HOXB13

Summary

HOXB13 (homeobox B13, HGNC:5112) is a protein-coding gene on chromosome 17q21.32, encoding Homeobox protein Hox-B13 (Q92826). 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 encodes a transcription factor that belongs to the homeobox gene family. Genes of this family are highly conserved among vertebrates and essential for vertebrate embryonic development. This gene has been implicated to play a role in fetal skin development and cutaneous regeneration. In mice, a similar gene was shown to exhibit temporal and spatial colinearity in the main body axis of the embryo, but was not expressed in the secondary axes, which suggests functions in body patterning along the axis. This gene and other HOXB genes form a gene cluster at chromosome the 17q21-22 region.

Source: NCBI Gene 10481 — RefSeq curated summary.

At a glance

• Gene–disease (curated): prostate cancer (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 1,930 total — 1 pathogenic
• Transcription factor: yes — 13 downstream targets (CollecTRI)
• MANE Select transcript: NM_006361

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5112
Approved symbol	HOXB13
Name	homeobox B13
Location	17q21.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000159184
Ensembl biotype	protein_coding
OMIM	604607
Entrez	10481

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000290295

RefSeq mRNA: 1 — MANE Select: NM_006361 NM_006361

CCDS: CCDS11536

Canonical transcript exons

ENST00000290295 — 2 exons

Exon	Start	End
ENSE00001043851	48724763	48727043
ENSE00001043852	48727993	48728750

Expression profiles

Bgee: expression breadth broad, 38 present calls, max score 92.53.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2476 / max 262.2697, expressed in 272 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166757	0.4918	217
166756	0.2278	56
166758	0.2235	145
166761	0.1304	34
166755	0.0945	17
166759	0.0429	13
166760	0.0285	9
166762	0.0083	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	92.53	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.12	gold quality
prostate gland	UBERON:0002367	88.76	gold quality
colonic mucosa	UBERON:0000317	86.01	gold quality
mucosa of transverse colon	UBERON:0004991	81.56	gold quality
frontal pole	UBERON:0002795	72.15	gold quality
paraflocculus	UBERON:0005351	72.04	gold quality
middle frontal gyrus	UBERON:0002702	71.60	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.53	gold quality
endometrium epithelium	UBERON:0004811	65.79	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	65.30	gold quality
vagina	UBERON:0000996	64.57	gold quality
Brodmann (1909) area 10	UBERON:0013541	62.76	gold quality
sigmoid colon	UBERON:0001159	62.72	gold quality
vastus lateralis	UBERON:0001379	61.95	gold quality
quadriceps femoris	UBERON:0001377	61.65	gold quality
cerebellar vermis	UBERON:0004720	61.58	gold quality
biceps brachii	UBERON:0001507	61.31	gold quality
large intestine	UBERON:0000059	60.97	gold quality
nasal cavity epithelium	UBERON:0005384	60.97	gold quality
colonic epithelium	UBERON:0000397	60.45	gold quality
colon	UBERON:0001155	60.09	gold quality
vena cava	UBERON:0004087	59.31	gold quality
left ventricle myocardium	UBERON:0006566	58.26	gold quality
gingival epithelium	UBERON:0001949	58.13	gold quality
transverse colon	UBERON:0001157	57.71	gold quality
cardiac muscle of right atrium	UBERON:0003379	57.46	gold quality
myocardium	UBERON:0002349	56.79	gold quality
muscle layer of sigmoid colon	UBERON:0035805	56.70	gold quality
heart right ventricle	UBERON:0002080	56.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	21.17
E-ANND-3	no	2.59

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

13 targets.

Target	Regulation
AR	Repression
CCND1	Repression
DISC1
DNMT3B
ESR1
GNA11
IL6
KLK3
MECP2
MYC	Repression
RFX6	Unknown
SLIT1
TCF4	Repression

JASPAR motifs

Motif	Name	Family
MA0901.1	HOXB13	HOX
MA0901.2	HOXB13	HOX
MA0901.3	HOXB13	HOX
MA1932.1	ELK1::HOXB13	Ets-related::HOX-related factors
MA1932.2	ELK1::HOXB13	Ets-related::HOX-related factors
MA1937.1	ERF::HOXB13	Ets-related::HOX-related factors
MA1937.2	ERF::HOXB13	Ets-related::HOX-related factors
MA1943.1	ETV2::HOXB13	Ets-related::HOX-related factors
MA1943.2	ETV2::HOXB13	Ets-related::HOX-related factors

