ARMCX3

Summary

ARMCX3 (armadillo repeat containing X-linked 3, HGNC:24065) is a protein-coding gene on chromosome Xq22.1, encoding Armadillo repeat-containing X-linked protein 3 (Q9UH62). Regulates mitochondrial aggregation and transport in axons in living neurons.

This gene encodes a member of the ALEX family of proteins which may play a role in tumor suppression. The encoded protein contains a potential N-terminal transmembrane domain and a single Armadillo (arm) repeat. Other proteins containing the arm repeat are involved in development, maintenance of tissue integrity, and tumorigenesis. This gene is closely localized with other family members on the X chromosome. Three transcript variants encoding the same protein have been identified for this gene.

Source: NCBI Gene 51566 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 39 total
• MANE Select transcript: NM_177947

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24065
Approved symbol	ARMCX3
Name	armadillo repeat containing X-linked 3
Location	Xq22.1
Locus type	gene with protein product
Status	Approved
Aliases	ALEX3, GASP6
Ensembl gene	ENSG00000102401
Ensembl biotype	protein_coding
OMIM	300364
Entrez	51566

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 26 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000341189, ENST00000467808, ENST00000471229, ENST00000477980, ENST00000479298, ENST00000491568, ENST00000537169, ENST00000892644, ENST00000892645, ENST00000892646, ENST00000892647, ENST00000892648, ENST00000892649, ENST00000892650, ENST00000892651, ENST00000892652, ENST00000892653, ENST00000892654, ENST00000892655, ENST00000892656, ENST00000892657, ENST00000892658, ENST00000939728, ENST00000939729, ENST00000939730, ENST00000960636, ENST00000960637, ENST00000960638

RefSeq mRNA: 3 — MANE Select: NM_177947 NM_016607, NM_177947, NM_177948

CCDS: CCDS14489

Canonical transcript exons

ENST00000471229 — 5 exons

Exon	Start	End
ENSE00001032443	101624158	101624218
ENSE00001032444	101624480	101624550
ENSE00001558541	101623814	101623893
ENSE00001859138	101623151	101623276
ENSE00001945387	101624834	101627843

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 98.09.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.1856 / max 688.9735, expressed in 1809 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196967	57.0650	1809
196966	1.1206	782

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	98.09	gold quality
adrenal tissue	UBERON:0018303	97.95	gold quality
substantia nigra pars compacta	UBERON:0001965	97.65	gold quality
lateral globus pallidus	UBERON:0002476	97.27	gold quality
dorsal root ganglion	UBERON:0000044	97.02	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.01	gold quality
corpus epididymis	UBERON:0004359	96.97	gold quality
pons	UBERON:0000988	96.87	gold quality
cardia of stomach	UBERON:0001162	96.63	gold quality
superior vestibular nucleus	UBERON:0007227	96.58	gold quality
pylorus	UBERON:0001166	96.51	gold quality
inferior vagus X ganglion	UBERON:0005363	96.42	gold quality
mammary duct	UBERON:0001765	96.39	gold quality
body of pancreas	UBERON:0001150	96.35	gold quality
renal medulla	UBERON:0000362	96.30	gold quality
medulla oblongata	UBERON:0001896	96.12	gold quality
epithelium of mammary gland	UBERON:0003244	96.11	gold quality
right adrenal gland cortex	UBERON:0035827	96.04	gold quality
trigeminal ganglion	UBERON:0001675	95.94	gold quality
right adrenal gland	UBERON:0001233	95.93	gold quality
parietal pleura	UBERON:0002400	95.83	gold quality
hair follicle	UBERON:0002073	95.81	gold quality
adrenal cortex	UBERON:0001235	95.68	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	95.66	gold quality
parietal lobe	UBERON:0001872	95.59	gold quality
postcentral gyrus	UBERON:0002581	95.58	gold quality
visceral pleura	UBERON:0002401	95.52	gold quality
adrenal gland	UBERON:0002369	95.51	gold quality
parotid gland	UBERON:0001831	95.48	gold quality
stromal cell of endometrium	CL:0002255	95.43	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	16.31
E-ANND-3	yes	10.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

89 targeting ARMCX3, 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-3646	100.00	73.56	5283
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509

Literature-anchored findings (GeneRIF, showing 2)

• The Wnt pathway regulates mitochondrial distribution and dynamics through Alex3 protein degradation. (PMID:23844091)
• reduction of Alex3 correlates with the development of non-small cell lung cancer and predicts adverse clinical outcome of non-small cell lung cancer patients. The effect of Alex3 on inhibiting invasion and migration may attribute to upregulation of E-cadherin expression through AKT-Slug pathway inactivation. (PMID:28705116)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	armc10	ENSDARG00000062960
mus_musculus	Armcx3	ENSMUSG00000049047
rattus_norvegicus	Armcx3	ENSRNOG00000025730
caenorhabditis_elegans		WBGENE00013456

Paralogs (10): ARMCX5 (ENSG00000125962), ARMCX1 (ENSG00000126947), ARMC12 (ENSG00000157343), GPRASP2 (ENSG00000158301), ARMC10 (ENSG00000170632), ARMCX2 (ENSG00000184867), ARMCX4 (ENSG00000196440), GPRASP3 (ENSG00000198908), GPRASP1 (ENSG00000198932), ARMCX6 (ENSG00000198960)

Protein

Protein identifiers

Armadillo repeat-containing X-linked protein 3 — Q9UH62 (reviewed: Q9UH62)

Alternative names: ARM protein lost in epithelial cancers on chromosome X 3

All UniProt accessions (3): Q9UH62, H3BM63, H3BV87

UniProt curated annotations — full annotation on UniProt →

Function. Regulates mitochondrial aggregation and transport in axons in living neurons. May link mitochondria to the TRAK2-kinesin motor complex via its interaction with Miro and TRAK2. Mitochondrial distribution and dynamics is regulated through ARMCX3 protein degradation, which is promoted by PCK and negatively regulated by WNT1. Enhances the SOX10-mediated transactivation of the neuronal acetylcholine receptor subunit alpha-3 and beta-4 subunit gene promoters.

Subunit / interactions. Interacts (via ARM domain) with MIRO1, MIRO2 and TRAK2. The interaction with Miro is calcium-dependent. Interacts with SOX10.

Subcellular location. Mitochondrion outer membrane. Cytoplasm. Nucleus.

Similarity. Belongs to the eutherian X-chromosome-specific Armcx family.

RefSeq proteins (3): NP_057691, NP_808816, NP_808817 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000225	Armadillo	Repeat
IPR006911	ARM-rpt_dom	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR051303	Armcx_regulator	Family

Pfam: PF04826

UniProt features (17 total): region of interest 4, modified residue 4, repeat 3, topological domain 2, chain 1, compositionally biased region 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UH62-F1	76.53	0.50

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 (4): 61, 67, 72, 110

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 202 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GOBP_AXO_DENDRITIC_TRANSPORT, GOZGIT_ESR1_TARGETS_DN, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, FONTAINE_PAPILLARY_THYROID_CARCINOMA_UP, GGGCATT_MIR365, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOCC_MITOCHONDRIAL_ENVELOPE, AACTTT_UNKNOWN, MORI_PLASMA_CELL_UP, GOCC_NEURON_PROJECTION, YY1_01, CUI_TCF21_TARGETS_2_DN, PTF1BETA_Q6

GO Biological Process (4): mitochondrion organization (GO:0007005), intracellular protein localization (GO:0008104), axonal transport of mitochondrion (GO:0019896), positive regulation of transcription by RNA polymerase II (GO:0045944)

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

GO Cellular Component (7): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), cytosol (GO:0005829), axon cytoplasm (GO:1904115), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular membrane-bounded organelle	2
cytoplasm	2
organelle organization	1
macromolecule localization	1
mitochondrion transport along microtubule	1
axonal transport	1
axon cytoplasm	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
binding	1
mitochondrial membrane	1
organelle outer membrane	1
axon	1
neuron projection cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1181 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARMCX3	TRAK2	O60296	845
ARMCX3	SPTAN1	Q13813	669
ARMCX3	RB1	P06400	547
ARMCX3	SOX10	P56693	514
ARMCX3	LRRC19	Q9H756	482
ARMCX3	ESYT2	A0FGR8	468
ARMCX3	TMEM214	Q6NUQ4	465
ARMCX3	TRMT11	Q7Z4G4	444
ARMCX3	NIPSNAP1	Q9BPW8	443
ARMCX3	CRBN	Q96SW2	402
ARMCX3	RHOT1	Q8IXI2	397
ARMCX3	ARMC1	Q9NVT9	395
ARMCX3	RNF11	Q9Y3C5	383
ARMCX3	FGF1	P05230	374
ARMCX3	SPRYD4	Q8WW59	366

IntAct

90 interactions, top by confidence:

A	B	Type	Score
BRAF	HRAS	psi-mi:“MI:0914”(association)	0.940
ARMCX3	RANBP6	psi-mi:“MI:0914”(association)	0.730
MAF1	ARMCX3	psi-mi:“MI:0915”(physical association)	0.710
RANBP6	SLC27A2	psi-mi:“MI:0914”(association)	0.640
SLC12A2	CLGN	psi-mi:“MI:0914”(association)	0.640
EHHADH	ARMCX3	psi-mi:“MI:0915”(physical association)	0.560
FAM25C	ARMCX3	psi-mi:“MI:0915”(physical association)	0.560
MAF1	POLR3A	psi-mi:“MI:0914”(association)	0.530
P2RX1	ATE1	psi-mi:“MI:0914”(association)	0.530
CCDC59	GAPDHS	psi-mi:“MI:0914”(association)	0.530
VTN	HAT1	psi-mi:“MI:0914”(association)	0.530
IPO5	SLC27A2	psi-mi:“MI:0914”(association)	0.530
GNAS	CPT2	psi-mi:“MI:0914”(association)	0.530
SIDT2	AP3D1	psi-mi:“MI:0914”(association)	0.530
HCCS	NPAT	psi-mi:“MI:0914”(association)	0.530
KCNA2	FADS1	psi-mi:“MI:0914”(association)	0.530
ARMCX3	CSNK2A1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
ARMCX3	PCNA	psi-mi:“MI:0915”(physical association)	0.370
	ESYT2	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
SPHK1	MYO1C	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
FBL	GXYLT2	psi-mi:“MI:0914”(association)	0.350
VWA5A	PIPSL	psi-mi:“MI:0914”(association)	0.350
PACC1	DEGS1	psi-mi:“MI:0914”(association)	0.350
PNKD	EXOC5	psi-mi:“MI:0914”(association)	0.350

BioGRID (173): ARMCX3 (Affinity Capture-MS), ARMCX3 (Affinity Capture-MS), ARMCX3 (Affinity Capture-MS), ARMCX3 (Affinity Capture-MS), ARMCX3 (Affinity Capture-MS), ARMCX3 (Affinity Capture-MS), ARMCX3 (Affinity Capture-MS), ARMCX3 (Affinity Capture-MS), ARMCX3 (Affinity Capture-MS), ARMCX3 (Affinity Capture-MS), ARMCX3 (Affinity Capture-MS), ARMCX3 (Affinity Capture-MS), ARMCX3 (Affinity Capture-MS), ARMCX3 (Affinity Capture-MS), ARMCX3 (Affinity Capture-MS)

ESM2 similar proteins: A0JP94, A1A5P5, A2BFL2, B0BF33, B1WBW4, E7FBU4, F1QWA8, O35095, P28658, Q1MX18, Q2KI89, Q2KJ97, Q2TBM9, Q2TBW0, Q32PZ3, Q3HNM7, Q3U213, Q3V129, Q4R4Y2, Q5R5R2, Q5R629, Q5R9J3, Q5RAG3, Q5XID7, Q5ZIG0, Q640K1, Q68F70, Q6AI08, Q6DRJ9, Q6WRX3, Q7Z4Q2, Q7Z7L7, Q80ZG0, Q80ZJ6, Q86XA9, Q8BHS6, Q8BQM4, Q8BW49, Q8CIM8, Q8JFV4

Diamond homologs: B1WBW4, Q3UZB0, Q5H9R4, Q5JY77, Q5R4B2, Q5R7U0, Q5R9J3, Q5RDG2, Q5U310, Q5U4C1, Q5XID7, Q6A058, Q6P1M9, Q6PI77, Q7L311, Q8BHS6, Q8BUY8, Q8N2F6, Q920R4, Q96D09, Q9BE11, Q9CX83, Q9D0L7, Q9P291, Q9UH62, Q6PB60, Q71HP2, Q7L4S7, Q66HF0, Q8K3A6

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	17
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

885 predictions. Top by Δscore:

Variant	Effect	Δscore
X:101624196:G:GT	donor_gain	1.0000
X:101624995:A:T	donor_gain	1.0000
X:101623784:A:AG	acceptor_gain	0.9900
X:101623784:AGTG:A	acceptor_gain	0.9900
X:101623785:G:GG	acceptor_gain	0.9900
X:101623785:GTGG:G	acceptor_gain	0.9900
X:101623892:GG:G	donor_gain	0.9900
X:101623893:GG:G	donor_gain	0.9900
X:101624193:G:T	donor_gain	0.9900
X:101624213:G:GG	donor_gain	0.9900
X:101624217:AGG:A	donor_loss	0.9900
X:101624218:GGT:G	donor_loss	0.9900
X:101624219:G:GA	donor_loss	0.9900
X:101624895:GCT:G	donor_gain	0.9900
X:101624928:GCC:G	donor_gain	0.9900
X:101624994:G:GT	donor_gain	0.9900
X:101623890:GAGG:G	donor_gain	0.9800
X:101623891:AGGGT:A	donor_loss	0.9800
X:101623895:T:G	donor_loss	0.9800
X:101624192:G:GT	donor_gain	0.9800
X:101624212:A:AG	donor_gain	0.9800
X:101624216:GAG:G	donor_gain	0.9800
X:101624896:C:T	donor_gain	0.9800
X:101623784:AGT:A	acceptor_gain	0.9700
X:101623785:GTG:G	acceptor_gain	0.9700
X:101624153:TGCAG:T	acceptor_loss	0.9700
X:101624154:GCAGG:G	acceptor_loss	0.9700
X:101624155:CAGG:C	acceptor_loss	0.9700
X:101624156:A:AC	acceptor_loss	0.9700
X:101624829:CCTA:C	acceptor_loss	0.9700

AlphaMissense

2505 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:101625482:T:A	V168D	0.997
X:101625550:A:C	S191R	0.997
X:101625552:T:A	S191R	0.997
X:101625552:T:G	S191R	0.997
X:101625029:G:A	G17E	0.995
X:101625347:T:C	L123P	0.995
X:101625035:G:A	G19D	0.994
X:101625040:T:C	C21R	0.994
X:101625404:C:A	A142D	0.994
X:101625416:T:C	L146P	0.994
X:101625526:G:C	A183P	0.994
X:101625653:T:C	L225P	0.994
X:101625407:T:C	L143S	0.993
X:101625428:C:A	A150D	0.993
X:101625567:T:A	N196K	0.993
X:101625567:T:G	N196K	0.993
X:101625026:T:A	I16N	0.992
X:101625519:G:C	K180N	0.992
X:101625519:G:T	K180N	0.992
X:101625536:T:A	V186D	0.992
X:101625662:T:C	L228P	0.992
X:101625028:G:A	G17R	0.991
X:101625028:G:C	G17R	0.991
X:101625416:T:A	L146Q	0.991
X:101625527:C:A	A183D	0.991
X:101625539:T:C	L187P	0.991
X:101625368:T:A	V130D	0.990
X:101625403:G:C	A142P	0.990
X:101625455:T:A	I159N	0.990
X:101625032:C:A	A18D	0.989

dbSNP variants (sampled 300 via entrez): RS1000301038 (X:101624715 A>G,T), RS1000578063 (X:101623053 G>A), RS1000630204 (X:101622703 G>A,T), RS1001870399 (X:101624131 C>A,G), RS1003142103 (X:101622066 A>G), RS1003499290 (X:101622496 G>A,T), RS1004377670 (X:101627097 T>C), RS1004724978 (X:101623438 G>T), RS1006385836 (X:101622012 T>C), RS1009223064 (X:101622989 A>G), RS1009275307 (X:101622638 T>C), RS1012605718 (X:101627743 T>A), RS1015779939 (X:101627105 G>A,T), RS1015833706 (X:101626514 C>T), RS1016115364 (X:101624061 G>T)

Disease associations

OMIM: gene MIM:300364 | 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

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression, affects cotreatment	4
Cyclosporine	increases expression	4
Air Pollutants	decreases expression, increases abundance, increases expression	3
Particulate Matter	increases abundance, increases expression, decreases expression	3
bisphenol A	increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	increases expression	2
FR900359	affects phosphorylation	1
tremortin	increases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
K 7174	increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1

Clinical trials (associated diseases)

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