RELN

Summary

RELN (reelin, HGNC:9957) is a protein-coding gene on chromosome 7q22.1, encoding Reelin (P78509). Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment.

This gene encodes a large secreted extracellular matrix protein thought to control cell-cell interactions critical for cell positioning and neuronal migration during brain development. This protein may be involved in schizophrenia, autism, bipolar disorder, major depression and in migration defects associated with temporal lobe epilepsy. Mutations of this gene are associated with autosomal recessive lissencephaly with cerebellar hypoplasia. Two transcript variants encoding distinct isoforms have been identified for this gene. Other transcript variants have been described but their full length nature has not been determined.

Source: NCBI Gene 5649 — RefSeq curated summary.

At a glance

• Gene–disease (curated): lissencephaly with cerebellar hypoplasia (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 21
• Clinical variants (ClinVar): 3,712 total — 68 pathogenic, 39 likely-pathogenic
• Phenotypes (HPO): 80
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_005045

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9957
Approved symbol	RELN
Name	reelin
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	RL, PRO1598
Ensembl gene	ENSG00000189056
Ensembl biotype	protein_coding
OMIM	600514
Entrez	5649

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 14 retained_intron, 3 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000343529, ENST00000424685, ENST00000428762, ENST00000429186, ENST00000473457, ENST00000473945, ENST00000478148, ENST00000679371, ENST00000679689, ENST00000679867, ENST00000679952, ENST00000680248, ENST00000680706, ENST00000680712, ENST00000681034, ENST00000681182, ENST00000681199, ENST00000681315, ENST00000681364, ENST00000681401, ENST00000681921, ENST00000681931

RefSeq mRNA: 2 — MANE Select: NM_005045 NM_005045, NM_173054

CCDS: CCDS34722, CCDS47680

Canonical transcript exons

ENST00000428762 — 65 exons

Exon	Start	End
ENSE00001368017	103500745	103500922
ENSE00001369491	103498077	103498252
ENSE00001369922	103510851	103511005
ENSE00001370228	103497820	103497926
ENSE00001371835	103515185	103515441
ENSE00001384462	103503016	103503230
ENSE00001388019	103519323	103519516
ENSE00001411170	103522022	103522199
ENSE00001417076	103489742	103489899
ENSE00001417391	103490668	103490829
ENSE00001417999	103491953	103492026
ENSE00001418589	103495723	103495898
ENSE00001421020	103486197	103486416
ENSE00001423585	103496526	103496768
ENSE00002433253	103635425	103635586
ENSE00002433492	103556977	103557159
ENSE00002434757	103753182	103753214
ENSE00002439350	103589596	103589828
ENSE00002442576	103542731	103542878
ENSE00002444364	103574092	103574299
ENSE00002444629	103593682	103593882
ENSE00002445259	103723140	103723191
ENSE00002446145	103596456	103596661
ENSE00002447610	103523391	103523531
ENSE00002450856	103594321	103594492
ENSE00002453374	103553660	103553831
ENSE00002455254	103654093	103654205
ENSE00002460435	103728111	103728207
ENSE00002461437	103566601	103566759
ENSE00002468234	103700910	103701006
ENSE00002471017	103603304	103603490
ENSE00002472313	103610695	103610807
ENSE00002473681	103682116	103682261
ENSE00002476573	103833537	103833672
ENSE00002479065	103575548	103575705
ENSE00002479504	103697853	103698093
ENSE00002479556	103611611	103611803
ENSE00002483711	103566224	103566412
ENSE00002483853	103636235	103636468
ENSE00002484629	103565278	103565551
ENSE00002488877	103478389	103478394
ENSE00002489998	103540197	103540455
ENSE00002491367	103652551	103652759
ENSE00002491484	103551067	103551296
ENSE00002491587	103561813	103561953
ENSE00002494169	103539078	103539327
ENSE00002496767	103749426	103749504
ENSE00002500169	103604346	103604483
ENSE00002506569	103650274	103650383
ENSE00002507959	103572184	103572260
ENSE00002510114	103917075	103917185
ENSE00002514020	103661376	103661527
ENSE00002514474	103776557	103776627
ENSE00002521067	103545124	103545344
ENSE00002523441	103553461	103553563
ENSE00002526992	103651661	103651789
ENSE00002527436	103561532	103561709
ENSE00002527586	103640543	103640609
ENSE00002528830	103557965	103558049
ENSE00002533387	103629940	103630176
ENSE00003486932	103535316	103535484
ENSE00003552620	103482873	103482971
ENSE00003604440	103483653	103483850
ENSE00003841765	103989131	103989658
ENSE00003847243	103471789	103472908

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 99.09.

