ARMC6

Summary

ARMC6 (armadillo repeat containing 6, HGNC:25049) is a protein-coding gene on chromosome 19p13.11, encoding Armadillo repeat-containing protein 6 (Q6NXE6). It is a selective cancer dependency (DepMap: 21.6% of cell lines).

The function of this gene’s protein product has not been determined. A related protein in mouse suggests that this protein has a conserved function. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 93436 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 98 total
• Cancer dependency (DepMap): dependent in 21.6% of screened cell lines
• MANE Select transcript: NM_001199196

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25049
Approved symbol	ARMC6
Name	armadillo repeat containing 6
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	MGC19595
Ensembl gene	ENSG00000105676
Ensembl biotype	protein_coding
Entrez	93436

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 19 protein_coding, 3 nonsense_mediated_decay

ENST00000269932, ENST00000392335, ENST00000392336, ENST00000535288, ENST00000535478, ENST00000535612, ENST00000535758, ENST00000535795, ENST00000536098, ENST00000537263, ENST00000538663, ENST00000539985, ENST00000540634, ENST00000540707, ENST00000540792, ENST00000541725, ENST00000541898, ENST00000543877, ENST00000545091, ENST00000546344, ENST00000867259, ENST00000931200

RefSeq mRNA: 2 — MANE Select: NM_001199196 NM_001199196, NM_033415

CCDS: CCDS32965, CCDS56089

Canonical transcript exons

ENST00000535612 — 9 exons

Exon	Start	End
ENSE00000690835	19055265	19055396
ENSE00000690839	19055791	19055928
ENSE00002233299	19033603	19033930
ENSE00003480510	19054152	19054321
ENSE00003581826	19034131	19034238
ENSE00003638311	19043992	19044074
ENSE00003662728	19042711	19042877
ENSE00003787461	19051622	19052195
ENSE00003851104	19057416	19058176

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 95.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.0249 / max 119.2531, expressed in 1800 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174754	12.3742	1787
174758	5.9380	1660
174756	0.9938	562
174755	0.3527	162
174757	0.2489	94
174759	0.0496	7
174761	0.0398	8
174760	0.0280	8

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	95.54	gold quality
cortical plate	UBERON:0005343	93.42	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.72	gold quality
liver	UBERON:0002107	90.39	gold quality
apex of heart	UBERON:0002098	89.73	gold quality
ganglionic eminence	UBERON:0004023	88.90	gold quality
granulocyte	CL:0000094	88.20	gold quality
mucosa of transverse colon	UBERON:0004991	87.76	gold quality
right lobe of thyroid gland	UBERON:0001119	87.57	gold quality
prefrontal cortex	UBERON:0000451	87.29	gold quality
left testis	UBERON:0004533	87.10	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.94	gold quality
right testis	UBERON:0004534	86.94	gold quality
left lobe of thyroid gland	UBERON:0001120	86.58	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.54	gold quality
right frontal lobe	UBERON:0002810	86.50	gold quality
adenohypophysis	UBERON:0002196	86.09	gold quality
lower esophagus mucosa	UBERON:0035834	86.04	gold quality
gastrocnemius	UBERON:0001388	85.99	gold quality
ventricular zone	UBERON:0003053	85.91	gold quality
cerebellar hemisphere	UBERON:0002245	85.72	gold quality
cerebellar cortex	UBERON:0002129	85.49	gold quality
muscle of leg	UBERON:0001383	85.48	gold quality
testis	UBERON:0000473	85.31	gold quality
thyroid gland	UBERON:0002046	85.29	gold quality
right adrenal gland	UBERON:0001233	85.06	gold quality
pituitary gland	UBERON:0000007	85.05	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.04	gold quality
right adrenal gland cortex	UBERON:0035827	84.83	gold quality
esophagus mucosa	UBERON:0002469	84.63	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

