POU2F3

Summary

POU2F3 (POU class 2 homeobox 3, HGNC:19864) is a protein-coding gene on chromosome 11q23.3, encoding POU domain, class 2, transcription factor 3 (Q9UKI9). Transcription factor that binds to the octamer motif (5’-ATTTGCAT-3’) and regulates cell type-specific differentiation pathways.

This gene encodes a member of the POU domain family of transcription factors. POU domain transcription factors bind to a specific octamer DNA motif and regulate cell type-specific differentiation pathways. The encoded protein is primarily expressed in the epidermis, and plays a critical role in keratinocyte proliferation and differentiation. The encoded protein is also a candidate tumor suppressor protein, and aberrant promoter methylation of this gene may play a role in cervical cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 25833 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 60 total
• Transcription factor: yes — 10 downstream targets (CollecTRI)
• MANE Select transcript: NM_014352

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19864
Approved symbol	POU2F3
Name	POU class 2 homeobox 3
Location	11q23.3
Locus type	gene with protein product
Status	Approved
Aliases	OCT11, PLA-1, Skn-1a, Epoc-1
Ensembl gene	ENSG00000137709
Ensembl biotype	protein_coding
OMIM	607394
Entrez	25833

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000260264, ENST00000529039, ENST00000532638, ENST00000532663, ENST00000533620, ENST00000543440, ENST00000606153

RefSeq mRNA: 2 — MANE Select: NM_014352 NM_001244682, NM_014352

CCDS: CCDS58190, CCDS8431

Canonical transcript exons

ENST00000543440 — 13 exons

Exon	Start	End
ENSE00002182210	120240140	120240371
ENSE00002206207	120318353	120319945
ENSE00003695000	120307479	120307615
ENSE00003696147	120299624	120299726
ENSE00003696360	120315361	120315427
ENSE00003697534	120246449	120246517
ENSE00003698775	120298265	120298390
ENSE00003699048	120305030	120305212
ENSE00003699391	120302286	120302368
ENSE00003699723	120269210	120269244
ENSE00003700265	120305644	120305785
ENSE00003700836	120309425	120309586
ENSE00003789546	120317229	120317364

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 95.52.

FANTOM5 (CAGE): breadth broad, TPM avg 3.7765 / max 140.9599, expressed in 590 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117147	3.4751	541
117149	0.2026	49
117148	0.0988	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	95.52	gold quality
skin of leg	UBERON:0001511	94.79	gold quality
zone of skin	UBERON:0000014	94.06	gold quality
upper leg skin	UBERON:0004262	93.95	gold quality
skin of hip	UBERON:0001554	91.24	gold quality
nipple	UBERON:0002030	85.98	gold quality
upper arm skin	UBERON:0004263	84.24	gold quality
mammalian vulva	UBERON:0000997	78.92	gold quality
palpebral conjunctiva	UBERON:0001812	78.24	gold quality
Brodmann (1909) area 10	UBERON:0013541	77.10	gold quality
penis	UBERON:0000989	76.69	gold quality
lower esophagus mucosa	UBERON:0035834	73.53	gold quality
mucosa of transverse colon	UBERON:0004991	72.79	gold quality
esophagus mucosa	UBERON:0002469	71.75	gold quality
pancreatic ductal cell	CL:0002079	71.12	silver quality
vagina	UBERON:0000996	70.56	gold quality
hair follicle	UBERON:0002073	69.37	silver quality
gingival epithelium	UBERON:0001949	67.41	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	67.29	gold quality
minor salivary gland	UBERON:0001830	66.83	gold quality
amniotic fluid	UBERON:0000173	65.97	gold quality
gingiva	UBERON:0001828	65.63	silver quality
mouth mucosa	UBERON:0003729	65.55	gold quality
epithelium of nasopharynx	UBERON:0001951	65.33	silver quality
ileal mucosa	UBERON:0000331	64.98	silver quality
left lobe of thyroid gland	UBERON:0001120	64.26	gold quality
placenta	UBERON:0001987	64.24	gold quality
thyroid gland	UBERON:0002046	63.83	gold quality
mucosa of paranasal sinus	UBERON:0005030	63.76	gold quality
islet of Langerhans	UBERON:0000006	63.74	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	8.89
E-ANND-3	yes	5.17
E-MTAB-8410	no	3.07

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

10 targets.

