AMIGO2

Summary

AMIGO2 (adhesion molecule with Ig like domain 2, HGNC:24073) is a protein-coding gene on chromosome 12q13.11, encoding Amphoterin-induced protein 2 (Q86SJ2). Required for depolarization-dependent survival of cultured cerebellar granule neurons.

Predicted to be involved in several processes, including heterophilic cell-cell adhesion; homophilic cell-cell adhesion; and positive regulation of synapse assembly. Predicted to be located in nucleus and plasma membrane. Predicted to be active in membrane. Biomarker of gastric adenocarcinoma.

Source: NCBI Gene 347902 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): craniofacial microsomia (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 74 total — 1 pathogenic
• GTEx eGene: eQTL in 21 tissues, sQTL in 3 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.97 (unconstrained)
• MANE Select transcript: NM_001370299
• Notable: 74 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24073
Approved symbol	AMIGO2
Name	adhesion molecule with Ig like domain 2
Location	12q13.11
Locus type	gene with protein product
Status	Approved
Aliases	ALI1, DEGA
Ensembl gene	ENSG00000139211
Ensembl biotype	protein_coding
OMIM	615690
Entrez	347902

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 13 protein_coding

MANE Select: ENST00000550413

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3

ENST00000550413, ENST00000266581, ENST00000429635, ENST00000872221, ENST00000872222, ENST00000872223, ENST00000872224, ENST00000872225, ENST00000872226, ENST00000962916, ENST00000962917, ENST00000962918, ENST00001135445

RefSeq mRNA: 3 — MANE Select: NM_001370299 NM_001143668, NM_001370299, NM_181847

CCDS: CCDS8751

Canonical transcript exons

ENST00000550413 — 3 exons

Exon	Start	End
ENSE00002354530	47079462	47079959
ENSE00002392496	47079142	47079248
ENSE00002413473	47076447	47079065

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 99.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.3244 / max 398.6528, expressed in 1302 samples.

Highest expression (Bgee): blood vessel layer, germinal epithelium of ovary, renal glomerulus, metanephric glomerulus, epithelium of mammary gland.

Genetic regulation across tissues (GTEx eQTL / sQTL)

AMIGO2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 21 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 24 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Aorta	eqtl	1.4e-20	+0.35	12:47154052:G:A
Brain Nucleus accumbens basal ganglia	eqtl	8.0e-13	-0.72	12:47546964:G:A
Cells Cultured fibroblasts	eqtl	7.9e-11	-0.19	12:47102144:A:G
Thyroid	eqtl	3.7e-10	+0.23	12:47113548:C:T
Brain Caudate basal ganglia	eqtl	2.6e-09	-0.68	12:47545143:G:T
Whole Blood	eqtl	4.0e-07	-0.17	12:47085745:C:A
Artery Tibial	eqtl	1.1e-05	+0.12	12:47117647:G:A
Artery Tibial	sqtl	3.6e-05	-0.25	12:47092364:T:C
Lung	eqtl	1.0e-04	-0.20	12:47199733:T:A
Brain Putamen basal ganglia	eqtl	1.1e-04	-0.59	12:47568462:T:G
Spleen	eqtl	2.7e-04	+0.26	12:47115673:A:C
Brain Spinal cord cervical c-1	eqtl	6.3e-04	-0.58	12:47527918:C:A
Esophagus Mucosa	eqtl	1.5e-03	-0.27	12:47304313:C:T
Brain Amygdala	eqtl	4.0e-03	-0.61	12:47514049:G:A
Brain Hypothalamus	eqtl	9.6e-03	+1.03	12:47457867:C:T
Brain Hippocampus	eqtl	1.1e-02	-0.48	12:47546203:T:C
Brain Cerebellum	eqtl	1.5e-02	+0.30	12:47125619:C:T
Liver	eqtl	1.7e-02	-0.33	12:46716412:G:A
Colon Sigmoid	eqtl	3.6e-02	+0.13	12:47099652:C:T
Muscle Skeletal	eqtl	3.6e-02	-0.24	12:47408523:G:C

FANTOM5 promoters

showing 10 of 12 alternative TSS:

Promoter ID	TPM avg	Samples expressed
130651	7.0576	1085
130645	2.0803	839
130648	1.8040	650
130654	0.5374	310
130653	0.4863	280
130649	0.3284	199
130650	0.2575	144
130643	0.2204	108
130647	0.2101	126
130644	0.1200	79