FANTOM5 (CAGE): breadth broad, TPM avg 7.1437 / max 397.1296, expressed in 592 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85389	5.3904	532
85388	0.7178	289
85387	0.4446	245
85379	0.2450	61
85386	0.1221	67
204629	0.0990	22
85390	0.0646	15
204630	0.0603	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory bulb	UBERON:0002264	99.09	gold quality
cerebellar vermis	UBERON:0004720	98.93	gold quality
cerebellum	UBERON:0002037	98.62	gold quality
cerebellar cortex	UBERON:0002129	98.60	gold quality
cerebellar hemisphere	UBERON:0002245	98.58	gold quality
paraflocculus	UBERON:0005351	98.38	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.28	gold quality
dorsal root ganglion	UBERON:0000044	98.07	gold quality
trigeminal ganglion	UBERON:0001675	98.07	gold quality
endothelial cell	CL:0000115	94.91	gold quality
tibial nerve	UBERON:0001323	94.09	gold quality
pons	UBERON:0000988	94.07	gold quality
sural nerve	UBERON:0015488	93.69	gold quality
pancreatic ductal cell	CL:0002079	92.07	silver quality
epithelial cell of pancreas	CL:0000083	91.89	gold quality
Brodmann (1909) area 46	UBERON:0006483	89.59	gold quality
entorhinal cortex	UBERON:0002728	89.49	gold quality
CA1 field of hippocampus	UBERON:0003881	89.47	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	89.45	gold quality
liver	UBERON:0002107	89.31	gold quality
pigmented layer of retina	UBERON:0001782	89.23	gold quality
decidua	UBERON:0002450	87.94	gold quality
periodontal ligament	UBERON:0008266	87.40	gold quality
orbitofrontal cortex	UBERON:0004167	87.09	gold quality
vena cava	UBERON:0004087	86.95	gold quality
superior vestibular nucleus	UBERON:0007227	85.56	gold quality
buccal mucosa cell	CL:0002336	85.50	silver quality
medial globus pallidus	UBERON:0002477	85.03	gold quality
ventral tegmental area	UBERON:0002691	84.95	gold quality
right lobe of liver	UBERON:0001114	84.89	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-ANND-2	yes	2159.52
E-HCAD-5	yes	1605.66
E-MTAB-8530	yes	473.98
E-HCAD-9	yes	17.88
E-MTAB-6701	yes	17.12
E-CURD-46	yes	15.92
E-MTAB-8410	yes	9.36
E-ANND-3	yes	7.50
E-MTAB-6108	no	209.37
E-GEOD-124858	no	16.30
E-MTAB-6678	no	3.54

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CXXC1, DNMT1, ESR1, FOXG1, FOXP1, FOXP2, HDAC1, KLF2, LHX1, MECP2, PAX6, PITX2, SNAI1, TBR1, TFCP2, TOP2B, ZBTB18, ZNF263

miRNA regulators (miRDB)

138 targeting RELN, 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-12118	100.00	65.88	1270
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-6077	99.99	68.04	2299
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-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-497-5P	99.92	71.83	2674

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• Upregulation of reelin is associated with tumorigenesis of esophagus (PMID:11880184)
• a single nucleotide polymorphism at the 5’ promoter region is associated with schizophrenia (PMID:12082559)
• Decreased expression of reelin mRNA by hippocampal Cajal-Retzius cells correlates with the extent of migration defects in the dentate gyrus of patients with temporal lobe epilepsy (PMID:12122039)
• GGC polymorphism of the reelin gene is unlikely to be a major susceptibility factor in autism and/or genetic heterogeneity. (PMID:12192627)
• We found significant reductions in 410 kDa Reelin species in autistic twins, their fathers, mothers,and phenotypically normal siblings versus controls, suggesting that Reelin 410 deficiency may be a vulnerability factor in the pathology of autism. (PMID:12363196)
• reelin has a role in PI3-kinase signaling in neuronal growth cones, and in contributes to final neuron positioning in the mammalian brain by local modulation of protein kinase B and glycogen synthase kinase 3beta kinase activities (PMID:12376533)
• case-control and affected sib-pair findings did not support a role for RELN in susceptibility to ASD, family-based association study show that RELN alleles with larger numbers of CGG repeats may affect the etiology of autism without delayed phrase speech. (PMID:12399956)
• Increased levels of the 180-kDa isoform of reelin in the cerebrospinal fluid of patients with frontotemporal dementia and Alzheimer’s disease suggests the involvement of reelin signaling in neurodegenerative pathologies. (PMID:12645087)
• RELN and DAB1 coexpression in these neurons is necessary for both normal cortical development and mature function. (PMID:12834112)
• Study replicates findings of increased interstitial white matter neurons (IWMNs). density, and decreased reelin expression, in schizophrenia. The loss of reelin reflects, at least partly, its decreased expression by IWMNs. (PMID:12931209)
• The analysis of RELN suggests that it probably does not play a major role in autism aetiology (PMID:14515139)
• Reelin was detected in comparable concentrations in the CSF in children and adults, and varied largely from subject to subject with no obvious correlation with age or neurological disease state. (PMID:15006702)
• Our results are not consistent with a major role for Reelin alleles in liability to autism. (PMID:15048647)
• Our interpretation of these findings is that it is unlikely that DNA variations in RELN and WNT2 play a significant role in the genetic predisposition to autism. (PMID:15048648)
• Reelin might be an extracellular matrix molecule involved in the terminal innervation of the dentin-pulp complex, promoting adhesion between dental nerve endings and odontoblasts. (PMID:15464360)
• An association analysis of five single-nucleotide polymorphisms (SNPs) of reelin (RELN) and a repeat in the 5’-untranslated region (5’-UTR) were conducted. Results strongly suggest RELN is involved in autism susceptiblity. (PMID:15558079)
• In this review of the role of reelin during cerebral cortex development, specific emphasis is placed on the mechanisms by which the extracellular protein reelin regulates neuronal positioning at the end of migration. (PMID:15655250)
• In the adult human neocortex, reelin-i was widespread and present in intracellular locations in cortical neuron somata and in glial cells. (PMID:15690491)
• Dab1 regulates both cell surface expression and internalization of Reelin receptors (PMID:15718228)
• The mRNAs for Reln were reduced significantly in superior frontal and cerebellar areas of autistic brains. (PMID:15820235)
• promoter methylation is important for reduced expression of reelin in schizophrenia (PMID:15961543)
• Results weakly support an association of reelin gene variants with schizophrenia as a whole, yet suggest that reelin could be associated with treatment-resistant schizophrenia. (PMID:15965968)
• loss of Reelin results in a type of lissencephaly with severe cortical and cerebellar malformation [review] (PMID:16266828)
• High prevalence of the silencing of RELN pathway components and its reversal by histone deacetylase inhibitors suggest the importance of this pathway as a diagnostic and therapeutic target for pancreatic cancer. (PMID:16472607)
• Reelin signals by binding to two transmembrane receptors, apolipoprotein E receptor 2 (Apoer2) and very-low-density lipoprotein receptor. (PMID:16481437)
• We found no difference in the expression of DISC1 or reelin mRNA in schizophrenia and no association with previously identified risk DISC1 SNPs (PMID:16510495)
• 5’UTR of reelin gene may have a role in the susceptibility towards autism with the paternal transmission and non-transmission respectively of 10- and > or =11-repeat alleles, to the affected offspring. (PMID:16941662)
• The effect of Dab1 on APP and apoEr2 processing in transfected cells and primary neurons is reported. (PMID:16951405)
• our analysis produces a tentative model of the core region of the Reelin subrepeat sequences and suggests the presence in this 3D model of structural features common to polysaccharide-binding modules which are often found on proteoglycans (PMID:16979599)
• A statistically significant correlation between the levels of DNA methylation in RELN and age was detected in healthy individuals, no such correlations were seen in either schizophrenic or bipolar patients. (PMID:17310238)
• Alterations in Reelin processing or signaling may be involved in Alzheimer’s disease-related neuronal dysfunction. (PMID:17360894)
• The distribution of reelin in the primary visual cortex is different from other cortical areas examined; reelin is mostly present in the neurons of second and sixth layer. (PMID:17365098)
• homozygous balanced reciprocal translocations led to RELN gene inactivation (PMID:17431900)
• Structure of a recptor-binding fragment of reelin reveals a recognition mechanism simlar to endocytic recptors. (PMID:17548821)
• RELN seems to be a good candidate for autism susceptibility. (PMID:17621165)
• allelic variants of RELN may contribute to the endophenotypes of schizophrenia. (PMID:17684500)
• reelin binds to apoE receptors activating the PI3 K/Akt pathway causing phosphorylation of BAD which protects cells from apoptosis (PMID:17696989)
• The DNA methylation status of the promoter region of RELN was examined by using the pyrosequencing method in the prefrontal cortices of 14 patients with schizophrenia and 13 control subjects. (PMID:17870056)
• the possible involvement of RELN gene in the susceptibility to autistic spectrum disorder (PMID:17955477)
• found a female-specific association with rs7341475, a SNP in the fourth intron of the reelin (RELN) gene (p = 2.9 x 10(-5) in women with schizophrenia), with a significant gene-sex effect (p = 1.8 x 10(-4)) (PMID:18282107)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000110545
danio_rerio		ENSDARG00000112431
mus_musculus	Reln	ENSMUSG00000042453
rattus_norvegicus	Reln	ENSRNOG00000021441

