FOXP2

Summary

FOXP2 (forkhead box P2, HGNC:13875) is a protein-coding gene on chromosome 7q31.1, encoding Forkhead box protein P2 (O15409). Transcriptional repressor that may play a role in the specification and differentiation of lung epithelium. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the forkhead/winged-helix (FOX) family of transcription factors. It is expressed in fetal and adult brain as well as in several other organs such as the lung and gut. The protein product contains a FOX DNA-binding domain and a large polyglutamine tract and is an evolutionarily conserved transcription factor, which may bind directly to approximately 300 to 400 gene promoters in the human genome to regulate the expression of a variety of genes. This gene is required for proper development of speech and language regions of the brain during embryogenesis, and may be involved in a variety of biological pathways and cascades that may ultimately influence language development. Mutations in this gene cause speech-language disorder 1 (SPCH1), also known as autosomal dominant speech and language disorder with orofacial dyspraxia. Multiple alternative transcripts encoding different isoforms have been identified in this gene.

Source: NCBI Gene 93986 — RefSeq curated summary.

At a glance

• Gene–disease (curated): specific language disorder (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 68
• Clinical variants (ClinVar): 457 total — 57 pathogenic, 21 likely-pathogenic
• Phenotypes (HPO): 72
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 11 downstream targets (CollecTRI)
• MANE Select transcript: NM_014491

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13875
Approved symbol	FOXP2
Name	forkhead box P2
Location	7q31.1
Locus type	gene with protein product
Status	Approved
Aliases	CAGH44
Ensembl gene	ENSG00000128573
Ensembl biotype	protein_coding
OMIM	605317
Entrez	93986

Gene structure

Transcript identifiers

Ensembl transcripts: 48 — 39 protein_coding, 5 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

ENST00000350908, ENST00000360232, ENST00000378237, ENST00000390668, ENST00000393489, ENST00000393494, ENST00000393495, ENST00000393498, ENST00000403559, ENST00000408937, ENST00000412402, ENST00000440349, ENST00000441290, ENST00000452963, ENST00000459666, ENST00000462331, ENST00000495516, ENST00000634372, ENST00000634411, ENST00000634623, ENST00000634664, ENST00000635109, ENST00000635534, ENST00000635563, ENST00000635638, ENST00000703612, ENST00000703613, ENST00000703614, ENST00000703615, ENST00000703616, ENST00000703617, ENST00000703618, ENST00000901759, ENST00000901760, ENST00000901761, ENST00000901762, ENST00000901763, ENST00000901764, ENST00000901765, ENST00000901766, ENST00000901767, ENST00000901768, ENST00000960355, ENST00000960356, ENST00000960357, ENST00000960358, ENST00000960359, ENST00000960360

RefSeq mRNA: 6 — MANE Select: NM_014491 NM_001172766, NM_001172767, NM_014491, NM_148898, NM_148899, NM_148900

CCDS: CCDS43635, CCDS55154, CCDS5760, CCDS5761

Canonical transcript exons

ENST00000350908 — 17 exons

Exon	Start	End
ENSE00001914177	114414815	114415360
ENSE00003357185	114689782	114693765
ENSE00003491906	114652203	114652290
ENSE00003498832	114664273	114664436
ENSE00003527883	114662065	114662186
ENSE00003543277	114663450	114663519
ENSE00003561477	114628540	114628677
ENSE00003569605	114644685	114644789
ENSE00003572969	114658066	114658267
ENSE00003585047	114659356	114659432
ENSE00003592860	114426502	114426679
ENSE00003598938	114534617	114534706
ENSE00003599193	114642410	114642623
ENSE00003606163	114659572	114659673
ENSE00003652522	114653926	114654009
ENSE00003689434	114631528	114631705
ENSE00003989485	114629805	114630005

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 93.37.

FANTOM5 (CAGE): breadth broad, TPM avg 3.6055 / max 125.1893, expressed in 819 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
80553	2.9325	785
80552	0.2493	106
80556	0.1081	39
80560	0.0790	38
80558	0.0720	35
80555	0.0600	27
80557	0.0458	17
80559	0.0397	21
80561	0.0190	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	93.37	gold quality
tibialis anterior	UBERON:0001385	89.48	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.36	gold quality
bronchial epithelial cell	CL:0002328	88.67	gold quality
endothelial cell	CL:0000115	88.24	gold quality
bronchus	UBERON:0002185	88.03	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.65	gold quality
colonic epithelium	UBERON:0000397	87.03	gold quality
adrenal tissue	UBERON:0018303	86.24	gold quality
sperm	CL:0000019	85.90	gold quality
deltoid	UBERON:0001476	85.03	silver quality
sural nerve	UBERON:0015488	84.89	gold quality
calcaneal tendon	UBERON:0003701	84.56	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	84.26	gold quality
smooth muscle tissue	UBERON:0001135	83.29	gold quality
mucosa of stomach	UBERON:0001199	83.02	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	82.88	gold quality
lower esophagus	UBERON:0013473	82.73	gold quality
lower esophagus muscularis layer	UBERON:0035833	82.73	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	82.62	gold quality
biceps brachii	UBERON:0001507	82.61	gold quality
vastus lateralis	UBERON:0001379	82.44	silver quality
quadriceps femoris	UBERON:0001377	82.36	silver quality
cortical plate	UBERON:0005343	81.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.69	gold quality
cartilage tissue	UBERON:0002418	81.18	gold quality
large intestine	UBERON:0000059	80.89	gold quality
colon	UBERON:0001155	80.73	gold quality
skeletal muscle tissue	UBERON:0001134	80.43	gold quality
rectum	UBERON:0001052	80.40	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-131882	yes	1559.69
E-HCAD-35	yes	710.26
E-ANND-3	yes	7.51
E-ANND-2	no	735.80
E-ENAD-27	no	3.62
E-CURD-112	no	2.82

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

11 targets.

