HMGB3

Summary

HMGB3 (high mobility group box 3, HGNC:5004) is a protein-coding gene on chromosome Xq28, encoding High mobility group protein B3 (O15347). Multifunctional protein with various roles in different cellular compartments.

This gene encodes a member of a family of proteins containing one or more high mobility group DNA-binding motifs. The encoded protein plays an important role in maintaining stem cell populations, and may be aberrantly expressed in tumor cells. A mutation in this gene was associated with microphthalmia, syndromic 13. There are numerous pseudogenes of this gene on multiple chromosomes. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 3149 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome (Limited, GenCC)
• Clinical variants (ClinVar): 58 total
• Phenotypes (HPO): 16
• Druggable target: yes
• MANE Select transcript: NM_005342

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5004
Approved symbol	HMGB3
Name	high mobility group box 3
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	HMG2A, MGC90319
Ensembl gene	ENSG00000029993
Ensembl biotype	protein_coding
OMIM	300193
Entrez	3149

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 15 protein_coding

ENST00000325307, ENST00000419110, ENST00000430118, ENST00000448905, ENST00000455596, ENST00000854897, ENST00000854898, ENST00000854899, ENST00000854900, ENST00000854901, ENST00000854902, ENST00000918046, ENST00000918047, ENST00000918048, ENST00000918049

RefSeq mRNA: 4 — MANE Select: NM_005342 NM_001301228, NM_001301229, NM_001301231, NM_005342

CCDS: CCDS35428

Canonical transcript exons

ENST00000325307 — 5 exons

Exon	Start	End
ENSE00001132453	150987128	150987302
ENSE00001132458	150986051	150986190
ENSE00001287109	150985595	150985749
ENSE00001293896	150987777	150990771
ENSE00001452489	150983335	150983376

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 99.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.5297 / max 332.3969, expressed in 1695 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197976	8.9944	1621
197977	2.3226	923
197975	0.1881	73
197974	0.0139	4
197973	0.0106	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.65	gold quality
oocyte	CL:0000023	99.15	gold quality
ganglionic eminence	UBERON:0004023	98.89	gold quality
ventricular zone	UBERON:0003053	98.44	gold quality
embryo	UBERON:0000922	98.19	gold quality
cortical plate	UBERON:0005343	96.84	gold quality
buccal mucosa cell	CL:0002336	96.74	gold quality
placenta	UBERON:0001987	94.96	gold quality
islet of Langerhans	UBERON:0000006	94.47	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.16	gold quality
right lobe of liver	UBERON:0001114	93.05	gold quality
mucosa of transverse colon	UBERON:0004991	92.79	gold quality
sural nerve	UBERON:0015488	92.58	gold quality
rectum	UBERON:0001052	91.77	gold quality
left testis	UBERON:0004533	91.55	gold quality
right testis	UBERON:0004534	91.37	gold quality
endometrium epithelium	UBERON:0004811	90.95	gold quality
endometrium	UBERON:0001295	90.64	gold quality
testis	UBERON:0000473	90.25	gold quality
gastrocnemius	UBERON:0001388	89.05	gold quality
esophagus squamous epithelium	UBERON:0006920	88.02	gold quality
esophagus mucosa	UBERON:0002469	87.99	gold quality
bone marrow	UBERON:0002371	87.71	gold quality
tibial nerve	UBERON:0001323	87.40	gold quality
transverse colon	UBERON:0001157	87.25	gold quality
minor salivary gland	UBERON:0001830	87.07	gold quality
muscle of leg	UBERON:0001383	86.95	gold quality
pancreas	UBERON:0001264	86.78	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.66	gold quality
decidua	UBERON:0002450	86.61	gold quality

Single-cell (SCXA)

Detected in 16 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	1141.11
E-MTAB-8530	yes	1008.12
E-HCAD-10	yes	42.24
E-HCAD-31	yes	27.01
E-HCAD-13	yes	24.04
E-GEOD-125970	yes	22.54
E-GEOD-81608	yes	20.13
E-HCAD-5	yes	19.63
E-MTAB-6678	yes	17.31
E-CURD-122	yes	16.26
E-ANND-3	yes	14.07
E-ENAD-27	yes	10.66
E-GEOD-130148	yes	5.04
E-GEOD-86618	no	569.29
E-MTAB-6911	no	549.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4, REST

miRNA regulators (miRDB)

105 targeting HMGB3, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
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-3658	99.96	73.87	4379

Literature-anchored findings (GeneRIF, showing 40)

• Data indicate that myomiR-206 modulates Hmgb3 expression during myogenesis. (PMID:22912879)
• HMGB3 has a role in gastric cancer disease onset and progression by regulating the cell cycle (PMID:23326140)
• HMGB3 plays an important role in non-small cell lung cancer progression. (PMID:23609034)
• regulation of HMGB3 by miR-205 reduced both proliferation and invasion of breast cancer cells. (PMID:24098490)
• Association between co-expression networks involving HMGB3 and differentially-expressed genes in gastric cancer. (PMID:24338397)
• In this family, microphthalmia, microcephaly, intellectual disability, and short stature are associated with a mutation on the X chromosome in the HMGB3 gene. (PMID:24993872)
• High expression of HMGB3 is associated with lymph node metastases in gastric cancer. (PMID:25095979)
• our data suggests HMGB3 may serve as an important oncoprotein and indicate that overexpression of HMGB3 in urinary bladder cancer could be used as a potential prognostic marker. (PMID:25647262)
• these findings demonstrate that HMBG3 may be a potential molecular marker for predicting the prognosis of esophageal squamous cell carcinoma patients (PMID:25755721)
• Therefore, we infer that HMGB3 is a functional target of miR-27b in modulation of tamoxifen resistance and EMT. (PMID:27363334)
• HMGB3 regulates the genes expression of WNT/beta-catenin pathway (PMID:28678825)
• Luciferase reporter assays showed that HMGB3 was directly regulated by miR-205-5p in prostate cancer cells. (PMID:29196733)
• HMGB3 is involved in malignant transformation of hepatocytes and could be a useful biomarker for diagnosis and a potential target for therapy of liver cancer. (PMID:30166860)
• The study strongly suggests that HMGB3 promotes GBM oncogenesis through the MAPK signalling pathway while miR-200b-3p and miR-200c-3p inhibit its expression. (PMID:30232806)
• HMGB3 overexpression or miR-200b downregulation was associated with poor prognosis. Our findings suggest HMGB3 may serve as an important oncoprotein whose expression is negatively regulated by miR-200b in hepatocellular carcinoma. (PMID:30343649)
• HMGB3 has higher expression in non-small cell lung cancer tissues.HMGB3 is the target gene of miR-758. (PMID:30446524)
• HMGB3 might be of very great significance to the pathogenesis of FGR and might play the role by leading the dysfunction of placental villous trophoblast cells and through the interaction with some other proteins (PMID:30543931)
• High HMGB3 expression is associated with Chemo-resistance in Ovarian Cancer. (PMID:31061066)
• HOTTIP was upregulated and miR-615-3p was downregulated in non-small cell lung cancer (NSCLC) tissues and cells. Hypoxia induced glycolysis, increased HOTTIP and HMGB3 mRNA levels and repressed miR-615-3p expression in NSCLC cells. HOTTIP deficiency or miR-615-3p expression restoration repressed hypoxia-induced glycolysis. HOTTIP acted as a molecular sponge for miR-615-3p and HMGB3 was a direct target of miR-615-3p. (PMID:31422060)
• Bioinformatics analysis of the prognosis and biological significance of HMGB1, HMGB2, and HMGB3 in gastric cancer. (PMID:31621076)
• HMGB3 small interfere RNA suppresses mammosphere formation of MDA-MB-231 cells by down-regulating expression of HIF1alpha. (PMID:31773719)
• Circ-0001801 contributes to cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT) in glioblastoma by regulating miR-628-5p/HMGB3 axis. (PMID:31858556)
• LncRNA SNHG5 promotes nasopharyngeal carcinoma progression by regulating miR-1179/HMGB3 axis. (PMID:32131767)
• High-mobility group box 3 (HMGB3) silencing inhibits non-small cell lung cancer development through regulating Wnt/beta-catenin pathway. (PMID:32386184)
• Long Noncoding RNA SOX2-OT Knockdown Inhibits Proliferation and Metastasis of Prostate Cancer Cells Through Modulating the miR-452-5p/HMGB3 Axis and Inactivating Wnt/beta-Catenin Pathway. (PMID:32407168)
• LncRNA PITPNA-AS1 boosts the proliferation and migration of lung squamous cell carcinoma cells by recruiting TAF15 to stabilize HMGB3 mRNA. (PMID:32871048)
• CircRNA_102179 promotes the proliferation, migration and invasion in non-small cell lung cancer cells by regulating miR-330-5p/HMGB3 axis. (PMID:32911346)
• High mobility group box 3 promotes cervical cancer proliferation by regulating Wnt/beta-catenin pathway. (PMID:33078596)
• The role of high mobility group protein B3 (HMGB3) in tumor proliferation and drug resistance. (PMID:33428061)
• MiR-93/HMGB3 regulatory axis exerts tumor suppressive effects in colorectal carcinoma cells. (PMID:33773992)
• LINC00319 promotes cancer stem cell-like properties in laryngeal squamous cell carcinoma via E2F1-mediated upregulation of HMGB3. (PMID:34408262)
• LINC00857 promotes colorectal cancer progression by sponging miR-150-5p and upregulating HMGB3 (high mobility group box 3) expression. (PMID:34753396)
• miR-142-3p simultaneously targets HMGA1, HMGA2, HMGB1, and HMGB3 and inhibits tumorigenic properties and in-vivo metastatic potential of human cervical cancer cells. (PMID:34973275)
• HMGB3 promotes PARP inhibitor resistance through interacting with PARP1 in ovarian cancer. (PMID:35332131)
• Long Noncoding RNA Brain Cytoplasmic RNA 1 Induces Cisplatin-Resistance of Cervical Cancer Cells by Sponging MicroRNA-330-5p and Upregulating High-Mobility Group Box 3. (PMID:35705019)
• SOX9 and HMGB3 co-operatively transactivate NANOG and promote prostate cancer progression. (PMID:36541373)
• Circ-IGF1R Affects the Progression of Colorectal Cancer by Activating the miR-362-5p/HMGB3-Mediated Wnt/beta-Catenin Signal Pathway. (PMID:36542208)
• HMGB3 promotes the malignant phenotypes and stemness of epithelial ovarian cancer through the MAPK/ERK signaling pathway. (PMID:37328851)
• Exosomal HMGB3 released by glioma cells confers the activation of NLRP3 inflammasome and pyroptosis in tumor-associated macrophages. (PMID:38761792)
• Structure and Functions of HMGB3 Protein. (PMID:39062899)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	hmgb3b	ENSDARG00000006408
danio_rerio	hmgb3a	ENSDARG00000056725
mus_musculus	Hmgb3	ENSMUSG00000015217
rattus_norvegicus	Hmgb3l1	ENSRNOG00000011096
rattus_norvegicus	Hmgb3l1	ENSRNOG00000063351
drosophila_melanogaster	Dsp1	FBGN0278608
caenorhabditis_elegans		WBGENE00001972

Paralogs (20): HMG20B (ENSG00000064961), SP100 (ENSG00000067066), SMARCE1 (ENSG00000073584), SP140 (ENSG00000079263), TOX4 (ENSG00000092203), HMGXB4 (ENSG00000100281), TOX3 (ENSG00000103460), TFAM (ENSG00000108064), UBTF (ENSG00000108312), HMGB1P1 (ENSG00000124097), TOX2 (ENSG00000124191), SP110 (ENSG00000135899), HMG20A (ENSG00000140382), SSRP1 (ENSG00000149136), HMGB2 (ENSG00000164104), HMGB4 (ENSG00000176256), SP140L (ENSG00000185404), HMGB1 (ENSG00000189403), TOX (ENSG00000198846), UBTFL1 (ENSG00000255009)

Protein

Protein identifiers

High mobility group protein B3 — O15347 (reviewed: O15347)

Alternative names: High mobility group protein 2a, High mobility group protein 4

All UniProt accessions (4): E7EQU1, E7ES08, E9PES6, O15347

UniProt curated annotations — full annotation on UniProt →

Function. Multifunctional protein with various roles in different cellular compartments. May act in a redox sensitive manner. Associates with chromatin and binds DNA with a preference for non-canonical DNA structures such as single-stranded DNA. Can bend DNA and enhance DNA flexibility by looping thus providing a mechanism to promote activities on various gene promoters. Proposed to be involved in the innate immune response to nucleic acids by acting as a cytoplasmic promiscuous immunogenic DNA/RNA sensor. Negatively regulates B-cell and myeloid cell differentiation. In hematopoietic stem cells may regulate the balance between self-renewal and differentiation. Involved in negative regulation of canonical Wnt signaling.

Subcellular location. Nucleus. Chromosome. Cytoplasm.

Tissue specificity. Expressed predominantly in placenta.

Post-translational modifications. Reduction/oxidation of cysteine residues Cys-23, Cys-45 and Cys-104 and a possible intramolecular disulfide bond involving Cys-23 and Cys-45 give rise to different redox forms with specific functional activities in various cellular compartments: 1- fully reduced HMGB3 (HMGB3C23hC45hC104h), 2- disulfide HMGB3 (HMGB3C23-C45C104h) and 3- sulfonyl HMGB3 (HMGB3C23soC45soC104so).

Disease relevance. Microphthalmia, syndromic, 13 (MCOPS13) [MIM:300915] A form of microphthalmia, a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities. MCOPS13 patients exhibit colobomatous microphthalmia with microcephaly, short stature, and psychomotor retardation. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the HMGB family.

RefSeq proteins (4): NP_001288157, NP_001288158, NP_001288160, NP_005333* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009071	HMG_box_dom	Domain
IPR017967	HMG_boxA_CS	Conserved_site
IPR036910	HMG_box_dom_sf	Homologous_superfamily
IPR050342	HMGB	Family

Pfam: PF00505, PF09011

UniProt features (28 total): modified residue 9, helix 6, sequence conflict 3, DNA-binding region 2, sequence variant 2, region of interest 2, chain 1, disulfide bond 1, strand 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2EQZ	SOLUTION NMR
2YQI	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15347-F1	80.31	0.54

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 (9): 45, 98, 104, 112, 139, 3, 23, 30, 43

Disulfide bonds (1): 23–45

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 343 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_B_CELL_ACTIVATION, TGCACTT_MIR519C_MIR519B_MIR519A, RIZ_ERYTHROID_DIFFERENTIATION_CCNE1, GOBP_NEGATIVE_REGULATION_OF_B_CELL_ACTIVATION, TGACCTY_ERR1_Q2, YY1_Q6, PUJANA_CHEK2_PCC_NETWORK, GOBP_REGULATION_OF_LEUKOCYTE_DIFFERENTIATION, GOBP_DNA_CONFORMATION_CHANGE, IRF7_01

GO Biological Process (6): DNA recombination (GO:0006310), DNA geometric change (GO:0032392), innate immune response (GO:0045087), negative regulation of B cell differentiation (GO:0045578), negative regulation of myeloid cell differentiation (GO:0045638), immune system process (GO:0002376)

GO Molecular Function (6): four-way junction DNA binding (GO:0000400), double-stranded DNA binding (GO:0003690), RNA binding (GO:0003723), DNA binding, bending (GO:0008301), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), chromosome (GO:0005694), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA binding	2
nucleic acid binding	2
DNA metabolic process	1
DNA conformation change	1
immune response	1
defense response to symbiont	1
B cell differentiation	1
regulation of B cell differentiation	1
negative regulation of lymphocyte differentiation	1
negative regulation of B cell activation	1
myeloid cell differentiation	1
negative regulation of cell differentiation	1
regulation of myeloid cell differentiation	1
biological_process	1
DNA secondary structure binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1994 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HMGB3	GM2A	P17900	650
HMGB3	IRF3	Q14653	587
HMGB3	AGER	Q15109	573
HMGB3	TLR3	O15455	570
HMGB3	TLR7	Q9NYK1	563
HMGB3	TLR9	Q9NR96	555
HMGB3	TCEA1	P23193	469
HMGB3	NFKB1	P19838	451
HMGB3	FEN1	P39748	446
HMGB3	H1-3	P16402	426
HMGB3	H1-6	P22492	407
HMGB3	GSN	P06396	392
HMGB3	DVL1	O14640	389
HMGB3	GAP43	P17677	378
HMGB3	MMD	Q15546	358

IntAct

64 interactions, top by confidence:

A	B	Type	Score
SDCBP	HMGB3	psi-mi:“MI:0915”(physical association)	0.780
HMGB3	SDCBP	psi-mi:“MI:0915”(physical association)	0.780
HMGB3	PAX5	psi-mi:“MI:0915”(physical association)	0.560
HMGB3	PAX6	psi-mi:“MI:0915”(physical association)	0.560
HMGB3	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
HMGB3	MEOX1	psi-mi:“MI:0915”(physical association)	0.560
HMGB3	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
CYP2B6	HMGB3	psi-mi:“MI:0915”(physical association)	0.400
HMGB1	HMGB3	psi-mi:“MI:0915”(physical association)	0.400
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
SDHA	HMGB3	psi-mi:“MI:0914”(association)	0.350
SOD1	NPEPPSL1	psi-mi:“MI:0914”(association)	0.350
MAPT	C11orf98	psi-mi:“MI:0914”(association)	0.350
MAPT	POTEF	psi-mi:“MI:0914”(association)	0.350
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
HMGA1	HNRNPDL	psi-mi:“MI:0914”(association)	0.350
RAC1	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
HTRA4	PSMD12	psi-mi:“MI:0914”(association)	0.350
	ARID1A	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (116): SDCBP (Two-hybrid), HMGB3 (Affinity Capture-RNA), HMGB3 (Affinity Capture-RNA), EXOSC4 (Co-fractionation), NUCKS1 (Co-fractionation), SSRP1 (Co-fractionation), SUPT16H (Co-fractionation), HMGB3 (Proximity Label-MS), HMGB3 (Proximity Label-MS), HMGB3 (Affinity Capture-MS), HMGB3 (Affinity Capture-MS), HMGB3 (Affinity Capture-MS), HMGB3 (Affinity Capture-MS), HMGB3 (Affinity Capture-MS), HMGB3 (Affinity Capture-MS)

ESM2 similar proteins: A9RA84, B0CM99, B1MTB0, B2RPK0, O15347, O54879, P07156, P07746, P09429, P0CO24, P0CO25, P10103, P11873, P12682, P17741, P25979, P25980, P26583, P26584, P26586, P30681, P40618, P40620, P40621, P40622, P40623, P40625, P40626, P40632, P40644, P40673, P52925, P63158, P63159, P87057, Q05783, Q06943, Q07053, Q08IE6, Q09390

Diamond homologs: A4QNP0, B2RPK0, B7SBD2, O15347, O15405, O54879, O94842, O94900, P0CO24, P0CO25, P11632, P11633, P11873, P12682, P40618, Q0P5K4, Q32L31, Q4IQX3, Q4PBZ9, Q4WY33, Q5B995, Q5R6A9, Q66JW3, Q6BRB4, Q6CC79, Q6CVH3, Q6DJL0, Q6IRR0, Q75B82, Q76IQ7, Q7S045, Q80W03, Q8BU11, Q96NM4, Q99PM1, Q9UVL1, Q9YH06, A9RA84, B0CM99, B1MTB0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

828 predictions. Top by Δscore:

Variant	Effect	Δscore
X:150983373:ACAGG:A	donor_loss	1.0000
X:150983374:CAGG:C	donor_loss	1.0000
X:150983375:AGGT:A	donor_loss	1.0000
X:150983377:G:C	donor_loss	1.0000
X:150983378:T:A	donor_loss	1.0000
X:150985588:A:AG	acceptor_gain	1.0000
X:150985589:T:G	acceptor_gain	1.0000
X:150985593:A:AG	acceptor_gain	1.0000
X:150985593:A:C	acceptor_loss	1.0000
X:150985594:G:GA	acceptor_gain	1.0000
X:150985594:GT:G	acceptor_gain	1.0000
X:150985594:GTC:G	acceptor_gain	1.0000
X:150985594:GTCA:G	acceptor_gain	1.0000
X:150985728:G:GT	donor_gain	1.0000
X:150985745:GGAA:G	donor_loss	1.0000
X:150985746:G:GT	donor_gain	1.0000
X:150985746:GAAG:G	donor_loss	1.0000
X:150985747:A:T	donor_gain	1.0000
X:150985748:AG:A	donor_loss	1.0000
X:150986046:TGCA:T	acceptor_loss	1.0000
X:150986048:CA:C	acceptor_loss	1.0000
X:150986049:A:AG	acceptor_gain	1.0000
X:150986049:AGAC:A	acceptor_gain	1.0000
X:150986050:G:GT	acceptor_gain	1.0000
X:150986050:GA:G	acceptor_gain	1.0000
X:150986050:GAC:G	acceptor_gain	1.0000
X:150986050:GACG:G	acceptor_gain	1.0000
X:150986050:GACGA:G	acceptor_gain	1.0000
X:150986186:CCACC:C	donor_gain	1.0000
X:150986187:CACC:C	donor_gain	1.0000

AlphaMissense

1343 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:150985645:T:C	Y16H	1.000
X:150985654:T:C	F19L	1.000
X:150985655:T:C	F19S	1.000
X:150985656:T:A	F19L	1.000
X:150985656:T:G	F19L	1.000
X:150985670:G:C	R24T	1.000
X:150985671:A:C	R24S	1.000
X:150985671:A:T	R24S	1.000
X:150985720:T:C	F41L	1.000
X:150985721:T:C	F41S	1.000
X:150985722:T:A	F41L	1.000
X:150985722:T:G	F41L	1.000
X:150985732:T:C	C45R	1.000
X:150985733:G:A	C45Y	1.000
X:150985734:C:G	C45W	1.000
X:150985744:T:A	W49R	1.000
X:150985744:T:C	W49R	1.000
X:150985745:G:C	W49S	1.000
X:150985746:G:C	W49C	1.000
X:150985746:G:T	W49C	1.000
X:150986071:A:C	K57N	1.000
X:150986071:A:T	K57N	1.000
X:150986078:T:C	F60L	1.000
X:150986080:T:A	F60L	1.000
X:150986080:T:G	F60L	1.000
X:150986178:C:A	P93H	1.000
X:150987133:G:A	G99E	1.000
X:150987135:T:C	F100L	1.000
X:150987137:C:A	F100L	1.000
X:150987137:C:G	F100L	1.000

dbSNP variants (sampled 300 via entrez): RS1000038319 (X:150989146 A>G), RS1001262740 (X:150989703 C>G), RS1003740428 (X:150981385 T>A), RS1004217384 (X:150981790 G>A), RS1004869097 (X:150988363 T>G), RS1005348276 (X:150988782 A>G), RS1005944707 (X:150990448 A>G), RS1006465424 (X:150979734 T>C), RS1007249661 (X:150980739 G>T), RS1007327159 (X:150982907 C>T), RS1007743327 (X:150990968 C>G,T), RS1007919739 (X:150986417 C>T), RS1009186025 (X:150981257 G>C), RS1010024616 (X:150989169 C>T), RS1010115192 (X:150978797 A>T)

Disease associations

OMIM: gene MIM:300193 | disease phenotypes: MIM:300915, MIM:310440

GenCC curated gene-disease

Disease	Classification	Inheritance
X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome	Limited	Unknown

Mondo (2): X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome (MONDO:0010485), X-linked myopathy with excessive autophagy (MONDO:0010684)

Orphanet (2): X-linked colobomatous microphthalmia-microcephaly-intellectual disability-short stature syndrome (Orphanet:431140), X-linked myopathy with excessive autophagy (Orphanet:25980)

HPO phenotypes

16 total (16 of 16 shown, HPO-id order):

HPO	Term
HP:0000252	Microcephaly
HP:0000482	Microcornea
HP:0000508	Ptosis
HP:0000565	Esotropia
HP:0000567	Chorioretinal coloboma
HP:0000568	Microphthalmia
HP:0000612	Iris coloboma
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001417	X-linked inheritance
HP:0002751	Kyphoscoliosis
HP:0003577	Congenital onset
HP:0004322	Short stature
HP:0006304	Widely-spaced incisors
HP:0012043	Pendular nystagmus
HP:0040080	Anteverted ears

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536522	Vacuolar myopathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067046 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	5
bisphenol A	decreases expression	3
sodium arsenite	decreases expression, increases expression	3
Air Pollutants	affects cotreatment, increases abundance, increases expression, decreases expression	3
Particulate Matter	affects cotreatment, increases expression, decreases expression, increases abundance	3
Benzo(a)pyrene	affects methylation, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
propionaldehyde	decreases expression	1
geraniol	decreases expression	1
arsenite	affects binding, increases reaction	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	decreases expression	1
methacrylaldehyde	increases expression, increases abundance, affects cotreatment	1
isobutyl alcohol	decreases expression, increases abundance, affects cotreatment	1
beta-methylcholine	affects expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
entinostat	decreases expression	1
ICG 001	decreases expression	1
abrine	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
NSC 689534	affects binding, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651562	Binding	Binding affinity to human HMGB3 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1WR	Abcam A-549 HMGB3 KO	Cancer cell line	Male
CVCL_D2B4	Abcam HCT 116 HMGB3 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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