ARMH4

Summary

ARMH4 (armadillo like helical domain containing 4, HGNC:19846) is a protein-coding gene on chromosome 14q23.1, encoding Armadillo-like helical domain-containing protein 4 (Q86TY3). May modulate immune response and may play a role in inflammation.

Predicted to enable TORC2 complex binding activity. Involved in regulation of inflammatory response. Located in membrane.

Source: NCBI Gene 145407 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 26 total
• MANE Select transcript: NM_001001872

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19846
Approved symbol	ARMH4
Name	armadillo like helical domain containing 4
Location	14q23.1
Locus type	gene with protein product
Status	Approved
Aliases	UT2
Ensembl gene	ENSG00000139971
Ensembl biotype	protein_coding
Entrez	145407

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000267485, ENST00000334342, ENST00000554218, ENST00000555101, ENST00000556788, ENST00000557175, ENST00000880249, ENST00000880250, ENST00000880251, ENST00000880252, ENST00000912025, ENST00000962094

RefSeq mRNA: 2 — MANE Select: NM_001001872 NM_001001872, NM_001320173

CCDS: CCDS32089

Canonical transcript exons

ENST00000267485 — 8 exons

Exon	Start	End
ENSE00001217094	58096724	58096981
ENSE00001297731	58005048	58005182
ENSE00001312291	58012119	58012150
ENSE00001318733	58000761	58004804
ENSE00001421310	58152075	58152213
ENSE00003499455	58133090	58133341
ENSE00003570155	58137990	58139414
ENSE00003582990	58131512	58131721

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 92.35.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.8856 / max 82.4359, expressed in 1025 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143432	48.8892	1818
143424	4.2058	1006
143423	0.6798	335

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	92.35	gold quality
calcaneal tendon	UBERON:0003701	89.37	gold quality
adrenal tissue	UBERON:0018303	88.95	gold quality
ventricular zone	UBERON:0003053	87.89	gold quality
ganglionic eminence	UBERON:0004023	87.15	gold quality
stromal cell of endometrium	CL:0002255	86.37	gold quality
smooth muscle tissue	UBERON:0001135	83.45	gold quality
corpus callosum	UBERON:0002336	82.92	gold quality
right uterine tube	UBERON:0001302	82.76	gold quality
islet of Langerhans	UBERON:0000006	81.92	gold quality
tendon	UBERON:0000043	81.39	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.79	gold quality
popliteal artery	UBERON:0002250	80.77	gold quality
tibial artery	UBERON:0007610	80.70	gold quality
substantia nigra pars compacta	UBERON:0001965	80.52	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.47	gold quality
aorta	UBERON:0000947	79.92	gold quality
adult mammalian kidney	UBERON:0000082	79.43	gold quality
gall bladder	UBERON:0002110	79.43	gold quality
ascending aorta	UBERON:0001496	79.02	gold quality
thoracic aorta	UBERON:0001515	79.01	gold quality
prefrontal cortex	UBERON:0000451	78.51	gold quality
descending thoracic aorta	UBERON:0002345	78.46	gold quality
medial globus pallidus	UBERON:0002477	78.24	gold quality
kidney	UBERON:0002113	78.13	gold quality
cortex of kidney	UBERON:0001225	78.03	gold quality
left ovary	UBERON:0002119	77.32	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.84	gold quality
right adrenal gland cortex	UBERON:0035827	76.34	gold quality
globus pallidus	UBERON:0001875	76.33	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	31.43
E-HCAD-10	yes	20.04
E-ANND-3	yes	4.70

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

68 targeting ARMH4, 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-4682	100.00	68.89	1258
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-497-5P	99.92	71.83	2674
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-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-4762-5P	99.57	68.54	1424

Literature-anchored findings (GeneRIF, showing 1)

• Identification of ARMH4 and WIPF3 as human podocyte proteins with potential roles in immunomodulation and cytoskeletal dynamics. (PMID:36649229)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Armh4	ENSMUSG00000036242
rattus_norvegicus	Armh4	ENSRNOG00000031849

Protein

Protein identifiers

Armadillo-like helical domain-containing protein 4 — Q86TY3 (reviewed: Q86TY3)

Alternative names: Upstream of mTORC2 protein

All UniProt accessions (2): Q86TY3, A0A087WT98

UniProt curated annotations — full annotation on UniProt →

Function. May modulate immune response and may play a role in inflammation. Down-modulates STAT3 signaling throught direct interaction with IL6ST, resulting in the inhibition of phosphorylation of STAT3 at ‘Tyr-705’. May negatively regulates AKT signaling by modulating the activity of mTORC2 complex through RICTOR interaction.

Subunit / interactions. Interacts with IL6ST; this interaction prevents IL6ST protein homodimerization and bridges ARMH4 with IL6R and STAT3 and therefore inhibits phosphorylation of STAT3 at ‘Tyr-705’. Interacts (via cytoplasmic tail) with RICTOR; this interaction bridges ARMH4 to the mTORC2 complex and inhibits the mTORC2 kinase activity.

Subcellular location. Membrane.

