage in diabetes. (PMID:33232298)
• Exploring the role of the multiple sclerosis susceptibility gene CLEC16A in T cells. (PMID:34643957)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	clec16a	ENSDARG00000038094
mus_musculus	Clec16a	ENSMUSG00000068663
rattus_norvegicus	Clec16a	ENSRNOG00000057378
drosophila_melanogaster	ema	FBGN0038427
caenorhabditis_elegans		WBGENE00001660

Protein

Protein identifiers

Protein CLEC16A — Q2KHT3 (reviewed: Q2KHT3)

Alternative names: C-type lectin domain family 16 member A

All UniProt accessions (6): A0A2R8YDG4, A0A8V8TR67, Q2KHT3, H7BXG1, H7BZI2, H7BZJ9

UniProt curated annotations — full annotation on UniProt →

Function. Regulator of mitophagy through the upstream regulation of the RNF41/NRDP1-PRKN pathway. Mitophagy is a selective form of autophagy necessary for mitochondrial quality control. The RNF41/NRDP1-PRKN pathway regulates autophagosome-lysosome fusion during late mitophagy. May protect RNF41/NRDP1 from proteasomal degradation, RNF41/NRDP1 which regulates proteasomal degradation of PRKN. Plays a key role in beta cells functions by regulating mitophagy/autophagy and mitochondrial health.

Subunit / interactions. Interacts with RNF41/NRDP1.

Subcellular location. Endosome membrane. Lysosome membrane.

Tissue specificity. Almost exclusively expressed in immune cells, including dendritic cells, B-lymphocytes and natural killer cells.

Disease relevance. Type 1 diabetes mellitus (T1D) [MIM:222100] A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Three common non-coding variants of CLEC16A in strong linkage disequilibrium reach genome-wide significance for association with the disease. The non-coding variant rs12708716 is associated with reduced expression of CLEC16A in beta cells and reduced beta cell function.

Similarity. Belongs to the CLEC16A/gop-1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q2KHT3-1	1	yes
Q2KHT3-2	2
Q2KHT3-3	3

RefSeq proteins (3): NP_001230332, NP_001397834, NP_056041* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019155	CLEC16A/TT9_N	Domain
IPR039272	CLEC16A/TT9	Family
IPR045820	CLEC16A/TT9_C	Domain

Pfam: PF09758, PF19439

UniProt features (14 total): splice variant 6, region of interest 3, compositionally biased region 2, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2KHT3-F1	72.17	0.45

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 158 (showing top): GCM_MAP4K4, GOBP_REGULATION_OF_AUTOPHAGY, YAGI_AML_WITH_INV_16_TRANSLOCATION, GCM_GSPT1, GOCC_VACUOLAR_MEMBRANE, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, GOBP_VACUOLAR_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MACROAUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, STARK_HYPPOCAMPUS_22Q11_DELETION_UP, GOBP_NEGATIVE_REGULATION_OF_AUTOPHAGY, DAWSON_METHYLATED_IN_LYMPHOMA_TCL1, GOBP_REGULATION_OF_CATABOLIC_PROCESS, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_CIS

GO Biological Process (8): mitophagy (GO:0000423), vacuolar transport (GO:0007034), cellular response to starvation (GO:0009267), endosomal transport (GO:0016197), regulation of autophagosome maturation (GO:1901096), negative regulation of autophagosome maturation (GO:1901097), positive regulation of TORC1 signaling (GO:1904263), autophagy (GO:0006914)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (9): lysosomal membrane (GO:0005765), Golgi apparatus (GO:0005794), cytosol (GO:0005829), endosome membrane (GO:0010008), vesicle (GO:0031982), lysosome (GO:0005764), endosome (GO:0005768), late endosome (GO:0005770), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular transport	2
autophagosome maturation	2
cytoplasm	2
endomembrane system	2
cellular anatomical structure	2
endosome	2
autophagy of mitochondrion	1
macroautophagy	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
vesicle-mediated transport	1
regulation of macroautophagy	1
regulation of organelle organization	1
regulation of protein-containing complex disassembly	1
negative regulation of macroautophagy	1
negative regulation of protein-containing complex disassembly	1
regulation of autophagosome maturation	1
positive regulation of TOR signaling	1
TORC1 signaling	1
regulation of TORC1 signaling	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
binding	1
lysosome	1
lytic vacuole membrane	1
intracellular membrane-bounded organelle	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
membrane-bounded organelle	1
lytic vacuole	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