JASPAR matrix evidence (PMIDs): PMID:18585359, PMID:23332764, PMID:24218641

Upstream regulators (CollecTRI, top): DNMT3B, EZH2, FOXA1, HDAC4, YY1

miRNA regulators (miRDB)

56 targeting HOXB13, 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-9-5P	100.00	72.28	2361
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-3194-3P	98.83	66.22	1167

Literature-anchored findings (GeneRIF, showing 40)

• Epidermal HOXB13 signal was detected over the entire body surface, but surprisingly, essentially all of the signal was cytoplasmic in developing skin. (PMID:12761847)
• This study suggests that HOXB13, a transcription factor, functions as a cell growth suppressor by negatively regulating the expression of TCF-4, which eventually provides negative signals for cell proliferation in prostate cancer. (PMID:15126340)
• HOXB13 functions as an androgen receptor repressor to modulate the complex AR signaling and subsequent growth regulation of prostate cancer cells. (PMID:15604291)
• HOXB13 may have a role in the invasive ability of endometrial cancer cells through regulation by estrogen (PMID:15756448)
• Loss of HOXB13 may be an important event for colorectal cell transformation. (PMID:15928669)
• The HOXB13 protein expression increases during disease progression of breast cancer to hormonal therapy. (PMID:16609001)
• The HOXB13 protein expression increases during disease progression of breast cancer to hormonal therapy. (PMID:16609019)
• transcripts are differently expressed in normal mucous and serous acini [which] may reflect a different role in salivary gland carcinogenesis (PMID:16792730)
• HOXB13 and IL17BR has a role in progression of early-stage breast cancer (PMID:17008703)
• HOXB13 is downregulated by methylation and functions as a tumor suppressor in malignant melanoma. (PMID:17145863)
• HOXB13 and IL17BR have roles in breast cancer (PMID:17453342)
• These results support a pro-proliferative and pro-survival role for HOXB13 in ovarian cancer. (PMID:17942676)
• HOXA7, HOXB3, HOXA3, and HOXB13 expression levels changed during angiogenesis, sugessting these proteins might be involved in the angiogenesis of hMSCs. (PMID:17972163)
• HOXB13, IL17BR, and CHDH are regulated by estrogen in breast cancer (PMID:17975144)
• characterizeation of the promoter region of the HOXB13 gene (PMID:18163187)
• Hypermethylation of HOXB13 is a late event of breast tumorigenesis. (PMID:18499701)
• An index composed of inherited (CYP2D6) and tumor (HOXB13/IL17BR) gene variation identifies patients with varying degrees of resistance to tamoxifen. (PMID:18794098)
• Data show that the profound effects of HOXB13 knockdown on androgen-regulated proliferation, migration, and lipogenesis in prostate cancer cells highlight the importance of the observed changes in gene expression. (PMID:19917249)
• Data demonstrate that FOXA1 directly regulates HOXB13 in human prostate epithelial cells, and show that this prostate-specific regulatory mechanism is conserved in mice. (PMID:20018680)
• HOXB13 is associated with an additive growth advantage of prostate cancer cells in the absence of or low androgen concentrations, by the regulation of p21-mediated E2F signaling. (PMID:20504375)
• Data show that a high HOXB13 expression was associated with decreased benefit from tamoxifen, which indicates that HOXB13 protein level may be used as a predictive marker for tamoxifen treatment. (PMID:20649975)
• Stromal expression of KRT15, TCN1, and HOXB13 was significantly correlated with tumor grade, stromal hypercellularity, mitotic activity and microscopic borders. (PMID:21574054)
• The novel HOXB13 G84E variant is associated with a significantly increased risk of hereditary prostate cancer. (PMID:22236224)
• The Hoxb13-transgenic system provides a powerful tool for conditional Tet operator-driven transgene expression in the normal prostate and during disease progression. (PMID:22297979)
• This study independently confirms the association of a germline HOXB13 mutation with familial prostate cancer. (PMID:22714738)
• A rare mutation–HOXB13 Gly135Glu–is identified in Chinese men with prostate cancer. (PMID:22718278)
• The G84E mutation was more frequent among white case subjects than among white control subjects and was associated with an increased risk of prostate cancer. (PMID:22781434)
• HOXB13 G84E is prevalent in >1% of the Swedish population and is associated with a 3.5-fold increased risk of prostate cancer (PMID:22841674)
• findings show an association of this HOXB13 variant and a risk of BRCA1/2 wild-type, familial breast cancer (PMID:22853031)
• The HOXB13 G84E variant is rare in this cohort, even among those with a positive family history. Our findings question the utility of testing for this variant among unselected men presenting for a diagnostic prostate biopsy. (PMID:23036981)
• findings demonstrate that the HOXB13 G84E mutation is present in ~5 % of prostate cancer families, predominantly of European descent, and confirm its association with prostate cancer risk (PMID:23064873)
• Women who carry the HOXB13 Gly84Glu mutation are not at increased risk of breast cancer. (PMID:23099437)
• These results confirm the association of a rare HOXB13 mutation with prostate cancer in the general population and suggest that this variant may be associated with features of more aggressive disease. (PMID:23129385)
• In the series of Non Muscle Invasive Bladder Transitional Cancer nuclear HOX B13 expression loss is significantly associated to shorter disease free survival (p-value=0.038) defining a potential prognostic role. (PMID:23276138)
• HOXB13 G84E mutation is associated with prostate cancer. (PMID:23292082)
• The G84E mutation predisposes to prostate cancer in Poland, but accounts for only a small proportion of cases; the G84E founder mutation might be present in other Slavic populations. (PMID:23334858)
• SFMBT2 may regulate cell growth via epigenetic regulation of HOXB13 gene expression in prostate cancer cells. (PMID:23385818)
• the G84E mutation of HOXB13, a relatively recent mutation that likely occurred in Northern Europe, significantly increases risk for prostate cancer (PMID:23393222)
• HOXB13 mutation is associated with prostate cancer. (PMID:23396964)
• This study has provided an estimate of the cumulative risk of prostate cancer for HOXB13 missense mutation G84E carriers that can be used to guide clinical practice and research. (PMID:23457453)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	hoxb13a	ENSDARG00000056015
mus_musculus	Hoxb13	ENSMUSG00000049604
rattus_norvegicus	Hoxb13	ENSRNOG00000007491

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), TLX3 (ENSG00000164438), HOXD4 (ENSG00000170166), HOXD12 (ENSG00000170178), HOXB9 (ENSG00000170689), HOXC5 (ENSG00000172789), HOXB2 (ENSG00000173917), HOXD8 (ENSG00000175879), GSX2 (ENSG00000180613), HOXC9 (ENSG00000180806), HOXC10 (ENSG00000180818), HOXB4 (ENSG00000182742), HOXA4 (ENSG00000197576), HOXC6 (ENSG00000197757), HOXC4 (ENSG00000198353)

Protein

Protein identifiers

Homeobox protein Hox-B13 — Q92826 (reviewed: Q92826)

All UniProt accessions (1): Q92826

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. Binds preferentially to methylated DNA.

Subunit / interactions. Heterodimer with MEIS1. Heterodimer with MEIS2 (Ref.8).

Subcellular location. Nucleus.

Disease relevance. Prostate cancer, hereditary, 9 (HPC9) [MIM:610997] A condition associated with familial predisposition to cancer of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Similarity. Belongs to the Abd-B homeobox family.

RefSeq proteins (1): NP_006352* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR022067	HoxA13_N	Domain
IPR051003	AP_axis_regulatory_Homeobox	Family

Pfam: PF00046, PF12284

UniProt features (17 total): sequence variant 7, helix 3, region of interest 3, sequence conflict 2, chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
9O6B	X-RAY DIFFRACTION	1.95
7PSX	X-RAY DIFFRACTION	2
5EEA	X-RAY DIFFRACTION	2.19
5EGO	X-RAY DIFFRACTION	2.54
5NO6	X-RAY DIFFRACTION	2.88
5EF6	X-RAY DIFFRACTION	3
8BYX	X-RAY DIFFRACTION	3
5EG0	X-RAY DIFFRACTION	3.1
5EDN	X-RAY DIFFRACTION	3.2
2CRA	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92826-F1	62.34	0.23

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 145 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_GLAND_MORPHOGENESIS, GOBP_PROSTATE_GLAND_MORPHOGENESIS, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_GROWTH, SCHLESINGER_METHYLATED_DE_NOVO_IN_CANCER, GGGTGGRR_PAX4_03, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_RESPONSE_TO_TESTOSTERONE, GOBP_REPRODUCTIVE_SYSTEM_DEVELOPMENT, GOBP_RESPONSE_TO_KETONE, GOBP_CELL_MATURATION

GO Biological Process (12): negative regulation of transcription by RNA polymerase II (GO:0000122), angiogenesis (GO:0001525), regulation of transcription by RNA polymerase II (GO:0006357), epidermis development (GO:0008544), response to wounding (GO:0009611), response to testosterone (GO:0033574), regulation of growth (GO:0040008), prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis (GO:0060527), epithelial cell maturation involved in prostate gland development (GO:0060743), morphogenesis of an epithelium (GO:0002009), regulation of DNA-templated transcription (GO:0006355), prostate gland development (GO:0030850)

GO Molecular Function (8): 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 repressor activity, RNA polymerase II-specific (GO:0001227), methyl-CpG binding (GO:0008327), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (4): chromatin (GO:0000785), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
sequence-specific DNA binding	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
regulation of DNA-templated transcription	1
tissue development	1
response to stress	1
response to lipid	1
response to ketone	1
growth	1
regulation of biological process	1
branching involved in prostate gland morphogenesis	1
prostate glandular acinus morphogenesis	1
epithelial cell maturation	1
prostate gland development	1
epithelial cell differentiation involved in prostate gland development	1
tissue morphogenesis	1
epithelium development	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
urogenital system development	1
reproductive structure development	1
gland development	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
nucleotide binding	1
DNA binding	1
double-stranded DNA binding	1
nucleic acid binding	1
binding	1
chromosome	1

Protein interactions and networks

STRING

1072 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HOXB13	PRAC1	Q96KF2	961
HOXB13	PRAC2	D3DTV9	916
HOXB13	PRRX2	Q99811	829
HOXB13	AR	P10275	822
HOXB13	IL17RB	Q9NRM6	747
HOXB13	FOXA1	P55317	666
HOXB13	PRRX1	P54821	654
HOXB13	MEIS1	O00470	640
HOXB13	BRCA2	P51587	599
HOXB13	GRHL2	Q6ISB3	584
HOXB13	KLK3	P07288	581
HOXB13	BRCA1	P38398	575
HOXB13	TGM1	P22735	542
HOXB13	PALB2	Q86YC2	526
HOXB13	SMARCA4	P51532	508

IntAct

28 interactions, top by confidence:

A	B	Type	Score
PRKCA	HOXB13	psi-mi:“MI:0915”(physical association)	0.560
HOXB13	YWHAG	psi-mi:“MI:0915”(physical association)	0.560
HOXB13	SETDB1	psi-mi:“MI:0915”(physical association)	0.560
KAT5	HOXB13	psi-mi:“MI:0915”(physical association)	0.560
LMO3	HOXB13	psi-mi:“MI:0915”(physical association)	0.560
ELK1	HOXB13	psi-mi:“MI:0915”(physical association)	0.370
HOXD4	HOXB13	psi-mi:“MI:0915”(physical association)	0.370
IRF4	HOXB13	psi-mi:“MI:0915”(physical association)	0.370
POU2F1	HOXB13	psi-mi:“MI:0915”(physical association)	0.370
HOXB13	ZNF490	psi-mi:“MI:0915”(physical association)	0.370
HOXB13	ALX4	psi-mi:“MI:0915”(physical association)	0.370
FOXA2	FOXN2	psi-mi:“MI:0914”(association)	0.350
FOXC2	ZNF536	psi-mi:“MI:0914”(association)	0.350
FOXE1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXF1	HOXB9	psi-mi:“MI:0914”(association)	0.350
FOXS1	DDX39A	psi-mi:“MI:0914”(association)	0.350
TEAD2	DDX39A	psi-mi:“MI:0914”(association)	0.350

BioGRID (293): HOXB13 (Affinity Capture-MS), HOXB13 (Affinity Capture-MS), HOXB13 (Affinity Capture-MS), HOXB13 (Affinity Capture-MS), HOXB13 (Affinity Capture-MS), HOXB13 (Affinity Capture-MS), HOXB13 (Affinity Capture-MS), HOXB13 (Affinity Capture-MS), HOXB13 (Affinity Capture-MS), HOXB13 (Affinity Capture-RNA), HOXB13 (Affinity Capture-MS), HOXB13 (Affinity Capture-RNA), HOXB13 (Affinity Capture-MS), HOXB13 (Proximity Label-MS), WDR33 (Affinity Capture-MS)

ESM2 similar proteins: A1YFD8, A1YGA4, A2T779, A2T7T2, A5YC49, A6NJ46, A6NMT0, A9L937, B0VXK3, F1Q4R9, O35137, O42367, O43364, O70137, P09019, P09632, P09633, P10628, P17278, P17482, P20615, P31245, P31246, P31259, P31272, P31274, P31276, P32043, P32442, P43688, P50221, P52947, P70321, Q00444, Q08624, Q08727, Q0VCS4, Q1KKR7, Q1KKT2, Q1KKY2

Diamond homologs: A1YFT7, A2D5V0, A2D635, A2T6F8, A2T7D1, A2T7H7, G5EFY5, O14627, O42502, O42506, O43248, P02835, P09013, P09067, P09079, P09087, P09631, P09633, P10038, P10179, P17482, P17919, P20615, P23812, P24061, P24341, P24342, P24343, P24344, P28358, P28359, P31257, P31260, P31263, P31268, P31269, P31271, P31272, P31274, P31275

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
EZH2	“down-regulates quantity by repression”	HOXB13	“transcriptional regulation”
DNMT3B	“down-regulates quantity by repression”	HOXB13	“transcriptional regulation”
HDAC4	“down-regulates quantity by repression”	HOXB13	“transcriptional regulation”
YY1	“down-regulates quantity by repression”	HOXB13	“transcriptional regulation”
HOXB13	“down-regulates quantity by repression”	AR	“transcriptional regulation”
HOXB13	“down-regulates quantity by repression”	TCF4	“transcriptional regulation”

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

1930 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	1501
Likely benign	150
Benign	41

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1801667	NM_006361.6(HOXB13):c.814A>T (p.Lys272Ter)	Pathogenic

SpliceAI

242 predictions. Top by Δscore:

Variant	Effect	Δscore
17:48727040:GAGT:G	acceptor_gain	1.0000
17:48727041:AGTC:A	acceptor_loss	1.0000
17:48727043:TC:T	acceptor_loss	1.0000
17:48727044:C:CC	acceptor_gain	1.0000
17:48727045:T:G	acceptor_loss	1.0000
17:48727049:CGGCG:C	acceptor_gain	1.0000
17:48727052:C:CT	acceptor_gain	1.0000
17:48727053:G:C	acceptor_gain	1.0000
17:48727053:G:GC	acceptor_gain	1.0000
17:48727053:G:T	acceptor_gain	1.0000
17:48727039:GGAGT:G	acceptor_gain	0.9900
17:48727041:AGT:A	acceptor_gain	0.9900
17:48727042:GT:G	acceptor_gain	0.9900
17:48727043:TCTGC:T	acceptor_gain	0.9900
17:48727050:G:T	acceptor_gain	0.9900
17:48727040:GAGTC:G	acceptor_gain	0.9800
17:48727041:AGTCT:A	acceptor_gain	0.9800
17:48727042:GTCTG:G	acceptor_gain	0.9800
17:48727044:C:G	acceptor_gain	0.9800
17:48727045:T:A	acceptor_gain	0.9800
17:48727047:C:CT	acceptor_gain	0.9800
17:48727989:GTAC:G	donor_loss	0.9800
17:48727991:A:T	donor_loss	0.9800
17:48728037:C:CA	donor_gain	0.9600
17:48728008:T:TA	donor_gain	0.9400
17:48728160:T:TA	donor_gain	0.9300
17:48727146:CAGG:C	donor_gain	0.9100
17:48726999:C:CT	acceptor_gain	0.8700
17:48728242:C:A	donor_gain	0.8200
17:48727131:T:TA	donor_gain	0.8000

AlphaMissense

1816 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:48726835:T:A	K270N	1.000
17:48726835:T:G	K270N	1.000
17:48726845:C:G	R267P	1.000
17:48726846:G:T	R267S	1.000
17:48726847:G:C	N266K	1.000
17:48726847:G:T	N266K	1.000
17:48726848:T:A	N266I	1.000
17:48726848:T:C	N266S	1.000
17:48726848:T:G	N266T	1.000
17:48726849:T:C	N266D	1.000
17:48726850:C:A	Q265H	1.000
17:48726850:C:G	Q265H	1.000
17:48726851:T:G	Q265P	1.000
17:48726853:A:C	F264L	1.000
17:48726853:A:T	F264L	1.000
17:48726854:A:C	F264C	1.000
17:48726854:A:G	F264S	1.000
17:48726855:A:C	F264V	1.000
17:48726855:A:G	F264L	1.000
17:48726855:A:T	F264I	1.000
17:48726856:C:A	W263C	1.000
17:48726856:C:G	W263C	1.000
17:48726858:A:G	W263R	1.000
17:48726858:A:T	W263R	1.000
17:48726860:A:C	I262S	1.000
17:48726860:A:G	I262T	1.000
17:48726860:A:T	I262N	1.000
17:48726881:A:G	L255P	1.000
17:48726907:C:A	R246S	1.000
17:48726907:C:G	R246S	1.000

dbSNP variants (sampled 300 via entrez): RS1000161662 (17:48727625 G>A), RS1000231825 (17:48724469 T>C), RS1000765465 (17:48726315 C>T), RS1000832817 (17:48724735 G>A,C), RS1000842945 (17:48726195 C>T), RS1000872621 (17:48726389 G>A), RS1001563933 (17:48730355 T>C), RS1001642809 (17:48727247 T>G), RS1002163313 (17:48730617 C>A), RS1002766293 (17:48729115 G>A), RS1002822221 (17:48730275 G>C), RS1002929419 (17:48730417 A>G), RS1003273521 (17:48724421 G>A,C), RS1004306352 (17:48725480 G>C), RS1004609525 (17:48726730 G>A,T)

Disease associations

OMIM: gene MIM:604607 | disease phenotypes: MIM:610997, MIM:176807, MIM:613659, MIM:601518

GenCC curated gene-disease

Disease	Classification	Inheritance
prostate cancer	Definitive	Autosomal dominant
prostate cancer, hereditary, 9	Strong	Autosomal dominant

Mondo (7): prostate cancer, hereditary, 9 (MONDO:0012597), hereditary neoplastic syndrome (MONDO:0015356), prostate cancer (MONDO:0008315), exocrine pancreatic carcinoma (MONDO:0005192), prostate cancer, hereditary (MONDO:0700275), gastric cancer (MONDO:0001056), prostate cancer, hereditary, 1 (MONDO:0011098)

Orphanet (4): Familial prostate cancer (Orphanet:1331), Inherited cancer-predisposing syndrome (Orphanet:140162), Familial pancreatic carcinoma (Orphanet:1333), Rare carcinoma of pancreas (Orphanet:217074)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001719_1	Prostate cancer	6.000000e-34
GCST001942_17	Prostate cancer	2.000000e-09
GCST010396_20	Gut microbiota (bacterial taxa, hurdle binary method)	4.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750
C567031	Prostate Cancer, Hereditary, 9 (supp.)
C537243	Prostate cancer, familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
methylmercuric chloride	affects response to substance, affects binding, increases reaction, affects reaction, increases expression	1
geraniol	decreases expression	1
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	increases expression	1
ferrous chloride	decreases expression	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
CGP 52608	affects binding, increases reaction	1
perfluorohexanesulfonic acid	increases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Decitabine	affects expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Copper	affects binding, decreases expression	1
Dactinomycin	increases expression, affects cotreatment	1
Drugs, Chinese Herbal	decreases expression	1
Ethylmaleimide	increases response to substance	1
Hydrogen Peroxide	increases response to substance	1
Methylmercury Compounds	increases response to substance	1
Paraquat	increases response to substance	1
Silicon Dioxide	decreases expression	1
Cyclosporine	decreases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer