ARMC3

Summary

ARMC3 (armadillo repeat containing 3, HGNC:30964) is a protein-coding gene on chromosome 10p12.2, encoding Armadillo repeat-containing protein 3 (Q5W041). Essential for male fertility and sperm motility.

Armadillo/beta-catenin (CTNNB1; MIM 116806)-like (ARM) domains are imperfect 45-amino acid repeats involved in protein-protein interactions. ARM domain-containing proteins, such as ARMC3, function in signal transduction, development, cell adhesion and mobility, and tumor initiation and metastasis (Li et al., 2006 [PubMed 16915934]).

Source: NCBI Gene 219681 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 140 total
• MANE Select transcript: NM_173081

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30964
Approved symbol	ARMC3
Name	armadillo repeat containing 3
Location	10p12.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32827, CT81, VAC8
Ensembl gene	ENSG00000165309
Ensembl biotype	protein_coding
OMIM	611226
Entrez	219681

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 6 protein_coding_CDS_not_defined, 5 protein_coding, 2 retained_intron

ENST00000298032, ENST00000376528, ENST00000409049, ENST00000409983, ENST00000447081, ENST00000464017, ENST00000465729, ENST00000468003, ENST00000473919, ENST00000483596, ENST00000484642, ENST00000491803, ENST00000496741

RefSeq mRNA: 4 — MANE Select: NM_173081 NM_001282745, NM_001282746, NM_001282747, NM_173081

CCDS: CCDS60499, CCDS60500, CCDS7142, CCDS73073

Canonical transcript exons

ENST00000298032 — 19 exons

Exon	Start	End
ENSE00001092034	23032861	23033023
ENSE00001092036	23030596	23030796
ENSE00001092044	23001919	23002055
ENSE00001092048	23003246	23003414
ENSE00001092049	23008815	23008931
ENSE00001092050	22981595	22981700
ENSE00001092055	22961884	22962078
ENSE00001092056	22998148	22998397
ENSE00001092058	23006884	23006981
ENSE00002310134	23037270	23038523
ENSE00003458922	22981340	22981492
ENSE00003531319	23008276	23008374
ENSE00003534556	22946144	22946261
ENSE00003570742	22959399	22959574
ENSE00003579653	22968306	22968489
ENSE00003650655	22931996	22932044
ENSE00003655388	22959070	22959138
ENSE00003689696	22955807	22955932
ENSE00003843373	22928053	22928106

Expression profiles

Bgee: expression breadth ubiquitous, 149 present calls, max score 98.44.

FANTOM5 (CAGE): breadth broad, TPM avg 1.1659 / max 111.6242, expressed in 297 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
104266	1.0733	259
104267	0.0600	26
104265	0.0327	14

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.44	gold quality
bronchial epithelial cell	CL:0002328	97.39	gold quality
sperm	CL:0000019	96.42	gold quality
bronchus	UBERON:0002185	95.68	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.75	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.41	gold quality
left testis	UBERON:0004533	88.20	gold quality
right testis	UBERON:0004534	87.96	gold quality
oviduct epithelium	UBERON:0004804	86.96	gold quality
testis	UBERON:0000473	85.90	gold quality
fallopian tube	UBERON:0003889	85.71	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.81	gold quality
epithelium of nasopharynx	UBERON:0001951	82.15	gold quality
nasopharynx	UBERON:0001728	82.14	gold quality
monocyte	CL:0000576	80.23	gold quality
leukocyte	CL:0000738	79.35	gold quality
nasal cavity epithelium	UBERON:0005384	78.34	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.19	gold quality
right lung	UBERON:0002167	74.07	gold quality
nasal cavity mucosa	UBERON:0001826	73.32	gold quality
caudate nucleus	UBERON:0001873	72.49	gold quality
nucleus accumbens	UBERON:0001882	71.45	gold quality
left uterine tube	UBERON:0001303	70.12	gold quality
hypothalamus	UBERON:0001898	70.11	gold quality
pancreatic ductal cell	CL:0002079	69.72	silver quality
adenohypophysis	UBERON:0002196	69.63	gold quality
body of pancreas	UBERON:0001150	67.73	gold quality
corpus callosum	UBERON:0002336	67.60	gold quality
endometrium	UBERON:0001295	67.16	gold quality
pituitary gland	UBERON:0000007	67.05	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	62.22
E-MTAB-10287	yes	25.52
E-ANND-3	yes	11.38
E-MTAB-9388	yes	7.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