Tissue specificity. Expressed in podocytes.

Isoforms (3)

UniProt ID	Names	Canonical?
Q86TY3-1	1	yes
Q86TY3-2	2
Q86TY3-3	3

RefSeq proteins (1): NP_001001872* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031524	ARMH4	Family

Pfam: PF15767

UniProt features (25 total): compositionally biased region 4, sequence variant 4, region of interest 4, splice variant 3, modified residue 2, glycosylation site 2, topological domain 2, signal peptide 1, chain 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86TY3-F1	43.94	0.00

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): 769, 770

Glycosylation sites (2): 57, 189

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 138 (showing top): GOBP_INFLAMMATORY_RESPONSE, ATGCAGT_MIR217, SREBP1_02, GOBP_RESPONSE_TO_METAL_ION, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, chr14q23, HOOI_ST7_TARGETS_DN, GOBP_TOR_SIGNALING, GOBP_RESPONSE_TO_LITHIUM_ION, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_DEFENSE_RESPONSE, PITX2_Q2, YATGNWAAT_OCT_C, THUM_SYSTOLIC_HEART_FAILURE_DN

GO Biological Process (2): regulation of inflammatory response (GO:0050727), regulation of TORC2 signaling (GO:1903939)

GO Molecular Function (2): TORC2 complex binding (GO:1904841), protein binding (GO:0005515)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
regulation of TOR signaling	1
TORC2 signaling	1
protein-containing complex binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

282 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARMH4	ARMH2	H3BNL8	559
ARMH4	TSACC	Q96A04	547
ARMH4	ARMH1	Q6PIY5	480
ARMH4	PRRT4	C9JH25	434
ARMH4	CCDC198	Q9NVL8	401
ARMH4	TCEAL4	Q96EI5	394
ARMH4	PPDPF	Q9H3Y8	393
ARMH4	KRTAP13-3	Q3SY46	390
ARMH4	XKR4	Q5GH76	378
ARMH4	SLC35F4	A4IF30	370
ARMH4	ANKDD1B	A6NHY2	367
ARMH4	ZNF665	Q9H7R5	366
ARMH4	RPL7A	P11518	352
ARMH4	ZPBP	Q9BS86	320
ARMH4	PIP	P12273	318

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ARMH4	ELAPOR2	psi-mi:“MI:0914”(association)	0.500
ARMH4	ELAPOR2	psi-mi:“MI:0915”(physical association)	0.500
ARMH4	FGFR1	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): BMPR2 (Affinity Capture-MS), BMPR1A (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), CD320 (Affinity Capture-MS), FGFR1 (Affinity Capture-MS), C14orf37 (Affinity Capture-RNA), C14orf37 (Affinity Capture-RNA), C14orf37 (Proximity Label-MS), CD320 (Affinity Capture-MS), BMPR1A (Affinity Capture-MS), NDFIP1 (Affinity Capture-MS), KIAA1324L (Affinity Capture-MS), FGFR1 (Affinity Capture-MS), C14orf37 (Synthetic Lethality), C14orf37 (Affinity Capture-RNA)

ESM2 similar proteins: A0A2R8Y7Y5, A1KXC4, A6QLF8, C9JL84, E9Q7X6, I3L273, J3KML8, O00592, O14594, O35188, O55145, O57604, O60667, O95196, P06484, P07141, P09603, P13838, P15702, P16150, P55067, P59647, P78423, Q1ECS6, Q28645, Q2TA21, Q2TB54, Q3TNW5, Q3TYV2, Q4V7A5, Q52S86, Q58Y74, Q5IS41, Q5M871, Q5SWP3, Q6MG22, Q6NXZ1, Q6UXF1, Q71M36, Q7Z434

Diamond homologs: Q2TA21, Q86TY3, Q8BT18

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

5044 predictions. Top by Δscore:

Variant	Effect	Δscore
14:58004628:ACGG:A	donor_gain	1.0000
14:58004629:CGGC:C	donor_gain	1.0000
14:58005042:CCATA:C	donor_loss	1.0000
14:58005043:CATA:C	donor_loss	1.0000
14:58005044:ATACC:A	donor_loss	1.0000
14:58005045:TACCT:T	donor_loss	1.0000
14:58005046:A:C	donor_loss	1.0000
14:58005047:C:CT	donor_loss	1.0000
14:58005047:CCTTT:C	donor_gain	1.0000
14:58005178:CCAGC:C	acceptor_gain	1.0000
14:58005179:CAGC:C	acceptor_gain	1.0000
14:58005179:CAGCC:C	acceptor_gain	1.0000
14:58005181:GC:G	acceptor_gain	1.0000
14:58005182:CC:C	acceptor_gain	1.0000
14:58005183:C:CC	acceptor_gain	1.0000
14:58005183:CT:C	acceptor_loss	1.0000
14:58096718:TCTTA:T	donor_loss	1.0000
14:58096719:CTTA:C	donor_loss	1.0000
14:58096720:TTACC:T	donor_loss	1.0000
14:58096721:TA:T	donor_loss	1.0000
14:58096722:A:AC	donor_gain	1.0000
14:58096722:AC:A	donor_gain	1.0000
14:58096723:C:A	donor_loss	1.0000
14:58096723:C:CC	donor_gain	1.0000
14:58096723:CC:C	donor_gain	1.0000
14:58096726:AGG:A	donor_gain	1.0000
14:58096906:T:TA	donor_gain	1.0000
14:58096977:TCCCT:T	acceptor_gain	1.0000
14:58096978:CCCT:C	acceptor_gain	1.0000
14:58096978:CCCTC:C	acceptor_gain	1.0000

