AMER2

Summary

AMER2 (APC membrane recruitment protein 2, HGNC:26360) is a protein-coding gene on chromosome 13q12.13, encoding APC membrane recruitment protein 2 (Q8N7J2). Negative regulator of the canonical Wnt signaling pathway involved in neuroectodermal patterning.

Enables phosphatidylinositol-4,5-bisphosphate binding activity. Involved in negative regulation of canonical Wnt signaling pathway. Located in plasma membrane.

Source: NCBI Gene 219287 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 119 total — 2 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_152704

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26360
Approved symbol	AMER2
Name	APC membrane recruitment protein 2
Location	13q12.13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25477
Ensembl gene	ENSG00000165566
Ensembl biotype	protein_coding
OMIM	614659
Entrez	219287

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000357816, ENST00000515384

RefSeq mRNA: 2 — MANE Select: NM_152704 NM_152704, NM_199138

CCDS: CCDS53859, CCDS9312

Canonical transcript exons

ENST00000515384 — 1 exons

Exon	Start	End
ENSE00002027051	25161679	25172288

Expression profiles

Bgee: expression breadth ubiquitous, 108 present calls, max score 99.79.

FANTOM5 (CAGE): breadth broad, TPM avg 7.1034 / max 508.3882, expressed in 311 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
136452	2.8630	219
136455	1.3954	107
136456	1.3315	88
136444	0.6427	130
136443	0.2994	137
136453	0.2347	91
136454	0.1617	64
136445	0.1146	74
136451	0.0605	42

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	99.79	gold quality
lateral globus pallidus	UBERON:0002476	99.03	gold quality
inferior vagus X ganglion	UBERON:0005363	98.73	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.66	gold quality
corpus callosum	UBERON:0002336	98.59	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.58	gold quality
subthalamic nucleus	UBERON:0001906	98.56	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.36	gold quality
medulla oblongata	UBERON:0001896	98.35	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.35	gold quality
ventral tegmental area	UBERON:0002691	98.29	gold quality
superior vestibular nucleus	UBERON:0007227	98.16	gold quality
substantia nigra pars compacta	UBERON:0001965	97.97	gold quality
entorhinal cortex	UBERON:0002728	97.92	gold quality
parietal lobe	UBERON:0001872	97.86	gold quality
postcentral gyrus	UBERON:0002581	97.82	gold quality
globus pallidus	UBERON:0001875	97.65	gold quality
medial globus pallidus	UBERON:0002477	97.25	gold quality
cerebellar vermis	UBERON:0004720	96.44	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.14	gold quality
occipital lobe	UBERON:0002021	95.93	gold quality
pons	UBERON:0000988	95.87	gold quality
superior frontal gyrus	UBERON:0002661	95.84	gold quality
primary visual cortex	UBERON:0002436	95.11	gold quality
middle temporal gyrus	UBERON:0002771	94.39	gold quality
Ammon’s horn	UBERON:0001954	93.85	gold quality
adult organism	UBERON:0007023	93.82	gold quality
temporal lobe	UBERON:0001871	93.79	gold quality
cortical plate	UBERON:0005343	93.23	gold quality
midbrain	UBERON:0001891	93.12	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	653.60
E-GEOD-84465	yes	11.77
E-ANND-3	yes	4.72

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

327 targeting AMER2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-6870-5P	99.99	68.55	2115

Literature-anchored findings (GeneRIF, showing 3)

• data characterize Amer2 for the first time as a negative regulator of Wnt signaling both in cell lines and in vivo and define Amer proteins as a novel family of Wnt pathway regulators. (PMID:22128170)
• the Amer2-EB1-APC complex regulates cell migration by altering microtubule stability. (PMID:22898821)
• FAM123A binds to microtubules and inhibits the guanine nucleotide exchange factor ARHGEF2 to decrease actomyosin contractility. (PMID:22949735)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	amer2	ENSDARG00000075222
mus_musculus	Amer2	ENSMUSG00000021986
rattus_norvegicus	Amer2	ENSRNOG00000013623

Paralogs (2): AMER3 (ENSG00000178171), AMER1 (ENSG00000184675)

Protein

Protein identifiers

APC membrane recruitment protein 2 — Q8N7J2 (reviewed: Q8N7J2)

Alternative names: Protein FAM123A

All UniProt accessions (1): Q8N7J2

UniProt curated annotations — full annotation on UniProt →

Function. Negative regulator of the canonical Wnt signaling pathway involved in neuroectodermal patterning. Acts by specifically binding phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), translocating to the cell membrane and interacting with key regulators of the canonical Wnt signaling pathway, such as components of the beta-catenin destruction complex.

Subunit / interactions. Interacts with APC.

Subcellular location. Cell membrane.

Similarity. Belongs to the Amer family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N7J2-1	1	yes
Q8N7J2-2	2

RefSeq proteins (2): NP_689917, NP_954589 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019003	AMER	Family

Pfam: PF09422

UniProt features (29 total): compositionally biased region 10, sequence conflict 6, modified residue 5, region of interest 4, sequence variant 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N7J2-F1	51.91	0.01

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 (5): 162, 229, 233, 355, 358

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 157 (showing top): BENPORATH_ES_WITH_H3K27ME3, STAEGE_EWING_FAMILY_TUMOR, GOZGIT_ESR1_TARGETS_DN, CREBP1_Q2, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_ECTODERM_DEVELOPMENT, AAACCAC_MIR140, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, HTF_01, GOBP_NEGATIVE_REGULATION_OF_WNT_SIGNALING_PATHWAY, CUI_TCF21_TARGETS_2_UP, ATF_01, GCM_MAP1B, CREBP1CJUN_01, GOMF_BETA_CATENIN_BINDING

GO Biological Process (4): ectoderm development (GO:0007398), Wnt signaling pathway (GO:0016055), regulation of canonical Wnt signaling pathway (GO:0060828), negative regulation of canonical Wnt signaling pathway (GO:0090090)

GO Molecular Function (4): phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), beta-catenin binding (GO:0008013), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
canonical Wnt signaling pathway	2
binding	2
tissue development	1
cell surface receptor signaling pathway	1
regulation of Wnt signaling pathway	1
negative regulation of Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
phosphatidylinositol phosphate binding	1
phosphatidylinositol bisphosphate binding	1
protein binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1428 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AMER2	AMER3	Q8N944	533
AMER2	MAPRE3	Q9UPY8	513
AMER2	OR51G1	Q8NGK1	433
AMER2	RASSF6	Q6ZTQ3	429
AMER2	C9orf50	Q5SZB4	418
AMER2	TCHP	Q9BT92	409
AMER2	CFAP52	Q8N1V2	405
AMER2	ARRB1	P49407	397
AMER2	POF1B	Q8WVV4	394
AMER2	DNAH8	Q96JB1	389
AMER2	GAS2L2	Q8NHY3	378
AMER2	DTX1	Q86Y01	371
AMER2	GPSM1	Q86YR5	370
AMER2	OR52I2	Q8NH67	369
AMER2	ZNF726	A6NNF4	355

IntAct

4 interactions, top by confidence:

A	B	Type	Score
AMER2	APC	psi-mi:“MI:0915”(physical association)	0.400
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): AMER2 (Proximity Label-MS), AMER2 (Affinity Capture-MS), AMER2 (Affinity Capture-RNA), AMER2 (Affinity Capture-RNA), AMER2 (Cross-Linking-MS (XL-MS)), AMER2 (Affinity Capture-MS), RPL38 (Cross-Linking-MS (XL-MS)), RALA (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A8I5ZM56, A2AG50, A2AI08, A2AJI0, A5D7K1, D4A4L4, E1C2Q8, F1LR10, O00515, O14529, O75128, O88573, O88735, P51825, P57016, Q14244, Q32LQ1, Q3KQU3, Q3U2K0, Q5JTD0, Q5NBX1, Q5PR69, Q5R7F9, Q5XHX2, Q5ZIA2, Q5ZJJ1, Q68DK7, Q6IPM2, Q6NV74, Q6NZF1, Q6PDH0, Q6PDM1, Q6PG95, Q6ZU35, Q86UU1, Q8CCJ4, Q8K124, Q8N7J2, Q8TD55, Q96PV7

Diamond homologs: A4IGN8, E1C2Q8, F1QGH6, Q6INC4, Q8CCJ4, Q8N7J2, F1RDM5, Q6NS69, Q8N944, Q5JTC6, Q7TS75

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	111
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2426474	NC_000013.10:g.(?24293859)(26594123_?)del	Pathogenic
686932	GRCh37/hg19 13q12.11-12.13(chr13:20069228-27474401)x3	Pathogenic
443856	GRCh37/hg19 13q12.12-12.13(chr13:23552966-27027909)x1	Likely pathogenic

SpliceAI

284 predictions. Top by Δscore:

Variant	Effect	Δscore
13:25169535:A:AC	donor_gain	0.9400
13:25169536:C:CC	donor_gain	0.9400
13:25170478:CAGC:C	acceptor_gain	0.9400
13:25172132:T:TA	donor_gain	0.9400
13:25169385:T:C	donor_gain	0.9200
13:25172086:G:C	donor_gain	0.8800
13:25170482:C:CC	acceptor_gain	0.8700
13:25169536:CTTTA:C	donor_gain	0.8600
13:25172024:AT:A	donor_gain	0.8600
13:25172041:C:CA	donor_gain	0.8600
13:25172131:A:C	donor_gain	0.8600
13:25170482:C:CG	acceptor_loss	0.8300
13:25170483:T:A	acceptor_loss	0.8300
13:25170484:G:C	acceptor_loss	0.8200
13:25172129:ACAT:A	donor_gain	0.8200
13:25172130:CATC:C	donor_gain	0.8200
13:25164104:C:G	acceptor_gain	0.7900
13:25170485:TAAGA:T	acceptor_loss	0.7900
13:25170838:CCTG:C	donor_gain	0.7900
13:25172129:A:AC	donor_gain	0.7900
13:25172130:C:CC	donor_gain	0.7900
13:25172130:CAT:C	donor_gain	0.7900
13:25170833:GCTCA:G	donor_loss	0.7800
13:25170834:CTCA:C	donor_loss	0.7800
13:25170835:TCA:T	donor_loss	0.7800
13:25170836:CACCT:C	donor_loss	0.7800
13:25170837:AC:A	donor_loss	0.7800
13:25170838:C:CT	donor_loss	0.7800
13:25169528:AAAAC:A	donor_loss	0.7700
13:25169529:AAACT:A	donor_loss	0.7700

AlphaMissense

4346 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:25170495:A:C	F375L	0.999
13:25170495:A:T	F375L	0.999
13:25170497:A:G	F375L	0.999
13:25170498:G:C	S374R	0.999
13:25170498:G:T	S374R	0.999
13:25170500:T:G	S374R	0.999
13:25170505:A:G	L372P	0.999
13:25169704:A:G	I639T	0.998
13:25170493:T:A	D376V	0.998
13:25170496:A:C	F375C	0.998
13:25170496:A:G	F375S	0.998
13:25170501:T:A	K373N	0.998
13:25170501:T:G	K373N	0.998
13:25170491:A:G	S377P	0.997
13:25170509:A:G	S371P	0.997
13:25169698:A:T	V641D	0.996
13:25169704:A:C	I639S	0.996
13:25170475:C:A	G382V	0.996
13:25170475:C:T	G382E	0.996
13:25170481:C:T	G380D	0.996
13:25170505:A:T	L372Q	0.996
13:25171411:A:G	L70S	0.996
13:25169797:A:G	I608T	0.995
13:25170482:C:G	G380R	0.995
13:25170502:T:A	K373I	0.995
13:25170503:T:C	K373E	0.995
13:25170523:A:G	F366S	0.995
13:25169692:T:A	K643I	0.994
13:25170472:T:A	D383V	0.994
13:25170479:A:G	C381R	0.994

dbSNP variants (sampled 300 via entrez): RS1000251940 (13:25163306 A>G), RS1000372342 (13:25173077 C>G), RS1000590988 (13:25161906 A>G), RS1000622308 (13:25161567 C>A,T), RS1001202792 (13:25168001 C>G), RS1001280978 (13:25168259 A>G), RS1001485534 (13:25173407 C>G), RS1001717919 (13:25173977 A>G), RS1001729623 (13:25167348 T>C), RS1001768518 (13:25173720 G>A), RS1002334289 (13:25169120 T>C), RS1002688206 (13:25165302 G>A,T), RS1003128597 (13:25168704 A>G), RS1003174707 (13:25170918 C>T), RS1003254106 (13:25172359 G>A)

Disease associations

OMIM: gene MIM:614659 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, increases expression, decreases expression	6
trichostatin A	affects cotreatment, increases expression	3
mercuric bromide	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression, decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
indeno(1,2,3-cd)pyrene	increases expression	1
picene	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Diethylhexyl Phthalate	increases expression	1
Estradiol	increases expression	1
Triclosan	decreases expression	1
S-Nitrosoglutathione	increases expression	1

Clinical trials (associated diseases)

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