71 targeting ARMC3, 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-656-3P	100.00	72.15	2788
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-203A-3P	99.49	70.56	2806

Literature-anchored findings (GeneRIF, showing 4)

• KU-CT-1 is a new cancer testis antigen that is expressed in pancreatic, lung, and endometrial cancers (PMID:16397042)
• ARMC3_v2 was detected in human skeletal muscle, liver, spleen and thymus; in contrast, ARMC3_v1 in skeletal muscle, lung, prostate and testis (PMID:16915934)
• The Expansion of the Spectrum in Stuttering Disorders to a Novel ARMC Gene Family (ARMC3). (PMID:36553564)
• A homozygous ARMC3 splicing variant causes asthenozoospermia and flagellar disorganization in a consanguineous family. (PMID:39221575)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	armc3	ENSDARG00000074708
mus_musculus	Armc3	ENSMUSG00000037683
rattus_norvegicus	Armc3	ENSRNOG00000016716

Paralogs (4): ANKAR (ENSG00000151687), CTNNB1 (ENSG00000168036), ODAD2 (ENSG00000169126), JUP (ENSG00000173801)

Protein

Protein identifiers

Armadillo repeat-containing protein 3 — Q5W041 (reviewed: Q5W041)

Alternative names: Beta-catenin-like protein, Cancer/testis antigen 81, KU-CT-1

All UniProt accessions (3): B4DXS3, C9JC46, Q5W041

UniProt curated annotations — full annotation on UniProt →

Function. Essential for male fertility and sperm motility. During spermatogenesis, promotes the autophagic degradation of excessive ribosomes, providing energy resources for mitochondria and thus ensuring sperm flagellar motility.

Subunit / interactions. Homodimer. Interacts with PIK3C3, PIK3R4 and BECN1. Interacts (via ARM domains) with ATG14. Interacts with MYCBPAP.

Tissue specificity. Expressed in skeletal muscle, brain, lung, kidney, prostate and testis. Mainly expressed in skeletal muscle, liver, spleen and thymus. Expressed only in the testis among normal tissues but is expressed frequently in various cancer tissues and, particularly, in pancreatic, lung and endometrial cancers.

Post-translational modifications. Palmitoylation is important for its function in autophagy.

Isoforms (4)

UniProt ID	Names	Canonical?
Q5W041-2	1, ARMC3_Nu1, KU-CT-1L	yes
Q5W041-3	3, ARMC3_Nu2
Q5W041-4	4
Q5W041-5	5, KU-CT-1

RefSeq proteins (4): NP_001269674, NP_001269675, NP_001269676, NP_775104* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000225	Armadillo	Repeat
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR052441	Armadillo-Ser/Thr_Kinase	Family
IPR055164	EDR1/CTR1/ARMC3-like_pept-like	Domain
IPR055445	ARM_ARMC5	Domain

Pfam: PF00514, PF14381, PF24768

UniProt features (29 total): repeat 12, splice variant 5, sequence variant 4, compositionally biased region 3, lipid moiety-binding region 2, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5W041-F1	84.81	0.74