1360 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLEC16A	RNF41	Q9H4P4	851
CLEC16A	DEXI	O95424	805
CLEC16A	SH2B3	Q9UQQ2	727
CLEC16A	PTPN2	P17706	692
CLEC16A	HLA-DRB1	P01911	682
CLEC16A	CIITA	P33076	674
CLEC16A	BACH2	Q9BYV9	661
CLEC16A	CD6	P30203	646
CLEC16A	NAA25	Q14CX7	640
CLEC16A	IFIH1	Q9BYX4	631
CLEC16A	CD58	P19256	626
CLEC16A	C1QTNF6	Q9BXI9	624
CLEC16A	CTSH	P09668	621
CLEC16A	PTPN22	Q9Y2R2	621
CLEC16A	HLA-DQB1	P01917	620

IntAct

24 interactions, top by confidence:

A	B	Type	Score
ARPC1A	ARPC2	psi-mi:“MI:0914”(association)	0.900
RAB39B	CBL	psi-mi:“MI:0914”(association)	0.530
RNF41	CLEC16A	psi-mi:“MI:0914”(association)	0.350
	NAP1L1	psi-mi:“MI:0914”(association)	0.350
WRAP73	SDCBP	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
ACTR2		psi-mi:“MI:0914”(association)	0.350
ARPC2		psi-mi:“MI:0914”(association)	0.350
ARPC3		psi-mi:“MI:0914”(association)	0.350
PACSIN2	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
RNF41	SHTN1	psi-mi:“MI:0914”(association)	0.350
RAB43	TRAPPC13	psi-mi:“MI:0914”(association)	0.350
SLC18A2	UBXN8	psi-mi:“MI:0914”(association)	0.350
MFAP4	PEX1	psi-mi:“MI:0914”(association)	0.350
RASSF8	PAK3	psi-mi:“MI:0914”(association)	0.350
RAB39B	RAB5A	psi-mi:“MI:0914”(association)	0.350
SLC18A2	LGALS8	psi-mi:“MI:0914”(association)	0.350
FHIP1A	ILVBL	psi-mi:“MI:2364”(proximity)	0.270
FHIP2A	MED19	psi-mi:“MI:2364”(proximity)	0.270
dmsB	CLEC16A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (644): CLEC16A (Affinity Capture-MS), CLEC16A (Affinity Capture-MS), CLEC16A (Synthetic Lethality), CLEC16A (Affinity Capture-MS), CLEC16A (Affinity Capture-MS), CLEC16A (Affinity Capture-RNA), CLEC16A (Affinity Capture-MS), CLEC16A (Affinity Capture-RNA), CLEC16A (Proximity Label-MS), CLEC16A (Affinity Capture-RNA), CLEC16A (Proximity Label-MS), CLEC16A (Proximity Label-MS), CLEC16A (Proximity Label-MS), CLEC16A (Proximity Label-MS), CLEC16A (Affinity Capture-MS)

ESM2 similar proteins: A0A078CGE6, A2QHV0, A7KAX9, A7SNN5, A9RVK2, B0XPE7, B5X564, D0Z5N4, F4HYG2, F4I114, F4IRW0, F4J394, F4J6F6, F4JY37, O00444, O13839, O24527, O43065, P0CP71, P13185, P38623, P42858, P50526, Q03407, Q0CL79, Q0WPH8, Q14693, Q19192, Q2KHT3, Q2QAV0, Q4WJI7, Q5B4Z3, Q5R9Z7, Q60DG4, Q6GPD0, Q6H647, Q756Z0, Q75CH3, Q75DK7, Q75QN6

