ARMCX2

Summary

ARMCX2 (armadillo repeat containing X-linked 2, HGNC:16869) is a protein-coding gene on chromosome Xq22.1, encoding Armadillo repeat-containing X-linked protein 2 (Q7L311). May regulate the dynamics and distribution of mitochondria in neural cells.

This gene encodes a protein containing a potential N-terminal transmembrane domain and multiple armadillo (arm) repeats. Proteins containing arm repeats are involved in development, maintenance of tissue integrity, and tumorigenesis. This gene is located in a cluster of related genes on chromosome X. There is a pseudogene for this gene on chromosome 7. Alternative splicing in the 5’ UTR results in multiple transcript variants encoding the same protein.

Source: NCBI Gene 9823 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 71 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_177949

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16869
Approved symbol	ARMCX2
Name	armadillo repeat containing X-linked 2
Location	Xq22.1
Locus type	gene with protein product
Status	Approved
Aliases	ALEX2, KIAA0512, GASP9
Ensembl gene	ENSG00000184867
Ensembl biotype	protein_coding
OMIM	300363
Entrez	9823

Gene structure

Transcript identifiers

Ensembl transcripts: 93 — 88 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000328766, ENST00000330154, ENST00000356824, ENST00000413506, ENST00000431597, ENST00000433318, ENST00000440675, ENST00000458024, ENST00000467416, ENST00000475854, ENST00000479333, ENST00000488982, ENST00000496581, ENST00000889669, ENST00000889670, ENST00000889671, ENST00000889672, ENST00000889673, ENST00000889674, ENST00000889675, ENST00000889676, ENST00000889677, ENST00000889678, ENST00000889679, ENST00000889680, ENST00000889681, ENST00000889682, ENST00000889683, ENST00000889684, ENST00000889685, ENST00000889686, ENST00000889687, ENST00000889688, ENST00000889689, ENST00000889690, ENST00000889691, ENST00000937515, ENST00000937516, ENST00000937517, ENST00000937518, ENST00000937519, ENST00000937520, ENST00000937521, ENST00000937522, ENST00000937523, ENST00000937524, ENST00000937525, ENST00000937526, ENST00000937527, ENST00000937528, ENST00000937529, ENST00000937530, ENST00000937531, ENST00000937532, ENST00000937533, ENST00000937534, ENST00000937535, ENST00000937536, ENST00000937537, ENST00000937538, ENST00000937539, ENST00000937540, ENST00000937541, ENST00000937542, ENST00000937543, ENST00000937544, ENST00000937545, ENST00000937546, ENST00000937547, ENST00000971519, ENST00000971520, ENST00000971521, ENST00000971522, ENST00000971523, ENST00000971524, ENST00000971525, ENST00000971526, ENST00000971527, ENST00000971528, ENST00000971529, ENST00000971530, ENST00000971531, ENST00000971532, ENST00000971533, ENST00000971534, ENST00000971535, ENST00000971536, ENST00000971537, ENST00000971538, ENST00000971539, ENST00000971540, ENST00000971541, ENST00000971542

RefSeq mRNA: 3 — MANE Select: NM_177949 NM_001282231, NM_014782, NM_177949

CCDS: CCDS14490

Canonical transcript exons

ENST00000356824 — 6 exons

Exon	Start	End
ENSE00001295677	101658461	101658525
ENSE00001307563	101659419	101659501
ENSE00001318567	101658073	101658142
ENSE00001322738	101659076	101659148
ENSE00001347589	101655281	101657715
ENSE00001423403	101659758	101659850

Expression profiles

Bgee: expression breadth ubiquitous, 271 present calls, max score 98.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.6105 / max 627.8758, expressed in 1412 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199961	35.6105	1412

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	98.89	gold quality
seminal vesicle	UBERON:0000998	97.54	gold quality
pituitary gland	UBERON:0000007	97.52	gold quality
adrenal tissue	UBERON:0018303	97.29	gold quality
adenohypophysis	UBERON:0002196	97.21	gold quality
cauda epididymis	UBERON:0004360	96.36	gold quality
right lobe of thyroid gland	UBERON:0001119	96.35	gold quality
left lobe of thyroid gland	UBERON:0001120	96.07	gold quality
thyroid gland	UBERON:0002046	95.86	gold quality
caput epididymis	UBERON:0004358	95.65	gold quality
left ovary	UBERON:0002119	95.21	gold quality
right ovary	UBERON:0002118	95.20	gold quality
parotid gland	UBERON:0001831	95.19	gold quality
right adrenal gland	UBERON:0001233	94.84	gold quality
right adrenal gland cortex	UBERON:0035827	94.74	gold quality
stromal cell of endometrium	CL:0002255	94.62	gold quality
adrenal cortex	UBERON:0001235	94.60	gold quality
left adrenal gland cortex	UBERON:0035825	94.44	gold quality
endocervix	UBERON:0000458	94.37	gold quality
right coronary artery	UBERON:0001625	93.98	gold quality
left adrenal gland	UBERON:0001234	93.75	gold quality
right uterine tube	UBERON:0001302	93.74	gold quality
body of uterus	UBERON:0009853	93.61	gold quality
left uterine tube	UBERON:0001303	93.57	gold quality
tibia	UBERON:0000979	93.55	gold quality
descending thoracic aorta	UBERON:0002345	93.52	gold quality
adrenal gland	UBERON:0002369	93.48	gold quality
smooth muscle tissue	UBERON:0001135	93.45	gold quality
cartilage tissue	UBERON:0002418	93.43	gold quality
mucosa of stomach	UBERON:0001199	93.25	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.20
E-HCAD-5	no	2.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

45 targeting ARMCX2, 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-9-5P	100.00	72.28	2361
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-12122	99.56	69.33	1672

Literature-anchored findings (GeneRIF, showing 2)

• Data indicate that ARMCX2, COL1A1, MDK, MEST and MLH1 genes acquired methylation in drug-resistant ovarian cancer-sustaining (side population) cells. (PMID:22249249)
• ARMCX Family Gene Expression Analysis and Potential Prognostic Biomarkers for Prediction of Clinical Outcome in Patients with Gastric Carcinoma. (PMID:32685472)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	armc10	ENSDARG00000062960
mus_musculus	Armcx2	ENSMUSG00000033436
rattus_norvegicus	Armcx2	ENSRNOG00000025705
caenorhabditis_elegans		WBGENE00013456

Paralogs (10): ARMCX3 (ENSG00000102401), ARMCX5 (ENSG00000125962), ARMCX1 (ENSG00000126947), ARMC12 (ENSG00000157343), GPRASP2 (ENSG00000158301), ARMC10 (ENSG00000170632), ARMCX4 (ENSG00000196440), GPRASP3 (ENSG00000198908), GPRASP1 (ENSG00000198932), ARMCX6 (ENSG00000198960)

Protein

Protein identifiers

Armadillo repeat-containing X-linked protein 2 — Q7L311 (reviewed: Q7L311)

Alternative names: ARM protein lost in epithelial cancers on chromosome X 2

All UniProt accessions (6): A0A0B4J1X4, A0A1B0GXK8, Q7L311, Q5H9D7, Q5H9E0, Q5H9E1

UniProt curated annotations — full annotation on UniProt →

Function. May regulate the dynamics and distribution of mitochondria in neural cells.

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 expressed in pancreas and ovarian carcinomas.

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

RefSeq proteins (3): NP_001269160, NP_055597, NP_808818* (*=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 5, compositionally biased region 3, repeat 3, topological domain 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L311-F1	64.69	0.40

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 196 (showing top): RNGTGGGC_UNKNOWN, GOBP_AXO_DENDRITIC_TRANSPORT, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOZGIT_ESR1_TARGETS_DN, GOBP_ORGANELLE_TRANSPORT_ALONG_MICROTUBULE, MODULE_66, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_SUSTAINDED_IN_ERYTHROCYTE_UP, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, TGCTGAY_UNKNOWN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOCC_MITOCHONDRIAL_ENVELOPE, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13, ONDER_CDH1_TARGETS_2_UP, HTF_01, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP

GO Biological Process (0):

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
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

1193 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARMCX2	SPTAN1	Q13813	650
ARMCX2	RB1	P06400	548
ARMCX2	WDR49	Q8IV35	530
ARMCX2	HABP4	Q5JVS0	511
ARMCX2	PSME3IP1	Q9GZU8	508
ARMCX2	ATP6V1E2	Q96A05	494
ARMCX2	CCDC69	A6NI79	491
ARMCX2	DDX55	Q8NHQ9	490
ARMCX2	ATPAF1	Q5TC12	475
ARMCX2	BCAS4	Q8TDM0	473
ARMCX2	CCDC70	Q6NSX1	457
ARMCX2	ATP6V0D1	P12953	446
ARMCX2	DIS3L2	Q8IYB7	445
ARMCX2	ATP6V0A2	Q9Y487	437
ARMCX2	ATP5F1A	P25705	437