Target	Regulation
AUTS2	Activation
CNTNAP2	Repression
GRIN2B	Activation
MET	Repression
NKX2-1	Repression
PLAUR	Activation
RELN	Activation
SCGB1A1	Repression
SFTPC
SRPX	Activation
SRPX2	Unknown

JASPAR motifs

Motif	Name	Family
MA0593.1	FOXP2	FOX
MA0593.2	FOXP2	FOX

JASPAR matrix evidence (PMIDs): PMID:23625967

Upstream regulators (CollecTRI, top): FOXP4, POU3F2

miRNA regulators (miRDB)

155 targeting FOXP2, 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-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-9-3P	99.96	70.88	2068

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• FOXP2 is disrupted by a translocation in CS, a child with severe speech/language disorder. Moreover, a point mutation, altering a critical residue of the forkhead domain, segregates with speech/language deficits in all 15 affected members of family KE. (PMID:11586359)
• FOXP2 is not a major susceptibility gene for autism or specific language impairment (PMID:11894222)
• Although rare severe speech disorders may result from mutation in a single gene, common disorders are more likely to result from multiple genetic factors. (PMID:12060812)
• We genotyped the FOXP2 mutation for 270 4-year-old children selected for low general language scores from a representative community sample of more than 18,000 children. No language-impaired child had the FOXP2 mutation. (PMID:12060812)
• Human FOXP2 contains changes in amino-acid coding and a pattern of nucleotide polymorphism, which strongly suggest that this gene has been the target of selection during recent human evolution. (PMID:12192408)
• A survey of a diverse group of placental mammals reveals the uniqueness of the human FOXP2 sequence and a population genetic analysis indicates possible adaptive selection behind the accelerated evolution. (PMID:12524352)
• Genetic factors for regulation of common language impairment appear to reside in the vicinity of FOXP2. (PMID:12721956)
• FOXP2/foxp2 is expressed in several structures in developing human/mouse brain including cortical plate, basal ganglia, thalamus, inferior olives and cerebellum. These data suggest a conserved mammalian role in development of motor-related neural circuits (PMID:12876151)
• This experiment findings suggest that the FOXP2 gene is critically involved in the development of the neural systems that mediate speech and language. (PMID:14555953)
• complex regulatory mechanism underlying Foxp1, Foxp2, and Foxp4 activity, demonstrating that Foxp1, Foxp2, and Foxp4 are the first Fox proteins reported whose activity is regulated by homo- and heterodimerization (PMID:14701752)
• impact of disease-causing missense mutations on the three-dimensional structure, stability, and surface electrostatic charge distribution of the forkhead domains is examined (PMID:14997560)
• FOXP1 and FOXP2 expression patterns in human fetal brain are strikingly similar to those in the songbird, including localization to subcortical structures that function in sensorimotor integration and the control of skilled, coordinated movement (PMID:15056695)
• Findings suggest that the FOXP2 gene may be involved in the pathogenesis of autism in Chinese population. (PMID:15108192)
• a mutation in FOXP2 had been found in a family with a speech and language disorder. (PMID:15685218)
• Truncation of FOXP2 is the cause of developmental speech and language deficits. (PMID:15877281)
• Review. FOXP2 codes for a CNS transcriptional repressor, expressed in the basal ganglia, cortex, cerebellum & the thalamus, involved in thalamic-cortical-striatal circuits for motor planning & learning. Its loss causes specific language impairment. (PMID:15948071)
• Disease-causing mutations in FOXP2 map either to the DNA binding surface or the domain-swapping dimer interface, functionally corroborating the crystal structure. (PMID:16407075)
• The single nucleotide polymorphism rs2396753 appears to confer vulnerability to schizophrenia with auditory hallucinations. (PMID:16538183)
• study of a mutation in FOXP2 using human cell-lines; focus was on three unusual FOXP2 coding variants uniquely identified in cases of verbal dyspraxia; expression, subcellular localization, DNA-binding and transactivation properties were assessed (PMID:16984964)
• absence of paternal FOXP2 is the cause of developmental verbal dyspraxia in patients with Silver-Russell Syndrome with maternal uniparental disomy of chromosome 7 (PMID:17033973)
• Mutant and wild type FOXP2 heterodimers in the nucleus or FOXP2 R553H in the cytoplasm may underlie the pathogenesis of the autosomal dominant speech/language disorder. (PMID:17196932)
• REVIEW evidence that FOXP2, a gene within the SPCH1 region, is involved with speech and language development. It is unclear however whether the AUTS1 (autistic spectrum 1) locus, highly linked to 7q31, overlaps with the SPCH1 and FOXP2. (PMID:17330859)
• First insight into the functional network of genes directly regulated by FOXP2 in human brain and by evolutionary comparisons, highlighting genes likely to be involved in the development of human higher-order cognitive processes. (PMID:17999357)
• FOXP2 has funcionality in modulating synaptic plasticity, neurodevelopment, neurotransmission, and axon guidance in the brain and is mutated in speech and language disorders. (PMID:17999362)
• identified four transcription start sites for FOXP2, the fourth being in a novel exon (PMID:18316164)
• Results describe the timing of selection at the human FOXP2 gene. (PMID:18413354)
• The FOXP2-CNTNAP2 pathway provides a mechanistic link between clinically distinct syndromes involving disrupted language. (PMID:18987363)
• FOXP2 has a role in speech and language [review] (PMID:19304338)
• Study introduced 2 amino acid substitutions selected during human evolution into Foxp2 gene of mice; these mice have different vocalizations, decreased exploratory behavior and decreased dopamine showing the humanized Foxp2 allele affects basal ganglia. (PMID:19490899)
• The selective sweep reflected in FOXP2 polymorphism data was not associated with the two amino acid substitutions. (PMID:19608635)
• study provides additional evidence that language-in particular, grammar-is likely to be influenced by abnormalities of FOXP2 function (PMID:19797137)
• data provide experimental support for the functional relevance of changes in FOXP2 that occur on the human lineage, highlighting specific pathways with direct consequences for human brain development and disease in the central nervous system (PMID:19907493)
• FOXP2 gene was detected higher degree of methylation of CpG island in the left parahippocampus gyrus than in the right one. (PMID:20649982)
• The FOXP2-SRPX2/uPAR network provides exciting insights into molecular pathways underlying speech-related disorders. (PMID:20858596)
• Genetic variations within FOXP2 modulate frontotemporal lobar degeneration, leading to hypoperfusion in language-associated brain areas affecting language performances. (PMID:20858950)
• Our data support a possible role of FOXP2 in the vulnerability to speech sound disorder (PMID:20923434)
• Although FOXP2 transgene is expressed in many brain regions and has multiple roles during mammalian development, the protein affects the brain regions that are connected via cortico-basic ganglia circuits. (PMID:21111790)
• The common single nucleotide polymorphism (SNP) rs2396753 (C>A) variant of FOXP2 has significant effects on grey matter concentrations in patients with schizophrenia, within regions of the brain known to be affected by this disease. (PMID:21334420)
• Word repetition in members affected by an inherited speech-language disorder is severely impaired, and brain activation is significantly reduced in the premotor, supplementary and primary motor cortices, as well as in the cerebellum and basal ganglia. (PMID:21576028)
• This paper will review evidence (referring to the «language gene»FOXP2 as a leading example), try to suggest plausible reasons for such a perplexing output, and discuss if such reasons really explain the aetiology of language disorders–{REVIEW} (PMID:21652119)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	foxp2	ENSDARG00000005453
mus_musculus	Foxp2	ENSMUSG00000029563
rattus_norvegicus	Foxp2	ENSRNOG00000054508
caenorhabditis_elegans		WBGENE00001439

