# AMIGO2

> Gene · canonical: https://sugi.bio/atlas/gene/AMIGO2/
> Atlas v1.12.2 · generated 2026-10-13T13:32:47+00:00

## 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](https://www.ncbi.nlm.nih.gov/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](https://www.ebi.ac.uk/gxa/sc/experiments/E-CURD-7) | yes | 413.00 |
| [E-ENAD-21](https://www.ebi.ac.uk/gxa/sc/experiments/E-ENAD-21) | yes | 409.50 |
| [E-ANND-3](https://www.ebi.ac.uk/gxa/sc/experiments/E-ANND-3) | yes | 10.48 |
| [E-MTAB-5061](https://www.ebi.ac.uk/gxa/sc/experiments/E-MTAB-5061) | yes | 9.62 |
| [E-GEOD-81608](https://www.ebi.ac.uk/gxa/sc/experiments/E-GEOD-81608) | yes | 5.42 |
| [E-ENAD-27](https://www.ebi.ac.uk/gxa/sc/experiments/E-ENAD-27) | yes | 4.37 |
| [E-MTAB-8060](https://www.ebi.ac.uk/gxa/sc/experiments/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](https://gnomad.broadinstitute.org/)

**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](https://www.informatics.jax.org/marker/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](https://www.uniprot.org/uniprotkb/Q5R7M3/entry) | 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](/atlas/gene/PCED1B-AS1/) | ncRNA | 100233209 |
| [PCED1B](/atlas/gene/PCED1B/) | protein-coding | 91523 |
| [SLC38A4](/atlas/gene/SLC38A4/) | protein-coding | 55089 |
| [MIR4698](/atlas/gene/MIR4698/) | ncRNA | 100616486 |

<a id="protein-Q86SJ2"></a>

## 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 →](https://www.uniprot.org/uniprotkb/Q86SJ2/entry)

**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](#clinvar) (1 pathogenic / likely pathogenic); [1 GWAS association](#gwas-assoc). Per-variant detail is on [Sugi Variant](https://sugi.bio/variant/gene/AMIGO2).

#### 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](https://sugi.bio/variant/gene/AMIGO2).

#### 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](/atlas/disease/craniofacial-microsomia/) | Limited | Autosomal dominant |  |

**Mondo (1):** [craniofacial microsomia](/atlas/disease/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 |

## Related Atlas pages

- **Associated diseases:** [craniofacial microsomia](/atlas/disease/craniofacial-microsomia/)
- **Disease cohort memberships** *(association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases)*: [craniofacial microsomia](/atlas/disease/craniofacial-microsomia/)