Protein

Protein identifiers

Reelin — P78509 (reviewed: P78509)

All UniProt accessions (4): A0A7P0TA83, P78509, H7C2B0, J3KQ66

UniProt curated annotations — full annotation on UniProt →

Function. Extracellular matrix serine protease secreted by pioneer neurons that plays a role in layering of neurons in the cerebral cortex and cerebellum by coordinating cell positioning during neurodevelopment. Regulates microtubule function in neurons and neuronal migration. Binding to the extracellular domains of lipoprotein receptors VLDLR and LRP8/APOER2 induces tyrosine phosphorylation of DAB1 and modulation of TAU phosphorylation. Affects migration of sympathetic preganglionic neurons in the spinal cord, where it seems to act as a barrier to neuronal migration. Enzymatic activity is important for the modulation of cell adhesion.

Subunit / interactions. Oligomer of disulfide-linked homodimers.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Abundantly produced during brain ontogenesis by the Cajal-Retzius cells and other pioneer neurons located in the telencephalic marginal zone and by granule cells of the external granular layer of the cerebellum. In adult brain, preferentially expressed in GABAergic interneurons of prefrontal cortices, temporal cortex, hippocampus and glutamatergic granule cells of cerebellum. Expression is reduced to about 50% in patients with schizophrenia. Also expressed in fetal and adult liver.

Post-translational modifications. N-glycosylated and to a lesser extent also O-glycosylated.

Disease relevance. Lissencephaly 2 (LIS2) [MIM:257320] A classic type lissencephaly associated with ataxia, intellectual disability, seizures and abnormalities of the cerebellum, hippocampus and brainstem. The disease is caused by variants affecting the gene represented in this entry. Epilepsy, familial temporal lobe, 7 (ETL7) [MIM:616436] A focal form of epilepsy characterized by recurrent seizures that arise from foci within the temporal lobe. Seizures are usually accompanied by sensory symptoms, most often auditory in nature. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The basic C-terminal region is essential for secretion.

Polymorphism. A polymorphic GGC triplet repeat located in the 5’-UTR region of RELN gene, which harbors in the normal population 8 to 10 repeats, is significantly increased in autistic patients to carry 4 to 23 additional repeats.

Similarity. Belongs to the reelin family.