Paralogs (4): FOXP4 (ENSG00000137166), FOXF2 (ENSG00000137273), FOXI1 (ENSG00000168269), FOXG1 (ENSG00000176165)

Protein

Protein identifiers

Forkhead box protein P2 — O15409 (reviewed: O15409)

Alternative names: CAG repeat protein 44, Trinucleotide repeat-containing gene 10 protein

All UniProt accessions (17): O15409, A0A0U1RQE0, A0A0U1RQE6, A0A0U1RQM2, A0A0U1RQR8, A0A0U1RQY3, A0A994J3Y0, A0A994J6H2, A0A994J6W1, A8MTU2, A8MUV4, C9JQP8, F8WDL6, Q0PRL4, Q75MZ5, Q8N6B5, X5D2H2

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor that may play a role in the specification and differentiation of lung epithelium. May also play a role in developing neural, gastrointestinal and cardiovascular tissues. Can act with CTBP1 to synergistically repress transcription but CTPBP1 is not essential. Plays a role in synapse formation by regulating SRPX2 levels. Involved in neural mechanisms mediating the development of speech and language.

Subunit / interactions. Forms homodimers and heterodimers with FOXP1 and FOXP4. Dimerization is required for DNA-binding. Interacts with CTBP1. Interacts with FOXP1. Isoform 1 and isoform 3 interact with TBR1. Interacts with ZMYM2.

Subcellular location. Nucleus.

Tissue specificity. Isoform 1 and isoform 6 are expressed in adult and fetal brain, caudate nucleus and lung.

Disease relevance. Speech-language disorder 1 (SPCH1) [MIM:602081] A disorder characterized by severe orofacial dyspraxia resulting in largely incomprehensible speech. Affected individuals have severe impairment in the selection and sequencing of fine orofacial movements which are necessary for articulation, and deficits in several facets of grammatical skills and language processing, such as the ability to break up words into their constituent phonemes. The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberration involving FOXP2 is a cause of severe speech and language impairment. Translocation t(5;7)(q22;q31.2).

Domain organisation. The leucine zipper (ZIP) is required for dimerization and transcriptional repression.