Target	Regulation
CDK11B	Activation
CREBBP
KRT10	Activation
KRT14	Repression
LORICRIN	Unknown
MMP19	Repression
MX1
NPPA
RHOH
SPRR2A	Unknown

JASPAR motifs

Motif	Name	Family
MA0627.2	POU2F3	POU domain factors
MA0627.3	POU2F3	POU domain factors

JASPAR matrix evidence (PMIDs): PMID:28473536

miRNA regulators (miRDB)

119 targeting POU2F3, 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-3120-5P	100.00	65.56	965
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-605-3P	99.88	69.22	1833

Literature-anchored findings (GeneRIF, showing 22)

• the human Skn-1 locus encodes multifunctional protein isotypes, subjected to biochemical cross-talk, which are likely to play a major role in the fine-tuning of keratinocyte terminal differentiation (PMID:12624109)
• These results suggest that the expression of hSkn-1a represses the growth of the cervical cancer cells through the partial resumption of the differentiation pathway followed by slow suppression of cell replication and apoptosis. (PMID:15077167)
• Pla-1 protein binds to a POU-consensus DNA sequence in the human placental lactogen-3 (PL-3) promoter and it is capable of trans-activating its transcription up to 18-fold. (PMID:16005513)
• POU2F3 in cervical cancer cells may be CC-related tumor suppressor genes, which are disrupted by both epigenetic and genetic mechanisms. (PMID:16607278)
• Our results suggest that Tst-1 and Skn-1a regulate expression of MMPs in keratinocytes and effect both the expression and activation of these proteolytic enzymes. (PMID:17195013)
• splice variant induced in keratinocytes by high calcium (PMID:17989732)
• Skn-1a enhanced the transient replication of a plasmid containing the HPV16 replication origin in HEK293 cells when co-transfected with a plasmid expressing E1 and E2. (PMID:18479461)
• the antagonistic effects of Skn-1a and p63 on keratin promoter transactivation is probably through competition for overlapping binding sites on target gene promoter or through an indirect interaction. (PMID:20888799)
• It is possible that Skn-1a and the related isoforms have different functions in keratinocyte differentiation and proliferation. (PMID:21074976)
• Skn-1a is expressed in a minority of Mash1-positive olfactory progenitor cells and a majority of Trpm5-expressing microvillous cells in the main olfactory epithelium. (PMID:24428937)
• These results suggested that the epidermal differentiation signaling pathway, involving kinase and phosphatase activation, may regulate the NLS activity of Skn1a in keratinocytes (PMID:24954220)
• Analysis of the transcription factor POU2F3 revealed a DOPr-mediated extracellular signal-regulated kinase (ERK)-dependent downregulation of this factorThe delta-opioid receptor affects epidermal homeostasis (PMID:25178105)
• POU2F3 is a master regulator of tuft cell identity in a variant form of Small cell lung cancer (PMID:29945888)
• SCLC Subtypes Defined by ASCL1, NEUROD1, POU2F3, and YAP1: A Comprehensive Immunohistochemical and Histopathologic Characterization. (PMID:33011388)
• POU2F3 beyond thymic carcinomas: expression across the spectrum of thymomas hints to medullary differentiation in type A thymoma. (PMID:34988657)
• OCA-T1 and OCA-T2 are coactivators of POU2F3 in the tuft cell lineage. (PMID:35576971)
• POU2F3 in SCLC: Clinicopathologic and Genomic Analysis With a Focus on Its Diagnostic Utility in Neuroendocrine-Low SCLC. (PMID:35760287)
• POU2AF2/C11orf53 functions as a coactivator of POU2F3 by maintaining chromatin accessibility and enhancer activity. (PMID:36197978)
• The predictive value of YAP-1 and POU2F3 for the efficacy of immuno-chemotherapy in extensive-stage SCLC patients. (PMID:36716535)
• An integrated multiomics analysis of rectal cancer patients identified POU2F3 as a putative druggable target and entinostat as a cytotoxic enhancer of 5-fluorouracil. (PMID:36815540)
• POU2F3-Expressing Small Cell Lung Carcinoma and Large Cell Neuroendocrine Carcinoma Show Morphologic and Phenotypic Overlap. (PMID:37904277)
• Mammalian SWI/SNF complex activity regulates POU2F3 and constitutes a targetable dependency in small cell lung cancer. (PMID:39029464)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pou2f3	ENSDARG00000052387
mus_musculus	Pou2f3	ENSMUSG00000032015
rattus_norvegicus	Pou2f3	ENSRNOG00000009118

Paralogs (17): POU2F2 (ENSG00000028277), POU1F1 (ENSG00000064835), POU4F3 (ENSG00000091010), POU6F2 (ENSG00000106536), POU2F1 (ENSG00000143190), POU4F2 (ENSG00000151615), POU4F1 (ENSG00000152192), HDX (ENSG00000165259), POU6F1 (ENSG00000184271), POU3F2 (ENSG00000184486), POU3F1 (ENSG00000185668), POU3F4 (ENSG00000196767), POU3F3 (ENSG00000198914), CCDC160 (ENSG00000203952), POU5F1 (ENSG00000204531), POU5F1B (ENSG00000212993), POU5F2 (ENSG00000248483)

Protein

Protein identifiers

POU domain, class 2, transcription factor 3 — Q9UKI9 (reviewed: Q9UKI9)

Alternative names: Octamer-binding protein 11, Octamer-binding transcription factor 11, Transcription factor PLA-1, Transcription factor Skn-1

All UniProt accessions (3): Q9UKI9, E9PIN6, H0YLC5

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that binds to the octamer motif (5’-ATTTGCAT-3’) and regulates cell type-specific differentiation pathways. Involved in the regulation of keratinocytes differentiation. The POU2F3-POU2AF2/POU2AF3 complex drives the expression of tuft-cell-specific genes, a rare chemosensory cells that coordinate immune and neural functions within mucosal epithelial tissues.

Subunit / interactions. Interacts (via the POU domain) with POU2AF1 and POU2AF2 in a DNA-dependent manner; this interaction recruits POU2AF2 to chromatin and increases POU2F3 transactivation activity.

Subcellular location. Nucleus.

Tissue specificity. Specifically expressed in epidermis and cultured keratinocytes.

Similarity. Belongs to the POU transcription factor family. Class-2 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UKI9-1	1, Skn-1a	yes
Q9UKI9-2	2
Q9UKI9-3	3, Skn-1n

RefSeq proteins (2): NP_001231611, NP_055167* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000327	POU_dom	Domain
IPR000972	TF_octamer	Family
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR010982	Lambda_DNA-bd_dom_sf	Homologous_superfamily
IPR013847	POU	Domain
IPR017970	Homeobox_CS	Conserved_site
IPR050255	POU_domain_TF	Family

Pfam: PF00046, PF00157

UniProt features (17 total): region of interest 4, sequence conflict 3, compositionally biased region 3, splice variant 2, sequence variant 2, chain 1, domain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9PFP	X-RAY DIFFRACTION	1.7
9PFO	X-RAY DIFFRACTION	2.1
9PFN	X-RAY DIFFRACTION	2.79

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKI9-F1	60.57	0.28

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 143 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, CREL_01, GOBP_EPITHELIUM_DEVELOPMENT, JAEGER_METASTASIS_DN, AAGCCAT_MIR135A_MIR135B, GOBP_HOST_MEDIATED_SUPPRESSION_OF_VIRAL_TRANSCRIPTION, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GOBP_HOST_MEDIATED_PERTURBATION_OF_VIRAL_PROCESS, GOBP_WOUND_HEALING, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, MARTINEZ_RB1_TARGETS_UP, CCANNAGRKGGC_UNKNOWN, GGGNNTTTCC_NFKB_Q6_01, GOBP_EPIDERMIS_DEVELOPMENT, GATA1_03

GO Biological Process (8): regulation of transcription by RNA polymerase II (GO:0006357), epidermis development (GO:0008544), keratinocyte differentiation (GO:0030216), wound healing (GO:0042060), host-mediated suppression of viral transcription (GO:0043922), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355), cell differentiation (GO:0030154)

GO Molecular Function (9): 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 transcription activator activity, RNA polymerase II-specific (GO:0001228), identical protein binding (GO:0042802), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (8): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), nucleolus (GO:0005730), cytosol (GO:0005829), plasma membrane (GO:0005886), nuclear body (GO:0016604)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
cellular anatomical structure	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
nuclear lumen	2
intracellular membraneless organelle	2
tissue development	1
epidermal cell differentiation	1
skin development	1
response to wounding	1
tissue regeneration	1
host-mediated perturbation of viral transcription	1
host-mediated suppression of viral proces	1
positive regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cellular developmental process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
protein binding	1
DNA binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
protein-containing complex	1
cytoplasm	1
membrane	1
cell periphery	1
nucleoplasm	1

Protein interactions and networks

STRING

1211 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
POU2F3	DCAF11	Q8TEB1	940
POU2F3	PLA1A	Q53H76	918
POU2F3	LIPH	Q8WWY8	905
POU2F3	LIPG	Q9Y5X9	842
POU2F3	SPRR2A	P35326	803
POU2F3	TRPM5	Q9NZQ8	770
POU2F3	ELF3	P78545	734
POU2F3	LPAR3	Q9UBY5	719
POU2F3	NKRF	O15226	718
POU2F3	LPAR6	P43657	652
POU2F3	ASCL1	P50553	633
POU2F3	DCLK1	O15075	627
POU2F3	NEUROD1	Q13562	622
POU2F3	DDHD1	Q8NEL9	621
POU2F3	ITGB3	P05106	610

IntAct

3 interactions, top by confidence:

A	B	Type	Score
POU2F3	CDC27	psi-mi:“MI:0914”(association)	0.350
BCL6	CACNA1A	psi-mi:“MI:0914”(association)	0.350

BioGRID (8): POU2F3 (Affinity Capture-Western), POU2F3 (Reconstituted Complex), CDC27 (Affinity Capture-MS), ANAPC16 (Affinity Capture-MS), POU2F3 (Affinity Capture-MS), POU2F3 (Affinity Capture-Western), POU2F3 (Affinity Capture-Western), POU2F3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8FFY5, A1L0Z1, A1L1N5, A4IFD2, A8XJD0, B3DM25, B7ZQA9, D3ZTL1, P10037, P20268, P20912, P23899, P24350, P27889, P31362, P31363, P31364, P31365, P31369, P35680, P42571, P49335, P56224, P62515, P62516, P70030, P79364, P79745, P79746, Q00196, Q03365, Q05041, Q08478, Q15319, Q2LE08, Q4QQQ7, Q561L5, Q5RER5, Q5W1J5, Q6DJN3

Diamond homologs: A0A1L8FFY5, A1L0Z1, A7Y7W2, B3DM23, B3DM25, B7ZQA9, D3ZTL1, G3V7L5, O97552, P09086, P10036, P10037, P13528, P14859, P15143, P16143, P16241, P17208, P20263, P20264, P20265, P20266, P20267, P20268, P20912, P20913, P20914, P21952, P24350, P25425, P28069, P31360, P31361, P31362, P31363, P31364, P31365, P31367, P31368, P31369

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2109 predictions. Top by Δscore:

Variant	Effect	Δscore
11:120240256:G:GT	donor_gain	1.0000
11:120246445:GCAG:G	acceptor_loss	1.0000
11:120246446:CAGA:C	acceptor_loss	1.0000
11:120246447:A:AG	acceptor_gain	1.0000
11:120246447:AGATA:A	acceptor_loss	1.0000
11:120246448:G:GA	acceptor_gain	1.0000
11:120246448:GA:G	acceptor_gain	1.0000
11:120246448:GAT:G	acceptor_gain	1.0000
11:120246448:GATA:G	acceptor_gain	1.0000
11:120246513:GCCAG:G	donor_gain	1.0000
11:120246516:AGG:A	donor_loss	1.0000
11:120246517:GGTA:G	donor_loss	1.0000
11:120246518:G:T	donor_loss	1.0000
11:120246519:T:A	donor_loss	1.0000
11:120298257:A:AG	acceptor_gain	1.0000
11:120298258:C:G	acceptor_gain	1.0000
11:120298261:GCAG:G	acceptor_loss	1.0000
11:120298262:CA:C	acceptor_loss	1.0000
11:120298263:A:AC	acceptor_loss	1.0000
11:120298263:A:AG	acceptor_gain	1.0000
11:120298264:G:GA	acceptor_gain	1.0000
11:120298264:G:GT	acceptor_loss	1.0000
11:120298264:GATT:G	acceptor_gain	1.0000
11:120298264:GATTA:G	acceptor_gain	1.0000
11:120298387:TCAG:T	donor_loss	1.0000
11:120298388:CAGGT:C	donor_loss	1.0000
11:120298389:AGGTA:A	donor_loss	1.0000
11:120298390:GGTAA:G	donor_loss	1.0000
11:120298392:T:A	donor_loss	1.0000
11:120305637:C:G	acceptor_gain	1.0000

AlphaMissense

2849 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:120305157:T:A	L191Q	1.000
11:120305157:T:C	L191P	1.000
11:120305165:T:C	F194L	1.000
11:120305166:T:C	F194S	1.000
11:120305166:T:G	F194C	1.000
11:120305167:T:A	F194L	1.000
11:120305167:T:G	F194L	1.000
11:120305168:G:C	A195P	1.000
11:120305169:C:A	A195D	1.000
11:120305177:T:C	F198L	1.000
11:120305178:T:C	F198S	1.000
11:120305178:T:G	F198C	1.000
11:120305179:C:A	F198L	1.000
11:120305179:C:G	F198L	1.000
11:120305180:A:G	K199E	1.000
11:120305181:A:C	K199T	1.000
11:120305181:A:T	K199M	1.000
11:120305182:G:C	K199N	1.000
11:120305182:G:T	K199N	1.000
11:120305189:C:A	R202S	1.000
11:120305189:C:G	R202G	1.000
11:120305190:G:A	R202H	1.000
11:120305190:G:C	R202P	1.000
11:120305193:T:A	I203N	1.000
11:120305193:T:C	I203T	1.000
11:120305193:T:G	I203S	1.000
11:120305199:T:C	L205P	1.000
11:120305201:G:C	G206R	1.000
11:120305201:G:T	G206C	1.000
11:120305202:G:A	G206D	1.000

dbSNP variants (sampled 300 via entrez): RS1000008682 (11:120276517 C>G), RS1000022772 (11:120304525 T>C), RS1000042506 (11:120318708 G>C), RS1000075814 (11:120254284 G>C), RS1000109236 (11:120291601 G>A), RS1000120473 (11:120269531 C>T), RS1000128745 (11:120295691 T>A), RS1000173386 (11:120241523 G>A), RS1000187813 (11:120268530 A>G), RS1000221843 (11:120282906 T>C), RS1000325329 (11:120282833 T>G), RS1000327966 (11:120307164 G>A), RS1000357531 (11:120246778 A>G), RS1000448552 (11:120301470 T>C), RS1000452204 (11:120265672 C>T)

Disease associations

OMIM: gene MIM:607394 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): RASopathy (MONDO:0021060)

Orphanet (1): RASopathy (Orphanet:536391)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002874_35	Psoriasis	3.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	3
Estradiol	affects cotreatment, decreases expression	3
entinostat	increases expression, affects cotreatment	2
belinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	increases expression	2
Aflatoxin B1	increases methylation	2
sotorasib	decreases expression, affects cotreatment	1
kojic acid	decreases expression	1
trichostatin A	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	increases methylation	1
Benzo(a)pyrene	affects methylation	1
Ivermectin	increases expression	1
Mercury	increases expression	1
Nickel	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Zearalenone	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04888936	Not specified	RECRUITING	Clinical, Genetic, and Epidemiologic Study of Children and Adults With RASopathies
NCT05761314	Not specified	RECRUITING	Solid Tumors in RASopathies
NCT06331117	Not specified	UNKNOWN	Effect of RAS/MAPK Pathway Hyperactivation on Growth’ and Bone’ Profile of the RASopathies
NCT06355622	Not specified	UNKNOWN	Prevalence and Characterization of Pain in RASopathies
NCT06489067	Not specified	RECRUITING	Study of the Thyroid Function and Echostructural Morphology in Patients Affected With Rasopathies (ECORAS2023)
NCT06776380	Not specified	RECRUITING	Pubertal Development in Patients with RASopathies
NCT07005297	Not specified	NOT_YET_RECRUITING	Clinical Genetics Branch Eligibility Screening Survey
NCT07344480	Not specified	RECRUITING	Retrospective Natural History Study of RASopathy-associated Cardiomyopathy (RAS-CM)
NCT07464821	Not specified	RECRUITING	National Multicentre Study on Lipid Profile in Noonan Syndrome and Related Disorders: Trends by Age, Gender and Genotype