Isoforms (3)

UniProt ID	Names	Canonical?
P78509-1	1	yes
P78509-2	2
P78509-3	3

RefSeq proteins (2): NP_005036, NP_774959 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR002861	Reeler_dom	Domain
IPR013111	EGF_extracell	Domain
IPR034968	Reelin	Family
IPR036278	Sialidase_sf	Homologous_superfamily
IPR042307	Reeler_sf	Homologous_superfamily
IPR049419	Reelin_subrepeat-B	Repeat

Pfam: PF07974, PF21471, PF23106

UniProt features (99 total): disulfide bond 32, glycosylation site 19, repeat 16, sequence variant 10, domain 9, binding site 7, splice variant 2, signal peptide 1, chain 1, sequence conflict 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8G21	SOLUTION NMR

Predicted structure (AlphaFold)

No AlphaFold model available for P78509 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

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 (7): 2060; 2073; 2178; 2263; 2396; 2398; 2459

Disulfide bonds (32): 40–126, 154–178, 539–580, 608–613, 674–684, 691–700, 894–936, 967–974, 1033–1043, 1050–1059, 1270–1309, 1338–1347, 1632–1672, 1701–1708, 2100, 2132–2142, 2136–2148, 2150–2159, 2194–2234, 2347–2386 …

Glycosylation sites (19): 140, 257, 289, 305, 628, 1266, 1599, 1749, 1920, 2144, 2268, 2316, 2568, 2961, 3015, 3072, 3184, 3411, 3438

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8866376	Reelin signalling pathway

MSigDB gene sets: 529 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, GOBP_DENDRITE_DEVELOPMENT, GOBP_MEMORY, GOBP_POSITIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, RRAGTTGT_UNKNOWN, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, HOFFMANN_SMALL_PRE_BII_TO_IMMATURE_B_LYMPHOCYTE_DN, GOBP_REGULATION_OF_PHOSPHORYLATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, GOBP_ASSOCIATIVE_LEARNING, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP

GO Biological Process (51): cell morphogenesis (GO:0000902), neuron migration (GO:0001764), proteolysis (GO:0006508), cell adhesion (GO:0007155), axon guidance (GO:0007411), central nervous system development (GO:0007417), brain development (GO:0007420), long-term memory (GO:0007616), locomotory behavior (GO:0007626), associative learning (GO:0008306), glial cell differentiation (GO:0010001), regulation of gene expression (GO:0010468), positive regulation of neuron projection development (GO:0010976), dendrite development (GO:0016358), spinal cord patterning (GO:0021511), ventral spinal cord development (GO:0021517), hippocampus development (GO:0021766), cerebral cortex tangential migration (GO:0021800), layer formation in cerebral cortex (GO:0021819), positive regulation of TOR signaling (GO:0032008), protein localization to synapse (GO:0035418), reelin-mediated signaling pathway (GO:0038026), regulation of neuron differentiation (GO:0045664), response to pain (GO:0048265), regulation of behavior (GO:0050795), modulation of chemical synaptic transmission (GO:0050804), positive regulation of small GTPase mediated signal transduction (GO:0051057), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), positive regulation of synaptic transmission, glutamatergic (GO:0051968), radial glial cell differentiation (GO:0060019), regulation of synaptic activity (GO:0060025), long-term synaptic potentiation (GO:0060291), positive regulation of dendritic spine morphogenesis (GO:0061003), positive regulation of synapse maturation (GO:0090129), postsynaptic density assembly (GO:0097107), NMDA glutamate receptor clustering (GO:0097114), postsynaptic density protein 95 clustering (GO:0097119), receptor localization to synapse (GO:0097120), lateral motor column neuron migration (GO:0097477), positive regulation of long-term synaptic potentiation (GO:1900273)

GO Molecular Function (7): serine-type peptidase activity (GO:0008236), metal ion binding (GO:0046872), receptor ligand activity (GO:0048018), lipoprotein particle receptor binding (GO:0070325), very-low-density lipoprotein particle receptor binding (GO:0070326), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (8): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), plasma membrane (GO:0005886), dendrite (GO:0030425), extracellular matrix (GO:0031012), neuron projection (GO:0043005), reelin complex (GO:0110157)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Axon guidance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	3
neuron projection development	2
spinal cord development	2
signaling receptor binding	2
cellular anatomical structure	2
anatomical structure morphogenesis	1
cell migration	1
generation of neurons	1
protein metabolic process	1
cellular process	1
axonogenesis	1
neuron projection guidance	1
nervous system development	1
system development	1
central nervous system development	1
animal organ development	1
head development	1
memory	1
behavior	1
learning	1
cell differentiation	1
gliogenesis	1
gene expression	1
regulation of macromolecule biosynthetic process	1
regulation of neuron projection development	1
positive regulation of cell projection organization	1
regionalization	1
pallium development	1
limbic system development	1
cerebral cortex cell migration	1
cerebral cortex radial glia-guided migration	1
anatomical structure formation involved in morphogenesis	1
TOR signaling	1
regulation of TOR signaling	1
positive regulation of intracellular signal transduction	1
peptidase activity	1
serine hydrolase activity	1
cation binding	1
signal transduction	1
signaling receptor activator activity	1

Protein interactions and networks

STRING

2260 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RELN	VLDLR	P98155	984
RELN	LRP8	Q14114	954
RELN	TBR1	Q16650	804
RELN	PAFAH1B1	P43034	709
RELN	YWHAQ	P27348	706
RELN	APOE	P02649	701
RELN	STRADA	Q7RTN6	688
RELN	CALB2	P22676	682
RELN	STK25	O00506	650
RELN	GOLGA2	Q08379	650
RELN	DAB1	O75553	636
RELN	GAD1	Q99259	634
RELN	FOXP2	O15409	631
RELN	SLIT3	O75094	623
RELN	MAPT	P10636	623

IntAct

5 interactions, top by confidence:

A	B	Type	Score
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
CDH5	MYO1C	psi-mi:“MI:2364”(proximity)	0.270
RSPH1	RELN	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (40): RELN (Synthetic Lethality), RELN (Affinity Capture-RNA), LRP8 (Reconstituted Complex), VLDLR (Reconstituted Complex), LRP8 (Affinity Capture-Western), VLDLR (Affinity Capture-Western), RELN (Reconstituted Complex), RELN (Reconstituted Complex), RELN (Reconstituted Complex), RELN (Reconstituted Complex), VLDLR (Reconstituted Complex), RELN (Reconstituted Complex), RELN (Reconstituted Complex), RELN (Affinity Capture-Western), APP (Affinity Capture-Western)