Isoforms (9)

UniProt ID	Names	Canonical?
O15409-1	1, I	yes
O15409-3	2, II
O15409-2	3, III, IV
O15409-4	4
O15409-5	5
O15409-6	6, FOXP2-S
O15409-7	7
O15409-8	8
O15409-9	9

RefSeq proteins (6): NP_001166237, NP_001166238, NP_055306, NP_683696, NP_683697, NP_683698 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001766	Fork_head_dom	Domain
IPR030456	TF_fork_head_CS_2	Conserved_site
IPR032354	FOXP-CC	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR047412	FH_FOXP1_P2	Domain
IPR050998	FOXP	Family

Pfam: PF00250, PF16159

UniProt features (36 total): splice variant 10, region of interest 6, compositionally biased region 5, sequence conflict 4, helix 4, strand 2, chain 1, domain 1, zinc finger region 1, sequence variant 1, DNA-binding region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2A07	X-RAY DIFFRACTION	1.9
2AS5	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15409-F1	60.82	0.14

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9764790	Positive Regulation of CDH1 Gene Transcription

MSigDB gene sets: 542 (showing top): GOBP_HINDBRAIN_DEVELOPMENT, GOBP_EPITHELIUM_DEVELOPMENT, FREAC2_01, GOBP_LUNG_EPITHELIUM_DEVELOPMENT, GOBP_METENCEPHALON_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_COGNITION, HNF3ALPHA_Q6, GOBP_BEHAVIOR, CCAWYNNGAAR_UNKNOWN, NKX25_02, GCANCTGNY_MYOD_Q6, NIKOLSKY_OVERCONNECTED_IN_BREAST_CANCER, GOBP_CEREBELLAR_PURKINJE_CELL_LAYER_FORMATION, GOBP_LUNG_MORPHOGENESIS

GO Biological Process (24): positive regulation of mesenchymal cell proliferation (GO:0002053), regulation of transcription by RNA polymerase II (GO:0006357), skeletal muscle tissue development (GO:0007519), post-embryonic development (GO:0009791), gene expression (GO:0010467), cerebellar Purkinje cell differentiation (GO:0021702), caudate nucleus development (GO:0021757), putamen development (GO:0021758), cerebral cortex development (GO:0021987), vocal learning (GO:0042297), camera-type eye development (GO:0043010), negative regulation of DNA-templated transcription (GO:0045892), lung alveolus development (GO:0048286), smooth muscle tissue development (GO:0048745), righting reflex (GO:0060013), positive regulation of epithelial cell proliferation involved in lung morphogenesis (GO:0060501), epithelial cell proliferation involved in lung morphogenesis (GO:0060502), vocalization behavior (GO:0071625), negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), cerebellum development (GO:0021549), lung development (GO:0030324), animal organ development (GO:0048513), positive regulation of epithelial cell proliferation (GO:0050679)

GO Molecular Function (12): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), transcription coregulator binding (GO:0001221), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), sequence-specific DNA binding (GO:0043565), protein binding (GO:0005515), metal ion binding (GO:0046872)

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

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Regulation of CDH1 Gene Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
transcription by RNA polymerase II	2
striatum development	2
neural nucleus development	2
anatomical structure development	2
DNA-templated transcription	2
regulation of transcription by RNA polymerase II	2
positive regulation of cell population proliferation	1
mesenchymal cell proliferation	1
regulation of mesenchymal cell proliferation	1
striated muscle tissue development	1
skeletal muscle organ development	1
multicellular organism development	1
multicellular organismal process	1
macromolecule biosynthetic process	1
cell differentiation in hindbrain	1
cerebellar Purkinje cell layer formation	1
central nervous system neuron differentiation	1
pallium development	1
auditory behavior	1
imitative learning	1
learned vocalization behavior or vocal learning	1
eye development	1
negative regulation of RNA biosynthetic process	1
lung development	1
muscle tissue development	1
reflex	1
positive regulation of epithelial cell proliferation	1
epithelial cell proliferation involved in lung morphogenesis	1
regulation of epithelial cell proliferation involved in lung morphogenesis	1
epithelial cell proliferation	1
lung morphogenesis	1
lung epithelium development	1
behavior	1
negative regulation of 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

Protein interactions and networks

STRING

2336 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FOXP2	CNTNAP2	Q9UHC6	978
FOXP2	CTBP1	Q13363	839
FOXP2	ROBO1	Q9Y6N7	802
FOXP2	TBR1	Q16650	801
FOXP2	DNAAF4	Q8WXU2	698
FOXP2	NKX2-1	P43699	671
FOXP2	NRXN2	Q9P2S2	668
FOXP2	FOXP4	Q8IVH2	662
FOXP2	KIAA0319	Q5VV43	662
FOXP2	CUX1	P39880	656
FOXP2	NRXN1	Q9ULB1	650
FOXP2	CITED2	Q99967	632
FOXP2	RELN	P78509	631
FOXP2	ST7	Q9NRC1	629
FOXP2	BCL11B	Q9C0K0	626

IntAct

92 interactions, top by confidence:

