ARGFX

Summary

ARGFX (arginine-fifty homeobox, HGNC:30146) is a protein-coding gene on chromosome 3q13.33, encoding Arginine-fifty homeobox (A6NJG6). Transcription factor that acts as activator.

Homeobox genes encode DNA-binding proteins, many of which are thought to be involved in early embryonic development. Homeobox genes encode a DNA-binding domain of 60 to 63 amino acids referred to as the homeodomain. This gene is a member of the ARGFX homeobox gene family.

Source: NCBI Gene 503582 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 42 total — 1 pathogenic
• MANE Select transcript: NM_001012659

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30146
Approved symbol	ARGFX
Name	arginine-fifty homeobox
Location	3q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000186103
Ensembl biotype	protein_coding
OMIM	611164
Entrez	503582

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000334384, ENST00000651603

RefSeq mRNA: 1 — MANE Select: NM_001012659 NM_001012659

CCDS: CCDS33834

Canonical transcript exons

ENST00000334384 — 5 exons

Exon	Start	End
ENSE00001340146	121584917	121585065
ENSE00001498042	121576784	121576900
ENSE00001498043	121570702	121570816
ENSE00003845215	121567949	121568013
ENSE00003850786	121586022	121590622

Expression profiles

Bgee: expression breadth tissue_specific, 2 present calls, max score 53.79.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0070 / max 8.2516, expressed in 2 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38194	0.0070	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	53.79	gold quality
sural nerve	UBERON:0015488	51.26	gold quality
skeletal muscle tissue	UBERON:0001134	51.17	gold quality
colonic epithelium	UBERON:0000397	50.20	gold quality
stromal cell of endometrium	CL:0002255	49.22	gold quality
muscle tissue	UBERON:0002385	48.81	gold quality
bone marrow	UBERON:0002371	47.68	gold quality
ventricular zone	UBERON:0003053	46.77	gold quality
cortical plate	UBERON:0005343	46.71	gold quality
mucosa of transverse colon	UBERON:0004991	46.48	gold quality
ganglionic eminence	UBERON:0004023	45.49	gold quality
blood	UBERON:0000178	41.31	gold quality
duodenum	UBERON:0002114	40.82	gold quality
liver	UBERON:0002107	40.65	gold quality
granulocyte	CL:0000094	39.42	gold quality
calcaneal tendon	UBERON:0003701	39.28	gold quality
gastrocnemius	UBERON:0001388	39.07	gold quality
lower esophagus mucosa	UBERON:0035834	38.82	gold quality
monocyte	CL:0000576	38.75	gold quality
apex of heart	UBERON:0002098	38.56	silver quality
primary visual cortex	UBERON:0002436	38.53	gold quality
leukocyte	CL:0000738	38.40	gold quality
cortex of kidney	UBERON:0001225	38.13	gold quality
smooth muscle tissue	UBERON:0001135	37.87	gold quality
superior frontal gyrus	UBERON:0002661	37.80	gold quality
adrenal tissue	UBERON:0018303	37.37	gold quality
endometrium	UBERON:0001295	37.32	gold quality
lymph node	UBERON:0000029	37.23	gold quality
prefrontal cortex	UBERON:0000451	35.91	gold quality
right coronary artery	UBERON:0001625	35.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.22

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA1463.1	ARGFX	Paired-related HD factors
MA1463.2	ARGFX	Paired-related HD factors

JASPAR matrix evidence (PMIDs): PMID:18585359

miRNA regulators (miRDB)

179 targeting ARGFX, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-9983-3P	99.94	71.48	3631

Cross-species orthologs

0 orthologs

Paralogs (50): ARX (ENSG00000004848), PAX6 (ENSG00000007372), PAX7 (ENSG00000009709), ALX4 (ENSG00000052850), GSC2 (ENSG00000063515), PITX1 (ENSG00000069011), PAX2 (ENSG00000075891), RHOXF1 (ENSG00000101883), CRX (ENSG00000105392), EVX1 (ENSG00000106038), PAX4 (ENSG00000106331), NOBOX (ENSG00000106410), PITX3 (ENSG00000107859), PHOX2B (ENSG00000109132), OTX1 (ENSG00000115507), PRRX1 (ENSG00000116132), VSX2 (ENSG00000119614), ESX1 (ENSG00000123576), PAX8 (ENSG00000125618), PAX1 (ENSG00000125813), RHOXF2 (ENSG00000131721), GSC (ENSG00000133937), RAX (ENSG00000134438), PAX3 (ENSG00000135903), ALX3 (ENSG00000156150), HESX1 (ENSG00000163666), PITX2 (ENSG00000164093), UNCX (ENSG00000164853), PHOX2A (ENSG00000165462), OTX2 (ENSG00000165588), DRGX (ENSG00000165606), PRRX2 (ENSG00000167157), SHOX2 (ENSG00000168779), OTP (ENSG00000171540), RAX2 (ENSG00000173976), EVX2 (ENSG00000174279), PROP1 (ENSG00000175325), ISX (ENSG00000175329), ALX1 (ENSG00000180318), MIXL1 (ENSG00000185155)

