ARID3C

Summary

ARID3C (AT-rich interaction domain 3C, HGNC:21209) is a protein-coding gene on chromosome 9p13.3, encoding AT-rich interactive domain-containing protein 3C (A6NKF2). Transcription factor involved in monocyte-to-macrophage differentiation.

This gene is a member of the ARID (AT-rich interaction domain) family of proteins. The ARID domain is a helix-turn-helix motif-based DNA-binding domain. ARID family members have roles in embryonic patterning, cell lineage gene regulation, cell cycle control, transcriptional regulation and possibly in chromatin structure modification.

Source: NCBI Gene 138715 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 73 total
• MANE Select transcript: NM_001017363

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21209
Approved symbol	ARID3C
Name	AT-rich interaction domain 3C
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000205143
Ensembl biotype	protein_coding
OMIM	620868
Entrez	138715

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000378909, ENST00000692051, ENST00000876981

RefSeq mRNA: 2 — MANE Select: NM_001017363 NM_001017363, NM_001371945

CCDS: CCDS35006

Canonical transcript exons

ENST00000378909 — 8 exons

Exon	Start	End
ENSE00001479230	34621049	34621558
ENSE00001479231	34622020	34622109
ENSE00001479232	34622347	34622529
ENSE00001479233	34623425	34623714
ENSE00001479234	34623864	34624047
ENSE00001479236	34627697	34628086
ENSE00001770344	34625742	34625814
ENSE00003966710	34628917	34629066

Expression profiles

Bgee: expression breadth broad, 62 present calls, max score 85.77.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.77	gold quality
right lobe of liver	UBERON:0001114	79.76	gold quality
liver	UBERON:0002107	75.09	gold quality
ventricular zone	UBERON:0003053	72.06	gold quality
ganglionic eminence	UBERON:0004023	70.32	gold quality
right hemisphere of cerebellum	UBERON:0014890	59.10	gold quality
cerebellar hemisphere	UBERON:0002245	58.79	gold quality
cerebellum	UBERON:0002037	58.64	gold quality
cerebellar cortex	UBERON:0002129	58.60	gold quality
stromal cell of endometrium	CL:0002255	57.12	gold quality
tibial nerve	UBERON:0001323	56.96	gold quality
Brodmann (1909) area 9	UBERON:0013540	55.20	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	54.28	gold quality
primary visual cortex	UBERON:0002436	54.10	gold quality
right frontal lobe	UBERON:0002810	53.92	gold quality
superior frontal gyrus	UBERON:0002661	53.64	gold quality
frontal cortex	UBERON:0001870	52.78	gold quality
prefrontal cortex	UBERON:0000451	51.89	gold quality
cerebral cortex	UBERON:0000956	51.32	gold quality
anterior cingulate cortex	UBERON:0009835	51.25	gold quality
hypothalamus	UBERON:0001898	51.17	gold quality
sural nerve	UBERON:0015488	50.87	gold quality
nucleus accumbens	UBERON:0001882	49.72	gold quality
lower esophagus mucosa	UBERON:0035834	49.61	gold quality
brain	UBERON:0000955	49.31	gold quality
skin of abdomen	UBERON:0001416	48.94	gold quality
zone of skin	UBERON:0000014	48.42	gold quality
skin of leg	UBERON:0001511	48.16	gold quality
caudate nucleus	UBERON:0001873	44.74	gold quality
amygdala	UBERON:0001876	44.71	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.14

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

Literature-anchored findings (GeneRIF, showing 1)

• this report introduces Brightlike as an additional functional member of the family of ARID proteins, which should be considered in regulatory circuits, previously ascribed to be mediated by Bright.[ARID3C] (PMID:21955986)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	arid3c	ENSDARG00000067729
mus_musculus	Arid3c	ENSMUSG00000066224
rattus_norvegicus	Arid3c	ENSRNOG00000013416
drosophila_melanogaster	retn	FBGN0004795
caenorhabditis_elegans	cfi-1	WBGENE00000476

Paralogs (2): ARID3A (ENSG00000116017), ARID3B (ENSG00000179361)

Protein

Protein identifiers

AT-rich interactive domain-containing protein 3C — A6NKF2 (reviewed: A6NKF2)

All UniProt accessions (2): A6NKF2, A0A8I5QL24

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor involved in monocyte-to-macrophage differentiation. Forms a complex with NPM1 to translocate to the nucleus, acting as a transcription factor that promotes the expression of the genes involved in macrophage differentiation, such as STAT3, STAT1 and JUNB.

Subunit / interactions. Interacts (via REKLES DOMAIN) with NPM1; the interaction mediates ARID3C nuclear shuttling.

Subcellular location. Nucleus.

Domain organisation. REKLES domain is required for interaction with NPM1 and nuclear shuttling.

