FOXI2

Summary

FOXI2 (forkhead box I2, HGNC:32448) is a protein-coding gene on chromosome 10q26.2, encoding Forkhead box protein I2 (Q6ZQN5). Possible transcriptional activator.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in anatomical structure morphogenesis; cell differentiation; and regulation of transcription by RNA polymerase II. Predicted to be located in chromatin.

Source: NCBI Gene 399823 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 82 total
• MANE Select transcript: NM_207426

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32448
Approved symbol	FOXI2
Name	forkhead box I2
Location	10q26.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ46831
Ensembl gene	ENSG00000186766
Ensembl biotype	protein_coding
OMIM	617202
Entrez	399823

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000388920

RefSeq mRNA: 1 — MANE Select: NM_207426 NM_207426

CCDS: CCDS7655

Canonical transcript exons

ENST00000388920 — 2 exons

Exon	Start	End
ENSE00001661838	127738520	127741183
ENSE00001713911	127737185	127737784

Expression profiles

Bgee: expression breadth broad, 72 present calls, max score 78.08.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1294 / max 24.6432, expressed in 55 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107615	0.1026	45
107614	0.0268	11

Top tissues by expression

117 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	78.08	silver quality
lower esophagus mucosa	UBERON:0035834	69.67	gold quality
sural nerve	UBERON:0015488	65.24	silver quality
esophagus mucosa	UBERON:0002469	64.53	gold quality
adult mammalian kidney	UBERON:0000082	63.35	gold quality
kidney	UBERON:0002113	59.56	gold quality
adenohypophysis	UBERON:0002196	57.59	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	57.57	gold quality
pituitary gland	UBERON:0000007	56.57	gold quality
esophagus	UBERON:0001043	56.16	gold quality
endocervix	UBERON:0000458	55.66	gold quality
apex of heart	UBERON:0002098	53.32	gold quality
cortex of kidney	UBERON:0001225	52.52	gold quality
saliva-secreting gland	UBERON:0001044	52.14	gold quality
minor salivary gland	UBERON:0001830	51.63	gold quality
lymph node	UBERON:0000029	50.69	gold quality
metanephros cortex	UBERON:0010533	49.55	gold quality
uterine cervix	UBERON:0000002	48.72	gold quality
mucosa of stomach	UBERON:0001199	48.47	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	48.05	gold quality
vermiform appendix	UBERON:0001154	47.66	gold quality
spleen	UBERON:0002106	47.54	gold quality
lower esophagus	UBERON:0013473	47.23	gold quality
lower esophagus muscularis layer	UBERON:0035833	47.17	gold quality
heart left ventricle	UBERON:0002084	47.10	gold quality
urinary bladder	UBERON:0001255	46.98	gold quality
subcutaneous adipose tissue	UBERON:0002190	46.86	gold quality
left uterine tube	UBERON:0001303	46.83	gold quality
skin of leg	UBERON:0001511	46.78	gold quality
tonsil	UBERON:0002372	46.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting FOXI2, 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-4455	100.00	65.48	1587
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-609	99.82	64.26	505
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-422A	99.18	65.83	550
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-496	98.66	69.80	931

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Foxi2	ENSMUSG00000048377
rattus_norvegicus	Foxi2	ENSRNOG00000018917

Paralogs (41): FOXP3 (ENSG00000049768), FOXC1 (ENSG00000054598), FOXJ2 (ENSG00000065970), FOXF1 (ENSG00000103241), FOXN1 (ENSG00000109101), FOXM1 (ENSG00000111206), FOXP1 (ENSG00000114861), FOXO3 (ENSG00000118689), FOXA2 (ENSG00000125798), FOXA1 (ENSG00000129514), FOXJ1 (ENSG00000129654), FOXK2 (ENSG00000141568), FOXO1 (ENSG00000150907), FOXH1 (ENSG00000160973), FOXQ1 (ENSG00000164379), FOXK1 (ENSG00000164916), FOXD4 (ENSG00000170122), FOXA3 (ENSG00000170608), FOXB1 (ENSG00000171956), FOXR1 (ENSG00000176302), FOXL1 (ENSG00000176678), FOXC2 (ENSG00000176692), FOXE1 (ENSG00000178919), FOXS1 (ENSG00000179772), FOXL2 (ENSG00000183770), FOXO4 (ENSG00000184481), FOXD4L1 (ENSG00000184492), FOXD4L4 (ENSG00000184659), FOXD2 (ENSG00000186564), FOXE3 (ENSG00000186790), FOXD3 (ENSG00000187140), FOXD4L3 (ENSG00000187559), FOXR2 (ENSG00000189299), FOXJ3 (ENSG00000198815), FOXO6 (ENSG00000204060), FOXB2 (ENSG00000204612), FOXD4L5 (ENSG00000204779), FOXI3 (ENSG00000214336), FOXL3 (ENSG00000248767), FOXD1 (ENSG00000251493)

Protein

Protein identifiers

Forkhead box protein I2 — Q6ZQN5 (reviewed: Q6ZQN5)

All UniProt accessions (1): Q6ZQN5

UniProt curated annotations — full annotation on UniProt →

Function. Possible transcriptional activator.

Subcellular location. Nucleus.

RefSeq proteins (1): NP_997309* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001766	Fork_head_dom	Domain
IPR018122	TF_fork_head_CS_1	Conserved_site
IPR030456	TF_fork_head_CS_2	Conserved_site
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR050211	FOX_domain-containing	Family

Pfam: PF00250

UniProt features (3 total): chain 1, DNA-binding region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZQN5-F1	63.62	0.24

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 35 (showing top): TANAKA_METHYLATED_IN_ESOPHAGEAL_CARCINOMA, TGGNNNNNNKCCAR_UNKNOWN, YOSHIMURA_MAPK8_TARGETS_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, MEISSNER_BRAIN_HCP_WITH_H3K4ME2_AND_H3K27ME3, MARTENS_TRETINOIN_RESPONSE_UP, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, MIR6867_5P, MIR4482_3P, MIR567, MIR4455, MIR6748_5P, MIR10401_5P, MIR574_5P

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), anatomical structure morphogenesis (GO:0009653), cell differentiation (GO:0030154), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (5): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), sequence-specific DNA binding (GO:0043565)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription by RNA polymerase II	1
developmental process	1
anatomical structure development	1
cellular developmental process	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
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
DNA binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

918 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FOXI2	FOXR2	Q6PJQ5	450
FOXI2	FOXN3	O00409	431
FOXI2	VAX1	Q5SQQ9	418
FOXI2	CCDC166	P0CW27	415
FOXI2	ZSCAN18	Q8TBC5	391
FOXI2	FOXG1	P55315	385
FOXI2	ZDHHC14	Q8IZN3	378
FOXI2	ZNF471	Q9BX82	374
FOXI2	INSL4	Q14641	371
FOXI2	SOX5	P35711	369
FOXI2	CLVS1	Q8IUQ0	368
FOXI2	SOX11	P35716	366
FOXI2	SOX1	O00570	365
FOXI2	KCNJ6	P48051	365
FOXI2	ABCD4	O14678	364

IntAct

3 interactions, top by confidence:

A	B	Type	Score
FOXI2	DDX39A	psi-mi:“MI:0914”(association)	0.350

BioGRID (52): FOXI1 (Affinity Capture-MS), YARS (Affinity Capture-MS), PDS5A (Affinity Capture-MS), VARS (Affinity Capture-MS), NUP205 (Affinity Capture-MS), PA2G4 (Affinity Capture-MS), DDX39A (Affinity Capture-MS), IARS (Affinity Capture-MS), RECQL (Affinity Capture-MS), IKBIP (Affinity Capture-MS), NSDHL (Affinity Capture-MS), NUP107 (Affinity Capture-MS), RCC1 (Affinity Capture-MS), XPO7 (Affinity Capture-MS), CTBP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1W2PRP0, A6NCS4, A7Y7W2, O14512, O43638, O57601, O70220, O96004, P07812, P09023, P10085, P10284, P17483, P22091, P24899, P50548, P52954, P52955, P55318, P57100, P63156, P63157, P70447, P79772, P97832, Q02346, Q05917, Q0VCE2, Q12952, Q1XID0, Q28555, Q3I5G5, Q3Y598, Q60688, Q61660, Q63244, Q63250, Q64279, Q64305, Q64731

Diamond homologs: A0A1W2PRP0, A0A8V0YY16, A3KNJ3, A8MTJ6, B5RHS5, D3Z120, O00358, O35392, O43638, O60548, O88470, P32027, P32030, P35583, P55316, P56260, P58012, P79772, Q00939, Q02360, Q02361, Q12948, Q12950, Q12951, Q12952, Q13461, Q16676, Q18694, Q1A1A1, Q1A1A2, Q1A1A3, Q1A1A4, Q1A1A5, Q1A1A6, Q28D67, Q28HT3, Q32NP8, Q3I5G5, Q3SYB3, Q4VUF1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	76
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

174 predictions. Top by Δscore:

Variant	Effect	Δscore
10:127737783:AGGTA:A	donor_loss	1.0000
10:127737784:GGT:G	donor_loss	1.0000
10:127737786:T:A	donor_loss	1.0000
10:127738515:TGCA:T	acceptor_loss	1.0000
10:127738517:CAG:C	acceptor_loss	1.0000
10:127738518:A:AG	acceptor_gain	1.0000
10:127738519:G:GA	acceptor_loss	1.0000
10:127738519:G:GG	acceptor_gain	1.0000
10:127738519:GGT:G	acceptor_gain	1.0000
10:127738518:AG:A	acceptor_gain	0.9900
10:127738519:GG:G	acceptor_gain	0.9900
10:127738519:GGTA:G	acceptor_gain	0.9900
10:127738519:GGTAA:G	acceptor_gain	0.9900
10:127738515:T:A	acceptor_gain	0.9800
10:127738515:TGCAG:T	acceptor_gain	0.9800
10:127738516:GCAGG:G	acceptor_gain	0.9800
10:127738517:CAGG:C	acceptor_gain	0.9800
10:127738518:AGG:A	acceptor_gain	0.9800
10:127738519:G:C	acceptor_gain	0.9700
10:127737775:G:GT	donor_gain	0.9600
10:127737785:G:GG	donor_gain	0.9600
10:127738514:CTGCA:C	acceptor_gain	0.9600
10:127737663:G:GG	donor_gain	0.9300
10:127737817:G:GT	donor_gain	0.9000
10:127737662:A:AG	donor_gain	0.8800
10:127738073:G:GT	donor_gain	0.8800
10:127737857:TGG:T	donor_gain	0.8700
10:127737858:GGG:G	donor_gain	0.8700
10:127738593:G:GT	donor_gain	0.8600
10:127737756:G:GT	donor_gain	0.8500

AlphaMissense

2032 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:127737709:T:A	W146R	1.000
10:127737709:T:C	W146R	1.000
10:127737711:G:C	W146C	1.000
10:127737711:G:T	W146C	1.000
10:127737722:T:A	I150N	1.000
10:127737727:C:G	H152D	1.000
10:127737751:T:C	F160L	1.000
10:127737752:T:C	F160S	1.000
10:127737752:T:G	F160C	1.000
10:127737753:C:A	F160L	1.000
10:127737753:C:G	F160L	1.000
10:127738536:G:C	W176C	1.000
10:127738536:G:T	W176C	1.000
10:127737605:T:A	I111N	0.999
10:127737647:T:A	L125H	0.999
10:127737656:T:C	I128T	0.999
10:127737679:T:C	F136L	0.999
10:127737681:C:A	F136L	0.999
10:127737681:C:G	F136L	0.999
10:127737685:T:C	F138L	0.999
10:127737687:C:A	F138L	0.999
10:127737687:C:G	F138L	0.999
10:127737716:A:T	N148I	0.999
10:127737717:C:A	N148K	0.999
10:127737717:C:G	N148K	0.999
10:127737719:C:T	S149F	0.999
10:127737722:T:C	I150T	0.999
10:127737722:T:G	I150S	0.999
10:127737727:C:A	H152N	0.999
10:127737729:C:A	H152Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000303459 (10:127741524 G>A,T), RS1000738069 (10:127736112 T>G), RS1001472598 (10:127736707 G>A), RS1001806315 (10:127739041 C>A,G,T), RS1001920693 (10:127738732 G>A,T), RS1002816203 (10:127740472 G>A), RS1003141427 (10:127737883 C>A,T), RS1003216677 (10:127737999 G>A), RS1003272765 (10:127740581 T>G), RS1003691270 (10:127736429 G>T), RS1003938950 (10:127741591 A>G), RS1004210675 (10:127736262 G>A,C), RS1004593196 (10:127735684 G>T), RS1004749216 (10:127741009 C>G), RS1004809468 (10:127737386 G>A,T)

Disease associations

OMIM: gene MIM:617202 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003945_4	Hepcidin/transferrin saturation ratio	2.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007902	hepcidin:transferrin saturation ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
ethyl-p-hydroxybenzoate	increases expression	1
arsenite	increases methylation	1
2-palmitoylglycerol	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	affects expression	1
Estradiol	affects expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Serpentine	decreases methylation	1
Asbestos, Crocidolite	decreases methylation	1
Asbestos, Amosite	decreases methylation	1

Clinical trials (associated diseases)

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