ESM2 similar proteins: A2AJX4, E2RK30, F1LW30, F1QVU0, F8VQ03, F8W3R9, O08721, O60486, O70362, O89103, P08F94, P0DV84, P35969, P53767, P58751, P78509, P80108, P80109, P97793, Q0V8T0, Q0V8T5, Q0V8T6, Q0V8T9, Q5VYJ5, Q60841, Q61592, Q63772, Q6DFV8, Q6UXZ4, Q6ZN44, Q80YN4, Q8C0Z1, Q8IZJ1, Q8K1S2, Q8K1S4, Q8N2E2, Q8N8Z6, Q8R2H5, Q8WY21, Q8WYK1

Diamond homologs: O93574, P58751, P78509, Q60841, Q9N117, A2VE04, B3EWY9, B3EWZ8, C5IAW9, D3YXG0, E9Q6D8, F1LW30, G5ECS8, O08721, O08747, O60241, O60242, O95185, P07996, P11680, P27918, P35440, P35441, P35442, P35446, P35447, P48770, P59384, P61135, P97857, Q03350, Q1EHB3, Q28178, Q29RU4, Q3MHN2, Q3UTY6, Q4VC17, Q5R328, Q5R7Y0, Q5RBP8

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
RELN	up-regulates	VLDLR	binding
TOP2B	“up-regulates quantity by expression”	RELN	“transcriptional regulation”
DNMT1	“down-regulates quantity by repression”	RELN	“transcriptional regulation”
HDAC1	“down-regulates quantity by repression”	RELN	“transcriptional regulation”
MECP2	“down-regulates quantity by repression”	RELN	“transcriptional regulation”
KLF2	“up-regulates quantity by expression”	RELN	“transcriptional regulation”
FOXP2	“up-regulates quantity by expression”	RELN	“transcriptional regulation”
RELN	up-regulates	Synaptic_plasticity

Disease & clinical

Clinical variants and AI predictions

ClinVar

3712 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	68
Likely pathogenic	39
Uncertain significance	1657
Likely benign	1312
Benign	262

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1074036	NM_005045.4(RELN):c.3871C>T (p.Arg1291Ter)	Pathogenic
1074751	NM_005045.4(RELN):c.4190del (p.Asn1397fs)	Pathogenic
130110	NM_005045.4(RELN):c.5193C>A (p.Tyr1731Ter)	Pathogenic
130111	NM_005045.4(RELN):c.5195_5208dup (p.Ile1737fs)	Pathogenic
130112	NM_005045.4(RELN):c.7490+1G>A	Pathogenic
1323526	NM_005045.4(RELN):c.265del (p.Leu88_Val89insTer)	Pathogenic
1338450	NM_005045.4(RELN):c.3495G>A (p.Trp1165Ter)	Pathogenic
1355125	NM_005045.4(RELN):c.4639C>T (p.Arg1547Ter)	Pathogenic
1363442	NM_005045.4(RELN):c.8047G>T (p.Glu2683Ter)	Pathogenic
1371832	NM_005045.4(RELN):c.4510A>T (p.Arg1504Ter)	Pathogenic
1377194	NM_005045.4(RELN):c.3378G>A (p.Trp1126Ter)	Pathogenic
1388018	NM_005045.4(RELN):c.4904_4905insA (p.Met1635fs)	Pathogenic
1397755	NM_005045.4(RELN):c.6474del (p.Cys2159fs)	Pathogenic
1447834	NM_005045.4(RELN):c.2364del (p.Asp789fs)	Pathogenic
1457198	NM_005045.4(RELN):c.4449_4450del (p.Tyr1484fs)	Pathogenic
1691105	NM_005045.4(RELN):c.204C>G (p.Tyr68Ter)	Pathogenic
199432	NM_005045.4(RELN):c.2392C>A (p.His798Asn)	Pathogenic
199433	NM_005045.4(RELN):c.8347G>T (p.Gly2783Cys)	Pathogenic
199434	NM_005045.4(RELN):c.2288A>G (p.Asp763Gly)	Pathogenic
1998872	NM_005045.4(RELN):c.6338_6342dup (p.Gly2115fs)	Pathogenic
2009258	NM_005045.4(RELN):c.2896G>T (p.Glu966Ter)	Pathogenic
2024605	NM_005045.4(RELN):c.6574C>T (p.Arg2192Ter)	Pathogenic
2036010	NM_005045.4(RELN):c.5455del (p.Glu1819fs)	Pathogenic
2086135	NM_005045.4(RELN):c.5489del (p.Gly1830fs)	Pathogenic
2091447	NM_005045.4(RELN):c.5115del (p.Ile1706fs)	Pathogenic
2116963	NM_005045.4(RELN):c.1475del (p.Asn492fs)	Pathogenic
212035	NM_005045.4(RELN):c.329dup (p.Gly111fs)	Pathogenic
212041	NM_005045.4(RELN):c.5587C>T (p.Gln1863Ter)	Pathogenic
225550	NM_005045.4(RELN):c.5969+1G>A	Pathogenic
2425283	NC_000007.13:g.(?103389853)(103474139_?)del	Pathogenic

SpliceAI

9821 predictions. Top by Δscore:

Variant	Effect	Δscore
7:103482871:A:AC	donor_gain	1.0000
7:103482872:C:CC	donor_gain	1.0000
7:103483651:A:AC	donor_gain	1.0000
7:103483652:C:CG	donor_gain	1.0000
7:103483652:CA:C	donor_gain	1.0000
7:103483652:CAG:C	donor_gain	1.0000
7:103483652:CAGG:C	donor_gain	1.0000
7:103483680:G:C	donor_gain	1.0000
7:103483692:T:TA	donor_gain	1.0000
7:103483825:CAATT:C	acceptor_gain	1.0000
7:103483829:T:C	acceptor_gain	1.0000
7:103483829:T:TC	acceptor_gain	1.0000
7:103483846:TTTTG:T	acceptor_gain	1.0000
7:103483847:TTTG:T	acceptor_gain	1.0000
7:103483848:TTG:T	acceptor_gain	1.0000
7:103486304:T:TA	donor_gain	1.0000
7:103489895:TTGCA:T	acceptor_gain	1.0000
7:103489897:GCAC:G	acceptor_loss	1.0000
7:103489898:CA:C	acceptor_gain	1.0000
7:103489900:C:CA	acceptor_loss	1.0000
7:103489900:C:CC	acceptor_gain	1.0000
7:103489901:T:G	acceptor_loss	1.0000
7:103489910:C:CT	acceptor_gain	1.0000
7:103490662:ACCTA:A	donor_loss	1.0000
7:103490667:C:CG	donor_loss	1.0000
7:103490825:CCGAT:C	acceptor_gain	1.0000
7:103490826:CGAT:C	acceptor_gain	1.0000
7:103490826:CGATC:C	acceptor_gain	1.0000
7:103490827:GAT:G	acceptor_gain	1.0000
7:103490829:TCT:T	acceptor_loss	1.0000

AlphaMissense

22961 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:103482899:C:A	W3418C	1.000
7:103482899:C:G	W3418C	1.000
7:103482901:A:G	W3418R	1.000
7:103482901:A:T	W3418R	1.000
7:103482938:C:A	W3405C	1.000
7:103482938:C:G	W3405C	1.000
7:103482940:A:G	W3405R	1.000
7:103482940:A:T	W3405R	1.000
7:103482942:C:G	R3404P	1.000
7:103483752:A:G	L3361P	1.000
7:103486331:C:A	W3283C	1.000
7:103486331:C:G	W3283C	1.000
7:103486333:A:G	W3283R	1.000
7:103486333:A:T	W3283R	1.000
7:103486406:G:C	C3258W	1.000
7:103489766:A:G	C3247R	1.000
7:103489800:G:C	C3235W	1.000
7:103489802:A:G	C3235R	1.000
7:103489883:A:G	W3208R	1.000
7:103489883:A:T	W3208R	1.000
7:103490709:C:A	W3188C	1.000
7:103490709:C:G	W3188C	1.000
7:103495875:A:G	W3073R	1.000
7:103495875:A:T	W3073R	1.000
7:103496660:C:G	R3020P	1.000
7:103500766:G:C	C2882W	1.000
7:103515345:C:A	W2653C	1.000
7:103515345:C:G	W2653C	1.000
7:103515347:A:G	W2653R	1.000
7:103515347:A:T	W2653R	1.000

dbSNP variants (sampled 300 via entrez): RS1000001802 (7:103514188 T>A), RS1000020783 (7:103474004 A>AGAG), RS1000030000 (7:103782272 T>A,C), RS1000030885 (7:103731959 A>G,T), RS1000040022 (7:103808825 G>A), RS1000051835 (7:103776504 A>G,T), RS1000060066 (7:103599029 C>A,T), RS1000060100 (7:103918099 T>C), RS1000061117 (7:103536347 C>G), RS1000069302 (7:103924651 C>T), RS1000069505 (7:103618616 A>G), RS1000072283 (7:103577720 A>G), RS1000076514 (7:103961673 G>A), RS1000077891 (7:103639382 TC>T), RS1000077900 (7:103618273 A>G)

Disease associations

OMIM: gene MIM:600514 | disease phenotypes: MIM:257320, MIM:616436, MIM:600512, MIM:117100, MIM:607432, MIM:604403, MIM:181500, MIM:108100

GenCC curated gene-disease

Disease	Classification	Inheritance
Norman-Roberts syndrome	Definitive	Autosomal recessive
familial temporal lobe epilepsy 7	Strong	Autosomal dominant
autosomal dominant epilepsy with auditory features	Supportive	Autosomal dominant
ankylosing spondylitis	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
lissencephaly with cerebellar hypoplasia	Definitive	AR
complex neurodevelopmental disorder	Disputed	AD

Mondo (17): Norman-Roberts syndrome (MONDO:0009760), familial temporal lobe epilepsy 7 (MONDO:0014639), epilepsy, familial temporal lobe, 1 (MONDO:0700090), epilepsy (MONDO:0005027), self-limited epilepsy with centrotemporal spikes (MONDO:0007295), intellectual disability (MONDO:0001071), lissencephaly spectrum disorders (MONDO:0018838), generalized epilepsy with febrile seizures plus, type 2 (MONDO:0011461), neurodevelopmental disorder (MONDO:0700092), schizophrenia (MONDO:0005090), synovitis (MONDO:0002400), scoliosis (MONDO:0005392), arthritic joint disease (MONDO:0005578), arthritis, sacroiliac (MONDO:0007156), enthesitis (MONDO:0024419)

Orphanet (7): Epilepsy with auditory features (Orphanet:101046), Lissencephaly syndrome, Norman-Roberts type (Orphanet:89844), Self-limited epilepsy with centrotemporal spikes (Orphanet:1945), Lissencephaly (Orphanet:48471), Genetic epilepsy with febrile seizure plus (Orphanet:36387), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

