IGLON5

Summary

IGLON5 (IgLON family member 5, HGNC:34550) is a protein-coding gene on chromosome 19q13.41, encoding IgLON family member 5 (A6NGN9).

Predicted to act upstream of or within motor behavior and neuromuscular process controlling balance. Predicted to be located in extracellular region.

Source: NCBI Gene 402665 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 61 total
• MANE Select transcript: NM_001101372

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34550
Approved symbol	IGLON5
Name	IgLON family member 5
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Aliases	LOC402665
Ensembl gene	ENSG00000142549
Ensembl biotype	protein_coding
OMIM	618861
Entrez	402665

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000270642

RefSeq mRNA: 1 — MANE Select: NM_001101372 NM_001101372

CCDS: CCDS46158

Canonical transcript exons

ENST00000270642 — 8 exons

Exon	Start	End
ENSE00001187441	51327732	51327886
ENSE00001187447	51327080	51327200
ENSE00001187457	51325346	51325465
ENSE00001187461	51323662	51323894
ENSE00001255133	51322064	51322142
ENSE00001372101	51328671	51330891
ENSE00001577197	51326764	51326898
ENSE00001589225	51311644	51311926

Expression profiles

Bgee: expression breadth ubiquitous, 158 present calls, max score 96.18.

FANTOM5 (CAGE): breadth broad, TPM avg 2.6233 / max 87.9663, expressed in 278 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177212	2.6233	278

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	96.18	gold quality
embryo	UBERON:0000922	96.17	gold quality
cortical plate	UBERON:0005343	95.78	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.90	gold quality
cerebellar hemisphere	UBERON:0002245	93.82	gold quality
cerebellar cortex	UBERON:0002129	93.70	gold quality
cerebellum	UBERON:0002037	92.91	gold quality
pons	UBERON:0000988	90.32	gold quality
ventricular zone	UBERON:0003053	89.36	gold quality
lateral nuclear group of thalamus	UBERON:0002736	89.29	gold quality
hypothalamus	UBERON:0001898	88.33	gold quality
superior vestibular nucleus	UBERON:0007227	86.16	gold quality
right frontal lobe	UBERON:0002810	85.58	gold quality
anterior cingulate cortex	UBERON:0009835	84.52	gold quality
prefrontal cortex	UBERON:0000451	84.11	gold quality
lower esophagus mucosa	UBERON:0035834	83.89	gold quality
neocortex	UBERON:0001950	83.00	gold quality
frontal cortex	UBERON:0001870	82.91	gold quality
midbrain	UBERON:0001891	82.62	gold quality
substantia nigra	UBERON:0002038	82.50	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.00	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.93	gold quality
substantia nigra pars compacta	UBERON:0001965	81.56	silver quality
cerebral cortex	UBERON:0000956	81.48	gold quality
amygdala	UBERON:0001876	81.40	gold quality
medulla oblongata	UBERON:0001896	80.97	silver quality
Ammon’s horn	UBERON:0001954	80.19	gold quality
dorsal plus ventral thalamus	UBERON:0001897	80.17	silver quality
ventral tegmental area	UBERON:0002691	79.94	silver quality
lateral globus pallidus	UBERON:0002476	79.80	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.14

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

123 targeting IGLON5, 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-6867-5P	100.00	82.21	3464
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-23B-5P	99.98	66.07	587
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-2110	99.96	66.68	1930
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-3681-3P	99.88	70.46	2254

Literature-anchored findings (GeneRIF, showing 4)

• The target antigen of patients with rapid-eye-movement parasomnia who produce antibodies (mainly IgG4) against IgLON5 is a neuronal cell adhesion molecule that suggests a tauopathy (PMID:24703753)
• Findings report 89 unpublished cell-surface ligand-receptor pairs and describe structural models of trans interactions of cell adhesion molecules, neuronal (IgLON5), showing that their structures are compatible with a model of interaction across the synaptic cleft. (PMID:30956130)
• Anti-IgLON5 Disease: A New Bulbar-Onset Motor Neuron Mimic Syndrome. (PMID:33531378)
• Papillitis associated with IgLON5 autoimmunity: A novel clinical phenotype. (PMID:38364528)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	iglon5	ENSDARG00000022176
mus_musculus	Iglon5	ENSMUSG00000013367
rattus_norvegicus	Iglon5	ENSRNOG00000017918
drosophila_melanogaster	Ama	FBGN0000071
drosophila_melanogaster	Lac	FBGN0010238
drosophila_melanogaster	klg	FBGN0017590
drosophila_melanogaster	fipi	FBGN0031627
drosophila_melanogaster	DIP-eta	FBGN0031725
drosophila_melanogaster	DIP-iota	FBGN0031837
drosophila_melanogaster	CG13506	FBGN0034723
drosophila_melanogaster	DIP-zeta	FBGN0051708
drosophila_melanogaster	DIP-kappa	FBGN0051814
drosophila_melanogaster	CG33543	FBGN0053543
drosophila_melanogaster	DIP-beta	FBGN0259245
drosophila_melanogaster	DIP-epsilon	FBGN0259714
caenorhabditis_elegans	rig-5	WBGENE00004372