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): 507, 518

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 114 (showing top): GOBP_MALE_GAMETE_GENERATION, EFC_Q6, GOBP_MACROAUTOPHAGY, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, CYTAGCAAY_UNKNOWN, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, chr10p12, DODD_NASOPHARYNGEAL_CARCINOMA_DN, CHEN_METABOLIC_SYNDROM_NETWORK, MIKKELSEN_ES_ICP_WITH_H3K4ME3, NOUSHMEHR_GBM_SILENCED_BY_METHYLATION

GO Biological Process (6): spermatid development (GO:0007286), flagellated sperm motility (GO:0030317), ribophagy (GO:0034517), autophagy (GO:0006914), spermatogenesis (GO:0007283), cell differentiation (GO:0030154)

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

GO Cellular Component (1): extracellular exosome (GO:0070062)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
germ cell development	1
spermatid differentiation	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
macroautophagy	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
binding	1
extracellular vesicle	1

Protein interactions and networks

STRING

2301 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARMC3	TMEM95	Q3KNT9	665
ARMC3	CFAP119	A1A4V9	617
ARMC3	CFAP96	A7E2U8	545
ARMC3	TEKT1	Q969V4	545
ARMC3	CFAP184	Q2M329	540
ARMC3	CFAP90	A4QMS7	524
ARMC3	IQUB	Q8NA54	507
ARMC3	FOXJ1	Q92949	505
ARMC3	CLXN	Q9HAE3	497
ARMC3	PIERCE1	Q5BN46	493
ARMC3	AKAP3	O75969	490
ARMC3	DRC10	Q96DY2	483
ARMC3	VWA3A	A6NCI4	476
ARMC3	FAM81B	Q96LP2	469
ARMC3	CIMAP3	Q8TCI5	459

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ARMC3	HSD17B12	psi-mi:“MI:0915”(physical association)	0.400
ARMC3	CRACR2A	psi-mi:“MI:0915”(physical association)	0.400
ARMC3	NMT2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (6): ARMC3 (Proximity Label-MS), CRACR2A (Proximity Label-MS), ARMC3 (Affinity Capture-RNA), NMT2 (Affinity Capture-MS), ARMC3 (Cross-Linking-MS (XL-MS)), ARMC3 (Affinity Capture-MS)

ESM2 similar proteins: A2AU72, B0F9L4, E9Q912, F1QWA8, O35099, O46563, O75165, O75602, O93614, P0C6R2, P39968, P42345, P42346, P52306, Q04173, Q1RMS6, Q21029, Q5EFZ4, Q5PPZ9, Q5W041, Q5ZL91, Q66L58, Q68FK4, Q6BTZ4, Q6C5Y8, Q6CX49, Q6DD21, Q6FJV1, Q6NUP7, Q6PIY5, Q757R0, Q7YRF1, Q80TR8, Q80W92, Q80WQ2, Q84ZC0, Q8BVE3, Q8BW49, Q8C0Y0, Q8NFP9

Diamond homologs: A2AU72, Q05609, Q5W041, Q9C9U5, Q9FPR3, O22161, Q9M224

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	121
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3771 predictions. Top by Δscore:

Variant	Effect	Δscore
10:22946142:A:AG	acceptor_gain	1.0000
10:22946143:G:GG	acceptor_gain	1.0000
10:22955798:T:TA	acceptor_gain	1.0000
10:22959397:A:AG	acceptor_gain	1.0000
10:22959398:G:GG	acceptor_gain	1.0000
10:22965236:GT:G	donor_gain	1.0000
10:22981327:T:A	acceptor_gain	1.0000
10:22981328:G:A	acceptor_gain	1.0000
10:22981592:TAG:T	acceptor_loss	1.0000
10:22981593:A:C	acceptor_loss	1.0000
10:22981593:AG:A	acceptor_gain	1.0000
10:22981593:AGG:A	acceptor_gain	1.0000
10:22981594:GG:G	acceptor_gain	1.0000
10:22981594:GGG:G	acceptor_gain	1.0000
10:22981696:GCAAA:G	donor_gain	1.0000
10:22981701:G:GG	donor_gain	1.0000
10:22998138:A:AG	acceptor_gain	1.0000
10:22998139:T:G	acceptor_gain	1.0000
10:22998142:A:AG	acceptor_gain	1.0000
10:22998143:C:G	acceptor_gain	1.0000
10:22998146:A:AG	acceptor_gain	1.0000
10:22998146:AGC:A	acceptor_gain	1.0000
10:22998147:G:GA	acceptor_gain	1.0000
10:22998147:GC:G	acceptor_gain	1.0000
10:22998147:GCG:G	acceptor_gain	1.0000
10:22998147:GCGC:G	acceptor_gain	1.0000
10:22998147:GCGCT:G	acceptor_gain	1.0000
10:22998395:GAG:G	donor_gain	1.0000
10:22998398:G:GG	donor_gain	1.0000
10:22998398:G:T	donor_loss	1.0000