Diamond homologs: P46578, Q2KHT3, Q54GS1, Q80U30, Q8W4P9, Q9VEV4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 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
EPH-Ephrin signaling	6	52.3×	8e-08
Clathrin-mediated endocytosis	7	31.4×	8e-08
RHO GTPase Effectors	5	17.9×	6e-05
Axon guidance	7	16.6×	4e-06
Nervous system development	7	15.8×	5e-06
Signaling by Rho GTPases	6	10.8×	1e-04
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	6	10.6×	1e-04
Membrane Trafficking	5	9.8×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	155
Likely benign	14
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

4824 predictions. Top by Δscore:

Variant	Effect	Δscore
16:10944798:G:GG	donor_gain	1.0000
16:10957772:T:G	acceptor_gain	1.0000
16:10957778:TCA:T	acceptor_loss	1.0000
16:10957779:CAG:C	acceptor_loss	1.0000
16:10957780:A:AG	acceptor_gain	1.0000
16:10957780:A:AT	acceptor_loss	1.0000
16:10957780:AG:A	acceptor_gain	1.0000
16:10957781:G:A	acceptor_loss	1.0000
16:10957781:G:GG	acceptor_gain	1.0000
16:10957781:GG:G	acceptor_gain	1.0000
16:10957781:GGT:G	acceptor_gain	1.0000
16:10957781:GGTAT:G	acceptor_gain	1.0000
16:10957882:G:T	donor_gain	1.0000
16:10957898:GCTCT:G	donor_gain	1.0000
16:10957899:C:G	donor_gain	1.0000
16:10957903:GTATT:G	donor_gain	1.0000
16:10957904:TATTT:T	donor_gain	1.0000
16:10957905:ATTTG:A	donor_gain	1.0000
16:10957907:T:G	donor_gain	1.0000
16:10957907:T:TG	donor_gain	1.0000
16:10957907:TTGA:T	donor_loss	1.0000
16:10957908:TGA:T	donor_gain	1.0000
16:10957909:GA:G	donor_gain	1.0000
16:10957909:GAG:G	donor_gain	1.0000
16:10957911:G:GG	donor_gain	1.0000
16:10957912:T:TC	donor_loss	1.0000
16:10962450:CCCA:C	acceptor_loss	1.0000
16:10962451:CCA:C	acceptor_loss	1.0000
16:10962452:CA:C	acceptor_loss	1.0000
16:10962453:A:AG	acceptor_gain	1.0000

AlphaMissense

6969 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:10944794:T:A	L26H	1.000
16:10944794:T:C	L26P	1.000
16:10957817:T:A	V39D	1.000
16:10957841:T:C	L47P	1.000
16:10957855:C:A	R52S	1.000
16:10957856:G:C	R52P	1.000
16:10957868:A:T	E56V	1.000
16:10957874:T:A	L58Q	1.000
16:10957874:T:C	L58P	1.000
16:10957874:T:G	L58R	1.000
16:10957877:T:A	I59N	1.000
16:10957879:T:A	W60R	1.000
16:10957879:T:C	W60R	1.000
16:10957881:G:C	W60C	1.000
16:10957881:G:T	W60C	1.000
16:10957882:G:A	G61R	1.000
16:10957882:G:C	G61R	1.000
16:10957883:G:A	G61E	1.000
16:10957883:G:T	G61V	1.000
16:10957886:A:T	D62V	1.000
16:10957906:T:C	F69L	1.000
16:10957908:T:A	F69L	1.000
16:10957908:T:G	F69L	1.000
16:10962456:T:C	F71L	1.000
16:10962458:C:A	F71L	1.000
16:10962458:C:G	F71L	1.000
16:10962459:T:C	F72L	1.000
16:10962461:C:A	F72L	1.000
16:10962461:C:G	F72L	1.000
16:10962463:T:C	L73P	1.000

dbSNP variants (sampled 300 via entrez): RS1000000718 (16:11144943 G>A), RS1000004510 (16:11011319 C>G), RS1000018374 (16:10979251 G>A,C,T), RS1000024527 (16:11115321 A>G), RS1000044194 (16:11073722 C>T), RS1000044206 (16:11161400 G>T), RS1000048100 (16:11179665 T>C), RS1000048394 (16:11132181 TTCCATCCCC>T), RS1000060251 (16:11143563 G>C), RS1000091923 (16:11016189 A>C,T), RS1000101102 (16:11057325 T>G), RS1000111775 (16:11041429 A>G), RS1000122552 (16:10957629 G>A,T), RS1000128206 (16:10950778 C>G), RS1000136042 (16:10998374 C>G)

