AMIGO1

Summary

AMIGO1 (adhesion molecule with Ig like domain 1, HGNC:20824) is a protein-coding gene on chromosome 1p13.3, encoding Amphoterin-induced protein 1 (Q86WK6). Promotes growth and fasciculation of neurites from cultured hippocampal neurons.

Predicted to enable potassium channel regulator activity. Predicted to be involved in several processes, including heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; nervous system development; and positive regulation of nervous system development. Predicted to be located in dendrite; neuronal cell body membrane; and voltage-gated potassium channel complex. Predicted to be active in membrane.

Source: NCBI Gene 57463 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 39 total
• MANE Select transcript: NM_020703

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20824
Approved symbol	AMIGO1
Name	adhesion molecule with Ig like domain 1
Location	1p13.3
Locus type	gene with protein product
Status	Approved
Aliases	AMIGO, KIAA1163
Ensembl gene	ENSG00000181754
Ensembl biotype	protein_coding
OMIM	615689
Entrez	57463

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000369862, ENST00000369864, ENST00000887776

RefSeq mRNA: 1 — MANE Select: NM_020703 NM_020703

CCDS: CCDS30795

Canonical transcript exons

ENST00000369864 — 2 exons

Exon	Start	End
ENSE00001339650	109509420	109509727
ENSE00001451127	109504178	109508999

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 88.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.4228 / max 187.1391, expressed in 1198 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13708	6.0561	1191
13707	0.3666	138

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	88.89	gold quality
prefrontal cortex	UBERON:0000451	88.45	gold quality
Brodmann (1909) area 23	UBERON:0013554	87.52	gold quality
lateral nuclear group of thalamus	UBERON:0002736	87.47	gold quality
frontal cortex	UBERON:0001870	87.13	gold quality
superior frontal gyrus	UBERON:0002661	87.02	gold quality
primary visual cortex	UBERON:0002436	86.37	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.22	gold quality
neocortex	UBERON:0001950	86.21	gold quality
postcentral gyrus	UBERON:0002581	86.17	gold quality
right frontal lobe	UBERON:0002810	86.05	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.96	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.95	gold quality
cerebellar cortex	UBERON:0002129	85.85	gold quality
cerebellar hemisphere	UBERON:0002245	85.83	gold quality
cerebellum	UBERON:0002037	85.79	gold quality
entorhinal cortex	UBERON:0002728	85.35	gold quality
parietal lobe	UBERON:0001872	85.16	gold quality
cerebral cortex	UBERON:0000956	84.94	gold quality
hindlimb stylopod muscle	UBERON:0004252	84.74	gold quality
occipital lobe	UBERON:0002021	84.62	gold quality
anterior cingulate cortex	UBERON:0009835	84.03	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	83.51	gold quality
skeletal muscle tissue	UBERON:0001134	83.27	gold quality
Brodmann (1909) area 46	UBERON:0006483	83.00	gold quality
muscle tissue	UBERON:0002385	82.98	gold quality
brain	UBERON:0000955	82.90	gold quality
forebrain	UBERON:0001890	82.77	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	82.74	silver quality
muscle of leg	UBERON:0001383	82.38	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

62 targeting AMIGO1, 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-12118	100.00	65.88	1270
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-4756-3P	99.62	66.30	1319

Literature-anchored findings (GeneRIF, showing 1)

• AMIGO1 is identified as a candidate gene for human schizophrenia and related psychiatric disorders. (PMID:26240432)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	amigo1	ENSDARG00000079620
mus_musculus	Amigo1	ENSMUSG00000050947
rattus_norvegicus	Amigo1	ENSRNOG00000045665

Paralogs (2): AMIGO2 (ENSG00000139211), AMIGO3 (ENSG00000176020)

Protein

Protein identifiers

Amphoterin-induced protein 1 — Q86WK6 (reviewed: Q86WK6)

Alternative names: AMIGO-1, Alivin-2

All UniProt accessions (1): Q86WK6

UniProt curated annotations — full annotation on UniProt →

Function. Promotes growth and fasciculation of neurites from cultured hippocampal neurons. May be involved in fasciculation as well as myelination of developing neural axons. May have a role in regeneration as well as neural plasticity in the adult nervous system. May mediate homophilic as well as heterophilic cell-cell interaction and contribute to signal transduction through its intracellular domain. Assembled with KCNB1 modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1.

Subunit / interactions. Homodimer, and heterodimer with AMIGO2 and AMIGO3. Interacts with KCNB1.

Subcellular location. Cell membrane. Perikaryon. Cell projection. Dendrite. Axon.

Domain organisation. The LRR repeat region mediates homodimerization.

Similarity. Belongs to the immunoglobulin superfamily. AMIGO family.

RefSeq proteins (1): NP_065754* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000483	Cys-rich_flank_reg_C	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR031283	AMIGO	Family
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF00560, PF07679, PF13855

UniProt features (30 total): repeat 6, glycosylation site 5, disulfide bond 5, domain 3, compositionally biased region 2, modified residue 2, topological domain 2, signal peptide 1, chain 1, region of interest 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86WK6-F1	78.86	0.57

Functional residue map

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

Post-translational modifications (2): 477, 481

Disulfide bonds (5): 34–40, 38–47, 225–253, 227–270, 290–341

Glycosylation sites (5): 72, 264, 315, 349, 360

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 166 (showing top): GSE18804_BRAIN_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_POTASSIUM_ION_TRANSPORT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEURON_RECOGNITION, GOBP_HETEROPHILIC_CELL_CELL_ADHESION, GOBP_RESPONSE_TO_ACID_CHEMICAL, MODULE_255, GOBP_SYNAPSE_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_SYNAPSE_ASSEMBLY, MODULE_317, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_CELLULAR_RESPONSE_TO_ACID_CHEMICAL, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (17): homophilic cell-cell adhesion (GO:0007156), heterophilic cell-cell adhesion (GO:0007157), axonogenesis (GO:0007409), axonal fasciculation (GO:0007413), brain development (GO:0007420), positive regulation of neuron projection development (GO:0010976), myelination (GO:0042552), positive regulation of axonogenesis (GO:0050772), positive regulation of synapse assembly (GO:0051965), positive regulation of potassium ion transmembrane transport (GO:1901381), cellular response to L-glutamate (GO:1905232), cell adhesion (GO:0007155), nervous system development (GO:0007399), cell differentiation (GO:0030154), positive regulation of cellular component organization (GO:0051130), positive regulation of nervous system development (GO:0051962), neuron projection fasciculation (GO:0106030)

GO Molecular Function (2): potassium channel regulator activity (GO:0015459), protein binding (GO:0005515)

GO Cellular Component (11): voltage-gated potassium channel complex (GO:0008076), membrane (GO:0016020), dendrite (GO:0030425), neuronal cell body membrane (GO:0032809), perikaryon (GO:0043204), pericellular basket (GO:1990030), plasma membrane (GO:0005886), axon (GO:0030424), cell projection (GO:0042995), neuron projection (GO:0043005), neuronal cell body (GO:0043025)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cell-cell adhesion	2
axon development	2
neuron projection development	2
positive regulation of cell projection organization	2
neuron projection	2
neuronal cell body	2
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
neuron recognition	1
neuron projection fasciculation	1
central nervous system development	1
animal organ development	1
head development	1
regulation of neuron projection development	1
axon ensheathment	1
axonogenesis	1
positive regulation of neurogenesis	1
regulation of axonogenesis	1
synapse assembly	1
positive regulation of nervous system development	1
regulation of synapse assembly	1
positive regulation of cell junction assembly	1
positive regulation of potassium ion transport	1
potassium ion transmembrane transport	1
regulation of potassium ion transmembrane transport	1
positive regulation of cation transmembrane transport	1
cellular response to amino acid stimulus	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
response to L-glutamate	1
cellular process	1
system development	1
cellular developmental process	1
cellular component organization	1
positive regulation of cellular process	1
regulation of cellular component organization	1
nervous system development	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1

Protein interactions and networks

STRING

962 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AMIGO1	DLG1	Q12959	586
AMIGO1	FN1	P02751	572
AMIGO1	KCNB1	Q14721	532
AMIGO1	SNF8	Q96H20	413
AMIGO1	DLG4	P78352	407
AMIGO1	TBL1X	O60907	398
AMIGO1	HAX1	O00165	397
AMIGO1	JAM3	Q9BX67	396
AMIGO1	SYNM	O15061	390
AMIGO1	PCDH17	O14917	384
AMIGO1	RTN4R	Q9BZR6	362
AMIGO1	LRFN2	Q9ULH4	348
AMIGO1	LRFN4	Q6PJG9	346
AMIGO1	LRFN1	Q9P244	343
AMIGO1	SLIT3	O75094	340

IntAct

146 interactions, top by confidence:

A	B	Type	Score
B3GNT3	PGRMC1	psi-mi:“MI:0914”(association)	0.670
ERLIN2	HSPA5	psi-mi:“MI:0914”(association)	0.640
C2CD2L	AMIGO1	psi-mi:“MI:0915”(physical association)	0.560
FAM3C	AMIGO1	psi-mi:“MI:0915”(physical association)	0.560
SLC41A2	AMIGO1	psi-mi:“MI:0915”(physical association)	0.560
MIP	AMIGO1	psi-mi:“MI:0915”(physical association)	0.560
CLDN9	AMIGO1	psi-mi:“MI:0915”(physical association)	0.560
PLPP6	AMIGO1	psi-mi:“MI:0915”(physical association)	0.560
CXCL9	AMIGO1	psi-mi:“MI:0915”(physical association)	0.560
STX8	AMIGO1	psi-mi:“MI:0915”(physical association)	0.560
AMIGO1	SLC38A7	psi-mi:“MI:0915”(physical association)	0.560
AMIGO1	FAM3C	psi-mi:“MI:0915”(physical association)	0.560
AMIGO1	SLC41A1	psi-mi:“MI:0915”(physical association)	0.560
AMIGO1	SLC38A1	psi-mi:“MI:0915”(physical association)	0.560
AMIGO1	TMEM60	psi-mi:“MI:0915”(physical association)	0.560
AMIGO1	STX8	psi-mi:“MI:0915”(physical association)	0.560
AMIGO1	SELENOK	psi-mi:“MI:0915”(physical association)	0.560
IGFBP5	AMIGO1	psi-mi:“MI:0915”(physical association)	0.560
EDDM3B	AMIGO1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (105): AMIGO1 (Affinity Capture-MS), AMIGO1 (Affinity Capture-MS), AMIGO1 (Affinity Capture-MS), AMIGO1 (Affinity Capture-MS), AMIGO1 (Affinity Capture-MS), AMIGO1 (Affinity Capture-MS), AMIGO1 (Affinity Capture-MS), AMIGO1 (Affinity Capture-MS), AMIGO1 (Affinity Capture-MS), AMIGO1 (Affinity Capture-MS), AMIGO1 (Affinity Capture-MS), AMIGO1 (Affinity Capture-MS), AMIGO1 (Affinity Capture-MS), AMIGO1 (Affinity Capture-MS), AMIGO1 (Affinity Capture-MS)

ESM2 similar proteins: A1A4H9, A2ARI4, A6NDA9, B0BLW3, B4F7C5, D3ZAL8, D3ZTV3, D4A6D8, D4A7P2, E7FE13, F1MT22, O14498, O43155, O43300, P0DM44, P83286, Q149C3, Q5NVQ6, Q5R6B1, Q5R7M3, Q5RAC4, Q6PFC5, Q6RKD8, Q80WD0, Q80XG9, Q80ZD7, Q80ZD8, Q80ZD9, Q810C0, Q810C1, Q86SJ2, Q86UE6, Q86UN2, Q86VH4, Q86VH5, Q86WK6, Q8BGA3, Q8BLU0, Q8BZ81, Q8C2S7

Diamond homologs: A3KNN3, A6H789, A6H793, A6NJW4, A8WHP9, E7FE13, F1MLX5, G5EFX6, O02678, O02833, O35367, O46378, O46379, O46542, O60938, O62702, O75093, O75094, O88279, O88280, O94813, P07359, P07585, P21793, P24014, P28654, P28675, P35858, P35859, P51884, P51885, P51886, P51888, P51890, P58874, P59034, P59035, P70186, P70389, P83286

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

214 predictions. Top by Δscore:

Variant	Effect	Δscore
1:109509001:T:C	acceptor_gain	0.9200
1:109508998:CA:C	acceptor_gain	0.8500
1:109509000:C:CC	acceptor_gain	0.8500
1:109509583:AC:A	donor_gain	0.8100
1:109509584:CC:C	donor_gain	0.8100
1:109509415:TG:T	donor_gain	0.7700
1:109508025:C:A	donor_gain	0.7600
1:109508010:CCA:C	donor_gain	0.7400
1:109508011:CAC:C	donor_gain	0.7400
1:109508012:ACA:A	donor_gain	0.7400
1:109508013:CAC:C	donor_gain	0.7400
1:109507503:G:A	donor_gain	0.7100
1:109509625:G:T	donor_gain	0.7100
1:109509090:C:CA	donor_gain	0.7000
1:109509416:GC:G	donor_gain	0.6900
1:109509417:C:T	donor_gain	0.6900
1:109509295:G:A	donor_gain	0.6400
1:109509325:CAGG:C	donor_gain	0.6300
1:109507468:A:AC	donor_gain	0.6100
1:109507469:C:CC	donor_gain	0.6100
1:109509414:CT:C	donor_gain	0.6100
1:109508998:CACT:C	acceptor_gain	0.5800
1:109509001:T:TG	acceptor_gain	0.5600
1:109507995:A:AC	donor_gain	0.5400
1:109507464:G:C	donor_gain	0.5300
1:109508100:G:A	donor_gain	0.5300
1:109508999:A:AC	acceptor_gain	0.5300
1:109509002:T:A	acceptor_gain	0.5300
1:109509125:T:TA	donor_gain	0.5300
1:109509586:C:T	donor_gain	0.5300

AlphaMissense

3231 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:109507764:A:C	S383R	1.000
1:109507764:A:T	S383R	1.000
1:109507766:T:G	S383R	1.000
1:109507775:A:G	C380R	1.000
1:109508409:G:C	N168K	1.000
1:109508409:G:T	N168K	1.000
1:109508553:G:C	N120K	1.000
1:109508553:G:T	N120K	1.000
1:109508563:A:G	L117P	1.000
1:109508569:A:G	L115P	1.000
1:109508625:G:C	N96K	1.000
1:109508625:G:T	N96K	1.000
1:109508675:A:G	W80R	1.000
1:109508675:A:T	W80R	1.000
1:109507774:C:T	C380Y	0.999
1:109507777:C:T	G379D	0.999
1:109507778:C:G	G379R	0.999
1:109507783:A:G	L377P	0.999
1:109507890:G:C	C341W	0.999
1:109507892:A:G	C341R	0.999
1:109507898:A:C	Y339D	0.999
1:109508010:C:A	W301C	0.999
1:109508010:C:G	W301C	0.999
1:109508012:A:G	W301R	0.999
1:109508012:A:T	W301R	0.999
1:109508044:C:G	C290S	0.999
1:109508045:A:G	C290R	0.999
1:109508045:A:T	C290S	0.999
1:109508328:G:C	N195K	0.999
1:109508328:G:T	N195K	0.999

dbSNP variants (sampled 300 via entrez): RS1000050694 (1:109510997 T>G), RS1000424964 (1:109511476 A>G), RS1000741031 (1:109511696 G>A), RS1000747878 (1:109504043 C>T), RS1000877494 (1:109504951 G>C), RS1001223291 (1:109508061 G>A), RS1001422869 (1:109507542 G>A,C,T), RS1002878905 (1:109508356 T>C), RS1002916564 (1:109509770 G>T), RS1003855025 (1:109506112 C>T), RS1004408285 (1:109506423 G>A), RS1005277760 (1:109507489 C>T), RS1005304795 (1:109510801 A>G), RS1005872933 (1:109510001 T>C), RS1006259239 (1:109509336 G>A,T)

Disease associations

OMIM: gene MIM:615689 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000649_1	Chronic kidney disease	1.000000e-07
GCST005316_284	Intelligence (MTAG)	5.000000e-09
GCST010245_55	LDL cholesterol levels	7.000000e-11
GCST012299_20	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction (3df)	4.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases methylation	4
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
lead acetate	decreases expression	1
trichostatin A	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
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Amiodarone	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Nickel	decreases expression	1
Ozone	increases abundance, affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Triclosan	decreases expression	1
Urethane	decreases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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