80 total (30 of 80 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000269	Prominent occiput
HP:0000308	Microretrognathia
HP:0000316	Hypertelorism
HP:0000340	Sloping forehead
HP:0000341	Narrow forehead
HP:0000350	Small forehead
HP:0000369	Low-set ears
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000445	Wide nose
HP:0000479	Abnormal retinal morphology
HP:0000708	Atypical behavior
HP:0000716	Depression
HP:0001004	Lymphedema
HP:0001181	Adducted thumb
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001274	Agenesis of corpus callosum
HP:0001321	Cerebellar hypoplasia
HP:0001339	Lissencephaly
HP:0001511	Intrauterine growth retardation
HP:0001631	Atrial septal defect
HP:0001655	Patent foramen ovale

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST000155_1	Schizophrenia	9.000000e-07
GCST000267_3	Multiple sclerosis (age of onset)	3.000000e-06
GCST000345_1	Otosclerosis	2.000000e-08
GCST000676_1	Alzheimer’s disease	2.000000e-06
GCST002118_20	Metabolite levels (Pyroglutamine)	8.000000e-06
GCST003542_194	Night sleep phenotypes	3.000000e-06
GCST004061_6	Sjögren’s syndrome	3.000000e-07
GCST004068_40	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	4.000000e-07
GCST006412_68	Intraocular pressure	5.000000e-09
GCST006867_60	Type 2 diabetes	1.000000e-08
GCST007565_177	Morning person	2.000000e-14
GCST008522_42	Bitter alcoholic beverage consumption	3.000000e-09
GCST008761_1	Sucrose liking	9.000000e-06
GCST009276_7	Response to placebo treatment in childhood asthma (FVC change)	3.000000e-06
GCST009379_73	Type 2 diabetes	7.000000e-06
GCST009379_74	Type 2 diabetes	4.000000e-08
GCST010988_165	Adult body size	5.000000e-15
GCST010989_123	Body size at age 10	3.000000e-11
GCST010989_124	Body size at age 10	5.000000e-10
GCST012319_6	LDL levels x SSRI levels (escitalopram or citalopram) interaction in schizophrenia or bipolar disorder	1.000000e-06
GCST012796_6	Sjögren’s syndrome	9.000000e-06

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0005408	pyroglutamine measurement
EFO:0004695	intraocular pressure measurement
EFO:0008328	chronotype measurement
EFO:0010092	bitter alcoholic beverage consumption measurement
EFO:0010157	sucrose liking measurement
EFO:0008344	response to placebo
EFO:0010339	FVC change measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004611	low density lipoprotein cholesterol measurement

MeSH disease descriptors (11)

Descriptor	Name	Tree numbers
D001168	Arthritis	C05.550.114
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D054082	Lissencephaly	C10.500.507.450.499; C16.131.666.507.450.499
D065886	Neurodevelopmental Disorders	F03.625
D012600	Scoliosis	C05.116.900.800.875
D013167	Spondylitis, Ankylosing	C05.116.900.853.625.800.744.500; C05.550.069.340.500; C05.550.114.865.800.744.500
D013585	Synovitis	C05.550.870
C563037	Arthritis, Sacroiliac (supp.)
C537297	Autosomal Dominant Lateral Temporal Lobe Epilepsy (supp.)
C565810	Generalized Epilepsy With Febrile Seizures Plus, Type 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