AlphaMissense

5747 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:23033007:G:C	R798P	0.998
10:23030790:T:C	L747P	0.996
10:23033023:G:C	K803N	0.996
10:23033023:G:T	K803N	0.996
10:23037276:G:C	A806P	0.994
10:23037304:T:C	L815P	0.994
10:22959425:A:C	S130R	0.993
10:22959427:T:A	S130R	0.993
10:22959427:T:G	S130R	0.993
10:23032991:G:A	G793R	0.992
10:23032991:G:C	G793R	0.992
10:23033006:C:G	R798G	0.992
10:23033016:T:C	L801P	0.992
10:23037274:T:C	L805P	0.992
10:23037277:C:A	A806D	0.992
10:23037310:G:C	R817P	0.992
10:23037330:T:A	W824R	0.992
10:23037330:T:C	W824R	0.992
10:22946196:T:C	L34P	0.991
10:23002000:G:C	A503P	0.991
10:23003368:T:C	L562S	0.991
10:23003397:T:C	F572L	0.991
10:23003399:C:A	F572L	0.991
10:23003399:C:G	F572L	0.991
10:23030792:G:C	A748P	0.991
10:22955828:T:C	L63P	0.990
10:23032868:G:C	A752P	0.990
10:23033010:C:A	A799D	0.990
10:23037335:T:A	N825K	0.990
10:23037335:T:G	N825K	0.990

dbSNP variants (sampled 300 via entrez): RS1000005073 (10:23009944 T>C), RS1000019192 (10:22994326 C>T), RS1000096909 (10:22970985 C>A), RS1000149536 (10:22971269 G>A,C), RS1000194476 (10:22934547 G>A), RS1000195988 (10:22941605 T>C), RS1000225963 (10:22958902 T>C), RS1000244366 (10:22997261 A>T), RS1000299567 (10:22944673 G>A), RS1000337045 (10:22984494 T>C), RS1000341075 (10:22938533 G>C), RS1000392186 (10:22977393 C>T), RS1000408319 (10:22997358 C>T), RS1000449785 (10:22964068 G>A), RS1000454559 (10:22965422 A>G)

Disease associations

OMIM: gene MIM:611226 | disease phenotypes: MIM:614668

GenCC curated gene-disease

Mondo (1): stuttering, familial persistent, 4 (MONDO:0013844)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002875_43	Diisocyanate-induced asthma	2.000000e-06
GCST004361_14	Estrone/androstenedione ratio in resected early stage-receptor positive breast cancer	5.000000e-06
GCST004867_14	Systemic lupus erythematosus	2.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate
EFO:0007970	estrone measurement
EFO:0007972	androstenedione measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
aflatoxin B2	decreases methylation	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	decreases expression	1
Fulvestrant	increases methylation	1
Air Pollutants	increases abundance, increases expression	1
Cadmium	decreases expression, increases abundance	1
Estradiol	increases expression	1
Malathion	decreases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Particulate Matter	decreases expression	1

Clinical trials (associated diseases)

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