IntAct

23 interactions, top by confidence:

A	B	Type	Score
SLC1A1	AGPAT2	psi-mi:“MI:0914”(association)	0.640
TUBA4A	TXNDC9	psi-mi:“MI:0914”(association)	0.640
HLA-DRA	ENTPD6	psi-mi:“MI:0914”(association)	0.530
VTN	HAT1	psi-mi:“MI:0914”(association)	0.530
ARMCX2	LYAR	psi-mi:“MI:0915”(physical association)	0.400
VIM	ARMCX2	psi-mi:“MI:0915”(physical association)	0.370
MAD2L2		psi-mi:“MI:0914”(association)	0.350
N	FLG	psi-mi:“MI:0914”(association)	0.350
ARMCX1	GYG1	psi-mi:“MI:0914”(association)	0.350
DNAJB2		psi-mi:“MI:0914”(association)	0.350
MAGEA8	B4GALT5	psi-mi:“MI:0914”(association)	0.350
MAGED2	PJA2	psi-mi:“MI:0914”(association)	0.350
MRAP2	A2ML1	psi-mi:“MI:0914”(association)	0.350
PPARD	LRP6	psi-mi:“MI:0914”(association)	0.350
VSIG4	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC30A10	GOLIM4	psi-mi:“MI:0914”(association)	0.350
SLC39A12	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC39A2	AGPAT2	psi-mi:“MI:0914”(association)	0.350
SLC39A9	TRAFD1	psi-mi:“MI:0914”(association)	0.350
TOMM22	DNM1L	psi-mi:“MI:2364”(proximity)	0.270
CDH5	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
ARMCX2	TULP3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (34): ARMCX2 (Two-hybrid), ARMCX2 (Affinity Capture-MS), ARMCX2 (Proximity Label-MS), ARMCX2 (Affinity Capture-MS), CHCHD3 (Co-fractionation), LRRC59 (Co-fractionation), ARMCX2 (Co-fractionation), ARMCX2 (Co-fractionation), ARMCX2 (Co-fractionation), ARMCX2 (Co-fractionation), ARMCX2 (Co-fractionation), ARMCX2 (Co-fractionation), KTN1 (Co-fractionation), ARMCX2 (Affinity Capture-MS), ARMCX2 (Proximity Label-MS)

ESM2 similar proteins: A3A8Q4, A3A8W6, A6QLI5, B0Y8Z0, B9F4I8, F4JFR7, F4JRP0, F4K5K6, F4KAV2, O15297, O81472, O82302, P48785, Q06003, Q0D598, Q0DZT4, Q10NB9, Q2PS26, Q4WWA0, Q5N712, Q5XUX6, Q651A1, Q6ITT4, Q6K1U0, Q6K1U4, Q6K5I0, Q6WLH4, Q6ZGY0, Q7L311, Q7TQI8, Q7XRV0, Q84T94, Q8GYY5, Q8L7S0, Q8RWN7, Q8W119, Q96JG8, Q9BE64, Q9ES73, Q9FNK5

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	45
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
691846	GRCh37/hg19 Xq22.1-22.2(chrX:100866604-103411980)x1	Pathogenic
442008	GRCh37/hg19 Xq22.1(chrX:100852505-101986687)x0	Likely pathogenic

SpliceAI

190 predictions. Top by Δscore:

Variant	Effect	Δscore
X:101658070:AACCT:A	donor_loss	0.9900
X:101658071:ACCTG:A	donor_loss	0.9900
X:101658072:C:A	donor_loss	0.9900
X:101658490:A:AC	donor_gain	0.9900
X:101658491:C:CC	donor_gain	0.9900
X:101658493:T:TA	donor_gain	0.9900
X:101658140:GACC:G	acceptor_loss	0.9800
X:101658141:ACCT:A	acceptor_loss	0.9800
X:101658143:C:CG	acceptor_loss	0.9800
X:101658459:AC:A	donor_gain	0.9800
X:101658460:CC:C	donor_gain	0.9800
X:101658491:CTT:C	donor_gain	0.9800
X:101657716:C:CC	acceptor_gain	0.9700
X:101658068:CCAA:C	donor_gain	0.9700
X:101658138:CAGAC:C	acceptor_gain	0.9600
X:101657714:GCCT:G	acceptor_loss	0.9200
X:101657716:C:CA	acceptor_loss	0.9200
X:101658460:CCCT:C	donor_gain	0.9200
X:101658143:C:CC	acceptor_gain	0.9100
X:101658491:CTTCA:C	donor_gain	0.9100
X:101658513:T:TA	donor_gain	0.9000
X:101658140:GAC:G	acceptor_gain	0.8700
X:101658459:ACCCT:A	donor_gain	0.8700
X:101658460:CCCTC:C	donor_gain	0.8700
X:101657712:GGGC:G	acceptor_gain	0.8500
X:101658067:A:AC	donor_gain	0.8500
X:101658068:C:CC	donor_gain	0.8500
X:101658491:CT:C	donor_gain	0.8500
X:101658150:C:CT	acceptor_gain	0.8400
X:101657711:AGGGC:A	acceptor_gain	0.8300

AlphaMissense

4069 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:101655877:A:G	L571P	1.000
X:101656111:A:G	L493P	1.000
X:101656120:A:G	L490P	1.000
X:101655706:A:G	L628P	0.999
X:101655751:A:G	L613S	0.999
X:101655877:A:T	L571H	0.999
X:101655881:C:G	A570P	0.999
X:101655889:A:G	L567P	0.999
X:101655955:A:G	L545P	0.999
X:101655994:A:G	L532P	0.999
X:101656039:A:G	L517P	0.999
X:101656124:C:G	G489R	0.999
X:101656124:C:T	G489R	0.999
X:101656221:A:C	S456R	0.999
X:101656221:A:T	S456R	0.999
X:101656223:T:G	S456R	0.999
X:101656225:A:G	L455P	0.999
X:101656246:G:T	A448D	0.999
X:101656247:C:G	A448P	0.999
X:101656254:C:A	K445N	0.999
X:101656254:C:G	K445N	0.999
X:101656291:A:T	I433N	0.999
X:101656357:A:G	L411P	0.999
X:101656366:A:C	L408W	0.999
X:101656369:G:T	A407D	0.999
X:101656405:A:G	L395P	0.999
X:101656426:A:G	L388P	0.999
X:101655736:T:C	D618G	0.998
X:101655760:A:C	I610S	0.998
X:101655760:A:T	I610N	0.998

dbSNP variants (sampled 300 via entrez): RS1001017323 (X:101655207 T>A,G), RS1002710385 (X:101661512 C>G), RS1003089202 (X:101661843 T>C), RS1005848217 (X:101661817 T>C), RS1005967098 (X:101661482 A>G), RS1005999642 (X:101661038 A>C), RS1007197225 (X:101660395 A>G), RS1008837440 (X:101658898 G>A), RS1009283160 (X:101658561 A>G), RS1011872681 (X:101659930 G>C,T), RS1012878601 (X:101659812 C>G,T), RS1012995225 (X:101659417 A>G), RS1015334122 (X:101658899 G>A,T), RS1015706938 (X:101656076 G>A), RS1017797723 (X:101655235 T>C)

Disease associations

OMIM: gene MIM:300363 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007576_17	Chronotype	1.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
sodium arsenite	decreases methylation, increases expression	2
Valproic Acid	affects expression, increases expression, increases methylation	2
triphenyl phosphate	affects expression	1
alpha-pinene	decreases expression, increases abundance, affects cotreatment	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	increases methylation	1
terbufos	increases methylation	1
cobaltous chloride	decreases expression	1
ferrous chloride	decreases expression	1
nickel sulfate	decreases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
MRK 003	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Cisplatin	affects response to substance	1
Doxorubicin	increases expression	1
Fonofos	increases methylation	1
Estradiol	affects cotreatment, increases expression	1
Naled	affects expression	1
Ozone	decreases expression, increases abundance, affects cotreatment	1
Parathion	increases methylation	1
Potassium Dichromate	decreases expression	1
Silicon Dioxide	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E1QZ	HAP1 ARMCX2 (-) 2	Cancer cell line	Male
CVCL_XL51	HAP1 ARMCX2 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

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