A	B	Type	Score
FOXP1	FOXP2	psi-mi:“MI:0914”(association)	0.910
FOXP2	FOXP1	psi-mi:“MI:2364”(proximity)	0.910
FOXP2	FOXP1	psi-mi:“MI:0403”(colocalization)	0.910
FOXP2	FOXP1	psi-mi:“MI:0915”(physical association)	0.910
FOXP1	FOXP2	psi-mi:“MI:0403”(colocalization)	0.910
FOXP1	FOXP2	psi-mi:“MI:0915”(physical association)	0.910
FOXP4	FOXP2	psi-mi:“MI:0914”(association)	0.770
FOXP2	FOXP4	psi-mi:“MI:0914”(association)	0.770
FOXP2	FOXP4	psi-mi:“MI:0915”(physical association)	0.770
FOXP2	CTBP1	psi-mi:“MI:0915”(physical association)	0.760
CTBP1	FOXP2	psi-mi:“MI:0915”(physical association)	0.760
FOXP2	FOXP2	psi-mi:“MI:0914”(association)	0.740
FOXP2	FOXP2	psi-mi:“MI:0407”(direct interaction)	0.740
FOXP2	FOXP2	psi-mi:“MI:2364”(proximity)	0.740
PIN1	FOXP2	psi-mi:“MI:0915”(physical association)	0.720
TSACC	FOXP2	psi-mi:“MI:0915”(physical association)	0.720
FOXP2	PIN1	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (129): FOXP2 (Two-hybrid), FOXP2 (Two-hybrid), FOXP2 (Two-hybrid), FOXP2 (Two-hybrid), FOXP2 (Two-hybrid), FOXP2 (Two-hybrid), FOXP2 (Two-hybrid), FOXP2 (Two-hybrid), TSACC (Two-hybrid), FAM124A (Two-hybrid), FOXP2 (Affinity Capture-MS), FOXP1 (Affinity Capture-MS), FOXP4 (Affinity Capture-MS), FOXP2 (Affinity Capture-MS), FOXP2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JTZ2, A2BEA6, A4IFD2, B1H349, B3DM43, B3DM47, F1M8W4, O15409, O75030, P0CF24, P23899, P27889, P35680, P35710, P35711, P35712, P40645, P40647, P58463, P70062, P70063, P70064, Q23045, Q2LE08, Q4VYR7, Q4VYS1, Q58NQ4, Q5QL03, Q5RCU4, Q5RER5, Q5W1J5, Q6GL68, Q800Q5, Q86MD3, Q8HZ00, Q8MJ97, Q8MJ98, Q8MJ99, Q8MJA0, Q8STF6

Diamond homologs: A4IFD2, F1QDF8, F1R8Z9, O00409, O13606, O15409, O42097, P0CF24, P23512, P32314, P32315, P33205, P33206, P35582, P35583, P55316, P55317, P56260, P58462, P58463, P84961, Q00939, Q01167, Q07342, Q16676, Q17381, Q1A1A1, Q1A1A2, Q1A1A3, Q1A1A4, Q1A1A5, Q1A1A6, Q28D67, Q28EM1, Q28G71, Q28HT3, Q2LE08, Q32NH9, Q33BP8, Q3BJS3

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
TBR1	“up-regulates activity”	FOXP2	binding
FOXP2	“up-regulates quantity by expression”	AUTS2	“transcriptional regulation”
FOXP2	“up-regulates quantity by expression”	RELN	“transcriptional regulation”
FOXP2	“up-regulates quantity by expression”	GRIN2B	“transcriptional regulation”
FOXP2	“down-regulates quantity by repression”	MET	“transcriptional regulation”
FOXP2	“up-regulates activity”	FOXP2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	57
Likely pathogenic	21
Uncertain significance	204
Likely benign	65
Benign	64

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1065476	NM_014491.4(FOXP2):c.586C>T (p.Gln196Ter)	Pathogenic
1069693	NM_014491.4(FOXP2):c.782del (p.Gly260_Leu261insTer)	Pathogenic
1072833	NM_014491.4(FOXP2):c.460C>T (p.Gln154Ter)	Pathogenic
1098279	NM_014491.4(FOXP2):c.559C>T (p.Gln187Ter)	Pathogenic
1098372	NM_014491.4(FOXP2):c.1168del (p.Gln390fs)	Pathogenic
1119985	NM_014491.4(FOXP2):c.1432C>T (p.Arg478Ter)	Pathogenic
1119990	NM_014491.4(FOXP2):c.1690C>T (p.Arg564Ter)	Pathogenic
167096	NM_014491.4(FOXP2):c.678dup (p.Leu227fs)	Pathogenic
1686660	NM_014491.4(FOXP2):c.538C>T (p.Gln180Ter)	Pathogenic
1702645	NM_014491.4(FOXP2):c.1266+1G>C	Pathogenic
1710219	NM_014491.4(FOXP2):c.1540del (p.Arg514fs)	Pathogenic
2024136	NM_014491.4(FOXP2):c.367C>T (p.Gln123Ter)	Pathogenic
2269641	NM_014491.4(FOXP2):c.1127_1128insT (p.Ser377fs)	Pathogenic
242953	t(3;7)(q23;q31.2)	Pathogenic
242954	t(5;7)(q22;q31.2)	Pathogenic
242955	t(7;13)(q31.1;q13.2)	Pathogenic
242957	NC_000007.12:g.111781517_120142536del	Pathogenic
242958	7q31.1-q31.2, 6.5 Mb deletion	Pathogenic
242959	7q31.1-q31.3, 14.8 Mb deletion	Pathogenic
242960	7q31.1-q31.2, 1.57 Mb deletion	Pathogenic
242961	7q31.1-q31.2, 9.1 Mb deletion	Pathogenic
242962	7q31.1-q31.3, 16 Mb deletion	Pathogenic
242963	7q31.1-q31.3, 11 Mb deletion	Pathogenic
242964	7q31.1-q31.3, 15 Mb deletion	Pathogenic
242965	NC_000007.12:g.112946520_114520576del	Pathogenic
242966	7q31.2-q32, 13 Mb deletion	Pathogenic
242967	7q31.2-q32, 14 Mb deletion	Pathogenic
242968	7q31.2-q32, 15 Mb deletion	Pathogenic
242969	7q31.2-q32, 26 Mb deletion	Pathogenic
242970	7q22-q31.3 deletion (15 Mb)	Pathogenic