Top tissues by expression

showing 100 of 291 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
blood vessel layer	UBERON:0004797	99.28	gold quality
germinal epithelium of ovary	UBERON:0001304	98.53	gold quality
renal glomerulus	UBERON:0000074	97.79	gold quality
metanephric glomerulus	UBERON:0004736	97.43	gold quality
epithelium of mammary gland	UBERON:0003244	96.89	gold quality
mammary duct	UBERON:0001765	96.83	gold quality
stromal cell of endometrium	CL:0002255	96.00	gold quality
visceral pleura	UBERON:0002401	95.80	gold quality
popliteal artery	UBERON:0002250	95.41	gold quality
tibial artery	UBERON:0007610	95.39	gold quality
artery	UBERON:0001637	94.87	gold quality
palpebral conjunctiva	UBERON:0001812	93.88	gold quality
mammary gland	UBERON:0001911	93.77	gold quality
thoracic mammary gland	UBERON:0005200	93.71	gold quality
left uterine tube	UBERON:0001303	93.28	gold quality
saphenous vein	UBERON:0007318	93.19	gold quality
aorta	UBERON:0000947	92.96	gold quality
adrenal tissue	UBERON:0018303	92.89	gold quality
caput epididymis	UBERON:0004358	92.58	gold quality
pleura	UBERON:0000977	92.00	gold quality
smooth muscle tissue	UBERON:0001135	91.62	gold quality
left coronary artery	UBERON:0001626	91.60	gold quality
cranial nerve II	UBERON:0000941	91.53	gold quality
hair follicle	UBERON:0002073	91.41	gold quality
coronary artery	UBERON:0001621	91.32	gold quality
right coronary artery	UBERON:0001625	91.26	gold quality
metanephros	UBERON:0000081	91.20	gold quality
endothelial cell	CL:0000115	91.05	gold quality
seminal vesicle	UBERON:0000998	91.01	gold quality
superior vestibular nucleus	UBERON:0007227	90.80	gold quality
parietal pleura	UBERON:0002400	90.77	gold quality
superficial temporal artery	UBERON:0001614	89.79	gold quality
ascending aorta	UBERON:0001496	89.72	gold quality
thoracic aorta	UBERON:0001515	89.68	gold quality
endometrium epithelium	UBERON:0004811	89.45	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.44	gold quality
adult organism	UBERON:0007023	89.41	gold quality
urethra	UBERON:0000057	89.20	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	88.91	gold quality
kidney epithelium	UBERON:0004819	88.65	gold quality
urinary bladder	UBERON:0001255	88.23	gold quality
mucosa of urinary bladder	UBERON:0001259	88.21	gold quality
gall bladder	UBERON:0002110	88.07	gold quality
right ovary	UBERON:0002118	87.75	gold quality
descending thoracic aorta	UBERON:0002345	87.73	gold quality
ovary	UBERON:0000992	87.68	gold quality
lower lobe of lung	UBERON:0008949	87.66	gold quality
myometrium	UBERON:0001296	87.63	gold quality
left ovary	UBERON:0002119	87.61	gold quality
corpus epididymis	UBERON:0004359	87.60	gold quality
endometrium	UBERON:0001295	87.23	gold quality
body of uterus	UBERON:0009853	86.72	gold quality
sigmoid colon	UBERON:0001159	86.53	gold quality
adrenal cortex	UBERON:0001235	86.53	gold quality
right adrenal gland	UBERON:0001233	86.36	gold quality
uterus	UBERON:0000995	86.33	gold quality
left adrenal gland cortex	UBERON:0035825	86.30	gold quality
adrenal gland	UBERON:0002369	86.21	gold quality
right adrenal gland cortex	UBERON:0035827	86.15	gold quality
left adrenal gland	UBERON:0001234	86.01	gold quality
fallopian tube	UBERON:0003889	85.45	gold quality
bronchial epithelial cell	CL:0002328	85.41	gold quality
skin of hip	UBERON:0001554	85.35	gold quality
ectocervix	UBERON:0012249	85.06	gold quality
female reproductive system	UBERON:0000474	85.03	gold quality
cauda epididymis	UBERON:0004360	85.01	gold quality
eye	UBERON:0000970	84.44	gold quality
cortex of kidney	UBERON:0001225	84.41	gold quality
epithelium of nasopharynx	UBERON:0001951	83.98	gold quality
nasopharynx	UBERON:0001728	83.97	gold quality
right uterine tube	UBERON:0001302	83.85	gold quality
endocervix	UBERON:0000458	83.69	gold quality
lung	UBERON:0002048	83.54	gold quality
placenta	UBERON:0001987	83.42	gold quality
adipose tissue	UBERON:0001013	83.38	gold quality
right lung	UBERON:0002167	82.99	gold quality
inferior olivary complex	UBERON:0002127	82.82	gold quality
substantia nigra pars reticulata	UBERON:0001966	82.78	gold quality
spleen	UBERON:0002106	82.46	gold quality
nephron tubule	UBERON:0001231	82.38	gold quality
choroid plexus epithelium	UBERON:0003911	82.35	gold quality
upper lobe of lung	UBERON:0008948	82.35	gold quality
connective tissue	UBERON:0002384	82.27	gold quality
upper lobe of left lung	UBERON:0008952	82.14	gold quality
lymph node	UBERON:0000029	81.90	gold quality
vena cava	UBERON:0004087	81.85	silver quality
epithelium of bronchus	UBERON:0002031	81.84	gold quality
medulla oblongata	UBERON:0001896	81.73	gold quality
synovial joint	UBERON:0002217	81.73	gold quality
bronchus	UBERON:0002185	81.58	gold quality
subcutaneous adipose tissue	UBERON:0002190	80.98	gold quality
adipose tissue of abdominal region	UBERON:0007808	80.85	gold quality
cardiac muscle of right atrium	UBERON:0003379	80.83	gold quality
large intestine	UBERON:0000059	80.74	gold quality
colon	UBERON:0001155	80.67	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.41	gold quality
peritoneum	UBERON:0002358	80.31	gold quality
omental fat pad	UBERON:0010414	80.27	gold quality
substantia nigra pars compacta	UBERON:0001965	80.25	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-7	yes	413.00
E-ENAD-21	yes	409.50
E-ANND-3	yes	10.48
E-MTAB-5061	yes	9.62
E-GEOD-81608	yes	5.42
E-ENAD-27	yes	4.37
E-MTAB-8060	no	491.46

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Spinal cord	tissue	40.2
Locus coeruleus	tissue	39.8
Medulla oblongata	tissue	33.9
Hypothalamus	tissue	33.4
Pons	tissue	32.0
Smooth muscle	tissue	32.0	not detected
Periaqueductal gray	tissue	31.1
Substantia nigra	tissue	30.5
Midbrain	tissue	29.2
Fallopian tube	tissue	26.9	low
Thalamus	tissue	24.1
Retina	tissue	23.8
Endometrium 1	tissue	21.8	low
Superior colliculi	tissue	21.6
Breast	tissue	21.4	low
Ovary	tissue	20.4	not detected
Urinary bladder	tissue	20.3	low
Lung	tissue	18.8	medium
Gallbladder	tissue	18.0	medium
Adrenal gland	tissue	17.9	medium
Septum	tissue	17.7
Cervix	tissue	16.9	not detected
Spleen	tissue	16.4	not detected
Olfactory bulb	tissue	15.5
Hippocampal formation	tissue	15.0
Placenta	tissue	12.4	medium
Vagina	tissue	11.7	low
Lymph node	tissue	11.6	not detected
Ventral forebrain	tissue	11.4
Corpus callosum	tissue	10.7
Seminal vesicle	tissue	10.4	not detected
Putamen	tissue	10.2
Testis	tissue	10.0	medium
Cerebral cortex	tissue	9.5	not detected
Motor cortex	tissue	9.5
Temporal cortex	tissue	9.3
Prefrontal cortex	tissue	9.2
Somatosensory cortex	tissue	9.2
Entorhinal cortex	tissue	9.1
Adipose tissue	tissue	8.9	not detected
Prostate	tissue	8.9	high
Colon	tissue	8.7	medium
Rectum	tissue	8.5	medium
Amygdala	tissue	8.2
Caudate putamen	tissue	7.6
Epididymis	tissue	7.5	high
Retrosplenial and cingulate cortex	tissue	7.4
Retrosplenial cortex	tissue	7.4
Occipital cortex	tissue	7.4
Tonsil	tissue	7.2	not detected
Insular cortex	tissue	7.2
Kidney	tissue	7.1	high
Appendix	tissue	6.6	high
Nucleus accumbens	tissue	6.4
Parathyroid gland	tissue	6.0	high
Basal ganglia	tissue	5.4	not detected
Frontal cortex	tissue	5.0
Small intestine	tissue	5.0	high
Cerebellum	tissue	4.7	not detected
Pituitary gland	tissue	4.5