13 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs362719	RELN		0.00	0
rs2237628	RELN		0.00	0
rs2535764	RELN		0.00	0
rs362626	RELN		0.00	0
rs362726	RELN		0.00	0
rs362731	RELN		0.00	0
rs362814	RELN		0.00	0
rs3808035	RELN		0.00	0
rs3819479	RELN		0.00	0
rs7341475	RELN		0.00	0
rs12705169	RELN		0.00	0
rs362813	RELN		0.00	0
rs39339	RELN		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, increases expression, affects expression, decreases expression	9
Benzo(a)pyrene	affects expression, affects methylation, decreases expression, decreases methylation	6
bisphenol A	affects expression, affects cotreatment, increases methylation, increases expression	3
trichostatin A	affects cotreatment, increases expression	3
arsenite	affects binding, decreases reaction, decreases methylation	2
mercuric bromide	increases expression, affects cotreatment	2
Resveratrol	increases expression, affects cotreatment, decreases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Doxorubicin	affects binding, decreases reaction, increases expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	affects cotreatment, decreases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
peracetylated N-azidoacetylmannosamine	decreases expression	1
Esketamine	decreases expression	1
methylmercuric chloride	increases expression	1
deoxynivalenol	decreases expression	1
decabromobiphenyl ether	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	affects methylation	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	increases expression	1
benzo(k)fluoranthene	decreases expression	1
benzo(e)pyrene	increases methylation	1
periodate-oxidized adenosine	affects expression	1
aflatoxin B2	increases methylation	1
tetrachlorodian	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00133315	PHASE4	COMPLETED	TNFalfa Blocking Treatment of Spondylarthropathies
NCT00247962	PHASE4	COMPLETED	Study Evaluating Etanercept and Sulphasalazine in Ankylosing Spondylitis
NCT00410046	PHASE4	COMPLETED	Extension Study Evaluating Etanercept in Ankylosing Spondylitis
NCT00420238	PHASE4	COMPLETED	Study Evaluating Etanercept for the Treatment of Active, Severe, and Advanced Axial Ankylosing Spondylitis
NCT00432432	PHASE4	COMPLETED	Combination Methotrexate and Infliximab
NCT00444340	PHASE4	COMPLETED	An Open-Label Multicentre Long-Term Extension Study of Etanercept for Ankylosing Spondylitis
NCT00458185	PHASE4	COMPLETED	Study Evaluating Etanercept in Patients With Ankylosing Spondylitis
NCT00507403	PHASE4	COMPLETED	Infliximab and Methotrexate in Ankylosing Spondylitis
NCT00647517	PHASE4	COMPLETED	Tramadol/Acetaminophen(Ultracet) AS add-on Therapy in the Treatment of Patients With Ankylosing Spondylitis
NCT00715091	PHASE4	COMPLETED	Effects of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) on RAdiographic Damage in Ankylosing Spondylitis
NCT00873730	PHASE4	COMPLETED	Study Evaluating Etanercept in Subjects With Ankylosing Spondylitis in Spain
NCT00910273	PHASE4	TERMINATED	Effects of Etanercept on the Heart, Veins and Thickness of Certain Major Arteries In Ankylosing Spondylitis Patients
NCT00953979	PHASE4	COMPLETED	Efficacy and Safety of Kunxian Capsule in Treatment Patients With Early Ankylosing Spondylitis
NCT01148901	PHASE4	WITHDRAWN	Effectiveness and Safety of Early Treatment With Infliximab for Hip Arthritis Associated With Ankylosing Spondylitis (AS) (P06451)
NCT01212653	PHASE4	COMPLETED	Effect of Anti-TNF (Alpha) Treatment on Vascular Stiffness in Ankylosing Spondylitis (AS)
NCT01422564	PHASE4	TERMINATED	Metal on Metal Versus Metal on Highly Crossed Linked Polyethylene Sytem
NCT01517620	PHASE4	COMPLETED	Total Glucosides Paeony Capsules in Maintaining Clinical Remission in Patients With Ankylosing Spondylitis Which Achieve Clinical Remission After Anti-TNF Therapy
NCT01668004	PHASE4	COMPLETED	The Incidence of Extra-Articular Manifestations in Participants With Ankylosing Spondylitis Treated With Golimumab (MK-8259-012)
NCT01895764	PHASE4	COMPLETED	Effect of the Combination of Methotrexate and Adalimumab on Reduction of Immunization in Ankylosing Spondylitis (COMARIS)
NCT01934933	PHASE4	COMPLETED	Etanercept and Celecoxib Alone/Combined Treatment in Effectiveness and Safety of Active Ankylosing Spondylitis
NCT02132234	PHASE4	UNKNOWN	Effects of Biological Treatment on Blood Pressure and Endothelial Function in Patients With Rheumatoid Arthritis, Psoriatic Arthritis and Ankylosing Spondylitis
NCT02313727	PHASE4	UNKNOWN	Combined Treatment With TNF Inhibitor and Pamidronate in AS Patients: Effect on the Radiographic Progression
NCT02489760	PHASE4	UNKNOWN	Etanercept Versus Adalimumab in the Treatment of Patients With Ankylosing Spondylitis. A Switch Study
NCT02492217	PHASE4	COMPLETED	Biomarkers Identification of Anti-tumor Necrosis Factor (TNF) α Agent’s Efficacy in Ankylosing Spondylitis Patients
NCT02528201	PHASE4	COMPLETED	A Study Of Celecoxib Versus Diclofenac In Patients With Ankylosing Spondylitis
NCT02638896	PHASE4	UNKNOWN	Dose Reduction of Etanercept in Patients With Ankylosing Spondylitis
NCT02758782	PHASE4	COMPLETED	NSAIDs Added to Anti-TNF Therapy Versus Anti-TNF Therapy Alone on Progression of Structural Damage in Ankylosing Spondylitis
NCT02763046	PHASE4	COMPLETED	Study to Examine the Clinical Efficacy and the Nonsteroidal Anti-inflammatory Drug (NSAID)-Sparing Effect of Secukinumab Over 16 Weeks in Patients With Ankylosing Spondylitis
NCT03350815	PHASE4	COMPLETED	Study Estimating the Clinical Difference Between 300 mg and 150 mg of Secukinumab Following Dose Escalation to 300 mg in Patients With Ankylosing Spondylitis
NCT03411798	PHASE4	COMPLETED	Sequential Application of Yisaipu® and DMARDs in Treating Mild-to-Moderate AS
NCT03473665	PHASE4	TERMINATED	Non-Steroidal Anti-inflammatory Drugs in Axial Spondyloarthritis
NCT03639740	PHASE4	UNKNOWN	Treat-to-target With Secukinumab in Axial Spondyloarthritis
NCT03800797	PHASE4	COMPLETED	Efficacy and Safety of Loxoprofen Hydrogel Patch in Patients With Ankylosing Spondylitis
NCT03932006	PHASE4	UNKNOWN	A Multicenter，Double-Blind and Randomized Controlled Trial of Fengshigutong Capsule in the Treatment of Ankylosing Spondylitis
NCT04077957	PHASE4	UNKNOWN	Treat-to-target Strategy in Ankylosing Spondylitis Using Etanercept and Conventional Synthetic DMARDs
NCT04885751	PHASE4	UNKNOWN	Compare the Effect of Eupatilin and Rebamipide on the Prevention of Gastroenteropathy
NCT04934059	PHASE4	UNKNOWN	Efficacy and Safety of Yuxuebi Tablet in Treating Night Pain of Ankylosing Spondylitis (AS).
NCT05164198	PHASE4	UNKNOWN	REduCed Dose of TNFi in Patients With Ankylosing SpondyliTis (RECAST)
NCT05303285	PHASE4	RECRUITING	A Study Evaluating the Efficacy of Secukinumab 300mg in Chinese Adults With Active Ankylosing Spondylitis
NCT05527444	PHASE4	UNKNOWN	The Clinical Efficacy and the Changes of Immune Cells Subsets With Bioagents in Ankylosing Spondylitis Patients