XYLB

Summary

XYLB (xylulokinase, HGNC:12839) is a protein-coding gene on chromosome 3p22.2, encoding Xylulose kinase (O75191). Phosphorylates D-xylulose to produce D-xylulose 5-phosphate, a molecule that may play an important role in the regulation of glucose metabolism and lipogenesis.

The protein encoded by this gene shares 22% sequence identity with Hemophilus influenzae xylulokinase, and even higher identity to other gene products in C.elegans (45%) and yeast (31-35%), which are thought to belong to a family of enzymes that include fucokinase, gluconokinase, glycerokinase and xylulokinase. These proteins play important roles in energy metabolism.

Source: NCBI Gene 9942 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 104 total
• MANE Select transcript: NM_005108

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12839
Approved symbol	XYLB
Name	xylulokinase
Location	3p22.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10343, FLJ12539
Ensembl gene	ENSG00000093217
Ensembl biotype	protein_coding
OMIM	604049
Entrez	9942

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000207870, ENST00000424034, ENST00000427323, ENST00000472721, ENST00000487569, ENST00000649234, ENST00000650590, ENST00000854434, ENST00000854435, ENST00000854436, ENST00000854437

RefSeq mRNA: 4 — MANE Select: NM_005108 NM_001349178, NM_001349179, NM_001349180, NM_005108

CCDS: CCDS2678, CCDS87062

Canonical transcript exons

ENST00000207870 — 19 exons

Exon	Start	End
ENSE00000762862	38362937	38363017
ENSE00000825674	38346785	38346925
ENSE00001318746	38360339	38360408
ENSE00003469155	38395505	38395563
ENSE00003470539	38375144	38375259
ENSE00003472594	38365608	38365736
ENSE00003475962	38397072	38397159
ENSE00003484823	38374462	38374502
ENSE00003524668	38412936	38414985
ENSE00003528017	38376918	38376991
ENSE00003557211	38348550	38348632
ENSE00003562999	38365199	38365285
ENSE00003576550	38400891	38400985
ENSE00003577804	38372655	38372736
ENSE00003579288	38376117	38376232
ENSE00003585517	38370056	38370174
ENSE00003596596	38379246	38379342
ENSE00003635764	38368185	38368257
ENSE00003648743	38366808	38366873

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 89.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.2852 / max 102.9013, expressed in 1701 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36102	8.2852	1701

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	89.78	gold quality
liver	UBERON:0002107	83.63	gold quality
buccal mucosa cell	CL:0002336	77.26	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.23	gold quality
rectum	UBERON:0001052	76.67	gold quality
stromal cell of endometrium	CL:0002255	75.54	gold quality
colonic epithelium	UBERON:0000397	75.04	gold quality
ventricular zone	UBERON:0003053	74.30	gold quality
sural nerve	UBERON:0015488	74.15	gold quality
mucosa of transverse colon	UBERON:0004991	74.03	gold quality
right adrenal gland cortex	UBERON:0035827	73.63	gold quality
body of pancreas	UBERON:0001150	73.12	gold quality
calcaneal tendon	UBERON:0003701	72.93	gold quality
right adrenal gland	UBERON:0001233	72.77	gold quality
ganglionic eminence	UBERON:0004023	72.74	gold quality
left adrenal gland	UBERON:0001234	72.43	gold quality
transverse colon	UBERON:0001157	71.88	gold quality
adult mammalian kidney	UBERON:0000082	71.73	gold quality
left adrenal gland cortex	UBERON:0035825	71.57	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.50	gold quality
adrenal cortex	UBERON:0001235	71.29	gold quality
adrenal gland	UBERON:0002369	71.07	gold quality
pancreas	UBERON:0001264	70.64	gold quality
cortical plate	UBERON:0005343	70.45	gold quality
cerebellar cortex	UBERON:0002129	70.38	gold quality
minor salivary gland	UBERON:0001830	70.37	gold quality
right hemisphere of cerebellum	UBERON:0014890	70.36	gold quality
cerebellar hemisphere	UBERON:0002245	70.33	gold quality
sperm	CL:0000019	70.07	gold quality
stomach	UBERON:0000945	69.88	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	46.72
E-ANND-3	yes	5.00
E-ENAD-17	no	66.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

128 targeting XYLB, 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-6758-5P	100.00	66.21	1470
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4510	100.00	66.60	2050
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-4682	100.00	68.89	1258
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
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-607	99.97	73.62	5593
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-335-3P	99.93	73.36	4958

Literature-anchored findings (GeneRIF, showing 3)

• crystals of D-xylulokinase proved to be trigonal, with point-group symmetry 3 and unit-cell parameters a = b = 101.87, c = 158.85 A degrees (PMID:23027762)
• Xylulose binds to domain-I and ADP to domain-II, but in an open form of D-xylulokinase they are 10 A apart, implying that a large scale conformational change is required for catalysis. (PMID:23179721)
• Single nucleotide polymorphisms in nNOS, renalase, MTHFR, CELSR1 and XYLB genes were found significantly associated with ischemic stroke in Chinese patients. (PMID:25855559)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	xylb	ENSDARG00000043260
mus_musculus	Xylb	ENSMUSG00000035769
rattus_norvegicus	Xylb	ENSRNOG00000014168
drosophila_melanogaster	CG3544	FBGN0031279
drosophila_melanogaster	CG3534	FBGN0038463
caenorhabditis_elegans		WBGENE00011147

Paralogs (6): FGGY (ENSG00000172456), GK5 (ENSG00000175066), GK2 (ENSG00000196475), SHPK (ENSG00000197417), GK (ENSG00000198814), GK3 (ENSG00000229894)

Protein

Protein identifiers

Xylulose kinase — O75191 (reviewed: O75191)

All UniProt accessions (5): O75191, A0A3B3IRM4, A0A3B3IS07, C9J0N9, F8WBF6

UniProt curated annotations — full annotation on UniProt →

Function. Phosphorylates D-xylulose to produce D-xylulose 5-phosphate, a molecule that may play an important role in the regulation of glucose metabolism and lipogenesis.

Subunit / interactions. Monomer.

Similarity. Belongs to the FGGY kinase family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75191-1	1	yes
O75191-2	2

RefSeq proteins (4): NP_001336107, NP_001336108, NP_001336109, NP_005099* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000577	Carb_kinase_FGGY	Family
IPR018484	FGGY_N	Domain
IPR018485	FGGY_C	Domain
IPR042024	D-XK_euk	Family
IPR043129	ATPase_NBD	Homologous_superfamily

Pfam: PF00370, PF02782

Enzyme classification (BRENDA):

• EC 2.7.1.17 — xylulokinase (BRENDA: 22 organisms, 52 substrates, 11 inhibitors, 27 Km, 15 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-XYLULOSE	0.024–1.24	10
ATP	0.14–8.2	9
(POLYPHOSPHATE)N	17	1
ADP	0.28	1
D-ARABITOL	141	1
D-RIBULOSE	14	1
D-XYLULOSE 5-PHOSPHATE	1.3	1
XYLITOL	127	1
XYLULOSE	0.09	1

Catalyzed reactions (Rhea), 1 shown:

• D-xylulose + ATP = D-xylulose 5-phosphate + ADP + H(+) (RHEA:10964)

UniProt features (63 total): helix 26, strand 22, binding site 7, sequence variant 5, chain 1, turn 1, splice variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
4BC3	X-RAY DIFFRACTION	1.68
4BC4	X-RAY DIFFRACTION	1.79
4BC2	X-RAY DIFFRACTION	1.97
4BC5	X-RAY DIFFRACTION	1.98

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75191-F1	96.07	0.95

Functional residue map

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

Ligand- & substrate-binding residues (7): 99; 170; 280; 281; 355; 441–442; 445

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5661270	Formation of xylulose-5-phosphate

MSigDB gene sets: 122 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_MONOSACCHARIDE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_PHOSPHORYLATION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, chr3p22, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_CATABOLIC_PROCESS

GO Biological Process (7): carbohydrate metabolic process (GO:0005975), xylulose metabolic process (GO:0005997), xylulose catabolic process (GO:0005998), generation of precursor metabolites and energy (GO:0006091), obsolete D-glucuronate catabolic process to D-xylulose 5-phosphate (GO:0019640), D-xylose metabolic process (GO:0042732), carbohydrate phosphorylation (GO:0046835)

GO Molecular Function (5): D-xylulokinase activity (GO:0004856), ATP binding (GO:0005524), nucleotide binding (GO:0000166), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (1): cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of carbohydrates and carbohydrate derivatives	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
pentose metabolic process	2
primary metabolic process	1
xylulose metabolic process	1
pentose catabolic process	1
metabolic process	1
carbohydrate metabolic process	1
phosphorylation	1
phosphotransferase activity, alcohol group as acceptor	1
carbohydrate kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1816 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
XYLB	SLC22A14	Q9Y267	962
XYLB	SORD	Q00796	916
XYLB	SLC22A13	Q9Y226	912
XYLB	OXSR1	O95747	839
XYLB	TALDO1	P37837	746
XYLB	RPE	Q96AT9	718
XYLB	TKT	P29401	702
XYLB	ACVR2B	Q13705	690
XYLB	PGK1	P00558	662
XYLB	RPIA	P49247	649
XYLB	TKTL2	Q9H0I9	647
XYLB	GALK1	P51570	646
XYLB	AKR1B1	P15121	640
XYLB	TKTL1	P51854	627
XYLB	GPI	P06744	626

IntAct

2 interactions, top by confidence:

A	B	Type	Score
rep	TMEM120B	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): RPE (Co-fractionation), SCRN2 (Co-fractionation), TALDO1 (Co-fractionation), XYLB (Co-fractionation), XYLB (Affinity Capture-RNA), XYLB (Synthetic Lethality), XYLB (Affinity Capture-MS), XYLB (Affinity Capture-MS), XYLB (Affinity Capture-MS), AGL (Co-fractionation), DUSP12 (Co-fractionation), XYLB (Affinity Capture-MS), XYLB (Affinity Capture-MS), XYLB (Co-fractionation)

ESM2 similar proteins: A0JPE9, A2AJL3, A2VD33, O46504, O75191, P12276, P12785, P13439, P17256, P19096, P31754, Q08D86, Q0IH28, Q0VFE7, Q3MIF4, Q3SYZ6, Q3TNA1, Q4V831, Q4V9P6, Q503J2, Q566S6, Q5M7T9, Q5R979, Q5RFE6, Q5U5V2, Q5XH07, Q5XIG6, Q5ZMJ4, Q64FG0, Q68FH4, Q6DCD1, Q6DH69, Q6GMR7, Q6GP95, Q6NUM9, Q6NUW9, Q6ZS86, Q71SP7, Q7TSQ8, Q80SY6

Diamond homologs: A1CAU3, A1DEK3, A2QMS4, B0Y4D5, B8NTI4, C5FSW4, O75191, P30646, P42826, Q0CIL2, Q2U3V4, Q3MIF4, Q3SYZ6, Q3TNA1, Q4WUV8, Q5ASE0, Q5R830, Q8X167, Q949W8, Q9C0U6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3132 predictions. Top by Δscore:

Variant	Effect	Δscore
3:38346921:AGCAG:A	donor_loss	1.0000
3:38346922:GCAG:G	donor_gain	1.0000
3:38346923:CAG:C	donor_loss	1.0000
3:38346924:AGG:A	donor_loss	1.0000
3:38346925:GGT:G	donor_loss	1.0000
3:38346926:GTAC:G	donor_loss	1.0000
3:38346927:T:G	donor_loss	1.0000
3:38362931:TCTTA:T	acceptor_loss	1.0000
3:38362932:CTTAG:C	acceptor_loss	1.0000
3:38362933:TTAG:T	acceptor_loss	1.0000
3:38362934:TAGG:T	acceptor_loss	1.0000
3:38362935:A:AG	acceptor_gain	1.0000
3:38362935:AGGCA:A	acceptor_loss	1.0000
3:38362936:G:A	acceptor_loss	1.0000
3:38362936:G:GG	acceptor_gain	1.0000
3:38365607:GGACT:G	acceptor_gain	1.0000
3:38365732:ATGAG:A	donor_loss	1.0000
3:38365733:TGAG:T	donor_loss	1.0000
3:38365734:GAGGT:G	donor_loss	1.0000
3:38365735:AGG:A	donor_loss	1.0000
3:38365736:GGTAG:G	donor_loss	1.0000
3:38365737:GTA:G	donor_loss	1.0000
3:38365738:T:G	donor_loss	1.0000
3:38372653:A:AG	acceptor_gain	1.0000
3:38372654:G:GG	acceptor_gain	1.0000
3:38372654:GGGA:G	acceptor_gain	1.0000
3:38372732:CCCAG:C	donor_gain	1.0000
3:38372733:CCAGG:C	donor_loss	1.0000
3:38372734:CAGGT:C	donor_loss	1.0000
3:38372737:G:GA	donor_loss	1.0000

AlphaMissense

3498 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:38372728:A:T	D280V	0.999
3:38372727:G:C	D280H	0.998
3:38372728:A:C	D280A	0.998
3:38375147:A:C	S298R	0.998
3:38375149:C:A	S298R	0.998
3:38375149:C:G	S298R	0.998
3:38365638:T:A	W137R	0.997
3:38365638:T:C	W137R	0.997
3:38372729:C:A	D280E	0.997
3:38372729:C:G	D280E	0.997
3:38375159:A:C	S302R	0.997
3:38375161:T:A	S302R	0.997
3:38375161:T:G	S302R	0.997
3:38368200:A:C	S197R	0.996
3:38368202:T:A	S197R	0.996
3:38368202:T:G	S197R	0.996
3:38395526:C:A	A438D	0.996
3:38368251:A:C	S214R	0.995
3:38368253:T:A	S214R	0.995
3:38368253:T:G	S214R	0.995
3:38372724:G:T	G279W	0.995
3:38372728:A:G	D280G	0.995
3:38372732:C:A	N281K	0.995
3:38372732:C:G	N281K	0.995
3:38376126:T:A	N338K	0.995
3:38376126:T:G	N338K	0.995
3:38376141:A:C	R343S	0.995
3:38376141:A:T	R343S	0.995
3:38366811:T:C	F171L	0.994
3:38366813:T:A	F171L	0.994

dbSNP variants (sampled 300 via entrez): RS1000004136 (3:38380018 GC>G), RS1000026313 (3:38422831 C>A), RS1000039786 (3:38415509 A>G), RS1000048689 (3:38371838 C>G,T), RS1000178304 (3:38449263 C>T), RS1000190988 (3:38395878 C>T), RS1000256920 (3:38405394 A>G,T), RS1000311728 (3:38405023 A>G), RS1000312208 (3:38421091 A>G), RS1000327658 (3:38398284 A>G), RS1000380119 (3:38398113 C>T), RS1000397609 (3:38367493 T>C), RS1000417544 (3:38350574 C>T), RS1000451662 (3:38437054 C>A,G), RS1000455778 (3:38367210 C>T)

Disease associations

OMIM: gene MIM:604049 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002457_2	P wave duration	8.000000e-27
GCST003119_2	Urinary metabolites	3.000000e-14
GCST005231_30	Major depressive disorder	6.000000e-06
GCST006134_1	Hippocampal volume	7.000000e-07
GCST007344_53	Estimated glomerular filtration rate	2.000000e-11
GCST007876_48	Estimated glomerular filtration rate	5.000000e-11
GCST008522_49	Bitter alcoholic beverage consumption	1.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005094	P wave duration
EFO:0005116	urinary metabolite measurement
EFO:0005035	hippocampal volume
EFO:0010092	bitter alcoholic beverage consumption measurement

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
Acetaminophen	decreases expression	3
Benzo(a)pyrene	decreases expression, decreases methylation	2
Hydrogen Peroxide	affects cotreatment, increases expression	2
Valproic Acid	affects cotreatment, increases expression, decreases methylation	2
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
K 7174	decreases expression	1
abrine	decreases expression	1
jinfukang	increases 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
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Estradiol	increases expression	1
Hydralazine	affects cotreatment, increases expression	1
Methapyrilene	decreases methylation	1
Silicon Dioxide	increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Theophylline	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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