RefSeq proteins (2): NP_001017363, NP_001358874 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001606	ARID_dom	Domain
IPR023334	REKLES_domain	Domain
IPR036431	ARID_dom_sf	Homologous_superfamily
IPR045147	ARI3A/B/C	Family

Pfam: PF01388

UniProt features (13 total): compositionally biased region 4, region of interest 3, domain 2, sequence variant 2, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NKF2-F1	67.29	0.34

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (1):

Position	Phenotype
381–385	strongly decreases interaction with npm1. located in cytoplasm and nucleus. reduced binding to target genes promoters.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 24 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, chr9p13, GOBP_MACROPHAGE_DIFFERENTIATION, GOMF_CHROMATIN_BINDING, MEISSNER_NPC_HCP_WITH_H3K4ME2_AND_H3K27ME3, MEISSNER_BRAIN_HCP_WITH_H3K4ME2_AND_H3K27ME3, MARTENS_TRETINOIN_RESPONSE_UP, GOBP_POSITIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_MONONUCLEAR_CELL_DIFFERENTIATION, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ZNF184_TARGET_GENES, ZNF407_TARGET_GENES, GOCC_MEMBRANE_MICRODOMAIN

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), macrophage differentiation (GO:0030225), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (4): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), chromatin binding (GO:0003682), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), membrane raft (GO:0045121)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
binding	2
regulation of DNA-templated transcription	1
myeloid leukocyte differentiation	1
mononuclear cell differentiation	1
positive regulation of DNA-templated transcription	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
nucleic acid binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
membrane microdomain	1

Protein interactions and networks

STRING

674 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARID3C	CROCC2	H7BZ55	453
ARID3C	BRK1	Q8WUW1	449
ARID3C	FAM219A	Q8IW50	448
ARID3C	SPATA31F1	Q6ZU69	433
ARID3C	PTPRR	Q15256	393
ARID3C	JARID2	Q92833	393
ARID3C	AGAP4	Q96P64	393
ARID3C	RPP25L	Q8N5L8	370
ARID3C	A0A087WTP8	A0A087WTP8	337
ARID3C	CHCHD1	Q96BP2	325
ARID3C	CPNE2	Q96FN4	320
ARID3C	MYORG	Q6NSJ0	315
ARID3C	SPMIP6	Q8NCR6	313
ARID3C	LINGO3	P0C6S8	311
ARID3C	TMEM147	Q9BVK8	310
ARID3C	ARID5A	Q03989	310

IntAct

15 interactions, top by confidence:

A	B	Type	Score
ARID3C	C14orf119	psi-mi:“MI:0915”(physical association)	0.560
ARID3C	CBX4	psi-mi:“MI:0915”(physical association)	0.560
ARID3C	RNF4	psi-mi:“MI:0915”(physical association)	0.560
ARID3A	ARID3C	psi-mi:“MI:0914”(association)	0.530
OR2T1	ARID3C	psi-mi:“MI:0915”(physical association)	0.400
SPRR2E	ARID3C	psi-mi:“MI:0915”(physical association)	0.400
ARID3C	ZNF609	psi-mi:“MI:0914”(association)	0.350
C14orf119	ARID3C	psi-mi:“MI:0915”(physical association)	0.000
ARID3C	CBX4	psi-mi:“MI:0915”(physical association)	0.000
ARID3C	RNF4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): ARID3C (Affinity Capture-MS), ARID3C (Two-hybrid), ARID3C (Two-hybrid), ARID3C (Two-hybrid), ARID3C (Affinity Capture-MS), ARID3C (Affinity Capture-MS), ARID3B (Affinity Capture-MS), C17orf70 (Affinity Capture-MS), ZNF609 (Affinity Capture-MS), ARID3C (Affinity Capture-MS)

ESM2 similar proteins: A2A5E6, A5PK23, A6NKF2, A6PWV5, B0K011, E9Q6W4, O02786, O95402, P09086, P13297, P55198, Q00196, Q08DS3, Q0VDQ9, Q29013, Q2NKI2, Q2VL80, Q2VL82, Q2VL83, Q2VL85, Q2VL86, Q569K4, Q5XI28, Q62255, Q66K41, Q6AXX3, Q6PBT9, Q86V15, Q8BXJ8, Q8IVH2, Q8K4J6, Q8TAX0, Q8VD12, Q8VDL9, Q8WUU4, Q92766, Q969V6, Q96PM9, Q9BXA9, Q9BZE0

Diamond homologs: A2BEA6, A2BH40, A2CG63, A6NKF2, A6PWV5, E1BLP6, E2R9X2, E7F888, E9Q4N7, F8VPQ2, O02326, O14497, O74365, P29374, P29375, P41229, P41230, Q03214, Q03989, Q14865, Q24573, Q30DN6, Q38JA7, Q3SWY1, Q3U108, Q3UXZ9, Q4H3P5, Q4LE39, Q5F3R2, Q5XGD9, Q5XUN4, Q5ZJ69, Q62431, Q6GQD7, Q6IQX0, Q8BM75, Q8IN94, Q8IVW6, Q8MQH7, Q8NFD5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

859 predictions. Top by Δscore:

Variant	Effect	Δscore
9:34623713:ACCTA:A	acceptor_loss	1.0000
9:34623714:CCTAG:C	acceptor_loss	1.0000
9:34623716:T:G	acceptor_loss	1.0000
9:34623837:C:A	donor_gain	1.0000
9:34623852:C:A	donor_gain	1.0000
9:34623862:A:AC	donor_gain	1.0000
9:34623863:C:CA	donor_gain	1.0000
9:34623927:T:TA	donor_gain	1.0000
9:34623928:C:A	donor_gain	1.0000
9:34624043:CGTCC:C	acceptor_gain	1.0000
9:34624045:TCCC:T	acceptor_loss	1.0000
9:34624048:C:CC	acceptor_gain	1.0000
9:34627691:TCCTA:T	donor_loss	1.0000
9:34627692:CCTAC:C	donor_loss	1.0000
9:34627693:CTA:C	donor_loss	1.0000
9:34627694:TAC:T	donor_loss	1.0000
9:34627696:CCTG:C	donor_gain	1.0000
9:34623449:G:C	donor_gain	0.9900
9:34623710:TGTAC:T	acceptor_gain	0.9900
9:34623715:C:CC	acceptor_gain	0.9900
9:34623859:CTCA:C	donor_loss	0.9900
9:34623861:CACT:C	donor_loss	0.9900
9:34623863:CTG:C	donor_gain	0.9900
9:34623873:A:AC	donor_gain	0.9900
9:34623874:G:C	donor_gain	0.9900
9:34623954:T:TA	donor_gain	0.9900
9:34623954:TCC:T	donor_gain	0.9900
9:34624045:TCC:T	acceptor_gain	0.9900
9:34624046:CC:C	acceptor_gain	0.9900
9:34624046:CCC:C	acceptor_gain	0.9900

AlphaMissense

2635 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:34623713:A:G	Y193H	1.000
9:34623873:A:G	L189P	1.000
9:34623878:G:C	F187L	1.000
9:34623878:G:T	F187L	1.000
9:34623879:A:C	F187C	1.000
9:34623880:A:G	F187L	1.000
9:34623932:C:A	W169C	1.000
9:34623932:C:G	W169C	1.000
9:34623934:A:G	W169R	1.000
9:34623934:A:T	W169R	1.000
9:34623939:T:A	K167I	1.000
9:34625776:A:C	F119L	1.000
9:34625776:A:T	F119L	1.000
9:34625778:A:G	F119L	1.000
9:34623643:G:T	A216D	0.999
9:34623652:A:G	L213P	0.999
9:34623666:G:C	S208R	0.999
9:34623666:G:T	S208R	0.999
9:34623668:T:G	S208R	0.999
9:34623692:A:C	Y200D	0.999
9:34623698:A:C	Y198D	0.999
9:34623700:A:G	L197P	0.999
9:34623700:A:T	L197Q	0.999
9:34623707:T:C	K195E	0.999
9:34623712:T:C	Y193C	0.999
9:34623871:G:T	R190S	0.999
9:34623873:A:T	L189Q	0.999
9:34623879:A:G	F187S	0.999
9:34623880:A:T	F187I	0.999
9:34623882:G:T	A186D	0.999

dbSNP variants (sampled 300 via entrez): RS1000222849 (9:34634014 AACT>A), RS1000284556 (9:34623572 G>A,C,T), RS1000447387 (9:34628472 GAGGCAGAGGTATC>G), RS1000729035 (9:34634301 C>A), RS1000867464 (9:34624492 C>T), RS1000872532 (9:34623409 C>A,T), RS1000969902 (9:34630558 C>T), RS1001126819 (9:34624761 C>T), RS1001154189 (9:34629214 G>A,C), RS1001197437 (9:34623004 G>A), RS1001220249 (9:34627460 C>A), RS1001389991 (9:34633665 A>G), RS1001705187 (9:34629221 G>A), RS1002051103 (9:34623033 C>A,T), RS1002225885 (9:34628795 G>T)

Disease associations

OMIM: gene MIM:620868 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects methylation, increases methylation	2
Benzo(a)pyrene	increases methylation, increases mutagenesis	2
ethyl-p-hydroxybenzoate	decreases expression	1
benzo(e)pyrene	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
bisphenol S	increases methylation	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
Methapyrilene	increases methylation	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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