Paralogs (5): NEGR1 (ENSG00000172260), NTM (ENSG00000182667), IGSF5 (ENSG00000183067), OPCML (ENSG00000183715), LSAMP (ENSG00000185565)

Protein

Protein identifiers

IgLON family member 5 — A6NGN9 (reviewed: A6NGN9)

All UniProt accessions (1): A6NGN9

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Similarity. Belongs to the immunoglobulin superfamily. IgLON family.

RefSeq proteins (1): NP_001094842* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050876	IgLON_domain	Family

Pfam: PF07686, PF13927

UniProt features (38 total): strand 21, glycosylation site 5, disulfide bond 3, helix 3, domain 3, signal peptide 1, chain 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6DLD	X-RAY DIFFRACTION	3.3
6DLE	X-RAY DIFFRACTION	3.99

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NGN9-F1	84.43	0.70

Functional residue map

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

Disulfide bonds (3): 54–112, 154–195, 238–291

Glycosylation sites (5): 41, 49, 67, 137, 288

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 79 (showing top): GOBP_NEURON_RECOGNITION, GOBP_HETEROPHILIC_CELL_CELL_ADHESION, GOBP_BEHAVIOR, GOBP_SYNAPSE_ASSEMBLY, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_NEUROMUSCULAR_PROCESS_CONTROLLING_BALANCE, GOBP_CELL_CELL_ADHESION, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_REGULATION_OF_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_SYNAPSE_STRUCTURE_OR_ACTIVITY, GOBP_CELL_JUNCTION_ASSEMBLY, GOBP_NEUROMUSCULAR_PROCESS, MARTENS_TRETINOIN_RESPONSE_UP

GO Biological Process (3): neuron recognition (GO:0008038), neuromuscular process controlling balance (GO:0050885), motor behavior (GO:0061744)

GO Molecular Function (0):

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell recognition	1
neuron development	1
musculoskeletal movement	1
neuromuscular process	1
behavior	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1086 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IGLON5	LGI1	O95970	881
IGLON5	DPP10	Q8N608	878
IGLON5	DPP6	P42658	872
IGLON5	CNTNAP2	Q9UHC6	800
IGLON5	PNMA2	Q9UL42	791
IGLON5	AMPH	P49418	712
IGLON5	DPYSL5	Q9BPU6	698
IGLON5	DNER	Q8NFT8	689
IGLON5	ZIC4	Q8N9L1	686
IGLON5	BIN1	O00499	670
IGLON5	GAD2	Q05329	623
IGLON5	GRM5	P41594	597
IGLON5	KLHL11	Q9NVR0	587
IGLON5	GRM1	Q13255	584
IGLON5	RCVRN	P35243	580

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SYNGAP1	POTEF	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	IGLON5	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A4IFA6, A6NGN9, B1AUH1, B3N666, B4Q599, O09127, O73791, P00545, P07333, P11834, P13369, P29322, P32736, P35590, P35916, P35917, Q06805, Q06806, Q13308, Q13449, Q14982, Q2EY13, Q2EY14, Q2EY15, Q2VWP9, Q58DA5, Q5IS61, Q5JZY3, Q5R412, Q62718, Q62813, Q6GU68, Q7Z3B1, Q80Z24, Q8BKG3, Q8BLK3, Q8BYG9, Q8HW98, Q8TDY8, Q90773

Diamond homologs: A2A8L5, A4IFW2, A6NGN9, A7MBJ4, B3N666, B4GBH0, B4GKZ8, B4HY03, B4KPU0, B4NZY8, B4Q599, P10586, P11834, P32736, Q03696, Q0E9H9, Q13449, Q14982, Q24372, Q26474, Q290N5, Q29JX6, Q58DA5, Q5IS61, Q5R412, Q62718, Q62813, Q64604, Q696W0, Q7Z3B1, Q80Z24, Q8BLK3, Q8HW98, Q90773, Q98892, Q98919, Q99PJ0, Q9P121, Q9VM64, Q9W6V2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1218 predictions. Top by Δscore:

Variant	Effect	Δscore
19:51323657:TGCA:T	acceptor_loss	1.0000
19:51323660:A:AG	acceptor_gain	1.0000
19:51323660:AGCT:A	acceptor_gain	1.0000
19:51323661:G:GT	acceptor_gain	1.0000
19:51323661:GC:G	acceptor_gain	1.0000
19:51323661:GCT:G	acceptor_gain	1.0000
19:51323661:GCTG:G	acceptor_gain	1.0000
19:51323661:GCTGC:G	acceptor_gain	1.0000
19:51323892:ACGGT:A	donor_loss	1.0000
19:51323893:CGGTG:C	donor_loss	1.0000
19:51323894:GGT:G	donor_loss	1.0000
19:51323895:G:GG	donor_gain	1.0000
19:51325344:A:AG	acceptor_gain	1.0000
19:51325345:G:GG	acceptor_gain	1.0000
19:51325345:GTC:G	acceptor_gain	1.0000
19:51325345:GTCC:G	acceptor_gain	1.0000
19:51325464:AGGTG:A	donor_loss	1.0000
19:51326761:CAGA:C	acceptor_loss	1.0000
19:51326762:A:AG	acceptor_gain	1.0000
19:51326762:A:T	acceptor_loss	1.0000
19:51326762:AGAC:A	acceptor_gain	1.0000
19:51326762:AGACG:A	acceptor_gain	1.0000
19:51326763:G:GT	acceptor_gain	1.0000
19:51326763:GAC:G	acceptor_gain	1.0000
19:51326763:GACG:G	acceptor_gain	1.0000
19:51326763:GACGG:G	acceptor_gain	1.0000
19:51326825:G:GT	donor_gain	1.0000
19:51326899:G:GG	donor_gain	1.0000
19:51327078:A:AG	acceptor_gain	1.0000
19:51327079:G:GG	acceptor_gain	1.0000

AlphaMissense

2139 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:51323698:G:C	W65C	1.000
19:51323698:G:T	W65C	1.000
19:51325452:G:C	W166C	1.000
19:51325452:G:T	W166C	1.000
19:51327181:T:A	W250R	1.000
19:51327181:T:C	W250R	1.000
19:51327183:G:C	W250C	1.000
19:51327183:G:T	W250C	1.000
19:51323831:T:G	Y110D	0.999
19:51323883:T:C	L127P	0.999
19:51325409:T:C	L152P	0.999
19:51325450:T:A	W166R	0.999
19:51325450:T:C	W166R	0.999
19:51326830:A:G	Y193C	0.999
19:51326835:T:A	C195S	0.999
19:51326836:G:C	C195S	0.999
19:51327176:T:G	F248C	0.999
19:51327182:G:C	W250S	0.999
19:51327791:T:C	L276P	0.999
19:51327823:G:T	G287C	0.999
19:51327824:G:T	G287V	0.999
19:51327830:A:G	Y289C	0.999
19:51327849:C:A	N295K	0.999
19:51327849:C:G	N295K	0.999
19:51323696:T:A	W65R	0.998
19:51323696:T:C	W65R	0.998
19:51323697:G:C	W65S	0.998
19:51323700:T:C	L66P	0.998
19:51323740:G:C	W79C	0.998
19:51323740:G:T	W79C	0.998

dbSNP variants (sampled 300 via entrez): RS1000170095 (19:51316045 C>A), RS1000191350 (19:51328158 T>C), RS1000199803 (19:51316680 G>A), RS1000475999 (19:51331377 T>C), RS1000934567 (19:51317805 C>T), RS1001095556 (19:51311986 C>T), RS1001224962 (19:51329198 T>C), RS1001478708 (19:51323101 C>G,T), RS1001553368 (19:51310366 T>C), RS1001813820 (19:51310005 A>G), RS1001850604 (19:51322573 C>T), RS1001870005 (19:51319337 G>A), RS1002149392 (19:51312782 G>A), RS1002171905 (19:51330917 T>C), RS1002245700 (19:51330532 A>G)

Disease associations

OMIM: gene MIM:618861 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_2662	Blood protein levels	4.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, increases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
bisphenol S	decreases methylation	1
Vorinostat	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Lipopolysaccharides	decreases expression, affects cotreatment	1
Thimerosal	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Triclosan	increases expression	1
Acrylamide	decreases expression	1
S-Nitrosoglutathione	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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