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Median raphe nucleus (75.4), Blood vessel (68.2), Dorsal raphe nucleus (45.0), Ventral spinal cord (40.2), Pontine raphe nucleus (36.3).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RELA

miRNA regulators (miRDB)

Targeting AMIGO2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 90 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3646	100.00	73.56	5283
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-489-3P	99.80	66.46	839
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4517	99.76	69.19	1867

Functional genomics

gnomAD constraint: pLI 0.000113, LOEUF 0.97, missense Z 1.59 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000550413 — one region, missense o/e 0.89.

Literature-anchored findings (GeneRIF, showing 13)

• Expression of ali1 promotes depolarization-dependent survival of cerebellar granule neurons. Mouse ali1 mapped to a chromosome 15 locus syntenic to candidate loci for familial Alzheimer’s disease type 5 and Parkinson’s disease 8 on human chromosome 12. (PMID:12843293)
• Stable expression of a DEGA/AMIGO-2 antisense construct led to altered morphology, increased ploidy, chromosomal instability, decreased cell adhesion/migration, and a nearly complete abrogation of tumorigenicity in nude mice. (PMID:15107827)
• AMIGO2 is an important regulator of the PDK1-Akt pathway. (PMID:26553931)
• Amigo2, which is a member of the Amigo family that shows high species conservation, may be involved in determining liver metastasis by preferential adhesion of the tumour cells to liver endothelial cells. (PMID:28272394)
• this study uncovers mechanisms underlying the therapeutic effects of BETi in melanoma and reveals the AMIGO2-PTK7 axis as a targetable pathway for metastatic melanoma. (PMID:29149598)
• AMIGO2 Expression as a Potential Prognostic Biomarker for Gastric Cancer. (PMID:33288564)
• In vivo selection of highly metastatic human ovarian cancer sublines reveals role for AMIGO2 in intra-peritoneal metastatic regulation. (PMID:33524500)
• AMIGO2 contained in cancer cell-derived extracellular vesicles enhances the adhesion of liver endothelial cells to cancer cells. (PMID:35039535)
• The impact of AMIGO2 on prognosis and hepatic metastasis in gastric cancer patients. (PMID:35296279)
• Liver Metastasis Formation Is Defined by AMIGO2 Expression via Adhesion to Hepatic Endothelial Cells in Human Gastric and Colorectal Cancer Cells. (PMID:35843033)
• AMIGO2 attenuates innate cisplatin sensitivity by suppression of GSDME-conferred pyroptosis in non-small cell lung cancer. (PMID:37438979)
• AMIGO2 is a pivotal therapeutic target related to M2 polarization of macrophages in pancreatic ductal adenocarcinoma. (PMID:38189855)
• AMIGO2 is involved in the spread of peritoneal metastasis in serous ovarian cancer via promoting adhesion to the peritoneal mesothelial cells. (PMID:38811439)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Amigo2	ENSMUSG00000048218
rattus_norvegicus	Amigo2	ENSRNOG00000007032

Paralogs (2): AMIGO3 (ENSG00000176020), AMIGO1 (ENSG00000181754)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2145995) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 4 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal retina rod bipolar cell morphology	1
abnormal retina ganglion cell morphology	1
increased grip strength	1
abnormal starburst amacrine cell morphology	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R7M3	99.2%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PCED1B-AS1	ncRNA	100233209
PCED1B	protein-coding	91523
SLC38A4	protein-coding	55089
MIR4698	ncRNA	100616486

Protein

Protein identifiers

Amphoterin-induced protein 2 — Q86SJ2 (reviewed: Q86SJ2)

Alternative names: AMIGO-2, Alivin-1, Differentially expressed in gastric adenocarcinomas

All UniProt accessions (1): Q86SJ2

UniProt curated annotations — full annotation on UniProt →

Function. Required for depolarization-dependent survival of cultured cerebellar granule neurons. May mediate homophilic as well as heterophilic cell-cell interaction with AMIGO1 or AMIGO3. May contribute to signal transduction through its intracellular domain. May be required for tumorigenesis of a subset of gastric adenocarcinomas.

Subunit / interactions. Binds itself as well as AMIGO1 and AMIGO3.

Subcellular location. Cell membrane. Nucleus.

