HOXB9

Summary

HOXB9 (homeobox B9, HGNC:5120) is a protein-coding gene on chromosome 17q21.32, encoding Homeobox protein Hox-B9 (P17482). 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 Abd-B homeobox family and encodes a protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox B genes located on chromosome 17. The encoded nuclear protein functions as a sequence-specific transcription factor that is involved in cell proliferation and differentiation. Increased expression of this gene is associated with some cases of leukemia, prostate cancer and lung cancer.

Source: NCBI Gene 3219 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_024017

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5120
Approved symbol	HOXB9
Name	homeobox B9
Location	17q21.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000170689
Ensembl biotype	protein_coding
OMIM	142964
Entrez	3219

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000311177

RefSeq mRNA: 1 — MANE Select: NM_024017 NM_024017

CCDS: CCDS11534

Canonical transcript exons

ENST00000311177 — 2 exons

Exon	Start	End
ENSE00001193282	48621156	48623135
ENSE00001307347	48625753	48626358

Expression profiles

Bgee: expression breadth broad, 100 present calls, max score 95.23.

FANTOM5 (CAGE): breadth broad, TPM avg 5.7872 / max 282.4937, expressed in 407 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166735	4.2823	317
166734	0.6776	203
166731	0.5798	88
166732	0.1582	45
166733	0.0893	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	95.23	gold quality
corpus epididymis	UBERON:0004359	92.21	gold quality
rectum	UBERON:0001052	87.46	gold quality
buccal mucosa cell	CL:0002336	86.67	silver quality
sperm	CL:0000019	86.26	silver quality
colonic mucosa	UBERON:0000317	84.68	gold quality
mucosa of sigmoid colon	UBERON:0004993	84.22	gold quality
male germ cell	CL:0000015	83.19	silver quality
metanephros cortex	UBERON:0010533	82.75	gold quality
transverse colon	UBERON:0001157	82.06	gold quality
caput epididymis	UBERON:0004358	79.45	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.17	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.15	gold quality
ileal mucosa	UBERON:0000331	77.93	silver quality
adult mammalian kidney	UBERON:0000082	77.91	gold quality
small intestine Peyer’s patch	UBERON:0003454	77.70	gold quality
cauda epididymis	UBERON:0004360	76.85	silver quality
colonic epithelium	UBERON:0000397	74.01	gold quality
seminal vesicle	UBERON:0000998	73.85	gold quality
kidney	UBERON:0002113	72.31	gold quality
pancreatic ductal cell	CL:0002079	71.18	silver quality
small intestine	UBERON:0002108	70.82	gold quality
large intestine	UBERON:0000059	70.04	gold quality
intestine	UBERON:0000160	69.85	gold quality
upper arm skin	UBERON:0004263	69.75	gold quality
colon	UBERON:0001155	69.65	gold quality
caecum	UBERON:0001153	69.37	gold quality
vermiform appendix	UBERON:0001154	67.62	gold quality
renal medulla	UBERON:0000362	66.46	silver quality
metanephros	UBERON:0000081	66.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	40.72
E-GEOD-125970	yes	4.23
E-ANND-3	yes	3.61

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
ANGPTL2	Activation
CDH1
CXCL8	Activation
FGF2	Activation
NCAM1
REN
VEGFA	Activation

JASPAR motifs

Motif	Name	Family
MA1503.1	HOXB9	HOX
MA1503.2	HOXB9	HOX

JASPAR matrix evidence (PMIDs): PMID:18585359

Upstream regulators (CollecTRI, top): E2F1, RNF2

miRNA regulators (miRDB)

112 targeting HOXB9, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-6875-3P	99.82	70.26	2983

Literature-anchored findings (GeneRIF, showing 40)