Disease associations

OMIM: gene MIM:611303 | disease phenotypes: MIM:156000

GenCC curated gene-disease

Disease	Classification	Inheritance
schizophrenia	No Known Disease Relationship	Unknown

Mondo (2): Meniere disease (MONDO:0007972), schizophrenia (MONDO:0005090)

Orphanet (1): NON RARE IN EUROPE: Menière disease (Orphanet:45360)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

107 associations (top):

Study	Trait	p-value
GCST000038_5	Type 1 diabetes	3.000000e-18
GCST000043_5	Type 1 diabetes	5.000000e-07
GCST000054_2	Type 1 diabetes	7.000000e-11
GCST000062_5	Multiple sclerosis	4.000000e-06
GCST000258_14	Type 1 diabetes	7.000000e-13
GCST000363_8	QT interval	5.000000e-15
GCST000392_33	Type 1 diabetes	2.000000e-16
GCST000424_8	Multiple sclerosis	2.000000e-07
GCST000612_10	Celiac disease	3.000000e-08
GCST000763_12	Immunoglobulin A	2.000000e-07
GCST001010_7	Primary biliary cholangitis	3.000000e-12
GCST001191_7	Type 1 diabetes	5.000000e-14
GCST001198_13	Multiple sclerosis	9.000000e-17
GCST001310_3	Allergic rhinitis	1.000000e-06
GCST001709_16	Atopic dermatitis	6.000000e-06
GCST001762_36	Obesity-related traits	2.000000e-06
GCST001762_473	Obesity-related traits	9.000000e-07
GCST001795_33	Systemic lupus erythematosus	5.000000e-07
GCST002083_30	Self-reported allergy	2.000000e-07
GCST002322_10	Asthma and hay fever	1.000000e-08
GCST003129_23	Primary biliary cholangitis	2.000000e-14
GCST003155_19	Systemic lupus erythematosus	7.000000e-17
GCST003184_21	Atopic dermatitis	3.000000e-11
GCST003566_16	Multiple sclerosis	1.000000e-09
GCST003814_33	Selective IgA deficiency	1.000000e-09
GCST003831_9	Asthma	9.000000e-06
GCST003833_5	Adult asthma	6.000000e-07
GCST003876_13	Gut microbiota (beta diversity)	5.000000e-08
GCST003987_11	Asthma	4.000000e-15
GCST003990_3	Allergy	2.000000e-16

EFO canonical traits (22, from GWAS)

EFO ID	Trait name
EFO:0004682	QT interval
EFO:0004747	protein measurement
EFO:0004267	biliary liver cirrhosis
EFO:0004626	IGFBP-3 measurement
EFO:0007874	gut microbiome measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0004587	lymphocyte count
EFO:0005763	pulse pressure measurement
EFO:0004847	age at onset
EFO:1002011	adult onset asthma
EFO:0009941	Inhalant adrenergic use measurement
EFO:0009942	Glucocorticoid use measurement
EFO:0008487	lateral ventricle volume measurement
EFO:0600008	mitochondrial heteroplasmy measurement
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004736	aspartate aminotransferase measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008575	Meniere Disease	C09.218.568.217.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6498169	CLEC16A		0.00	0

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	6
Valproic Acid	affects expression, increases expression	4
Aflatoxin B1	decreases expression, increases methylation	2
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
aflatoxin B2	increases methylation	1
beta-methylcholine	affects expression	1
ICG 001	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Theophylline	decreases expression	1
Urethane	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety