POU2AF3

Summary

POU2AF3 (POU class 2 homeobox associating factor 3, HGNC:26978) is a protein-coding gene on chromosome 11q23.1, encoding POU class 2 homeobox associating factor 3 (A8K830). Transcriptional coactivator that specifically associates with POU2F3.

Enables DNA binding activity and transcription coactivator activity. Predicted to be involved in positive regulation of DNA-templated transcription. Located in cytosol and nucleoplasm.

Source: NCBI Gene 120376 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 22 total
• MANE Select transcript: NM_001271458

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26978
Approved symbol	POU2AF3
Name	POU class 2 homeobox associating factor 3
Location	11q23.1
Locus type	gene with protein product
Status	Approved
Aliases	CASC13, OCA-T2
Ensembl gene	ENSG00000214290
Ensembl biotype	protein_coding
OMIM	615694
Entrez	120376

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 nonsense_mediated_decay

ENST00000398035, ENST00000526216, ENST00000528846, ENST00000610738, ENST00000614153, ENST00000638573, ENST00000639470

RefSeq mRNA: 4 — MANE Select: NM_001271458 NM_001136105, NM_001271457, NM_001271458, NM_001370484

CCDS: CCDS44728, CCDS73378

Canonical transcript exons

ENST00000610738 — 5 exons

Exon	Start	End
ENSE00002178172	111308069	111308735
ENSE00003718595	111304928	111304982
ENSE00003737088	111300527	111300621
ENSE00003739639	111306394	111306623
ENSE00003927720	111298546	111298588

Expression profiles

Bgee: expression breadth ubiquitous, 206 present calls, max score 93.90.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6527 / max 33.7986, expressed in 273 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116610	0.2731	150
116609	0.1846	116
116608	0.1332	83
116607	0.0495	24
116611	0.0122	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	93.90	gold quality
epithelial cell of pancreas	CL:0000083	93.43	gold quality
right uterine tube	UBERON:0001302	92.91	gold quality
bronchial epithelial cell	CL:0002328	91.43	gold quality
bronchus	UBERON:0002185	90.17	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.38	gold quality
seminal vesicle	UBERON:0000998	89.29	gold quality
sperm	CL:0000019	88.42	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.39	gold quality
mucosa of transverse colon	UBERON:0004991	87.64	gold quality
corpus epididymis	UBERON:0004359	85.92	gold quality
ileal mucosa	UBERON:0000331	85.91	gold quality
nasal cavity epithelium	UBERON:0005384	83.01	silver quality
kidney epithelium	UBERON:0004819	82.93	gold quality
left uterine tube	UBERON:0001303	82.47	gold quality
palpebral conjunctiva	UBERON:0001812	82.45	gold quality
fallopian tube	UBERON:0003889	82.09	gold quality
right ovary	UBERON:0002118	82.05	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	81.82	gold quality
transverse colon	UBERON:0001157	81.53	gold quality
caput epididymis	UBERON:0004358	81.46	gold quality
left ovary	UBERON:0002119	81.44	gold quality
metanephros cortex	UBERON:0010533	80.41	gold quality
muscle layer of sigmoid colon	UBERON:0035805	79.96	gold quality
mucosa of paranasal sinus	UBERON:0005030	79.93	gold quality
gall bladder	UBERON:0002110	79.72	gold quality
body of stomach	UBERON:0001161	79.55	gold quality
rectum	UBERON:0001052	79.32	gold quality
epithelium of nasopharynx	UBERON:0001951	79.25	gold quality
small intestine Peyer’s patch	UBERON:0003454	79.17	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting POU2AF3, 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-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 5)

• We found PLCE1, C11orf92-C11orf93, and NOC3L associated with colorectal cancer susceptibility (PMID:24146276)
• Data implicate COLCA1 and COLCA2 in the pathogenesis of colon cancer. (PMID:24154973)
• rs1944919 on chromosome 11q23.1 and its effector genes COLCA1/COLCA2 confer susceptibility to primary biliary cholangitis. (PMID:33633225)
• OCA-T1 and OCA-T2 are coactivators of POU2F3 in the tuft cell lineage. (PMID:35576971)
• COLCA2 (POU2AF3) and likely C11orf53 (POU2AF2) function as transcriptional co-activators of POU2F3 in tuft cell-like small cell lung cancer. (PMID:36253350)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pou2af3	ENSMUSG00000079559
rattus_norvegicus	Pou2af3	ENSRNOG00000042165

Protein

Protein identifiers

POU class 2 homeobox associating factor 3 — A8K830 (reviewed: A8K830)

Alternative names: Cancer susceptibility candidate protein 13, Colorectal cancer-associated protein 2, Protein OCA-T2

All UniProt accessions (3): A0A0A0MTE5, A0A1W2PQW7, A8K830

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional coactivator that specifically associates with POU2F3. This complex drives the development of tuft cells, a rare a rare chemosensory cells that coordinate immune and neural functions within mucosal epithelial tissues.