• ERK5 probably mediates HOXB9 expression by repressing BMI1 in Hodgkin lymphoma cell lines (PMID:17148583)
• Two WNT target genes, LEF1 and HOXB9, are identified as promoters of lung adenocarcinoma metastasis and mediators of chemotactic invasion and colony outgrowth. (PMID:19576624)
• deregulated expression of HOXB9 contributes to breast cancer progression and lung metastasis by inducing several growth factors that alter tumor-specific cell fates and the tumor stromal microenvironment (PMID:20080567)
• HOXB9 is an E2-responsive gene and ERs coordinate with MLL1 and MLL3 in E2-mediated transcriptional regulation of HOXB9. (PMID:21428455)
• The effect of HOXB9 on the response to ionizing radiation requires the baseline ATM activity before irradiation and epithelial-to-mesenchymal transition induced by TGF-beta. (PMID:21930940)
• reduced expression of CD56 is associated with homeobox B9 in papillary thyroid carcinomas. Further, silencing of homeobox B9 is more common in older age and is linked to extrathyroidal extension and advanced pathologic stage of papillary thyroid carcinoma (PMID:22225776)
• HOXB9 overexpression promoting tumor cell proliferation and angiogenesis is associated with breast cancer. (PMID:22396001)
• HOXB9 is overexpressed in breast cancer tissue. (PMID:22863320)
• HOXB9 is down-regulation in gastric carcinoma and may be a novel prognostic marker for poorer clinical outcome for patients with gastric carcinoma. (PMID:23332081)
• The expression of HOXB9, its relationship to clinical factors in breast cancer and efficacy as a prognostic factor were discussed. (PMID:23350386)
• Data show that the HOXB9 overexpression group had significantly shorter overall survival time than the HOXB9 downexpression group. (PMID:24462859)
• HOXB9 overexpression increased the tumorigenicity of glioma cells in vivo. Moreover, the activation of transforming growth factor-beta1 contributed to HOXB9-induced oncogenic activities. (PMID:24582746)
• rs2303486 may be associated with severity of developmental dysplaasia of the hip in Chinese Han females. (PMID:24600698)
• HOXB9 promoted colon adenocarcinoma differentiation. (PMID:25025961)
• HOXB9 promotes epithelial-to-mesenchymal transition via TGF-beta1 pathway in hepatocellular carcinoma cells. (PMID:25081022)
• Identification of the transcription factor binding site of the HOXB9 promoter region suggests that E2F1 is a direct regulator of HOXB9 expression in breast cancer. (PMID:25136922)
• High expression of HoxB9 is a prognostic marker for lung adenocarcinoma patients. (PMID:25324169)
• Low HOXB9 expression promotes pancreatic ductal adenocarcinoma progression. (PMID:25724625)
• Knock-down of HOXB9 expression decreased migration, invasion and proliferation but did not alter adhesion. (PMID:25860510)
• the results of the present study suggested that HOXB9 is a tumor suppressor in gastric carcinoma, and its activity was controlled by different regulatory mechanisms such as the hexapeptide motif as a “brake” in this case (PMID:26536658)
• Expression of GalNAc-T14 or HOXB9 was strongly correlated with reduced recurrence-free survival in lung adenocarcinomas. (PMID:26544896)
• HOXB9 interfered the activities of NF-kappaB, nuclear factor of activated T-cells (NFAT) and AP-1 but not retinoic acid receptor-related orphan receptor, resulting in attenuation of the production of selective cytokines in activated T cells. (PMID:26926958)
• These findings suggest that hoxb7 and hoxb9 proteins might play a role in salivary gland tumourigenesis, but in contrast to the reported for other human cancers, they were not significant prognostic determinants in the sample studied (PMID:26991799)
• We also found that FAT10 may act its oncogenic functions through regulating HOXB9. Collectively, the results suggested that FAT10 may be a novel therapeutic target for osteosarcoma patients (PMID:27279480)
• AcK27-HOXB9 suppresses the transcription of its target gene Jumonji domain-containing protein 6 (JMJD6) by direct occupying the promoter of JMJD6 gene. (PMID:27613418)
• These findings integrate the complexity of numerous mechanisms of anti-VEGF resistance into the single transcription factor HOXB9. Silencing HOXB9 could be a promising approach to modulate this resistance. Our results candidate HOXB9 as predictive biomarker for selecting colorectal cancer patients for antiangiogenic therapy (PMID:28298545)
• this study revealed that HOXB9, HOXB13, and HOXD13 were upregulated and may play important roles in laryngeal squamous cell carcinoma (LSCC). Moreover, HOXB9 may serve as a novel marker of poor prognosis and a potential therapeutic target in LSCC patients. (PMID:28808656)
• HOXB9 directly binds to the promoter of microRNA-765 and facilitates its transcription, which in turn targets FOXA2, resulting in a FOXA2 decrease and cancer stem cell increase. Elevated HOXB9 is found in human melanoma tissues, which is associated with microRNA-765 up-regulation and FOXA2 decreases. (PMID:29408459)
• Results show the AcK27-HOXB9 level decreased in colon cancer patients and predicted better outcome. HOXB9 upregulated oncogenic EZH2 expression, whereas AcK27-HOXB9 suppressed it by translocating HOXB9 from nuclei into cytoplasm. AcK27-HOXB9 inhibits while non-acetylated HOXB9 promotes EZH2 expression and colon cancer progression. Thus, AcK27-HOXB9 underlies the tumor suppressive role of HOXB9. (PMID:29654889)
• HOXB9 promotes endometrial cancer progression by targeting E2F3. (PMID:29724991)
• High HOXB9 expression is associated with invasion and metastasis of hepatocellular carcinoma by chaperoning LRP6. (PMID:31310747)
• Acetylated HOXB9 at lysine 27 is of differential diagnostic value in patients with pancreatic ductal adenocarcinoma. (PMID:31372881)
• Homeobox B9 integrates bone morphogenic protein 4 with inflammation at atheroprone sites. (PMID:31504243)
• Mutually exclusive antiproliferative effect of cell line-specific HOX inhibition in epithelial ovarian cancer cell lines: SKOV-3 vs RMUG-S. (PMID:31970886)
• Silencing of HOXB9 suppresses cellular proliferation, angiogenesis, migration and invasion of prostate cancer cells. (PMID:32098919)
• HOX genes promote cell proliferation and are potential therapeutic targets in adrenocortical tumours. (PMID:33214683)
• HOXB9 enhances the ability of lung cancer cells to penetrate the blood-brain barrier. (PMID:33411683)
• Genome-Wide Epigenetic Landscape of Lung Adenocarcinoma Links HOXB9 DNA Methylation to Intrinsic EGFR-TKI Resistance and Heterogeneous Responses. (PMID:34036228)
• Insights into homeobox B9: a propeller for metastasis in dormant prostate cancer progenitor cells. (PMID:34247196)
• WT1 regulates HOXB9 gene expression in a bidirectional way. (PMID:34508900)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	hoxb9a	ENSDARG00000056023
mus_musculus	Hoxb9	ENSMUSG00000020875
rattus_norvegicus	Hoxb9	ENSRNOG00000007573

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), 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-B9 — P17482 (reviewed: P17482)

Alternative names: Homeobox protein Hox-2.5, Homeobox protein Hox-2E

All UniProt accessions (1): P17482

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 Abd-B homeobox family.

RefSeq proteins (1): NP_076922* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR006711	Hox9_activation_N	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017112	HXA9/HXB9/HXC9	Family
IPR017970	Homeobox_CS	Conserved_site
IPR020479	HD_metazoa	Domain

Pfam: PF00046, PF04617

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17482-F1	65.26	0.25

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 (2): 133, 117

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 205 (showing top): AHRARNT_01, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_CELL_CHEMOTAXIS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, XU_GH1_AUTOCRINE_TARGETS_UP, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_EMBRYONIC_SKELETAL_SYSTEM_MORPHOGENESIS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, HNF1_Q6, GGGTGGRR_PAX4_03, HANN_RESISTANCE_TO_BCL2_INHIBITOR_UP, NFKB_Q6, GOBP_TAXIS

GO Biological Process (10): DNA-templated transcription (GO:0006351), regulation of transcription by RNA polymerase II (GO:0006357), anterior/posterior pattern specification (GO:0009952), proximal/distal pattern formation (GO:0009954), mammary gland development (GO:0030879), positive regulation of transcription by RNA polymerase II (GO:0045944), embryonic skeletal system morphogenesis (GO:0048704), cell chemotaxis (GO:0060326), regulation of DNA-templated transcription (GO:0006355), embryonic skeletal system development (GO:0048706)

GO Molecular Function (7): 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 factor activity (GO:0003700), 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 (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), RNA polymerase II transcription regulator complex (GO:0090575)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
regionalization	2
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription cis-regulatory region binding	2
cellular anatomical structure	2
gene expression	1
RNA biosynthetic process	1
gland development	1
positive regulation of DNA-templated transcription	1
embryonic organ morphogenesis	1
skeletal system morphogenesis	1
embryonic skeletal system development	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
skeletal system development	1
chordate embryonic development	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
transcription regulator activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
transcription regulator complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

1056 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HOXB9	BTG2	P78543	892
HOXB9	B4GALNT2	Q8NHY0	662
HOXB9	SIX3	O95343	593
HOXB9	GMNN	O75496	585
HOXB9	NGFR	P08138	561
HOXB9	CDT1	Q9H211	555
HOXB9	HOXB3	P14651	535
HOXB9	LEF1	Q9UJU2	534
HOXB9	HOXB5	P09067	513
HOXB9	EED	O75530	502
HOXB9	RNF2	Q99496	476
HOXB9	EZH2	Q15910	475
HOXB9	RBPMS	Q93062	467
HOXB9	HAND2	P61296	447
HOXB9	HOXA9	P31269	434

IntAct

226 interactions, top by confidence:

A	B	Type	Score
HOXB9	SAT1	psi-mi:“MI:0915”(physical association)	0.760
SAT1	HOXB9	psi-mi:“MI:0915”(physical association)	0.760
HOXB9	MDFI	psi-mi:“MI:0915”(physical association)	0.760
PNMA1	HOXB9	psi-mi:“MI:0915”(physical association)	0.720
HOXB9	MID2	psi-mi:“MI:0915”(physical association)	0.720
MID2	HOXB9	psi-mi:“MI:0915”(physical association)	0.720
HOXB9	PNMA1	psi-mi:“MI:0915”(physical association)	0.720
HOXB9	LZTS2	psi-mi:“MI:0915”(physical association)	0.670
JUN	NFATC1	psi-mi:“MI:0914”(association)	0.610
HOXB9	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	HOXB9	psi-mi:“MI:0915”(physical association)	0.560
GOLGA2	HOXB9	psi-mi:“MI:0915”(physical association)	0.560
CALCOCO2	HOXB9	psi-mi:“MI:0915”(physical association)	0.560
HOXB9	TRIP6	psi-mi:“MI:0915”(physical association)	0.560
HOXB9	GOLGA2	psi-mi:“MI:0915”(physical association)	0.560
HOXB9	CALCOCO2	psi-mi:“MI:0915”(physical association)	0.560
TRIP6	HOXB9	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (154): HOXB9 (Two-hybrid), KRTAP5-9 (Two-hybrid), SAT1 (Two-hybrid), TRIP6 (Two-hybrid), PNMA1 (Two-hybrid), CALCOCO2 (Two-hybrid), MID2 (Two-hybrid), KRTAP10-9 (Two-hybrid), HOXB9 (Affinity Capture-MS), HOXB9 (Affinity Capture-MS), KRTAP4-12 (Two-hybrid), MDFI (Two-hybrid), RBPMS (Two-hybrid), SAT1 (Two-hybrid), HOXB9 (Proximity Label-MS)

ESM2 similar proteins: A0A1W2PPF3, A1A546, A1YGA4, A2T779, A2T7T2, A5YC49, A6NFQ7, A6NMT0, A6NNA5, F1Q4R9, O08686, O42173, O42358, P17278, P17482, P20615, P31272, P43688, P52950, P70368, P70436, P97436, P97458, Q01703, Q28ET4, Q2M1V0, Q3LU38, Q3LU39, Q3LU40, Q5NSW5, Q5TIS6, Q5TM83, Q61658, Q62798, Q80Z64, Q8BYH0, Q8JJ26, Q8MJI9, Q91926, Q92988

Diamond homologs: A1YFT7, A2D5V0, A2D635, A2T6F8, A2T7D1, A2T7H7, B5DFK3, O42502, O42503, O42506, O43248, P09013, P09014, P09023, P09025, P09067, P09079, P09087, P09631, P09632, P09633, P10179, P14838, P15861, P17481, P17482, P17509, P18863, P18866, P20615, P23459, P23813, P24340, P24341, P24342, P28356, P28357, P28358, P28359, P31257

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
BTG2	“up-regulates activity”	HOXB9	binding
BTG1	“up-regulates activity”	HOXB9	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 119 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
RNA Polymerase III Transcription Termination	5	31.0×	7e-05
RNA Polymerase III Abortive And Retractive Initiation	5	17.4×	1e-03
Keratinization	19	13.2×	6e-14

GO biological processes:

GO term	Partners	Fold	FDR
neuron fate specification	5	35.5×	5e-05
DNA replication	6	10.0×	3e-03
anatomical structure morphogenesis	7	9.8×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

255 predictions. Top by Δscore:

Variant	Effect	Δscore
17:48625751:A:AC	donor_gain	1.0000
17:48625752:C:CC	donor_gain	1.0000
17:48625752:CT:C	donor_gain	1.0000
17:48625746:AACTT:A	donor_loss	0.9900
17:48625747:ACTT:A	donor_loss	0.9900
17:48625750:TACT:T	donor_loss	0.9900
17:48625751:A:T	donor_loss	0.9900
17:48625752:CTTTG:C	donor_gain	0.9800
17:48625781:T:TA	donor_gain	0.9800
17:48622902:A:AC	donor_gain	0.9700
17:48622903:C:CC	donor_gain	0.9700
17:48623132:TTGG:T	acceptor_gain	0.9700
17:48623133:TGG:T	acceptor_gain	0.9700
17:48623136:C:CC	acceptor_gain	0.9700
17:48625288:CGGT:C	donor_gain	0.9700
17:48625752:CTT:C	donor_gain	0.9700
17:48625752:CTTT:C	donor_gain	0.9700
17:48624335:A:C	acceptor_gain	0.9600
17:48625747:A:C	donor_gain	0.9600
17:48622903:CT:C	donor_gain	0.9500
17:48623134:GG:G	acceptor_gain	0.9400
17:48624966:C:CA	donor_gain	0.9400
17:48623133:TGGCT:T	acceptor_loss	0.9300
17:48623135:GCT:G	acceptor_loss	0.9300
17:48623136:C:CG	acceptor_loss	0.9300
17:48623137:T:C	acceptor_loss	0.9300
17:48623138:G:C	acceptor_loss	0.9300
17:48624967:C:A	donor_gain	0.9200
17:48625737:A:AC	donor_gain	0.9100
17:48625738:C:CC	donor_gain	0.9100

AlphaMissense

1634 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:48622930:C:A	K241N	1.000
17:48622930:C:G	K241N	1.000
17:48622932:T:C	K241E	1.000
17:48622936:T:A	K239N	1.000
17:48622936:T:G	K239N	1.000
17:48622937:T:A	K239I	1.000
17:48622938:T:C	K239E	1.000
17:48622939:C:A	M238I	1.000
17:48622939:C:G	M238I	1.000
17:48622939:C:T	M238I	1.000
17:48622940:A:G	M238T	1.000
17:48622943:C:G	R237P	1.000
17:48622944:G:C	R237G	1.000
17:48622946:C:A	R236L	1.000
17:48622946:C:G	R236P	1.000
17:48622947:G:C	R236G	1.000
17:48622948:G:C	N235K	1.000
17:48622948:G:T	N235K	1.000
17:48622949:T:A	N235I	1.000
17:48622949:T:C	N235S	1.000
17:48622949:T:G	N235T	1.000
17:48622950:T:C	N235D	1.000
17:48622950:T:G	N235H	1.000
17:48622951:C:A	Q234H	1.000
17:48622951:C:G	Q234H	1.000
17:48622952:T:G	Q234P	1.000
17:48622953:G:T	Q234K	1.000
17:48622954:A:C	F233L	1.000
17:48622954:A:T	F233L	1.000
17:48622955:A:C	F233C	1.000

dbSNP variants (sampled 300 via entrez): RS1000123927 (17:48621676 C>T), RS1000541350 (17:48620758 T>C), RS1000911501 (17:48624916 C>T), RS1001040440 (17:48624047 G>A,C), RS1001216259 (17:48623526 A>T), RS1002009510 (17:48625379 C>A), RS1003042803 (17:48626572 G>A), RS1003379625 (17:48628111 A>G), RS1003502982 (17:48626400 A>C,G), RS1004027657 (17:48622798 A>G), RS1004477905 (17:48626667 C>A,G), RS1004717504 (17:48621095 A>C,G), RS1004804631 (17:48625304 C>G,T), RS1004842714 (17:48624454 G>A,C), RS1004896736 (17:48624202 C>T)

Disease associations

OMIM: gene MIM:142964 | 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
GCST002520_5	Celiac disease	8.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases expression, increases expression	3
bisphenol A	increases expression, affects binding, decreases reaction, increases reaction, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases methylation	2
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment, decreases expression	2
Valproic Acid	decreases methylation, increases expression	2
Cyclosporine	decreases methylation, increases expression	2
aristolochic acid I	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
methyleugenol	increases expression	1
dimethylselenide	increases expression, increases oxidation, decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
arsenite	increases methylation	1
mono-(2-ethylhexyl)phthalate	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
perfluorooctanoic acid	decreases expression	1
tobacco tar	decreases reaction, increases expression	1
manganese chloride	decreases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
diallyl disulfide	decreases reaction, increases expression	1
allyl sulfide	decreases reaction, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
casticin	decreases expression	1
perfluoro-n-nonanoic acid	increases expression	1
azaspiracid	increases expression	1
Chir 99021	affects cotreatment, increases expression	1
abrine	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1661	ZR-75-30	Cancer cell line	Female

Clinical trials (associated diseases)

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