DLX2

Summary

DLX2 (distal-less homeobox 2, HGNC:2915) is a protein-coding gene on chromosome 2q31.1, encoding Homeobox protein DLX-2 (Q07687). Acts as a transcriptional activator.

Many vertebrate homeo box-containing genes have been identified on the basis of their sequence similarity with Drosophila developmental genes. Members of the Dlx gene family contain a homeobox that is related to that of Distal-less (Dll), a gene expressed in the head and limbs of the developing fruit fly. The Distal-less (Dlx) family of genes comprises at least 6 different members, DLX1-DLX6. The DLX proteins are postulated to play a role in forebrain and craniofacial development. This gene is located in a tail-to-tail configuration with another member of the gene family on the long arm of chromosome 2.

Source: NCBI Gene 1746 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 49 total
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• Transcription factor: yes — 26 downstream targets (CollecTRI)
• MANE Select transcript: NM_004405

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2915
Approved symbol	DLX2
Name	distal-less homeobox 2
Location	2q31.1
Locus type	gene with protein product
Status	Approved
Aliases	TES-1
Ensembl gene	ENSG00000115844
Ensembl biotype	protein_coding
OMIM	126255
Entrez	1746

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000234198, ENST00000466293

RefSeq mRNA: 1 — MANE Select: NM_004405 NM_004405

CCDS: CCDS2248

Canonical transcript exons

ENST00000234198 — 3 exons

Exon	Start	End
ENSE00000782182	172101462	172101646
ENSE00001073175	172099438	172100944
ENSE00001914452	172102139	172102900

Expression profiles

Bgee: expression breadth broad, 94 present calls, max score 84.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.8817 / max 640.4972, expressed in 1076 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31803	11.4295	979
31796	0.8016	319
31798	0.6447	308
31800	0.4390	203
31799	0.4305	216
31793	0.3230	169
31794	0.2893	142
31795	0.1543	75
31801	0.1538	80
31797	0.1304	60

Top tissues by expression

251 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	84.01	gold quality
buccal mucosa cell	CL:0002336	83.52	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	79.73	gold quality
tongue squamous epithelium	UBERON:0006919	77.28	silver quality
sperm	CL:0000019	75.73	silver quality
male germ cell	CL:0000015	75.27	silver quality
ganglionic eminence	UBERON:0004023	74.40	gold quality
periodontal ligament	UBERON:0008266	73.83	gold quality
pericardium	UBERON:0002407	73.76	silver quality
parotid gland	UBERON:0001831	73.04	gold quality
pons	UBERON:0000988	72.65	silver quality
cervix squamous epithelium	UBERON:0006922	71.89	gold quality
olfactory bulb	UBERON:0002264	71.10	gold quality
embryo	UBERON:0000922	71.00	gold quality
cortical plate	UBERON:0005343	70.53	gold quality
cartilage tissue	UBERON:0002418	70.08	gold quality
myocardium	UBERON:0002349	69.92	gold quality
vena cava	UBERON:0004087	69.90	gold quality
type B pancreatic cell	CL:0000169	69.88	gold quality
biceps brachii	UBERON:0001507	69.77	gold quality
saphenous vein	UBERON:0007318	69.73	gold quality
inferior olivary complex	UBERON:0002127	69.55	gold quality
triceps brachii	UBERON:0001509	69.43	gold quality
gluteal muscle	UBERON:0002000	69.29	gold quality
cerebellar vermis	UBERON:0004720	68.79	gold quality
cardia of stomach	UBERON:0001162	68.12	gold quality
squamous epithelium	UBERON:0006914	67.91	gold quality
nasal cavity epithelium	UBERON:0005384	67.66	gold quality
dorsal plus ventral thalamus	UBERON:0001897	67.61	gold quality
Brodmann (1909) area 10	UBERON:0013541	67.43	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-5	yes	1556.89
E-MTAB-10485	yes	398.41
E-GEOD-93593	yes	13.60
E-MTAB-8894	no	2401.40
E-ANND-3	no	0.79

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

26 targets.

Target	Regulation
ADRA1D
AMELX
ARX	Activation
CDKN1A	Activation
CDKN2A
CEL
COL2A1
DLX2
DLX4	Unknown
DLX5	Activation
DLX6	Unknown
FGFR1
FOXJ1	Unknown
GAD1	Activation
GAD2	Activation
GNRH1	Activation
KRT27
ME3
MSX2	Activation
MYC	Repression
NRP2	Unknown
NTRK2
TGFB1	Activation
TGFBR2
TPM1
WNT1

Upstream regulators (CollecTRI, top): DLX2, FOXJ1, KMT2A, MSX2, PITX2

miRNA regulators (miRDB)

72 targeting DLX2, 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-3134	100.00	66.43	777
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6870-5P	99.99	68.55	2115
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-12136	99.98	72.81	5713
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-124-3P	99.89	73.74	3043

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 26)

• In mice osteoblasts, both Dlx2 and Dlx5 are coordinately induced by BMP2 as early as 30 minutes into their growth and differentiation. (PMID:12957859)
• In corroboration with paired-like homeodomain protein 2 (PITX2) protein kinase C functional studies, a newly identified carboxyl-terminal PITX2 mutation associated with Axenfeld-Rieger syndrome demonstrates reduced phosphorylation. (PMID:15751970)
• The DLX1 and DLX2 genes lie head-to-head in 2q32; the findings support the presence of two functional polymorphisms, one in or near each of the DLX genes that increase susceptibility to, or cause, autism. (PMID:18728693)
• MDA-MB-231 breast neoplasms expressed DLX2. (PMID:21108812)
• These findings suggest that alterations in DLX1/2 contribute to the biological consequences of FLT3 activation. (PMID:21357706)
• Dlx-2 may be involved in tumor progression via the regulation of metabolic stress-induced necrosis (PMID:21917150)
• Dlx2 (and Dlx1) are required to generate cortical interneurons in the medial ganglionic eminence. (PMID:23312518)
• overexpression of DLX2 indicated poor survival in the 83 glioblastoma multiforme patients (PMID:23331016)
• Increased expression of DLX2 may correlate with the advanced stage of gastric adenocarcinoma, and it may contribute to tumor development. (PMID:23674878)
• The activation of DLX2 signaling might improve tissue regeneration mediated by MSCs of dental origin. Results provide insight into the mechanism underlying the directed differentiation of MSCs of dental origin. (PMID:24756434)
• Results showed that Dlx-2 is involved in TGF-beta- and Wnt-induced epithelial-mesenchymal transition, glycolytic switch, and mitochondrial repression by Snail activation. (PMID:25651912)
• High DLX-2 expression is associated with epithelial-mesenchymal transition in cancer. (PMID:26771232)
• DLX2 plays a crucial role in radioresistance, radiation-induced epithelial to mesenchymal transition and cancer stem cell marker expression, and the expression of DLX2 is regulated by Smad2/3 signaling in A549 and MDA-MB-231 cell lines. (PMID:26799321)
• DLX2 expression reduces the protein components of the TTI1/TTI2/TEL2 complex, a key complex required for the proper folding and stabilization of ATM and other members of the PIKK family kinase, leading to reduced ATM-p53 signaling and senescence bypass (PMID:26833729)
• DLX2 is a novel marker of poor prognosis and sorafenib resistance in patients with hepatocellular carcinoma. (PMID:27302463)
• High Ki67 expression is only present in 6.8% of CaP patients and is predictive of reduced survival and increased risk of metastasis, independent of PSA, Gleason score and D’Amico risk category. DLX2 is a novel marker of increased metastasis risk found in 73% patients and 8.2% showed co-expression with a high Ki67 score (PMID:27336609)
• Our results provided evidence that polymorphisms in TIMP1, DLX1 and DLX2 genes may be associated with DF phenotypes. (PMID:28131910)
• Authors characterized a BMP target gene, Distal-less homeobox 2 (DLX2), and found that DLX2 promoted apoptosis and neural differentiation of glioma-initiating cells. (PMID:28459464)
• Expression of ventral telencephalon transcription factors ASCL1 and DLX2 in the early fetal human cerebral cortex. (PMID:30861584)
• Results suggest that by up-regulation of Wnt/beta-Catenin signaling, DLX2 accelerated human osteogenic differentiation. (PMID:32165291)
• Knockdown of circ_HIPK3 inhibits tumorigenesis of hepatocellular carcinoma via the miR-582-3p/DLX2 axis. (PMID:32977948)
• DLX2 Is a Potential Immune-Related Prognostic Indicator Associated with Remodeling of Tumor Microenvironment in Lung Squamous Cell Carcinoma: An Integrated Bioinformatical Analysis. (PMID:36317140)
• JMJD3 is Involved in Intracranial Aneurysm Development by Regulating DLX2 Expression through H3K27me3 Modification. (PMID:37286519)
• results in mutated mice suggest that Dlx2 controls development of branchial arches and the forebrian, suggesting a role in craniofacil evolution (PMID:7590232)
• provides the sequence of human DLX2 and compares it to the murine gene. (PMID:8812481)
• In mice, biological and biochemical observations suggest that functional antagonism through heterodimer formation is a mechanism for regulating the transcriptional actions of Msx and Dlx homeoproteins. (PMID:9111364)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	dlx2b	ENSDARG00000017174
danio_rerio	dlx2a	ENSDARG00000079964
mus_musculus	Dlx2	ENSMUSG00000023391
rattus_norvegicus	Dlx2	ENSRNOG00000001519
drosophila_melanogaster	Dll	FBGN0000157
caenorhabditis_elegans		WBGENE00000463

Paralogs (9): DLX6 (ENSG00000006377), DLX3 (ENSG00000064195), DLX5 (ENSG00000105880), DLX4 (ENSG00000108813), NANOG (ENSG00000111704), DLX1 (ENSG00000144355), VENTX (ENSG00000151650), BSX (ENSG00000188909), NANOGP8 (ENSG00000255192)

Protein

Protein identifiers

Homeobox protein DLX-2 — Q07687 (reviewed: Q07687)

All UniProt accessions (3): Q07687, Q53QU7, X5D7D8

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional activator. Activates transcription of CGA/alpha-GSU, via binding to the downstream activin regulatory element (DARE) in the gene promoter. Plays a role in terminal differentiation of interneurons, such as amacrine and bipolar cells in the developing retina. Likely to play a regulatory role in the development of the ventral forebrain. May play a role in craniofacial patterning and morphogenesis.

Subunit / interactions. Interacts (via homeobox DNA-binding domain) with POU4F2; this interaction enhances retinal ganglion cell (RGC) differentiation.

Subcellular location. Nucleus.

Similarity. Belongs to the distal-less homeobox family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q07687-1	1	yes
Q07687-2	2

RefSeq proteins (1): NP_004396* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000047	HTH_motif	Conserved_site
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR020479	HD_metazoa	Domain
IPR022135	Distal-less_N	Domain
IPR050460	Distal-less_Homeobox_TF	Family

Pfam: PF00046, PF12413

UniProt features (12 total): region of interest 3, compositionally biased region 3, splice variant 2, chain 1, DNA-binding region 1, sequence conflict 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q07687-F1	60.10	0.19

Functional residue map

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

Post-translational modifications (1): 232

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 222 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_CARTILAGE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_OLIGODENDROCYTE_DIFFERENTIATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_GLIOGENESIS, PEREZ_TP63_TARGETS, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_NEURON_DIFFERENTIATION, GOBP_EMBRYONIC_SKELETAL_SYSTEM_MORPHOGENESIS, GOBP_NEGATIVE_REGULATION_OF_GLIAL_CELL_DIFFERENTIATION, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (28): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), Notch signaling pathway (GO:0007219), brain development (GO:0007420), proximal/distal pattern formation (GO:0009954), neuroblast differentiation (GO:0014016), subpallium development (GO:0021544), hippocampus development (GO:0021766), olfactory bulb development (GO:0021772), forebrain neuron fate commitment (GO:0021877), cerebral cortex GABAergic interneuron fate commitment (GO:0021893), cell differentiation (GO:0030154), odontogenesis of dentin-containing tooth (GO:0042475), positive regulation of cell differentiation (GO:0045597), negative regulation of Notch signaling pathway (GO:0045746), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of photoreceptor cell differentiation (GO:0046533), embryonic cranial skeleton morphogenesis (GO:0048701), embryonic skeletal system development (GO:0048706), oligodendrocyte differentiation (GO:0048709), negative regulation of oligodendrocyte differentiation (GO:0048715), branching morphogenesis of a nerve (GO:0048755), cartilage development (GO:0051216), positive regulation of amacrine cell differentiation (GO:1902871), regulation of DNA-templated transcription (GO:0006355), forebrain neuron differentiation (GO:0021879), cerebral cortex GABAergic interneuron differentiation (GO:0021892), GABAergic neuron differentiation (GO:0097154)

GO Molecular Function (11): transcription cis-regulatory region binding (GO:0000976), 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), chromatin binding (GO:0003682), DNA-binding transcription factor activity (GO:0003700), single-stranded RNA binding (GO:0003727), sequence-specific double-stranded DNA binding (GO:1990837), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA binding (GO:0003677), protein binding (GO:0005515)

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 transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
anatomical structure development	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
central nervous system development	2
cell differentiation	2
neuron fate commitment	2
binding	2
transcription cis-regulatory region binding	2
negative regulation of DNA-templated transcription	1
cell surface receptor signaling pathway	1
animal organ development	1
head development	1
regionalization	1
generation of neurons	1
telencephalon development	1
pallium development	1
limbic system development	1
olfactory lobe development	1
forebrain neuron differentiation	1
cerebral cortex GABAergic interneuron differentiation	1
cellular developmental process	1
odontogenesis	1
regulation of cell differentiation	1
positive regulation of cellular process	1
positive regulation of developmental process	1
Notch signaling pathway	1
regulation of Notch signaling pathway	1
negative regulation of signal transduction	1
positive regulation of DNA-templated transcription	1
negative regulation of neuron differentiation	1
photoreceptor cell differentiation	1
regulation of photoreceptor cell differentiation	1
negative regulation of multicellular organismal process	1
embryonic skeletal system morphogenesis	1
cranial skeletal system development	1
skeletal system development	1
chordate embryonic development	1
glial cell differentiation	1

Protein interactions and networks

STRING

1528 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DLX2	ASCL1	P50553	926
DLX2	MEIS2	O14770	807
DLX2	PAX6	P26367	801
DLX2	LHX6	Q9UPM6	774
DLX2	BMP4	P12644	724
DLX2	MYT1L	Q9UL68	713
DLX2	NEUROG2	Q9H2A3	708
DLX2	TBR1	Q16650	692
DLX2	LMCD1	Q9NZU5	687
DLX2	CALB2	P22676	686
DLX2	FGF8	P55075	685
DLX2	LHX8	Q68G74	679
DLX2	GAD1	Q99259	659
DLX2	OLIG2	Q13516	649
DLX2	FOXG1	P55315	642

IntAct

22 interactions, top by confidence:

A	B	Type	Score
GRN	DLX2	psi-mi:“MI:0915”(physical association)	0.560
DLX2	GRN	psi-mi:“MI:0915”(physical association)	0.560
gag	DLX2	psi-mi:“MI:0915”(physical association)	0.490
AVP	DLX2	psi-mi:“MI:0915”(physical association)	0.370
BZRAP1	DLX2	psi-mi:“MI:0915”(physical association)	0.370
DGCR6	DLX2	psi-mi:“MI:0915”(physical association)	0.370
MVP	DLX2	psi-mi:“MI:0915”(physical association)	0.370
PRKN	DLX2	psi-mi:“MI:0915”(physical association)	0.370
PIK3R1	DLX2	psi-mi:“MI:0915”(physical association)	0.370
RYBP	FAM186A	psi-mi:“MI:0914”(association)	0.350
GRHL1	POLRMT	psi-mi:“MI:0914”(association)	0.350

BioGRID (23): GRN (Two-hybrid), DLX2 (Reconstituted Complex), MSX1 (Reconstituted Complex), MSX2 (Reconstituted Complex), DLX2 (Reconstituted Complex), DLX2 (Reconstituted Complex), DLX2 (Reconstituted Complex), DLX2 (Reconstituted Complex), DLX5 (Reconstituted Complex), HOXC8 (Reconstituted Complex), DLX2 (Two-hybrid), DLX2 (Affinity Capture-MS), DLX2 (Affinity Capture-RNA), DLX2 (Affinity Capture-RNA), DLX2 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2TED3, O00570, O57401, O95409, P06602, P07548, P09085, P14734, P16241, P20264, P22544, P23441, P23757, P31361, P32027, P32182, P32242, P35583, P39768, P40764, P41225, P43241, P43698, P43699, P48430, P48431, P48432, P50220, P53783, P53784, P54231, P54269, P56224, P80205, Q04649, Q07687, Q24255, Q24533, Q2PG84, Q2Z1R2

Diamond homologs: A1YF16, A1YG93, A2RU54, A2T764, A6NCS4, A6NHT5, G5EE18, M0R6D8, O02786, O35767, O42230, O57601, O60479, O70218, P10181, P13297, P15857, P19601, P20009, P23410, P28360, P28361, P28362, P35548, P35993, P40764, P42580, P42581, P43687, P43688, P48031, P50219, P50223, P50574, P50575, P50576, P50577, P52953, P53547, P53770

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
DLX2	“up-regulates quantity by expression”	ARX	“transcriptional regulation”
DLX2	“down-regulates activity”	MSX2	binding
DLX2	“down-regulates activity”	MSX1	binding
MSX1	“down-regulates activity”	DLX2	binding
MSX2	“down-regulates activity”	DLX2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

411 predictions. Top by Δscore:

Variant	Effect	Δscore
2:172101456:CCCCA:C	donor_loss	1.0000
2:172101457:CCCA:C	donor_loss	1.0000
2:172101458:CCACC:C	donor_loss	1.0000
2:172101459:CA:C	donor_loss	1.0000
2:172101461:C:G	donor_loss	1.0000
2:172101642:CTTCT:C	acceptor_gain	1.0000
2:172101643:TTCT:T	acceptor_gain	1.0000
2:172101645:CT:C	acceptor_gain	1.0000
2:172101647:C:CC	acceptor_gain	1.0000
2:172102138:CCAGG:C	donor_gain	1.0000
2:172100943:ACC:A	acceptor_loss	0.9900
2:172100945:CTTT:C	acceptor_loss	0.9900
2:172101644:TCTC:T	acceptor_loss	0.9900
2:172101646:TC:T	acceptor_loss	0.9900
2:172101648:T:A	acceptor_loss	0.9900
2:172101654:G:T	acceptor_gain	0.9900
2:172102123:T:TA	donor_gain	0.9900
2:172102136:TACCA:T	donor_loss	0.9900
2:172102137:A:AC	donor_gain	0.9900
2:172102138:C:CC	donor_gain	0.9900
2:172102138:C:CG	donor_loss	0.9900
2:172100945:C:CC	acceptor_gain	0.9800
2:172100946:T:C	acceptor_gain	0.9800
2:172100947:T:TC	acceptor_gain	0.9800
2:172101462:C:G	donor_loss	0.9800
2:172101650:C:CT	acceptor_gain	0.9800
2:172101651:A:T	acceptor_gain	0.9800
2:172100947:T:C	acceptor_gain	0.9700
2:172101653:CGA:C	acceptor_gain	0.9700
2:172102164:A:AC	donor_gain	0.9700

AlphaMissense

2129 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:172100905:T:C	K209E	1.000
2:172100906:C:A	K208N	1.000
2:172100906:C:G	K208N	1.000
2:172100907:T:A	K208M	1.000
2:172100908:T:C	K208E	1.000
2:172100912:C:A	K206N	1.000
2:172100912:C:G	K206N	1.000
2:172100913:T:A	K206M	1.000
2:172100914:T:C	K206E	1.000
2:172100916:G:A	S205F	1.000
2:172100917:A:G	S205P	1.000
2:172100919:C:G	R204P	1.000
2:172100919:C:T	R204Q	1.000
2:172100920:G:A	R204W	1.000
2:172100920:G:C	R204G	1.000
2:172100922:C:G	R203P	1.000
2:172100923:G:C	R203G	1.000
2:172100923:G:T	R203S	1.000
2:172100924:G:C	N202K	1.000
2:172100924:G:T	N202K	1.000
2:172100925:T:A	N202I	1.000
2:172100925:T:C	N202S	1.000
2:172100925:T:G	N202T	1.000
2:172100926:T:A	N202Y	1.000
2:172100926:T:C	N202D	1.000
2:172100926:T:G	N202H	1.000
2:172100927:C:A	Q201H	1.000
2:172100927:C:G	Q201H	1.000
2:172100928:T:C	Q201R	1.000
2:172100928:T:G	Q201P	1.000

dbSNP variants (sampled 300 via entrez): RS1000356188 (2:172099263 C>G,T), RS1001472089 (2:172101302 GC>G), RS1001589175 (2:172100824 A>G,T), RS1002206531 (2:172099249 G>A), RS1002856405 (2:172102576 T>A), RS1003543648 (2:172103128 C>T), RS1004077348 (2:172102614 C>T), RS1004448870 (2:172102779 C>A), RS1004814567 (2:172100475 C>T), RS1005440636 (2:172103584 T>C), RS1005488140 (2:172103157 G>T), RS1006824543 (2:172101313 A>C,G), RS1007548638 (2:172101144 G>A), RS1007993070 (2:172101720 CGG>C,CG,CGGG), RS1008510610 (2:172099544 A>G)

Disease associations

OMIM: gene MIM:126255 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001937_49	Breast cancer	1.000000e-08
GCST006038_4	Food allergy	2.000000e-08
GCST006039_1	Peanut allergy	9.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007016	food allergy measurement
EFO:0007017	peanut allergy measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, increases reaction, decreases expression, affects cotreatment, increases abundance	6
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	5
Benzo(a)pyrene	affects methylation, increases expression	4
Silicon Dioxide	increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Arsenic	affects cotreatment, decreases expression, decreases methylation, increases abundance	2
Estradiol	increases expression, affects cotreatment	2
Formaldehyde	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
methylmercuric chloride	increases expression	1
apocarotenal	increases expression	1
propionaldehyde	increases expression	1
lead acetate	increases expression	1
titanium dioxide	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
arsenite	increases methylation	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
nickel sulfate	increases expression	1
15-acetyldeoxynivalenol	increases expression	1
cylindrospermopsin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A0Y0	SEES3-1V human DLX2, clone1	Embryonic stem cell	Male
CVCL_A0Y1	SEES3-1V human DLX2, clone2	Embryonic stem cell	Male
CVCL_A0Y2	SEES3-1V human DLX2, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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