ARMCX1

Summary

ARMCX1 (armadillo repeat containing X-linked 1, HGNC:18073) is a protein-coding gene on chromosome Xq22.1, encoding Armadillo repeat-containing X-linked protein 1 (Q9P291). Regulates mitochondrial transport during axon regeneration.

This gene encodes a member of the ALEX family of proteins and may play a role in tumor suppression. The encoded protein contains a potential N-terminal transmembrane domain and two Armadillo (arm) repeats. 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, including ALEX2 and ALEX3, on the X chromosome.

Source: NCBI Gene 51309 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 58 total — 3 pathogenic
• MANE Select transcript: NM_016608

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18073
Approved symbol	ARMCX1
Name	armadillo repeat containing X-linked 1
Location	Xq22.1
Locus type	gene with protein product
Status	Approved
Aliases	ALEX1, GASP7
Ensembl gene	ENSG00000126947
Ensembl biotype	protein_coding
OMIM	300362
Entrez	51309

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 31 protein_coding

ENST00000372829, ENST00000898854, ENST00000898855, ENST00000898856, ENST00000898857, ENST00000898858, ENST00000898859, ENST00000898860, ENST00000898861, ENST00000898862, ENST00000898863, ENST00000898864, ENST00000898865, ENST00000936538, ENST00000936539, ENST00000936540, ENST00000936541, ENST00000936542, ENST00000936543, ENST00000936544, ENST00000936545, ENST00000936546, ENST00000936547, ENST00000936548, ENST00000964328, ENST00000964329, ENST00000964330, ENST00000964331, ENST00000964332, ENST00000964333, ENST00000964334

RefSeq mRNA: 1 — MANE Select: NM_016608 NM_016608

CCDS: CCDS14487

Canonical transcript exons

ENST00000372829 — 4 exons

Exon	Start	End
ENSE00001032388	101551569	101551633
ENSE00001032390	101550547	101550660
ENSE00001032391	101550971	101551024
ENSE00001458756	101552809	101554700

Expression profiles

Bgee: expression breadth ubiquitous, 284 present calls, max score 98.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.8695 / max 240.7400, expressed in 1527 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196964	14.1680	1506
196965	6.2925	1398
196963	2.4089	1180

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	98.52	gold quality
choroid plexus epithelium	UBERON:0003911	97.91	gold quality
parietal pleura	UBERON:0002400	97.88	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.37	gold quality
heart right ventricle	UBERON:0002080	96.65	gold quality
pleura	UBERON:0000977	96.63	gold quality
cartilage tissue	UBERON:0002418	96.15	gold quality
visceral pleura	UBERON:0002401	95.66	gold quality
cauda epididymis	UBERON:0004360	95.64	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.52	gold quality
renal glomerulus	UBERON:0000074	95.46	gold quality
blood vessel layer	UBERON:0004797	95.40	gold quality
metanephric glomerulus	UBERON:0004736	95.26	gold quality
myocardium	UBERON:0002349	95.24	gold quality
seminal vesicle	UBERON:0000998	95.17	gold quality
biceps brachii	UBERON:0001507	95.17	gold quality
corpus epididymis	UBERON:0004359	95.05	gold quality
mammary duct	UBERON:0001765	95.04	gold quality
synovial joint	UBERON:0002217	95.01	gold quality
cortical plate	UBERON:0005343	94.99	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.89	gold quality
epithelium of mammary gland	UBERON:0003244	94.79	gold quality
hair follicle	UBERON:0002073	94.57	gold quality
middle temporal gyrus	UBERON:0002771	94.57	gold quality
amniotic fluid	UBERON:0000173	94.52	gold quality
urethra	UBERON:0000057	94.27	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.27	gold quality
calcaneal tendon	UBERON:0003701	94.27	gold quality
skin of hip	UBERON:0001554	94.23	gold quality
caput epididymis	UBERON:0004358	94.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.54
E-CURD-112	yes	4.48

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1

miRNA regulators (miRDB)

37 targeting ARMCX1, 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-6740-5P	100.00	65.64	932
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-548C-3P	99.99	74.01	7587
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-95-5P	99.89	72.17	3973
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-3122	99.50	66.33	821
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-21-5P	99.46	70.54	1035
HSA-MIR-16-2-3P	99.29	70.60	1954
HSA-MIR-195-3P	99.29	70.61	1954
HSA-MIR-590-5P	99.25	70.76	930
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-4704-3P	98.28	69.33	1300
HSA-MIR-6831-5P	98.26	67.20	990

Literature-anchored findings (GeneRIF, showing 8)

• Human Arm protein lost in epithelial cancers, on chromosome X 1 (ALEX1) gene is transcriptionally regulated by CREB and Wnt/beta-catenin signaling. (PMID:20398052)
• Findings suggest that overexpression of ALEX1 (armadillo repeat containing, X-linked [ARMCX]) plays a negative role in colorectal tumorigenesis. (PMID:22494058)
• ALEX1 is a crucial tumor suppressor gene involved in cell proliferation and apoptosis in breast cancer. (PMID:25921134)
• It is suggested that the ALEX1 protein is associated with tumorigenesis in cervical cancer and we speculate that the ALEX1 may plays a role as an oncogene in cervical cancer. (PMID:26464700)
• ALEX1 expression is reduced in gastric cancer; ALEX1 inhibits metastasis through the PAR-1/Rho GTPase signaling pathway. (PMID:28315004)
• Up-regulation of ALEX1 effectively rescued the cell apoptosis induced by miR-106b inhibitor and promoted the expression levels of phosphorylation of JAK1 and STAT3. (PMID:30907988)
• ARMCX Family Gene Expression Analysis and Potential Prognostic Biomarkers for Prediction of Clinical Outcome in Patients with Gastric Carcinoma. (PMID:32685472)
• The Expression of ARMCX1 in Gastric Cancer Contributes to Prognosis and Influences Chemotherapy. (PMID:36726491)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	armc10	ENSDARG00000062960
mus_musculus	Armcx1	ENSMUSG00000033460
rattus_norvegicus	Armcx1	ENSRNOG00000046862
caenorhabditis_elegans		WBGENE00013456

Paralogs (10): ARMCX3 (ENSG00000102401), ARMCX5 (ENSG00000125962), 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 1 — Q9P291 (reviewed: Q9P291)

Alternative names: ARM protein lost in epithelial cancers on chromosome X 1

All UniProt accessions (1): Q9P291

UniProt curated annotations — full annotation on UniProt →

Function. Regulates mitochondrial transport during axon regeneration. Increases the proportion of motile mitochondria by recruiting stationary mitochondria into the motile pool. Enhances mitochondria movement and neurite growth in both adult axons and embryonic neurons. Promotes neuronal survival and axon regeneration after nerve injury. May link mitochondria to the Trak1-kinesin motor complex via its interaction with MIRO1.

Subunit / interactions. Interacts with MIRO1.

Subcellular location. Mitochondrion. Mitochondrion outer membrane.

Tissue specificity. Expressed at high levels ovary, heart, testis, prostate, brain, spleen and colon. Expressed at very low levels in liver and thymus. Not expressed in peripheral blood leukocytes. Not or reduced expressed in lung, prostate, colon, pancreas and ovarian carcinomas.

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

RefSeq proteins (1): NP_057692* (*=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 (15 total): region of interest 4, repeat 4, topological domain 2, sequence conflict 2, chain 1, compositionally biased region 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P291-F1	74.28	0.56

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 175 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_UP, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, GOBP_AXO_DENDRITIC_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, CHANDRAN_METASTASIS_DN, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, AML_Q6, GOCC_MITOCHONDRIAL_ENVELOPE, DOUGLAS_BMI1_TARGETS_DN, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOCC_NEURON_PROJECTION

GO Biological Process (1): hematopoietic stem cell homeostasis (GO:0061484)

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

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
homeostasis of number of cells	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1059 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARMCX1	SPTAN1	Q13813	650
ARMCX1	RHOT1	Q8IXI2	630
ARMCX1	SNPH	O15079	597
ARMCX1	RB1	P06400	549
ARMCX1	TRAK2	O60296	548
ARMCX1	GPSM1	Q86YR5	441
ARMCX1	WDR49	Q8IV35	407
ARMCX1	KIF5C	O60282	389
ARMCX1	KIFC3	Q9BVG8	373
ARMCX1	CRISPLD1	Q9H336	359
ARMCX1	FSTL5	Q8N475	343
ARMCX1	PLS3	P13797	329
ARMCX1	GPSM2	P81274	318
ARMCX1	TRAK1	Q9UPV9	314
ARMCX1	ZBBX	A8MT70	312

IntAct

31 interactions, top by confidence:

A	B	Type	Score
ARMCX1	ZBTB8A	psi-mi:“MI:0915”(physical association)	0.720
ZBTB8A	ARMCX1	psi-mi:“MI:0915”(physical association)	0.720
TFIP11	ARMCX1	psi-mi:“MI:0915”(physical association)	0.670
ARMCX1	TFIP11	psi-mi:“MI:0915”(physical association)	0.670
ARMCX1	COIL	psi-mi:“MI:0915”(physical association)	0.560
COIL	ARMCX1	psi-mi:“MI:0915”(physical association)	0.560
GPKOW	ARMCX1	psi-mi:“MI:0915”(physical association)	0.560
PICK1	ARMCX1	psi-mi:“MI:0915”(physical association)	0.560
CEP70	ARMCX1	psi-mi:“MI:0915”(physical association)	0.560
BCAR1	MYO1C	psi-mi:“MI:0914”(association)	0.350
FECH	POTEF	psi-mi:“MI:0914”(association)	0.350
ARMCX1	GYG1	psi-mi:“MI:0914”(association)	0.350
LGALS3BP	ACACB	psi-mi:“MI:0914”(association)	0.350
PPARD	LRP6	psi-mi:“MI:0914”(association)	0.350
GATA2	C11orf98	psi-mi:“MI:0914”(association)	0.350
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
ARMCX1	ZBTB8A	psi-mi:“MI:0915”(physical association)	0.000
ARMCX1	PICK1	psi-mi:“MI:0915”(physical association)	0.000
ARMCX1	CEP70	psi-mi:“MI:0915”(physical association)	0.000
ARMCX1		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): ARMCX1 (Two-hybrid), ARMCX1 (Two-hybrid), ZBTB8A (Two-hybrid), ARMCX1 (Affinity Capture-MS), ARMCX1 (Affinity Capture-MS), ARMCX1 (Affinity Capture-MS), ARMCX1 (Affinity Capture-MS), ARMCX1 (Positive Genetic), ARMCX1 (Two-hybrid), ARMCX1 (Two-hybrid), ARMCX1 (Two-hybrid), ZBTB8A (Two-hybrid), ARMCX1 (Affinity Capture-MS), SPC25 (Cross-Linking-MS (XL-MS)), ARMCX1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A0M3U1B0, A1A5Q6, A2AFS9, A2AVR2, A2CI98, A2CJ06, A2RTY3, A2RUW0, O70167, O70173, P0C2Y1, P15304, P59729, Q08EC4, Q3SYK4, Q3TYG6, Q3U1D0, Q4R744, Q4R9E9, Q5R4B2, Q5T4T6, Q5TGP6, Q5VWK0, Q68CQ1, Q6AYJ3, Q6IFT4, Q6IRU7, Q6REY9, Q6ZUA9, Q7Z572, Q80VH0, Q86WZ0, Q86XG9, Q8C0X8, Q8CCC3, Q8ND61, Q8NDZ2, Q8TB24, Q96M43, Q96QP1

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, Q66HF0, Q7L4S7, Q8K3A6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	32
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3024654	GRCh37/hg19 Xq12-28(chrX:67292994-155240074)x3	Pathogenic
57972	GRCh38/hg38 Xq22.1(chrX:101323599-101596196)x1	Pathogenic
57973	GRCh38/hg38 Xq22.1-22.3(chrX:101407698-106274188)x1	Pathogenic

SpliceAI

796 predictions. Top by Δscore:

Variant	Effect	Δscore
X:101551634:G:GG	donor_gain	1.0000
X:101550657:GCAG:G	donor_gain	0.9800
X:101550969:A:AG	acceptor_gain	0.9800
X:101550969:AGTAG:A	acceptor_gain	0.9800
X:101550970:G:GG	acceptor_gain	0.9800
X:101550970:GTA:G	acceptor_gain	0.9800
X:101550970:GTAGG:G	acceptor_gain	0.9800
X:101552548:G:GT	donor_gain	0.9800
X:101552803:TCCTA:T	acceptor_loss	0.9800
X:101552804:CCTA:C	acceptor_loss	0.9800
X:101552805:CTAGG:C	acceptor_loss	0.9800
X:101552806:TA:T	acceptor_loss	0.9800
X:101552807:A:AC	acceptor_loss	0.9800
X:101552808:G:A	acceptor_loss	0.9800
X:101550656:AGCAG:A	donor_loss	0.9700
X:101550657:GCAGG:G	donor_loss	0.9700
X:101550658:CAGG:C	donor_loss	0.9700
X:101550659:AG:A	donor_loss	0.9700
X:101550660:G:GC	donor_loss	0.9700
X:101550661:G:A	donor_loss	0.9700
X:101550662:T:G	donor_loss	0.9700
X:101550730:G:GT	donor_gain	0.9700
X:101550970:GT:G	acceptor_gain	0.9700
X:101551156:G:GT	donor_gain	0.9700
X:101551634:GTA:G	donor_loss	0.9700
X:101551635:TAG:T	donor_loss	0.9700
X:101553057:GAGTC:G	donor_gain	0.9700
X:101551021:GCAGG:G	donor_loss	0.9600
X:101551022:CAG:C	donor_loss	0.9600
X:101551023:AGG:A	donor_loss	0.9600

AlphaMissense

2968 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:101553753:A:C	S275R	1.000
X:101553755:T:A	S275R	1.000
X:101553755:T:G	S275R	1.000
X:101553852:G:T	G308W	1.000
X:101553550:T:C	L207P	0.999
X:101553571:T:C	L214P	0.999
X:101553607:C:A	A226D	0.999
X:101553610:T:G	L227W	0.999
X:101553619:T:C	L230P	0.999
X:101553622:G:A	G231D	0.999
X:101553630:G:C	A234P	0.999
X:101553631:C:A	A234E	0.999
X:101553658:T:A	I243K	0.999
X:101553658:T:G	I243R	0.999
X:101553661:G:C	R244P	0.999
X:101553738:G:C	A270P	0.999
X:101553742:T:A	L271H	0.999
X:101553742:T:C	L271P	0.999
X:101553746:T:A	N272K	0.999
X:101553746:T:G	N272K	0.999
X:101553749:C:A	N273K	0.999
X:101553749:C:G	N273K	0.999
X:101553751:T:C	L274S	0.999
X:101553770:T:A	N280K	0.999
X:101553770:T:G	N280K	0.999
X:101553852:G:A	G308R	0.999
X:101553852:G:C	G308R	0.999
X:101553856:T:C	L309P	0.999
X:101553862:T:C	L311P	0.999
X:101553872:C:A	N314K	0.999

dbSNP variants (sampled 300 via entrez): RS1000683827 (X:101552196 A>G), RS1000709469 (X:101554625 A>G), RS1001011875 (X:101552493 A>C), RS1001442610 (X:101554230 C>T), RS1001512758 (X:101553492 C>T), RS1001846295 (X:101551290 G>C), RS1003447312 (X:101549895 A>G), RS1005199331 (X:101552999 T>C), RS1006801754 (X:101551244 T>C), RS1007632718 (X:101550435 G>C), RS1010907360 (X:101549937 G>C), RS1011399911 (X:101549388 T>C), RS1016586231 (X:101550633 G>A), RS1017345805 (X:101552508 G>T), RS1019022758 (X:101550436 G>A)

Disease associations

OMIM: gene MIM:300362 | 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	4
sodium arsenite	decreases expression, affects methylation	3
Silicon Dioxide	increases expression	3
bisphenol A	increases expression, affects cotreatment	2
Indomethacin	decreases expression, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Cyclosporine	decreases expression, increases expression	2
Particulate Matter	increases abundance, affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
TAK-243	increases sumoylation	1
dodecyldimethylamine oxide	increases expression	1
arsenite	increases methylation	1
butyraldehyde	increases expression	1
zinc chromate	increases abundance, increases expression	1
nickel sulfate	decreases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases response to substance, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Ethanol	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Camptothecin	increases expression	1
Dactinomycin	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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