HOXB4

Summary

HOXB4 (homeobox B4, HGNC:5115) is a protein-coding gene on chromosome 17q21.32, encoding Homeobox protein Hox-B4 (P17483). Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

This gene is a member of the Antp homeobox family and encodes a nuclear protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox B genes located on chromosome 17. The encoded protein functions as a sequence-specific transcription factor that is involved in development. Intracellular or ectopic expression of this protein expands hematopoietic stem and progenitor cells in vivo and in vitro, making it a potential candidate for therapeutic stem cell expansion.

Source: NCBI Gene 3214 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 6 total
• Transcription factor: yes — 12 downstream targets (CollecTRI)
• MANE Select transcript: NM_024015

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5115
Approved symbol	HOXB4
Name	homeobox B4
Location	17q21.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000182742
Ensembl biotype	protein_coding
OMIM	142965
Entrez	3214

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000332503

RefSeq mRNA: 1 — MANE Select: NM_024015 NM_024015

CCDS: CCDS11529

Canonical transcript exons

ENST00000332503 — 2 exons

Exon	Start	End
ENSE00001291179	48575507	48577020
ENSE00001315607	48577863	48578350

Expression profiles

Bgee: expression breadth ubiquitous, 106 present calls, max score 93.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.5068 / max 96.0809, expressed in 1077 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166679	2.8705	940
166678	1.6381	649
166677	0.5766	312
166676	0.2390	100
166675	0.1826	70

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
quadriceps femoris	UBERON:0001377	93.11	gold quality
cerebellar vermis	UBERON:0004720	91.69	silver quality
right uterine tube	UBERON:0001302	90.25	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.61	gold quality
lower esophagus muscularis layer	UBERON:0035833	83.41	gold quality
lower esophagus	UBERON:0013473	83.37	gold quality
muscle layer of sigmoid colon	UBERON:0035805	82.90	gold quality
fallopian tube	UBERON:0003889	81.74	gold quality
mucosa of stomach	UBERON:0001199	81.53	gold quality
endometrium	UBERON:0001295	80.02	gold quality
omental fat pad	UBERON:0010414	79.13	gold quality
metanephros cortex	UBERON:0010533	78.87	gold quality
descending thoracic aorta	UBERON:0002345	78.28	gold quality
esophagus	UBERON:0001043	78.03	gold quality
left uterine tube	UBERON:0001303	77.85	gold quality
colon	UBERON:0001155	76.94	gold quality
adult mammalian kidney	UBERON:0000082	76.77	gold quality
kidney	UBERON:0002113	76.49	gold quality
right lung	UBERON:0002167	76.34	gold quality
intestine	UBERON:0000160	75.93	gold quality
cortex of kidney	UBERON:0001225	75.79	gold quality
lower esophagus mucosa	UBERON:0035834	75.76	gold quality
fundus of stomach	UBERON:0001160	75.32	gold quality
right adrenal gland	UBERON:0001233	74.99	gold quality
adipose tissue	UBERON:0001013	74.55	gold quality
small intestine Peyer’s patch	UBERON:0003454	74.33	gold quality
small intestine	UBERON:0002108	74.30	gold quality
stromal cell of endometrium	CL:0002255	74.11	gold quality
endocervix	UBERON:0000458	73.87	gold quality
transverse colon	UBERON:0001157	73.85	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-10485	yes	504.32
E-ANND-3	no	1.52

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

12 targets.

Target	Regulation
AXIN1	Unknown
CASP8AP2	Activation
GNAS
HOXB4
IGFBP1	Activation
ITGA2B	Activation
ITGB3	Activation
NFYA
PGR	Activation
PRDM16
PROM1	Unknown
SCAI

JASPAR motifs

Motif	Name	Family
MA1499.1	HOXB4	HOX
MA1499.2	HOXB4	HOX

JASPAR matrix evidence (PMIDs): PMID:18585359

Upstream regulators (CollecTRI, top): CDX1, CTNNB1, HOXA10, HOXA9, HOXB4, MITF, NFYA, RARA, USF1, USF2, YY1

miRNA regulators (miRDB)

71 targeting HOXB4, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893

Literature-anchored findings (GeneRIF, showing 40)

• may play a role in the regulation of cellular proliferation/adhesion in developing fetal human epidermis and in hyperproliferation conditions, including cancers, in adult epidermis (PMID:11984874)
• Retrovirally mediated expression of HOXB4 rapidly triggers an increase in the number of stem cells without alternating the balance of lymphomyeloid reconstitution, suggesting that HOXB4 does not affect control of end-cell output. (PMID:12130496)
• In NOD/SCID mice HOXB4-overexpressing cord blood CD34+ cells had a selective growth advantage in vivo. However, high HOXB4 expression substantially impaired myeloerythroid differentiation & B-cell output. (PMID:12406897)
• NF-Y is a developmentally regulated inducer of the HOXB4 gene in hematopoietic cells. (PMID:12791656)
• Data report novel nucleoporin 98 fusions with homeobox (HOX)A10, HOXB3 and HOXB4, and describe the results of coexpression of these proteins with the Hox cofactor Meis1 in leukemic induction. (PMID:14966272)
• The growth promoting effects of HOXB4 are critically dependent on HOXB4 expression levels and that this can result in important species-specific differences in potency. (PMID:17510218)
• The protein transduction domain-Hoxb4protein can be used with other recombinant proteins to efficiently generate transplantable hemaat4opoietic stem cells from human embryonic stem cells. (PMID:17784829)
• contribution of HOXB4 in the maintenance of the intrinsic lymphomyeloid differentiation potential of defined hematopoietic progenitor cell subsets (PMID:17962697)
• overexpression of HoxB4 in differentiating hESCs increases hematopoietic colony formation and hematopoietic cell formation in vitro, but does not affect in vivo repopulation in adult mice hosts (PMID:18511880)
• These data suggest that HoxB4-induced effects on human embryonic stem cell-derived hematopoietic stem cells are concentration-dependent during in vitro development and reduce proliferation of other cell types in vitro and in vivo. (PMID:18617691)
• The demethylation of CpG island in the promoter region of HOXB4 gene may be correlated with the high expression of HOXB4 gene in CD34(+) cells, while the promoter methylation of HOXB4 gene may be associated with HOXB4 gene silencing in PBMCs. (PMID:19549386)
• overexpression of HOXB4 in human ESC did not improve the generation of CD34(+) hematopoietic cells via co-culture methodology (PMID:19878058)
• hoxb2 and hoxb4 expression is related to erythroid hematopoiesis, and hoxb4 has greater relevance to erythroid hematopoiesis as compared with hoxb2. (PMID:20030938)
• these data suggest that increased HoxB4 enhanced early megakaryocytic development in human TF1 cells and CD34 positively-selected cord blood cells primarily by upregulating TpoR and Fli-1 expression and downregulating c-Myb expression. (PMID:20599537)
• Downregulation of HoxB2, HoxB4 and Alx4 expression during the narrow window of early embryogenesis may cause omphalocele in the Cd chick model by interfering with molecular signaling required for proper VBW formation. (PMID:20625746)
• Studies suggest that HOXA4, HOXA5 and HOXB4 provide the spatial information needed to restrict the response to signals from the notochord, and not up regulated in pancreatic cancer. (PMID:21546695)
• These results indicate that transient, but not constitutive, HoxB4 expression is sufficient to augment the hematopoietic differentiation of embryonic stem and induced pluripotent stem cells. (PMID:22000550)
• Expressions of ABCB1, BMI-1, HOXB4 were not detected in the patients with non-malignant hematologic diseases, but were higher in de novo acute leukemia patients and lower in patients in complete remission. (PMID:22040961)
• Hox B4 protein is present in the precursor lesions as CC cells, suggesting that Hox B4 could be a protein related to the neoplastic state (non-differentiated cells) of human cervical epithelium. (PMID:22120585)
• Comparative transcriptome analysis of CD34(+) cells subjected or not to HOXB4 or HOXC4 demonstrated that both homeoproteins regulate the same set of genes, some of which encode key hematopoietic factors and signaling molecules. (PMID:22298821)
• cytomegalovirus infection markedly down-regulated HOXB4 expression which affected proliferation and differentiation of erythroid and lymphocyte progenitor cells. (PMID:22402911)
• Down-regulation of mitochondria and lysosomal genes by HoxB4 plays a role in the impaired lymphoid lineage development from embryonic stem cells-derived hematopoietic stem cells. (PMID:22438249)
• HOXB4-positivity as an independent predictor of overall survival of acute myeloid leukemia patients (PMID:22664110)
• our results outline the effects of HOXB4 in combination with stromal cells in the development of NK cells from embryonic stem cells. (PMID:22761810)
• GATA-2 directly regulates HOXB4 expression in hematopoietic stem cells, which may play an important role in the development and/or progression of aplastic anemia. (PMID:23028422)
• Our study demonstrates for the first time the regulation of HOXB4 by miR-23a (PMID:23630040)
• a crucial regulator of NK lytic function (PMID:24810639)
• Epigenetic analysis revealed that increased promoter methylation of HOXB4 correlates with decreased expression of its transcript in oral cancer cell lines. HOXB4 may work as an epigenetic biomarker gene. (PMID:24859765)
• decreased methylation at HOXB3 and HOXB4 was associated with increased gene expression of both HOXB genes specific to the mid-risk AML, while increased DNA methylation at DCC distinctive to the high-risk AML was associated with increased gene expression (PMID:25996682)
• HOXA4 increases short-term repopulation to higher levels than HOXB4, which may involve Notch signaling to induce self-renewal of primitive hematopoietic cells (PMID:26166023)
• showed that OAC1 treatment led to OCT4-mediated upregulation of HOXB4 (PMID:26202933)
• The analysis of HOX expression in primary mesothelioma tumors indicated that these cells could also be sensitive to the disruption of HOX activity by HXR9, and that the expression of HOXB4 is strongly associated with overall survival (PMID:26867567)
• This study provides novel evidences of the mechanisms integrating Notch and TNF-alpha signaling in the transcriptional induction of GATA3 and HOXB4. (PMID:27251160)
• Increased expression of HOXB4 in human embryonic stem cells enhances the production of hematopoietic Progenitors but does not effect the maturation of red blood cells. (PMID:27352929)
• HOXB4 knockout led to downregulation of P-glycoprotein, multidrug resistance-associated protein 1 and breast cancer resistance protein expression and PI3K/Akt signaling activity, suggesting that repression of HOXB4 might be a key point to reverse Multidrug resistance of K562/ADM cells. (PMID:27779650)
• Data suggests that an impaired capacity of eutopic and ectopic endometrial tissue to upregulate levels of HOXB4 during the proliferative phase may play a role in the pathogenesis of endometriosis and that further downregulation of HOXB4 may enhance ectopic implant invasiveness. (PMID:28969513)
• Authors observed that induced expression of HOXB4 in the UW473 cell line significantly reduced in vitro cell proliferation and migration capability of UW473 cells with no effect on the in vivo tumorigenicity. (PMID:29039487)
• Study revealed that HOXB4 was highly expressed in ovarian cancer cells. HOXB4 silencing enhanced the cytotoxic effect of Taxol and DDP by downregulating ABC transporters via inhibition of the PI3K/Akt signaling pathway. These results for the first time elucidated the critical roles and molecular basis of HOXB4 underlying drug resistance in ovarian cancer cells. (PMID:29660518)
• our data confirms that CaP growth and chemo-/radioresistance in vivo is associated with over-expression of EpCAM, which serves both a functional biomarker and promising therapeutic target. (PMID:30419846)
• HOXB4 promotes the malignant progression of ovarian cancer via DHDDS. (PMID:32178630)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	hoxb4a	ENSDARG00000013533
mus_musculus	Hoxb4	ENSMUSG00000038692
rattus_norvegicus	Hoxb4	ENSRNOG00000008191

Paralogs (42): HOXA11 (ENSG00000005073), HOXC8 (ENSG00000037965), HOXA1 (ENSG00000105991), HOXA2 (ENSG00000105996), HOXA3 (ENSG00000105997), HOXA5 (ENSG00000106004), HOXA6 (ENSG00000106006), HOXA13 (ENSG00000106031), TLX1 (ENSG00000107807), HOXB6 (ENSG00000108511), TLX2 (ENSG00000115297), HOXB8 (ENSG00000120068), HOXB5 (ENSG00000120075), HOXB3 (ENSG00000120093), HOXB1 (ENSG00000120094), HOXA7 (ENSG00000122592), HOXC13 (ENSG00000123364), HOXC11 (ENSG00000123388), HOXC12 (ENSG00000123407), HOXD1 (ENSG00000128645), HOXD3 (ENSG00000128652), HOXD9 (ENSG00000128709), HOXD10 (ENSG00000128710), HOXD11 (ENSG00000128713), HOXD13 (ENSG00000128714), PDX1 (ENSG00000139515), HOXB13 (ENSG00000159184), TLX3 (ENSG00000164438), HOXD4 (ENSG00000170166), HOXD12 (ENSG00000170178), HOXB9 (ENSG00000170689), HOXC5 (ENSG00000172789), HOXB2 (ENSG00000173917), HOXD8 (ENSG00000175879), GSX2 (ENSG00000180613), HOXC9 (ENSG00000180806), HOXC10 (ENSG00000180818), HOXA4 (ENSG00000197576), HOXC6 (ENSG00000197757), HOXC4 (ENSG00000198353)

Protein

Protein identifiers

Homeobox protein Hox-B4 — P17483 (reviewed: P17483)

Alternative names: Homeobox protein Hox-2.6, Homeobox protein Hox-2F

All UniProt accessions (1): P17483

UniProt curated annotations — full annotation on UniProt →

Function. Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

Subcellular location. Nucleus.

Similarity. Belongs to the Antp homeobox family. Deformed subfamily.

RefSeq proteins (1): NP_076920* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR001827	Homeobox_Antennapedia_CS	Conserved_site
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR017995	Homeobox_antennapedia	Family
IPR020479	HD_metazoa	Domain
IPR050609	Antp_homeobox_Deformed_sf	Family

Pfam: PF00046

UniProt features (8 total): region of interest 2, compositionally biased region 2, chain 1, DNA-binding region 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17483-F1	68.12	0.26

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): 90

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-9830364	Formation of the nephric duct

MSigDB gene sets: 199 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, FREAC2_01, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, CMYB_01, GOBP_EMBRYONIC_SKELETAL_SYSTEM_MORPHOGENESIS, RACCACAR_AML_Q6, MEF2_02, FOXO4_01, FOXO1_01, GGGTGGRR_PAX4_03, GOBP_HEMATOPOIETIC_STEM_CELL_DIFFERENTIATION

GO Biological Process (15): negative regulation of transcription by RNA polymerase II (GO:0000122), morphogenesis of an epithelial sheet (GO:0002011), anterior/posterior pattern specification (GO:0009952), positive regulation of transcription by RNA polymerase II (GO:0045944), somatic stem cell division (GO:0048103), spleen development (GO:0048536), bone marrow development (GO:0048539), embryonic skeletal system morphogenesis (GO:0048704), definitive hemopoiesis (GO:0060216), hematopoietic stem cell differentiation (GO:0060218), hematopoietic stem cell proliferation (GO:0071425), positive regulation of stem cell differentiation (GO:2000738), regulation of DNA-templated transcription (GO:0006355), hemopoiesis (GO:0030097), skeletal system morphogenesis (GO:0048705)

GO Molecular Function (5): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700)

GO Cellular Component (4): chromatin (GO:0000785), nucleoplasm (GO:0005654), centrosome (GO:0005813), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Activation of HOX genes during differentiation	1
Kidney development	1

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	2
hematopoietic or lymphoid organ development	2
hemopoiesis	2
stem cell differentiation	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
morphogenesis of an epithelium	1
regionalization	1
positive regulation of DNA-templated transcription	1
stem cell division	1
tissue development	1
bone development	1
embryonic organ morphogenesis	1
skeletal system morphogenesis	1
embryonic skeletal system development	1
hematopoietic progenitor cell differentiation	1
stem cell proliferation	1
positive regulation of cell differentiation	1
regulation of stem cell differentiation	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cell development	1
skeletal system development	1
animal organ morphogenesis	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
regulation of DNA-templated transcription	1
transcription regulator activity	1
chromosome	1
nuclear lumen	1
centriole	1
microtubule organizing center	1

Protein interactions and networks

STRING

1190 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HOXB4	DDB1	Q16531	667
HOXB4	NOTCH1	P46531	642
HOXB4	CUL4A	Q13619	624
HOXB4	LEF1	Q9UJU2	590
HOXB4	AXIN1	O15169	576
HOXB4	CD34	P28906	575
HOXB4	OTX2	P32243	572
HOXB4	FOXG1	P55315	556
HOXB4	CTNNB1	P35222	554
HOXB4	GATA2	P23769	541
HOXB4	WNT3A	P56704	534
HOXB4	MEIS1	O00470	529
HOXB4	HNF4A	P41235	510
HOXB4	FGF8	P55075	496
HOXB4	HOXD9	P28356	494

IntAct

5 interactions, top by confidence:

A	B	Type	Score
	HOXB4	psi-mi:“MI:0915”(physical association)	0.370
IFNA7	HOXB4	psi-mi:“MI:0915”(physical association)	0.370
RNH1	DUSP11	psi-mi:“MI:0914”(association)	0.350
RNH1	DDX3Y	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): HOXB4 (Affinity Capture-MS), HOXB4 (Affinity Capture-RNA), HOXB4 (Proximity Label-MS), HOXB4 (Reconstituted Complex), RBX1 (Affinity Capture-Western), CUL4A (Affinity Capture-Western), DDB1 (Affinity Capture-Western)

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

Diamond homologs: A1YER7, A1YFA5, A1YFD8, A1YFY3, A2D4P8, A2D5I1, A2D5K9, A2D5Y4, A2T6X6, A2T7F3, O13074, O42504, O57374, P02830, P02832, P02833, P04476, P06798, P07548, P09013, P09014, P09016, P09017, P09019, P09020, P09021, P09023, P09024, P09067, P09070, P09071, P09074, P09077, P09079, P09092, P09629, P09630, P10284, P10628, P10629

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
HOXB4	“up-regulates quantity by expression”	IGFBP1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	5
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

457 predictions. Top by Δscore:

Variant	Effect	Δscore
17:48576783:C:CT	donor_gain	1.0000
17:48576832:T:TA	donor_gain	1.0000
17:48577017:TTTA:T	acceptor_gain	1.0000
17:48577018:TTA:T	acceptor_gain	1.0000
17:48577019:TA:T	acceptor_gain	1.0000
17:48577020:AC:A	acceptor_loss	1.0000
17:48577021:C:CA	acceptor_loss	1.0000
17:48577021:C:CC	acceptor_gain	1.0000
17:48577022:T:A	acceptor_loss	1.0000
17:48577026:C:CT	acceptor_gain	1.0000
17:48577028:C:CT	acceptor_gain	1.0000
17:48577030:C:CT	acceptor_gain	1.0000
17:48577032:C:CT	acceptor_gain	1.0000
17:48577033:G:T	acceptor_gain	1.0000
17:48576764:T:TA	donor_gain	0.9900
17:48576784:C:CT	donor_gain	0.9900
17:48577016:GTTTA:G	acceptor_gain	0.9900
17:48577861:AC:A	donor_gain	0.9900
17:48577862:CC:C	donor_gain	0.9900
17:48576740:T:TA	donor_gain	0.9800
17:48577018:T:C	acceptor_gain	0.9800
17:48576215:T:TA	donor_gain	0.9700
17:48577858:CT:C	donor_loss	0.9700
17:48577859:T:TC	donor_loss	0.9700
17:48577860:C:CG	donor_loss	0.9700
17:48577861:A:AT	donor_loss	0.9700
17:48577862:C:CA	donor_loss	0.9700
17:48578299:C:CT	acceptor_gain	0.9700
17:48576706:C:CA	donor_gain	0.9600
17:48577861:A:AC	donor_gain	0.9600

AlphaMissense

1609 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:48576821:T:A	K219N	1.000
17:48576821:T:G	K219N	1.000
17:48576822:T:A	K219I	1.000
17:48576824:T:A	K218N	1.000
17:48576824:T:G	K218N	1.000
17:48576825:T:A	K218I	1.000
17:48576830:C:A	K216N	1.000
17:48576830:C:G	K216N	1.000
17:48576832:T:C	K216E	1.000
17:48576833:C:A	M215I	1.000
17:48576833:C:G	M215I	1.000
17:48576833:C:T	M215I	1.000
17:48576834:A:G	M215T	1.000
17:48576834:A:T	M215K	1.000
17:48576838:G:T	R214S	1.000
17:48576840:C:G	R213P	1.000
17:48576841:G:A	R213W	1.000
17:48576841:G:C	R213G	1.000
17:48576842:G:C	N212K	1.000
17:48576842:G:T	N212K	1.000
17:48576843:T:A	N212I	1.000
17:48576843:T:C	N212S	1.000
17:48576843:T:G	N212T	1.000
17:48576844:T:C	N212D	1.000
17:48576844:T:G	N212H	1.000
17:48576845:C:A	Q211H	1.000
17:48576845:C:G	Q211H	1.000
17:48576846:T:G	Q211P	1.000
17:48576848:G:C	F210L	1.000
17:48576848:G:T	F210L	1.000

dbSNP variants (sampled 300 via entrez): RS1000181354 (17:48575888 C>G), RS1000232979 (17:48580132 G>A), RS1001024298 (17:48575550 G>C), RS1001149074 (17:48575205 T>C), RS1001458729 (17:48579777 G>T), RS1001618462 (17:48580001 G>C), RS1002876166 (17:48578708 A>C,G), RS1003343529 (17:48579788 G>A), RS1003454710 (17:48577055 T>C), RS1003526980 (17:48578497 G>A), RS1003646973 (17:48580097 A>C), RS1004460368 (17:48575188 C>G,T), RS1004526428 (17:48579688 T>G), RS1004557479 (17:48579302 C>T), RS1005567244 (17:48576307 T>C)

Disease associations

OMIM: gene MIM:142965 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_17	Body mass index	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	affects cotreatment, decreases reaction, increases expression, increases reaction	3
sodium arsenite	decreases expression, increases expression	2
Smoke	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
LY2955303	affects cotreatment, decreases reaction, increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases reaction, increases expression, increases reaction, affects cotreatment	1
trichostatin A	affects cotreatment, increases expression	1
dimethylselenide	decreases expression, increases expression, increases oxidation	1
di-n-butylphosphoric acid	affects expression	1
LE 135	decreases reaction, increases expression, affects cotreatment	1
abrine	decreases expression	1
4-(2-(5,6-dihydro-5,5-dimethyl-8-(2-phenylethynyl)naphthalen-2-yl)ethen-1-yl)benzoic acid	increases expression, affects cotreatment, decreases reaction	1
4-(5,6-dihydro-5,5-dimethyl-8-(quinolin-3-yl)naphthalen-2-carboxamido)benzoic acid	affects cotreatment, decreases reaction, increases expression	1
4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta(c)quinoline	affects cotreatment, increases expression, increases reaction	1
Decitabine	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, increases expression, increases reaction	1
Vorinostat	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Cytarabine	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Lipopolysaccharides	affects expression, affects response to substance	1
Mercury	increases expression	1
Phthalic Acids	increases methylation	1
Triclosan	increases expression	1
Valproic Acid	affects expression	1
Aflatoxin B1	decreases methylation	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A2Y7	SEES3-1V human HOXB4, clone1	Embryonic stem cell	Male
CVCL_A2Y8	SEES3-1V human HOXB4, clone2	Embryonic stem cell	Male
CVCL_A2Y9	SEES3-1V human HOXB4, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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