Tissue specificity. Highest levels in breast, ovary, cervix, and uterus. Lower levels in lung, colon, and rectum. Differentially expressed in 56% of thyroid, 57% of pancreatic and 45% of stomach cancers.

Similarity. Belongs to the immunoglobulin superfamily. AMIGO family.

RefSeq proteins (3): NP_001137140, NP_001357228, NP_862830 (=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
IPR013783	Ig-like_fold	Homologous_superfamily
IPR031283	AMIGO	Family
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF13855, PF13927

UniProt features (28 total): glycosylation site 8, repeat 6, disulfide bond 5, domain 3, topological domain 2, signal peptide 1, chain 1, region of interest 1, transmembrane region 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86SJ2-F1	75.93	0.43

Human Protein Atlas

Protein class: Predicted membrane proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; plasma membrane; cytosol

Antibody reliability (HPA): IH uncertain · IF approved

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 (5)

Type	Positions
Disulfide bond	41–47, 45–54, 232–260, 234–282, 310–363

Glycosylation sites (8)

Type	Positions
N-linked (glcnac…) asparagine	58, 104, 281, 288, 345, 373, 381, 384

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 6; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

6 pathways:

ID	Pathway	Evidence
R-HSA-9013149	RAC1 GTPase cycle	curated
R-HSA-9013423	RAC3 GTPase cycle	curated
R-HSA-9012999	RHO GTPase cycle	—
R-HSA-162582	Signal Transduction	—
R-HSA-194315	Signaling by Rho GTPases	—
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3	—

MSigDB gene sets: 227 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, LI_CISPLATIN_RESISTANCE_DN, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_HETEROPHILIC_CELL_CELL_ADHESION, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_SYNAPSE_ASSEMBLY, FISCHER_G1_S_CELL_CYCLE, BOYAULT_LIVER_CANCER_SUBCLASS_G2, GOBP_POSITIVE_REGULATION_OF_SYNAPSE_ASSEMBLY, GOBP_REGULATION_OF_CELL_JUNCTION_ASSEMBLY, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_SUSTAINDED_IN_ERYTHROCYTE_UP, GOBP_CELL_CELL_ADHESION

GO Biological Process (6): homophilic cell-cell adhesion (GO:0007156), heterophilic cell-cell adhesion (GO:0007157), brain development (GO:0007420), negative regulation of programmed cell death (GO:0043069), positive regulation of synapse assembly (GO:0051965), cell adhesion (GO:0007155)

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

GO Cellular Component (3): nucleus (GO:0005634), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

4 top-level categories:

Category	Pathways
RHO GTPase cycle	2
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

17 GO namespaces:

Category	Terms
cell-cell adhesion	2
central nervous system development	1
animal organ development	1
head development	1
programmed cell death	1
regulation of programmed cell death	1
negative regulation of cellular process	1
synapse assembly	1
positive regulation of nervous system development	1
regulation of synapse assembly	1
positive regulation of cell junction assembly	1
cellular process	1
binding	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

showing 15 of 540 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AMIGO2	RGS14	O43566	633
AMIGO2	PCP4	P48539	622
AMIGO2	B3GNT5	Q9BYG0	596
AMIGO2	FKBP5	Q13451	564
AMIGO2	SERPING1	P05155	557
AMIGO2	TM4SF1	P30408	534
AMIGO2	EMP1	P54849	533
AMIGO2	CD109	Q6YHK3	477
AMIGO2	SRGN	P10124	417
AMIGO2	GRIK4	Q16099	413
AMIGO2	PSMB8	P28062	404
AMIGO2	SLC10A6	Q3KNW5	392
AMIGO2	FBLN5	Q9UBX5	390
AMIGO2	TSHZ1	Q6ZSZ6	370
AMIGO2	S100A10	P08206	369

IntAct

Human interaction partners of AMIGO2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
TMED8	physical association	0.560	3
CACNA1A	physical association	0.510	2

BioGRID (62 interactions; top human partners by supporting records): AMIGO1 (Affinity Capture-Western; 2 records), AMIGO3 (Affinity Capture-Western; 2 records), CACNA1A (Two-hybrid; 2 records), CDC42 (Affinity Capture-MS; 2 records), RAC1 (Affinity Capture-MS; 2 records), ADCY7 (Co-fractionation), ALDH5A1 (Co-fractionation), ALDH6A1 (Co-fractionation), ATG14 (Affinity Capture-MS), ATG16L1 (Proximity Label-MS), CA9 (Proximity Label-MS), DMWD (Co-fractionation), GNB2 (Proximity Label-MS), HACL1 (Co-fractionation), HRAS (Proximity Label-MS)

Disease & clinical

Genetic variants

Variant evidence for AMIGO2: 74 ClinVar records (1 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	64
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1710515	GRCh37/hg19 12q12-13.11(chr12:44661149-48921204)x1	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore AMIGO2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

AlphaMissense

837 missense substitutions predicted likely pathogenic (of 3,437 scored), across 220 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D198	8	0.981	0.992
N175	8	0.977	0.997
N151	8	0.973	0.996
N228	8	0.967	0.994
N78	8	0.965	0.996
D123	8	0.963	0.988
N127	8	0.963	0.995
N202	8	0.959	0.994
N103	8	0.957	0.995
D74	8	0.952	0.984
F468	8	0.940	0.993
F137	8	0.929	0.988
F113	8	0.915	0.987
F396	8	0.893	0.976
F161	8	0.854	0.954
H226	8	0.748	0.903
C54	7	0.990	0.996
W323	7	0.986	0.998
C310	7	0.985	0.993
C363	7	0.984	0.997

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Pancreatic Adenocarcinoma (TCGA)	unfavorable	7.72e-05

Disease associations

OMIM: gene MIM:615690 | disease phenotypes:

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
craniofacial microsomia	Limited	Autosomal dominant

Mondo (1): craniofacial microsomia (MONDO:0015397)

GWAS associations

1 associations:

Study	Trait	p-value
GCST006585_350	Blood protein levels	7e-7

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D006053	Goldenhar Syndrome	C05.116.099.370.231.576.410; C05.660.207.231.576.410; C16.131.621.207.231.576.410

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	7
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	5
Estradiol	affects cotreatment, decreases expression, increases expression	5
trichostatin A	affects cotreatment, increases expression	3
Air Pollutants	increases expression, decreases expression, increases abundance	3
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, affects expression	3
Particulate Matter	increases abundance, increases expression, decreases expression	3
ochratoxin A	affects expression, decreases acetylation, decreases expression	2
mercuric bromide	increases expression, affects cotreatment	2
monomethylarsonous acid	decreases expression, increases expression	2
(+)-JQ1 compound	decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression	2
Indomethacin	increases expression, affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	decreases expression, increases expression	2
Asbestos, Serpentine	affects expression, decreases methylation	2
Asbestos, Crocidolite	affects expression	2
Cadmium Chloride	increases abundance, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
TL8-506	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
deoxynivalenol	decreases expression	1
lead acetate	increases expression	1
beta-lapachone	decreases expression	1
mono-(2-ethylhexyl)phthalate	increases expression	1
butyraldehyde	decreases expression	1
potassium bromate	decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

12 trials:

NCT	Phase	Status	Title
NCT01674439	Phase 2	COMPLETED	Clinical Trial of Fat Grafts Supplemented With Adipose-derived Regenerative Cells
NCT05610878	Phase 1	RECRUITING	Efficacy of Preconditioned Adipose-Derived Stem Cells in Fat Grafting
NCT02224677	Not specified	COMPLETED	Craniofacial Microsomia: Longitudinal Outcomes in Children Pre-Kindergarten (CLOCK)
NCT02494752	Not specified	UNKNOWN	Role of Mesenchymal Stem Cells in Fat Grafting
NCT03806361	Not specified	COMPLETED	Fat Grafts With Adipose-derived Regenerative Cells for Soft Tissue Reconstruction in Children
NCT03861650	Not specified	COMPLETED	Evaluation of Effect of Bone Marrow Aspirate Concentrate on Distracted Mandibular Bone Properties
NCT03869021	Not specified	COMPLETED	Computer Guided for Mandibular Distraction Osteogenesis
NCT04056858	Not specified	COMPLETED	Study of a Candidate Gene Involved in Goldenhar Syndrome.
NCT04351893	Not specified	COMPLETED	Craniofacial Microsomia: Accelerating Understanding of the Significance and Etiology
NCT04931056	Not specified	COMPLETED	A Post Market Clinical Follow-up Study on Biomet Microfixation HTR PEKK (Midface), Facial & Mandibular Plates.
NCT07654647	Not specified	RECRUITING	Clinical Evaluation of Patient-Specific 3D-Printed Titanium Implants for Facial Reconstruction.
NCT07802639	Not specified	RECRUITING	Treatment for Asymmetric Crying Facies