Subunit / interactions. Interacts with POU2F3 in a DNA-dependent manner; this interaction increases POU2F3 transactivation activity.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed in many cell types of epithelial, mesenchymal and hematopoietic origins. Expressed in tufs cells.

Domain organisation. In the N-terminus possesses a conserved OCA domain for bivalent binding to class II POU domain-containing transcription factors and to an octamer DNA motif (5’-ATGAAAT-3’).

Similarity. Belongs to the POU2AF family.

Isoforms (4)

UniProt ID	Names	Canonical?
A8K830-5	5	yes
A8K830-1	1
A8K830-3	3
A8K830-4	4

RefSeq proteins (4): NP_001129577, NP_001258386, NP_001258387, NP_001357413 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR043265	OCAT2	Family
IPR047571	OCA	Domain

UniProt features (9 total): splice variant 3, mutagenesis site 2, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9PFO	X-RAY DIFFRACTION	2.1
9PFN	X-RAY DIFFRACTION	2.79

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A8K830-F1	55.86	0.10

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 (2):

Position	Phenotype
11	abolishes interaction with pou2f3.
17	abolishes interaction with pou2f3.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 32 (showing top): RICKMAN_HEAD_AND_NECK_CANCER_A, GOMF_TRANSCRIPTION_COACTIVATOR_ACTIVITY, GOMF_TRANSCRIPTION_COREGULATOR_ACTIVITY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, SUPT16H_TARGET_GENES, LET_7A_3P, MIR98_3P, LET_7F_1_3P, LET_7B_3P, MIR944, MIR4680_3P, MIR3685, MIR4650_3P, MIR155_3P, MIR4711_5P

GO Biological Process (1): positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (4): DNA binding (GO:0003677), transcription coactivator activity (GO:0003713), POU domain binding (GO:0070974), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
nucleic acid binding	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
protein domain specific binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

328 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POU2AF3	POU2AF2	Q8IXP5	878
POU2AF3	RLF	Q13129	565
POU2AF3	POU2AF1	Q16633	499
POU2AF3	WBP1L	Q9NX94	490
POU2AF3	EIF3H	O15372	474
POU2AF3	C11orf87	Q6NUJ2	468
POU2AF3	HIGD1A	Q9Y241	455
POU2AF3	DIP2B	Q9P265	402
POU2AF3	PLEKHD1	A6NEE1	386
POU2AF3	SERPINA11	Q86U17	384
POU2AF3	C11orf52	Q96A22	377
POU2AF3	POLD3	Q15054	370
POU2AF3	SERPINA9	Q86WD7	367
POU2AF3	MAP7D2	Q96T17	362
POU2AF3	SFMBT1	Q9UHJ3	358

IntAct

0 interactions, top by confidence:

BioGRID (1): COLCA2 (Synthetic Lethality)

ESM2 similar proteins: A0PJS5, A1YG01, A2D4R4, A2D649, A2T6H5, A2T6Z0, A3KNJ3, A7Y7W3, A8K830, F6W2R2, F8VPY8, O15353, O42506, O43186, O54751, P14653, P17919, P28322, P31276, P32243, P40646, P43268, P57082, P70056, P80206, P83758, Q00288, Q06710, Q08820, Q16633, Q1KL10, Q28GC4, Q28IU6, Q2KJA4, Q4G112, Q503Z8, Q64693, Q66IK1, Q66IT9, Q7T1C0

Diamond homologs: A8K830, F8VPY8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1040 predictions. Top by Δscore:

Variant	Effect	Δscore
11:111300622:G:GG	donor_gain	1.0000
11:111306393:GGACT:G	acceptor_gain	1.0000
11:111298927:G:GG	donor_gain	0.9900
11:111299047:G:GA	donor_gain	0.9900
11:111300027:G:GT	donor_gain	0.9900
11:111300525:A:AG	acceptor_gain	0.9900
11:111300526:G:GG	acceptor_gain	0.9900
11:111306388:CTCTA:C	acceptor_loss	0.9900
11:111306389:TCTAG:T	acceptor_loss	0.9900
11:111306390:CTA:C	acceptor_loss	0.9900
11:111306391:TAG:T	acceptor_loss	0.9900
11:111306392:A:AG	acceptor_gain	0.9900
11:111306392:A:AT	acceptor_loss	0.9900
11:111306392:AG:A	acceptor_gain	0.9900
11:111306393:G:GG	acceptor_gain	0.9900
11:111306393:GG:G	acceptor_gain	0.9900
11:111306619:GCCTG:G	donor_gain	0.9900
11:111299018:G:GT	donor_gain	0.9800
11:111299046:T:TA	donor_gain	0.9800
11:111299344:G:T	donor_gain	0.9800
11:111299718:G:GT	donor_gain	0.9800
11:111300526:GAA:G	acceptor_gain	0.9800
11:111300526:GAAA:G	acceptor_gain	0.9800
11:111308064:TCTA:T	acceptor_loss	0.9800
11:111308067:A:AG	acceptor_gain	0.9800
11:111308068:G:GG	acceptor_gain	0.9800
11:111300526:GA:G	acceptor_gain	0.9700
11:111300526:GAAAA:G	acceptor_gain	0.9700
11:111300617:GAACC:G	donor_gain	0.9700
11:111300618:AACCG:A	donor_loss	0.9700

AlphaMissense

1624 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:111308432:A:C	S154R	0.936
11:111308434:T:A	S154R	0.936
11:111308434:T:G	S154R	0.936
11:111308426:T:C	C152R	0.828
11:111308428:C:G	C152W	0.795
11:111308421:A:T	D150V	0.776
11:111308433:G:T	S154I	0.769
11:111308429:T:G	Y153D	0.744
11:111308396:T:C	F142L	0.739
11:111308398:C:A	F142L	0.739
11:111308398:C:G	F142L	0.739
11:111308120:A:C	S50R	0.729
11:111308122:T:A	S50R	0.729
11:111308122:T:G	S50R	0.729
11:111308420:G:C	D150H	0.725
11:111306618:A:C	S31R	0.724
11:111306620:C:A	S31R	0.724
11:111306620:C:G	S31R	0.724
11:111308284:C:G	C104W	0.710
11:111306609:T:C	F28L	0.689
11:111306611:T:A	F28L	0.689
11:111306611:T:G	F28L	0.689
11:111308422:C:A	D150E	0.686
11:111308422:C:G	D150E	0.686
11:111308433:G:A	S154N	0.679
11:111306588:T:C	F21L	0.674
11:111306590:C:A	F21L	0.674
11:111306590:C:G	F21L	0.674
11:111308421:A:C	D150A	0.662
11:111306603:T:C	F26L	0.656

dbSNP variants (sampled 300 via entrez): RS1000366266 (11:111306061 G>A), RS1000914326 (11:111305993 A>G), RS1001133494 (11:111299373 C>G,T), RS1001245819 (11:111305511 A>C), RS1001263073 (11:111305557 TAA>T), RS1001354288 (11:111299269 G>A), RS1001406712 (11:111299094 C>T), RS1001541293 (11:111300145 CCTCT>C,CCT,CCTCTCT), RS1001592475 (11:111305821 G>A), RS1002435934 (11:111304830 T>C), RS1002770244 (11:111305188 T>C), RS1003045804 (11:111297824 G>C), RS1003195182 (11:111302398 T>A,C), RS1003368001 (11:111296765 G>A), RS1003541375 (11:111297557 A>G)

Disease associations

OMIM: gene MIM:615694 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003017_17	Colorectal cancer	1.000000e-10
GCST004895_3	Colorectal cancer	2.000000e-09
GCST005523_29	Celiac disease	2.000000e-11
GCST007552_24	Colorectal cancer	5.000000e-07
GCST007856_51	Colorectal cancer or advanced adenoma	2.000000e-31
GCST009869_58	Colorectal cancer	3.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	3
Nickel	decreases expression	2
Cyclosporine	decreases expression, increases expression	2
propionaldehyde	decreases expression	1
butyraldehyde	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, decreases reaction	1
pentanal	decreases expression	1
abrine	decreases expression	1
Aldehydes	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Calcitriol	decreases expression, affects cotreatment	1
Hydrogen Peroxide	affects expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Methyl Methanesulfonate	increases expression	1
Quercetin	decreases expression	1
Silicon Dioxide	decreases expression	1
Testosterone	decreases expression, affects cotreatment	1
Tetrachlorodibenzodioxin	decreases expression	1
Tretinoin	increases expression	1
Urethane	decreases expression	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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