SpliceAI

4297 predictions. Top by Δscore:

Variant	Effect	Δscore
7:114426498:TTA:T	acceptor_loss	1.0000
7:114426499:TAGGT:T	acceptor_loss	1.0000
7:114426500:A:AG	acceptor_gain	1.0000
7:114426501:G:GC	acceptor_loss	1.0000
7:114426501:G:GG	acceptor_gain	1.0000
7:114426501:GGT:G	acceptor_gain	1.0000
7:114426501:GGTA:G	acceptor_gain	1.0000
7:114426676:GCAG:G	donor_gain	1.0000
7:114426677:CAG:C	donor_gain	1.0000
7:114426677:CAGG:C	donor_loss	1.0000
7:114426678:AG:A	donor_gain	1.0000
7:114426679:GG:G	donor_gain	1.0000
7:114426679:GGT:G	donor_loss	1.0000
7:114426680:G:GG	donor_gain	1.0000
7:114426680:GT:G	donor_loss	1.0000
7:114534702:TGCAG:T	donor_loss	1.0000
7:114534703:GCAGG:G	donor_loss	1.0000
7:114534704:CAGGT:C	donor_loss	1.0000
7:114534705:AG:A	donor_loss	1.0000
7:114534706:GGTT:G	donor_loss	1.0000
7:114534707:GTT:G	donor_loss	1.0000
7:114534708:T:G	donor_loss	1.0000
7:114628532:T:A	acceptor_gain	1.0000
7:114628534:T:TA	acceptor_gain	1.0000
7:114628535:GCAA:G	acceptor_loss	1.0000
7:114628536:CAA:C	acceptor_loss	1.0000
7:114628537:A:AG	acceptor_gain	1.0000
7:114628537:AAG:A	acceptor_gain	1.0000
7:114628537:AAGGT:A	acceptor_gain	1.0000
7:114628538:A:G	acceptor_gain	1.0000

AlphaMissense

4712 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:114628634:T:C	L118P	1.000
7:114644720:T:C	L342P	1.000
7:114644737:T:A	C348S	1.000
7:114644737:T:C	C348R	1.000
7:114644737:T:G	C348G	1.000
7:114644738:G:A	C348Y	1.000
7:114644738:G:C	C348S	1.000
7:114644738:G:T	C348F	1.000
7:114644739:C:G	C348W	1.000
7:114644743:T:A	W350R	1.000
7:114644743:T:C	W350R	1.000
7:114644744:G:C	W350S	1.000
7:114644745:G:C	W350C	1.000
7:114644745:G:T	W350C	1.000
7:114644747:C:A	P351Q	1.000
7:114644749:G:C	G352R	1.000
7:114644752:T:A	C353S	1.000
7:114644752:T:C	C353R	1.000
7:114644753:G:A	C353Y	1.000
7:114644753:G:C	C353S	1.000
7:114644753:G:T	C353F	1.000
7:114644754:T:G	C353W	1.000
7:114644782:T:A	F363I	1.000
7:114644782:T:C	F363L	1.000
7:114644783:T:C	F363S	1.000
7:114644784:T:A	F363L	1.000
7:114644784:T:G	F363L	1.000
7:114652204:C:G	H366D	1.000
7:114652205:A:C	H366P	1.000
7:114652205:A:G	H366R	1.000

dbSNP variants (sampled 300 via entrez): RS1000001435 (7:114177325 TG>T), RS1000005103 (7:114508964 T>C), RS1000014283 (7:114352781 A>G), RS1000016355 (7:114458489 AATC>A), RS1000016788 (7:114416914 C>A), RS1000026739 (7:114363734 G>A), RS1000030562 (7:114539144 T>A,C,G), RS1000031297 (7:114104234 G>A,T), RS1000035708 (7:114531376 T>A,C), RS1000036319 (7:114116131 G>C), RS1000039637 (7:114196657 A>G), RS1000040880 (7:114550210 T>C), RS1000043928 (7:114566551 T>A), RS1000047554 (7:114580383 G>A), RS1000048771 (7:114408326 T>A,C)

Disease associations

OMIM: gene MIM:605317 | disease phenotypes: MIM:602081

GenCC curated gene-disease

Disease	Classification	Inheritance
childhood apraxia of speech	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
specific language disorder	Definitive	AD

Mondo (4): childhood apraxia of speech (MONDO:0011184), lung adenocarcinoma (MONDO:0005061), squamous cell carcinoma (MONDO:0005096), intellectual disability (MONDO:0001071)

Orphanet (3): Isolated childhood apraxia of speech (Orphanet:209908), NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

72 total (30 of 72 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000154	Wide mouth
HP:0000176	Submucous cleft hard palate
HP:0000256	Macrocephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000327	Hypoplasia of the maxilla
HP:0000343	Long philtrum
HP:0000369	Low-set ears
HP:0000396	Overfolded helix
HP:0000448	Prominent nose
HP:0000473	Torticollis
HP:0000506	Telecanthus
HP:0000729	Autistic behavior
HP:0000736	Short attention span
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0001212	Prominent fingertip pads
HP:0001249	Intellectual disability
HP:0001260	Dysarthria
HP:0001328	Specific learning disability
HP:0001357	Plagiocephaly
HP:0001511	Intrauterine growth retardation
HP:0001611	Hypernasal speech
HP:0001631	Atrial septal defect
HP:0002015	Dysphagia
HP:0002020	Gastroesophageal reflux
HP:0002099	Asthma
HP:0002134	Abnormal basal ganglia morphology
HP:0002167	Abnormal speech pattern

GWAS associations

68 associations (top):

Study	Trait	p-value
GCST001652_1	Crohn’s disease	7.000000e-06
GCST002587_11	Blood pressure (smoking interaction)	3.000000e-07
GCST002587_12	Blood pressure (smoking interaction)	3.000000e-06
GCST002783_21	Body mass index	5.000000e-06
GCST002828_16	Urate levels in obese individuals	7.000000e-06
GCST003225_1	Pelvic organ prolapse (moderate/severe)	2.000000e-06
GCST003475_7	Beard thickness	1.000000e-08
GCST003723_6	Serum sulfate level	4.000000e-06
GCST003795_7	Age at first birth	2.000000e-10
GCST003980_3	Sleep duration	3.000000e-07
GCST004286_4	Midgestational circulating levels of PBDEs (fetal genetic effect)	6.000000e-07
GCST004370_6	Deep ovarian and/or rectovaginal disease with dense adhesions	5.000000e-07
GCST004721_14	Congenital heart disease (maternal effect)	5.000000e-06
GCST004723_12	Conotruncal heart defects (maternal effects)	8.000000e-06
GCST004904_39	Body mass index	4.000000e-08
GCST005232_5	Neuroticism	3.000000e-08
GCST006045_9	Age at first birth	8.000000e-09
GCST006461_2	Self-reported risk-taking behaviour	6.000000e-14
GCST006665_8	Social science traits (pleiotropy) (HIPO component 1)	1.000000e-08
GCST006810_2	Self-reported risk-taking behaviour	4.000000e-14
GCST006941_25	Irritable mood	9.000000e-09
GCST006941_26	Irritable mood	1.000000e-10
GCST006941_28	Irritable mood	8.000000e-10
GCST006952_29	Feeling tense	1.000000e-09
GCST006952_30	Feeling tense	4.000000e-09
GCST006952_31	Feeling tense	4.000000e-09
GCST006983_13	Attention deficit hyperactivity disorder or cannabis use	6.000000e-10
GCST006983_14	Attention deficit hyperactivity disorder or cannabis use	1.000000e-08
GCST007324_54	Adventurousness	1.000000e-19
GCST007325_17	General risk tolerance (MTAG)	3.000000e-08

EFO canonical traits (35, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006525	cigarettes per day measurement
EFO:0006526	pack-years measurement
EFO:0004340	body mass index
EFO:0004531	urate measurement
EFO:0007864	sulfate measurement
EFO:0009101	age at first birth measurement
EFO:0007959	fetal genotype effect measurement
EFO:0007961	polybrominated biphenyl measurement
EFO:0007962	polybrominated diphenyl ether measurement
EFO:0007964	gestational serum measurement
EFO:0007660	neuroticism measurement
EFO:0008579	risk-taking behaviour
EFO:0007006	depressive symptom measurement
EFO:0007869	wellbeing measurement
EFO:0009594	irritability measurement
EFO:0009596	feeling tense measurement
EFO:0007585	Cannabis use
EFO:0007876	insomnia measurement
EFO:0008328	chronotype measurement
EFO:0007010	drug use measurement
EFO:0004338	body weight
EFO:0010100	multisite chronic pain
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0007778	urinary albumin to creatinine ratio
EFO:0009695	household income
EFO:0007979	childhood trauma measurement
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D002294	Carcinoma, Squamous Cell	C04.557.470.200.400; C04.557.470.700.400
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases expression	5
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases methylation	2
Nickel	decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, decreases methylation	1
mivebresib	decreases expression	1
TAK-243	decreases sumoylation	1
bufotalin	decreases expression	1
bisphenol A	affects methylation, affects cotreatment, decreases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	decreases methylation	1
manganese chloride	increases expression	1
benzo(e)pyrene	increases methylation	1
crocin	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
avobenzone	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
NSC 689534	affects binding, increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Vorinostat	increases expression	1
Cadmium	decreases expression, increases abundance	1
Carbamazepine	affects expression	1
Copper	affects binding, increases expression	1
Coumestrol	affects cotreatment, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Folic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02399566	PHASE4	UNKNOWN	Clinical Trial of Erlotinib and Pemetrexed for Maintenance Treatment in Lung Adenocarcinoma
NCT02804646	PHASE4	UNKNOWN	Endostar Durative Transfusion Combined With Chemotherapy in the Treatment of Advanced Lung Adenocarcinoma
NCT00002852	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Stage I Non-small Cell Lung Cancer
NCT00005838	PHASE3	COMPLETED	Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00020709	PHASE3	COMPLETED	Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00049543	PHASE3	COMPLETED	Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery
NCT00946712	PHASE3	TERMINATED	S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer
NCT01798485	PHASE3	TERMINATED	A Phase 3 Study of Ganetespib in Combination With Docetaxel Versus Docetaxel Alone in Patients With Advanced NSCLC
NCT02011997	PHASE3	UNKNOWN	Comparison of cVATS Segmentectomy Versus Lobectomy for Lung Adenocarcinoma in Situ and With Microinvasion
NCT03391869	PHASE3	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab With or Without Local Consolidation Therapy in Treating Patients With Stage IV Non-Small Cell Lung Cancer
NCT03676192	PHASE3	COMPLETED	To Compare Efficacy and Safety of CT-P16 and European Union-Approved Avastin as First-Line Treatment for Metastatic or Recurrent Non-Squamous Non-Small Cell Lung Cancer
NCT04339218	PHASE3	RECRUITING	Cryoablation in Combination (or Not) With Pembrolizumab and Pemetrexed-carboplatin in 1st-line Treatment for Patients With Metastatic Lung Adenocarcinoma
NCT05204758	PHASE3	COMPLETED	Prophylactic TCM for Mitigation of EGFR-TKI Related Dermatological Adverse Effect
NCT05717803	PHASE3	RECRUITING	Segmentectomy for Ground Glass-dominant Invasive Lung Cancer (ECTOP-1012)
NCT05943795	PHASE3	ACTIVE_NOT_RECRUITING	A Clinical Study of SI-B001 Combined With Docetaxel in the Treatment of Non-small Cell Lung Adenocarcinoma and Lung Squamous Cell Carcinoma
NCT06031181	PHASE3	RECRUITING	Sublobar Resection for Adenocarcinoma in Situ/Minimally Invasive Adenocarcinoma Diagnosed by Intraoperative Frozen Section (ECTOP-1019)
NCT06031246	PHASE3	RECRUITING	Selective Lymph Node Dissection for cT1N0M0 Invasive NSCLC With CTR>0.5 Located in the Apical Segment (ECTOP-1018)
NCT06634966	PHASE3	RECRUITING	Segmentectomy for Solid-dominant Lung Cancer
NCT07169903	PHASE3	NOT_YET_RECRUITING	Segmentectomy vs Lobectomy for 2 - 3cm IASLC Grade 1-2 Lung Adenocarcinoma: A Multi-center RCT
NCT07481786	PHASE3	RECRUITING	Bevacizumab Plus FSRT Versus Hippocampus-Avoidant WBRT in Lung Adenocarcinoma With Extensive Brain Metastases
NCT05185583	PHASE2	COMPLETED	Methylphenidate in Childhood Apraxia of Speech
NCT07216001	PHASE2	NOT_YET_RECRUITING	Role of Omega-DEK in Childhood Apraxia of Speech
NCT00040794	PHASE2	COMPLETED	Combination Chemotherapy, Radiation Therapy, and Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer
NCT00087412	PHASE2	COMPLETED	S0341: Erlotinib in Treating Patients With Advanced Primary Non-Small Cell Lung Cancer
NCT00118144	PHASE2	COMPLETED	Bortezomib in Treating Patients With Stage IIIB or Stage IV Lung Cancer
NCT00118183	PHASE2	COMPLETED	Docetaxel With Either Cetuximab or Bortezomib as First-Line Therapy in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer
NCT00126581	PHASE2	COMPLETED	Erlotinib Hydrochloride With or Without Carboplatin and Paclitaxel in Treating Patients With Stage III-IV Non-small Cell Lung Cancer
NCT00334815	PHASE2	ACTIVE_NOT_RECRUITING	Combination Chemotherapy, Radiation Therapy, and Bevacizumab in Treating Patients With Newly Diagnosed Stage III Non-small Cell Lung Cancer That Cannot Be Removed by Surgery
NCT00368992	PHASE2	COMPLETED	S0536: Cetuximab, Paclitaxel, Carboplatin, and Bevacizumab in Treating Patients With Advanced Non-Small Cell Lung Cancer
NCT00511485	PHASE2	COMPLETED	Study of Vintafolide (MK-8109, EC145) in Participants With Progressive Adenocarcinoma of the Lung (MK-8109-008, EC-FV-03)
NCT00950365	PHASE2	COMPLETED	Pemetrexed Disodium With or Without Erlotinib Hydrochloride in Treating Patients With Stage IIIB-IV or Recurrent Non-Small Cell Lung Cancer
NCT00955305	PHASE2	TERMINATED	Paclitaxel, Carboplatin, and Bevacizumab With or Without Cixutumumab in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer
NCT01218516	PHASE2	COMPLETED	A Safety and Efficacy Study of Farletuzumab in Participants With Adenocarcinoma of the Lung
NCT01294306	PHASE2	COMPLETED	MK2206 and Erlotinib Hydrochloride in Treating Patients With Advanced Non-Small Cell Lung Cancer Who Have Progressed After Previous Response to Erlotinib Hydrochloride Therapy
NCT01557959	PHASE2	COMPLETED	Docetaxel, Cisplatin, Pegfilgrastim, and Erlotinib Hydrochloride in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer
NCT01561456	PHASE2	COMPLETED	Study of AXL1717 Compared to Docetaxel to Treat Squamous Cell Carcinoma or Adenocarcinoma of the Lung
NCT01578551	PHASE2	TERMINATED	Study of Metformin Plus Paclitaxel/Carboplatin/Bevacizumab in Patients With Adenocarcinoma.
NCT01578668	PHASE2	COMPLETED	Erlotinib Plus Pemetrexed to Treat Lung Adenocarcinoma With Brain Metastases
NCT01819428	PHASE2	TERMINATED	NOV120101 (Poziotinib) for 1st Line Monotherapy in Patients With Lung Adenocarcinoma
NCT01935336	PHASE2	COMPLETED	Study of Ponatinib in Patients With Lung Cancer Preselected Using Different Candidate Predictive Biomarkers