AlphaMissense

5077 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:58004739:A:C	F774L	0.999
14:58004739:A:T	F774L	0.999
14:58004740:A:C	F774C	0.999
14:58004741:A:G	F774L	0.999
14:58004764:A:G	L766S	0.999
14:58004767:A:G	L765P	0.999
14:58005102:G:C	S734R	0.999
14:58005102:G:T	S734R	0.999
14:58005104:T:G	S734R	0.999
14:58004752:G:A	S770F	0.998
14:58004761:G:T	A767D	0.998
14:58004770:A:G	M764T	0.998
14:58004793:G:C	F756L	0.998
14:58004793:G:T	F756L	0.998
14:58004795:A:G	F756L	0.998
14:58005136:G:T	A723D	0.998
14:58012129:A:G	L704S	0.998
14:58004740:A:G	F774S	0.997
14:58004754:G:C	S769R	0.997
14:58004754:G:T	S769R	0.997
14:58004756:T:G	S769R	0.997
14:58004762:C:G	A767P	0.997
14:58004767:A:T	L765H	0.997
14:58004769:C:A	M764I	0.997
14:58004769:C:G	M764I	0.997
14:58004769:C:T	M764I	0.997
14:58004776:C:G	R762P	0.997
14:58004779:T:A	D761V	0.997
14:58004779:T:G	D761A	0.997
14:58005115:C:T	G730E	0.997

dbSNP variants (sampled 300 via entrez): RS1000004846 (14:58149035 T>C), RS1000036507 (14:58080889 G>T), RS1000043790 (14:58124448 G>A), RS1000050068 (14:58107256 A>G), RS1000060433 (14:57997585 C>T), RS1000142137 (14:58137215 TG>T,TGG), RS1000155926 (14:58065548 T>A,C), RS1000171525 (14:58109715 G>A), RS1000190546 (14:58113593 T>C), RS1000204331 (14:58010225 C>G,T), RS1000243905 (14:58014459 T>C), RS1000311823 (14:58059824 C>A,T), RS1000318029 (14:58014681 T>A,C), RS1000331458 (14:58134998 T>A), RS1000339640 (14:58000347 T>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST002479_17	Lupus nephritis in systemic lupus erythematosus	2.000000e-06
GCST002593_18	Dementia and core Alzheimer’s disease neuropathologic changes	2.000000e-06
GCST003542_118	Night sleep phenotypes	1.000000e-06
GCST003875_12	Gut microbiota (bacterial taxa)	9.000000e-10
GCST004602_203	Mean corpuscular volume	5.000000e-10
GCST004621_66	Red cell distribution width	5.000000e-13
GCST004630_199	Mean corpuscular hemoglobin	3.000000e-11
GCST006804_28	Red cell distribution width	1.000000e-15
GCST008757_22	Alcohol consumption	2.000000e-11
GCST010244_351	Triglyceride levels	4.000000e-08
GCST010703_93	Brain morphology (MOSTest)	6.000000e-54
GCST90002386_169	High light scatter reticulocyte percentage of red cells	2.000000e-10
GCST90002391_255	Mean corpuscular hemoglobin concentration	1.000000e-10
GCST90002403_507	Red blood cell count	4.000000e-13
GCST90002404_390	Red cell distribution width	3.000000e-53
GCST90002406_420	Reticulocyte fraction of red cells	1.000000e-09
GCST90020024_771	A body shape index	3.000000e-08
GCST90020025_300	Waist-to-hip ratio adjusted for BMI	5.000000e-10
GCST90020025_426	Waist-to-hip ratio adjusted for BMI	4.000000e-14
GCST90020027_678	Waist-hip index	1.000000e-09
GCST90020027_679	Waist-hip index	9.000000e-14

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0006801	Alzheimer’s disease neuropathologic change
EFO:0007874	gut microbiome measurement
EFO:0007883	taxonomic microbiome measurement
EFO:0009188	Red cell distribution width
EFO:0004527	mean corpuscular hemoglobin
EFO:0004530	triglyceride measurement
EFO:0004346	neuroimaging measurement
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0004305	erythrocyte count
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
(+)-JQ1 compound	increases expression	2
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	decreases expression, decreases methylation, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
OTX015	increases expression	1
bisphenol F	affects cotreatment, decreases methylation	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases methylation	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
pentabromodiphenyl ether	decreases expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation, increases methylation	1
Vorinostat	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Doxorubicin	decreases expression	1
Estradiol	increases expression, affects cotreatment	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	increases expression	1

Clinical trials (associated diseases)

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