Protein

Protein identifiers

Arginine-fifty homeobox — A6NJG6 (reviewed: A6NJG6)

All UniProt accessions (1): A6NJG6

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that acts as activator.

Subcellular location. Nucleus.

Tissue specificity. Expressed at low level in testis and undifferentiated embryonic stem cells.

Similarity. Belongs to the paired homeobox family.

RefSeq proteins (1): NP_001012677* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site

Pfam: PF00046

UniProt features (7 total): compositionally biased region 2, chain 1, DNA-binding region 1, region of interest 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NJG6-F1	57.78	0.18

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 35 (showing top): GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, MIR616_5P, MIR371B_5P, MIR373_5P, MIR4659A_3P_MIR4659B_3P, MIR548AZ_5P, MIR548T_5P, MIR576_5P, MIR7106_5P, MIR3202, MIR6780A_5P, MIR4743_3P, MIR1273H_5P, MIR138_2_3P

GO Biological Process (2): regulation of transcription by RNA polymerase II (GO:0006357), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (4): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

542 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARGFX	TPRX1	Q8N7U7	797
ARGFX	DUXB	A0A1W2PPF3	730
ARGFX	DUXA	A6NLW8	693
ARGFX	NANOGNB	Q7Z5D8	623
ARGFX	KLF17	Q5JT82	591
ARGFX	VENTX	O95231	590
ARGFX	ANHX	E9PGG2	535
ARGFX	KHDC1L	Q5JSQ8	532
ARGFX	DPPA3	Q6W0C5	510
ARGFX	RHOXF2B	P0C7M4	497
ARGFX	PLAC9	Q5JTB6	460
ARGFX	KHDC1	Q4VXA5	440
ARGFX	DPPA5	A6NC42	434
ARGFX	GDF3	Q9NR23	417
ARGFX	DPPA2	Q7Z7J5	404

IntAct

0 interactions, top by confidence:

BioGRID (8): GNB2 (Proximity Label-MS), GNB2L1 (Proximity Label-MS), EP300 (Proximity Label-MS), NUP43 (Proximity Label-MS), CREBBP (Proximity Label-MS), WDR92 (Proximity Label-MS), MLST8 (Proximity Label-MS), DTL (Proximity Label-MS)

ESM2 similar proteins: A0A1W2PPF3, A0A1W2PPM1, A1A546, A1YGI6, A2T763, A5YC49, A6NFQ7, A6NJG6, D2HQI1, G3X9P6, O42173, O57374, P09632, P0C7M4, P10242, P14837, P17278, P31272, P31538, Q1KKS8, Q28ET4, Q28G02, Q3LTE0, Q3UT54, Q4JM65, Q4KL20, Q5TM83, Q5TM84, Q5W1J6, Q68EH7, Q6NSW7, Q80Z64, Q8IUE1, Q8JH55, Q8JIT7, Q8JJ26, Q8MIB7, Q8MIB8, Q8MIE9, Q91685

Diamond homologs: A0A096LPI5, A6NIU2, A6NJG6, F2Z398, P0DTE4, P51957, Q09FC8, Q5H9K5, Q5T7P6, Q68CZ1, Q6B4Z3, Q6UX73, Q86U02, Q8IV13, Q8N7M2, Q8N9N2, Q8NDZ0, Q8NEM8, Q8TDM0, Q92918, Q96J02, Q96MD7, Q9BUA6, Q9NXG0, A1A546, A1YEY5, A1YFI3, A1YG57, A1YGA2, A2T733, A2T777, A2T7P4, A6NFQ7, A6NJT0, A6NNA5, A6YP92, F1NEA7, G5EC89, O08934, O14813

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	35
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4819208	Single allele	Pathogenic

SpliceAI

693 predictions. Top by Δscore:

Variant	Effect	Δscore
3:121570812:TCCCA:T	donor_gain	1.0000
3:121570813:CCCA:C	donor_gain	1.0000
3:121570814:CCA:C	donor_gain	1.0000
3:121570815:CA:C	donor_gain	1.0000
3:121570816:AG:A	donor_loss	1.0000
3:121570817:G:GG	donor_gain	1.0000
3:121585060:G:GG	donor_gain	1.0000
3:121570820:A:AG	donor_gain	0.9900
3:121570821:G:GG	donor_gain	0.9900
3:121584907:T:TA	acceptor_gain	0.9900
3:121584912:T:TA	acceptor_gain	0.9900
3:121570789:A:AG	donor_gain	0.9800
3:121584915:A:AG	acceptor_gain	0.9800
3:121584916:G:GG	acceptor_gain	0.9800
3:121586019:CA:C	acceptor_loss	0.9700
3:121586020:A:AC	acceptor_loss	0.9700
3:121584918:A:AG	acceptor_gain	0.9600
3:121584916:GCA:G	acceptor_gain	0.9400
3:121570819:GA:G	donor_gain	0.9200
3:121585050:G:GT	donor_gain	0.9200
3:121586014:A:AG	acceptor_gain	0.9200
3:121586021:GGTTT:G	acceptor_gain	0.9200
3:121570818:T:A	donor_loss	0.9000
3:121585061:TAAAG:T	donor_loss	0.9000
3:121585062:AAAGG:A	donor_loss	0.9000
3:121585064:AGGTC:A	donor_loss	0.9000
3:121585065:GGTC:G	donor_loss	0.9000
3:121585067:T:G	donor_loss	0.9000
3:121570819:GAGTA:G	donor_gain	0.8900
3:121570820:AGTAT:A	donor_gain	0.8900

AlphaMissense

2066 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:121586028:T:C	F126L	0.994
3:121586030:C:A	F126L	0.994
3:121586030:C:G	F126L	0.994
3:121586029:T:C	F126S	0.988
3:121584949:T:C	F85L	0.987
3:121584951:C:A	F85L	0.987
3:121584951:C:G	F85L	0.987
3:121584985:T:C	F97L	0.986
3:121584987:T:A	F97L	0.986
3:121584987:T:G	F97L	0.986
3:121585000:T:C	F102L	0.986
3:121585002:C:A	F102L	0.986
3:121585002:C:G	F102L	0.986
3:121586038:G:C	R129P	0.985
3:121586025:T:A	W125R	0.974
3:121586025:T:C	W125R	0.974
3:121586029:T:G	F126C	0.971
3:121584950:T:C	F85S	0.969
3:121585046:T:C	L117P	0.969
3:121584986:T:C	F97S	0.966
3:121586041:G:C	R130P	0.964
3:121584950:T:G	F85C	0.960
3:121586027:G:C	W125C	0.959
3:121586027:G:T	W125C	0.959
3:121584974:T:C	L93P	0.958
3:121586028:T:G	F126V	0.957
3:121586048:A:C	K132N	0.957
3:121586048:A:T	K132N	0.957
3:121586043:T:C	F131L	0.954
3:121586045:C:A	F131L	0.954

dbSNP variants (sampled 300 via entrez): RS1000122614 (3:121574094 T>C), RS1000223165 (3:121571716 A>C), RS1000389820 (3:121577455 T>C), RS1000413149 (3:121584156 C>T), RS1000502538 (3:121571645 A>G), RS1000920095 (3:121579154 G>A,T), RS1000946194 (3:121566006 T>A,C), RS1001091660 (3:121566872 T>C), RS1001101024 (3:121584001 C>A,G), RS1001103748 (3:121572901 G>A,C), RS1001212735 (3:121570186 A>C), RS1001242385 (3:121569888 T>C), RS1001307144 (3:121572621 A>G), RS1001904956 (3:121569667 G>A), RS1001908842 (3:121582492 A>G)

Disease associations

OMIM: gene MIM:611164 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): partial duplication of the long arm of chromosome 3 (MONDO:0016954)

Orphanet (1): Partial duplication of the long arm of chromosome 3 syndrome (Orphanet:262851)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003014_5	Postprandial triglyceride response to high fat diet meal	9.000000e-07
GCST003014_6	Postprandial triglyceride response to high fat diet meal	4.000000e-07
GCST011741_49	LDL cholesterol levels in HIV infection	9.000000e-06
GCST90002395_380	Mean platelet volume	7.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007681	triglyceride change measurement
EFO:0007684	response to high fat food intake
EFO:0004611	low density lipoprotein cholesterol measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536813	Chromosome 3, trisomy 3q (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression	1
Niclosamide	decreases expression	1

Clinical trials (associated diseases)

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