28 targeting ARMC6, 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-6870-5P	99.99	68.55	2115
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-1912-3P	99.32	67.40	936
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-1295B-5P	99.03	67.50	810
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-4289	98.26	66.90	810
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-7154-3P	97.65	65.02	985
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-7847-3P	96.63	64.58	952
HSA-MIR-711	96.60	65.75	528
HSA-MIR-500B-3P	96.49	65.40	1087

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 21.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 1)

• Human ARMC6 binds in vitro to both cancer genes and telomeric RNA, favoring G-quadruplex structure recognition. (PMID:39029558)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ARMC6	ENSDARG00000103770
mus_musculus	Armc6	ENSMUSG00000002343
rattus_norvegicus	Armc6	ENSRNOG00000020280
drosophila_melanogaster	CG5721	FBGN0034315

Protein

Protein identifiers

Armadillo repeat-containing protein 6 — Q6NXE6 (reviewed: Q6NXE6)

All UniProt accessions (17): Q6NXE6, B4E1N1, F5GWV0, F5GYY4, F5GZP0, F5H052, F5H2K4, F5H2X2, F5H3X1, F5H3Y9, F5H4H6, F5H4P3, F5H6J3, F5H7V0, H0YGL0, H0YGQ5, H0YH65

UniProt curated annotations — full annotation on UniProt →

Post-translational modifications. Methylated at His-263 by METTL9.

Similarity. Belongs to the ARMC6 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6NXE6-1	1	yes
Q6NXE6-2	2

RefSeq proteins (2): NP_001186125, NP_219483 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000225	Armadillo	Repeat
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily

Pfam: PF00514

UniProt features (15 total): mutagenesis site 7, repeat 4, modified residue 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NXE6-F1	91.10	0.85

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 (2): 64, 263

Mutagenesis-validated functional residues (7):

Position	Phenotype
263	abolished histidine methylation by mettl9.
264	does not affect histidine methylation by mettl9.
265	does not affect histidine methylation by mettl9.
266	does not affect histidine methylation by mettl9.
267	does not affect histidine methylation by mettl9.
261	strongly reduced histidine methylation by mettl9.
262	does not affect histidine methylation by mettl9.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 112 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, WANG_CLIM2_TARGETS_UP, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, MUELLER_PLURINET, MYCMAX_01, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, KIM_GASTRIC_CANCER_CHEMOSENSITIVITY, P300_01, SCHLOSSER_MYC_AND_SERUM_RESPONSE_SYNERGY, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN, MARSON_BOUND_BY_FOXP3_STIMULATED, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, JAIN_NFKB_SIGNALING, chr19p13

GO Biological Process (1): hematopoietic progenitor cell differentiation (GO:0002244)

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

GO Cellular Component (1): cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
hemopoiesis	1
cell differentiation	1
binding	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

770 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARMC6	PLCXD2	Q0VAA5	547
ARMC6	PTGR3	Q8N4Q0	524
ARMC6	KLHDC4	Q8TBB5	510
ARMC6	WDR6	Q9NNW5	507
ARMC6	ARMC2	Q8NEN0	498
ARMC6	TANC2	Q9HCD6	485
ARMC6	GID8	Q9NWU2	472
ARMC6	NSMAF	Q92636	465
ARMC6	ARMC7	Q9H6L4	459
ARMC6	PI15	O43692	437
ARMC6	GALK2	Q01415	435
ARMC6	TMEM161A	Q9NX61	432
ARMC6	BRMS1	Q9HCU9	430
ARMC6	QPCTL	Q9NXS2	427
ARMC6	ARMC3	Q5W041	427

IntAct

53 interactions, top by confidence:

A	B	Type	Score
B3GAT3	GOLIM4	psi-mi:“MI:0914”(association)	0.640
ARMC6	SLC27A2	psi-mi:“MI:0914”(association)	0.530
ARMC6		psi-mi:“MI:0914”(association)	0.350
FOXA3	P4HA1	psi-mi:“MI:0914”(association)	0.350
	ZW10	psi-mi:“MI:0914”(association)	0.350
M	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350
NS1	ESYT2	psi-mi:“MI:0914”(association)	0.350
M2	ESYT2	psi-mi:“MI:0914”(association)	0.350
M2	IPO5	psi-mi:“MI:0914”(association)	0.350
M2	AGPS	psi-mi:“MI:0914”(association)	0.350
SH2D3C	TMEM14DP	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
SLC16A11	ESYT2	psi-mi:“MI:0914”(association)	0.350
CTDP1	ESYT2	psi-mi:“MI:0914”(association)	0.350
GPR17	TMEM120B	psi-mi:“MI:0914”(association)	0.350
CD80	POTEF	psi-mi:“MI:0914”(association)	0.350
METTL9	SLC27A2	psi-mi:“MI:0914”(association)	0.350
B3GNT2	NDUFA10	psi-mi:“MI:0914”(association)	0.350
GPR45	VWA8	psi-mi:“MI:0914”(association)	0.350
EEF1AKMT3	SMCHD1	psi-mi:“MI:0914”(association)	0.350
PLBD1	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
PSG11	ZSWIM8	psi-mi:“MI:0914”(association)	0.350
MFSD4A	UBXN8	psi-mi:“MI:0914”(association)	0.350
AQP3	UBXN8	psi-mi:“MI:0914”(association)	0.350
DNAI2	APAF1	psi-mi:“MI:0914”(association)	0.350
P2RY8	BTAF1	psi-mi:“MI:0914”(association)	0.350
AIFM1	HSPA12A	psi-mi:“MI:0914”(association)	0.350

BioGRID (178): ARMC6 (Affinity Capture-MS), ARMC6 (Affinity Capture-MS), ARMC6 (Affinity Capture-MS), ARMC6 (Co-fractionation), PFDN5 (Co-fractionation), ARCN1 (Affinity Capture-MS), C4BPA (Affinity Capture-MS), CCT6A (Affinity Capture-MS), CLU (Affinity Capture-MS), CPS1 (Affinity Capture-MS), HSPB1 (Affinity Capture-MS), PYCR1 (Affinity Capture-MS), RCN1 (Affinity Capture-MS), SSB (Affinity Capture-MS), TCP1 (Affinity Capture-MS)

ESM2 similar proteins: A2AQW0, A6QR40, A8MXQ7, B5DFG1, D3ZUM2, E1BP36, F1QWA8, H2LP95, I3L5V6, O43304, O95382, P0C6R2, P0CI65, Q0P5H9, Q27J81, Q3SZK4, Q3UMR0, Q3URY6, Q3V3E1, Q499U2, Q5BK48, Q5RD03, Q5REW9, Q5ZKD5, Q6NXE6, Q6NXR4, Q6PDS3, Q6SZW1, Q6ZN16, Q7TNH6, Q7YS91, Q8BGG7, Q8BYZ7, Q8N0Z6, Q8NDA8, Q969Z0, Q96NW4, Q96T76, Q99LG4, Q99MQ3

Diamond homologs: Q5RD03, Q6NXE6, Q7K486, Q8BNU0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1461 predictions. Top by Δscore:

Variant	Effect	Δscore
19:19042878:GTAGG:G	donor_loss	1.0000
19:19043987:A:AG	acceptor_gain	1.0000
19:19043987:AACAG:A	acceptor_gain	1.0000
19:19043988:ACAGG:A	acceptor_gain	1.0000
19:19043989:CA:C	acceptor_loss	1.0000
19:19043990:A:AC	acceptor_loss	1.0000
19:19043990:A:AG	acceptor_gain	1.0000
19:19043990:AG:A	acceptor_gain	1.0000
19:19043990:AGG:A	acceptor_gain	1.0000
19:19043990:AGGG:A	acceptor_gain	1.0000
19:19043991:G:GA	acceptor_gain	1.0000
19:19043991:GG:G	acceptor_gain	1.0000
19:19043991:GGG:G	acceptor_gain	1.0000
19:19043991:GGGG:G	acceptor_gain	1.0000
19:19043991:GGGGT:G	acceptor_gain	1.0000
19:19044070:TGCAG:T	donor_loss	1.0000
19:19044071:GCAGG:G	donor_loss	1.0000
19:19044072:CAGGT:C	donor_loss	1.0000
19:19051621:GAT:G	acceptor_gain	1.0000
19:19052194:AGGTA:A	donor_loss	1.0000
19:19052196:G:GG	donor_gain	1.0000
19:19052196:GTAAG:G	donor_loss	1.0000
19:19054146:CTGCA:C	acceptor_loss	1.0000
19:19054147:TGCA:T	acceptor_loss	1.0000
19:19054148:GCA:G	acceptor_loss	1.0000
19:19054149:CA:C	acceptor_loss	1.0000
19:19054150:A:AG	acceptor_gain	1.0000
19:19054150:A:C	acceptor_loss	1.0000
19:19054150:AGC:A	acceptor_gain	1.0000
19:19054151:G:GA	acceptor_gain	1.0000

AlphaMissense

3270 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:19055803:A:C	S390R	0.988
19:19055805:C:A	S390R	0.988
19:19055805:C:G	S390R	0.988
19:19042787:T:C	F36L	0.985
19:19042789:T:A	F36L	0.985
19:19042789:T:G	F36L	0.985
19:19051980:G:C	R213P	0.979
19:19055324:A:C	K361N	0.977
19:19055324:A:T	K361N	0.977
19:19042853:G:C	A58P	0.976
19:19042780:G:C	Q33H	0.972
19:19042780:G:T	Q33H	0.972
19:19057555:C:A	A478D	0.972
19:19057561:G:C	R480P	0.971
19:19057425:T:C	C435R	0.969
19:19057427:C:G	C435W	0.969
19:19052066:G:C	A242P	0.966
19:19055323:A:T	K361I	0.966
19:19057438:G:C	R439P	0.966
19:19055305:C:A	A355E	0.965
19:19042865:T:C	F62L	0.962
19:19042867:T:A	F62L	0.962
19:19042867:T:G	F62L	0.962
19:19057554:G:C	A478P	0.961
19:19052079:T:C	L246P	0.959
19:19055928:G:C	Q431H	0.959
19:19055928:G:T	Q431H	0.959
19:19052165:G:C	G275R	0.958
19:19055828:C:A	A398D	0.958
19:19051958:T:C	C206R	0.956

dbSNP variants (sampled 300 via entrez): RS1000002236 (19:19031960 G>A), RS1000034789 (19:19032282 C>T), RS1000076824 (19:19048222 T>C), RS1000188350 (19:19056471 A>G), RS1000246592 (19:19032645 T>G), RS1000386399 (19:19044756 A>G), RS1000606912 (19:19036977 G>A), RS1000752689 (19:19033831 C>G,T), RS1000800274 (19:19033656 C>G,T), RS1000956401 (19:19036630 A>C), RS1001019998 (19:19039213 C>T), RS1001546875 (19:19051367 CTCTCTCTCTGTGTG>C), RS1001578622 (19:19054015 G>A), RS1001621888 (19:19031683 A>T), RS1001739810 (19:19037428 G>C)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:616230, MIM:603387

GenCC curated gene-disease

Mondo (2): progressive myoclonic epilepsy type 8 (MONDO:0014545), megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 (MONDO:0011313)

Orphanet (2): Progressive myoclonic epilepsy type 8 (Orphanet:424027), Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome (Orphanet:83473)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566381	Megalancephaly Polymicrogyria-Polydactyly Hydrocephalus Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
GSK-J4	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	decreases expression	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
jinfukang	increases expression	1
LDN 193189	decreases expression, affects cotreatment	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Atrazine	increases expression	1
Copper	affects binding, decreases expression	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	affects expression	1
Cadmium Chloride	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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