GK5

Summary

GK5 (glycerol kinase 5, HGNC:28635) is a protein-coding gene on chromosome 3q23, encoding Glycerol kinase 5 (Q6ZS86). Skin-specific kinase that plays a key role in glycerol metabolism, catalyzing its phosphorylation to produce sn-glycerol 3-phosphate.

Predicted to enable glycerol kinase activity. Predicted to be involved in glycerol metabolic process; glycerol-3-phosphate biosynthetic process; and triglyceride metabolic process. Located in mitochondrion.

Source: NCBI Gene 256356 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_001039547

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28635
Approved symbol	GK5
Name	glycerol kinase 5
Location	3q23
Locus type	gene with protein product
Status	Approved
Aliases	MGC40579
Ensembl gene	ENSG00000175066
Ensembl biotype	protein_coding
OMIM	620801
Entrez	256356

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 4 retained_intron, 4 nonsense_mediated_decay, 2 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000392993, ENST00000460515, ENST00000460544, ENST00000460630, ENST00000463349, ENST00000466685, ENST00000472759, ENST00000480757, ENST00000486459, ENST00000487672, ENST00000489085, ENST00000492097

RefSeq mRNA: 1 — MANE Select: NM_001039547 NM_001039547

CCDS: CCDS33871

Canonical transcript exons

ENST00000392993 — 16 exons

Exon	Start	End
ENSE00001737874	142185929	142185989
ENSE00001743513	142186194	142186267
ENSE00001949730	142225309	142225585
ENSE00003493474	142170325	142170458
ENSE00003496122	142215599	142215692
ENSE00003526981	142213526	142213601
ENSE00003555926	142186452	142186513
ENSE00003561473	142198802	142198933
ENSE00003575406	142181461	142181565
ENSE00003581306	142187704	142187779
ENSE00003599137	142172353	142172456
ENSE00003636575	142204695	142204788
ENSE00003669846	142177482	142177576
ENSE00003670597	142171419	142171478
ENSE00003671173	142182923	142183049
ENSE00003708438	142157527	142165770

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 90.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.2059 / max 137.5056, expressed in 1767 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44839	8.4202	1759
44838	0.7857	439

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ascending aorta	UBERON:0001496	90.43	gold quality
thoracic aorta	UBERON:0001515	90.42	gold quality
mucosa of stomach	UBERON:0001199	89.77	gold quality
calcaneal tendon	UBERON:0003701	89.46	gold quality
tibial nerve	UBERON:0001323	89.41	gold quality
colonic epithelium	UBERON:0000397	89.40	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.36	gold quality
descending thoracic aorta	UBERON:0002345	89.31	gold quality
left ovary	UBERON:0002119	89.24	gold quality
jejunal mucosa	UBERON:0000399	89.05	gold quality
rectum	UBERON:0001052	88.98	gold quality
right ovary	UBERON:0002118	88.81	gold quality
adrenal tissue	UBERON:0018303	88.55	gold quality
muscle layer of sigmoid colon	UBERON:0035805	88.53	gold quality
minor salivary gland	UBERON:0001830	88.31	gold quality
nasal cavity epithelium	UBERON:0005384	88.17	gold quality
nasal cavity mucosa	UBERON:0001826	88.04	gold quality
left uterine tube	UBERON:0001303	88.02	gold quality
body of uterus	UBERON:0009853	87.70	gold quality
mucosa of paranasal sinus	UBERON:0005030	87.54	gold quality
aorta	UBERON:0000947	87.38	gold quality
palpebral conjunctiva	UBERON:0001812	86.99	gold quality
upper leg skin	UBERON:0004262	86.94	gold quality
duodenum	UBERON:0002114	86.87	gold quality
spinal cord	UBERON:0002240	86.65	gold quality
upper arm skin	UBERON:0004263	86.58	gold quality
sural nerve	UBERON:0015488	85.92	gold quality
colon	UBERON:0001155	85.82	gold quality
large intestine	UBERON:0000059	85.72	gold quality
mouth mucosa	UBERON:0003729	85.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

324 targeting GK5, 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-6873-3P	100.00	71.42	2626
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
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-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775

Literature-anchored findings (GeneRIF, showing 1)

• miR-135b may function as an oncogene by inhibiting GK5 in glioblastoma. (PMID:25936394)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gk5	ENSDARG00000062864
mus_musculus	Gk5	ENSMUSG00000041440
rattus_norvegicus	Gk5	ENSRNOG00000010942
drosophila_melanogaster	CG1271	FBGN0035392
caenorhabditis_elegans		WBGENE00016939

Paralogs (6): XYLB (ENSG00000093217), FGGY (ENSG00000172456), GK2 (ENSG00000196475), SHPK (ENSG00000197417), GK (ENSG00000198814), GK3 (ENSG00000229894)

Protein

Protein identifiers

Glycerol kinase 5 — Q6ZS86 (reviewed: Q6ZS86)

Alternative names: ATP:glycerol 3-phosphotransferase 5

All UniProt accessions (4): Q6ZS86, F8WBF0, H7C4F2, H7C5R4

UniProt curated annotations — full annotation on UniProt →

Function. Skin-specific kinase that plays a key role in glycerol metabolism, catalyzing its phosphorylation to produce sn-glycerol 3-phosphate. Involved in skin-specific regulation of sterol regulatory element-binding protein (SREBP) processing and lipid biosynthesis.

Subcellular location. Cytoplasm.

Pathway. Polyol metabolism; glycerol degradation via glycerol kinase pathway; sn-glycerol 3-phosphate from glycerol: step 1/1.

Similarity. Belongs to the FGGY kinase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6ZS86-1	1	yes
Q6ZS86-2	2
Q6ZS86-3	3

RefSeq proteins (1): NP_001034636* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000577	Carb_kinase_FGGY	Family
IPR018483	Carb_kinase_FGGY_CS	Conserved_site
IPR018484	FGGY_N	Domain
IPR018485	FGGY_C	Domain
IPR037444	GK5	Family
IPR043129	ATPase_NBD	Homologous_superfamily

Pfam: PF00370, PF02782

Enzyme classification (BRENDA):

• EC 2.7.1.30 — glycerol kinase (BRENDA: 72 organisms, 69 substrates, 70 inhibitors, 96 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

20 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.006–3.29	31
GLYCEROL	0.01–2	25
ADP	0.24–0.9	5
DIHYDROXYACETONE	0.5–100	5
SN-GLYCEROL 3-PHOSPHATE	1.09–5.54	4
L-GLYCERALDEHYDE	3–42	3
MONOTHIOGLYCEROL	4.9	2
1-DEOXY-SN-GLYCEROL	45	1
2-DEOXYGLYCEROL	88	1
2-MERCAPTOETHANOL	0.046	1
2-METHYLGLYCEROL	5.7	1
CTP	0.515	1
DICHLORO-MONOACETIN	0.14	1
GLYCERIC ACID	0.15	1
GLYCEROL-3-PHOSPHATE	12.56	1

Catalyzed reactions (Rhea), 1 shown:

• glycerol + ATP = sn-glycerol 3-phosphate + ADP + H(+) (RHEA:21644)

UniProt features (13 total): binding site 8, splice variant 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZS86-F1	93.85	0.88

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 (8): 28; 29; 98; 275; 276; 297; 340; 440

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 160 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_POLYOL_METABOLIC_PROCESS, GOBP_POLYOL_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, SLEBOS_HEAD_AND_NECK_CANCER_WITH_HPV_UP, GOBP_SMALL_MOLECULE_CATABOLIC_PROCESS, TTGGAGA_MIR5155P_MIR519E, GOBP_NEUTRAL_LIPID_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_CATABOLIC_PROCESS

GO Biological Process (5): glycerol metabolic process (GO:0006071), triglyceride metabolic process (GO:0006641), glycerol catabolic process (GO:0019563), glycerol-3-phosphate biosynthetic process (GO:0046167), carbohydrate metabolic process (GO:0005975)

GO Molecular Function (6): glycerol kinase activity (GO:0004370), ATP binding (GO:0005524), nucleotide binding (GO:0000166), kinase activity (GO:0016301), transferase activity (GO:0016740), phosphotransferase activity, alcohol group as acceptor (GO:0016773)

GO Cellular Component (2): cytoplasm (GO:0005737), mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transferase activity, transferring phosphorus-containing groups	2
carbohydrate metabolic process	1
polyol metabolic process	1
acylglycerol metabolic process	1
glycerol metabolic process	1
alditol catabolic process	1
glycerol-3-phosphate metabolic process	1
organophosphate biosynthetic process	1
carbohydrate derivative biosynthetic process	1
primary metabolic process	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
catalytic activity	1
intracellular anatomical structure	1
cellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2129 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GK5	CEACAM4	O75871	572
GK5	ICA1L	Q8NDH6	544
GK5	CYP20A1	Q6UW02	542
GK5	UNC80	Q8N2C7	538
GK5	DPY19L4	Q7Z388	512
GK5	ZNF429	Q86V71	493
GK5	TMEM9B	Q9NQ34	491
GK5	UNC79	Q9P2D8	488
GK5	CCNQ	Q8N1B3	477
GK5	NOC4L	Q9BVI4	474
GK5	VWA7	Q9Y334	474
GK5	ZDHHC23	Q8IYP9	463
GK5	SLC45A1	Q9Y2W3	459
GK5	LRRC3	Q9BY71	449
GK5	KCNK17	Q96T54	449
GK5	HABP4	Q5JVS0	449

IntAct

4 interactions, top by confidence:

A	B	Type	Score
GK5	HSPA2	psi-mi:“MI:0915”(physical association)	0.400
ROS1	ODAD3	psi-mi:“MI:0914”(association)	0.350
MST1R	SHTN1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (6): GK5 (Affinity Capture-RNA), HSPA2 (Affinity Capture-MS), GK5 (Affinity Capture-MS), GK5 (Proximity Label-MS), ANXA2 (Cross-Linking-MS (XL-MS)), GK5 (Affinity Capture-RNA)

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: A0JPE9, A0KAA1, A0RAP3, A1WT61, A4J8E6, A4SPA7, A5I5M0, A5ISI2, A5UU55, A6M1Y8, A6QGJ8, A6TKR6, A6U1B8, A7FX30, A7GH02, A7X1U3, A7Z2U3, A8F679, A8Z1X0, A9AFH2, A9BJ81, A9VI58, B0K643, B0K754, B0TWZ7, B1IKJ7, B1JY43, B1KYK0, B1YWB2, B2A2C4, B2RZV0, B2SYH7, B3E6Z6, B5RL65, B7HG04, B7HYU3, B7IKB1, B7J1G9, B7JCV9, B8CW97

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3102 predictions. Top by Δscore:

Variant	Effect	Δscore
3:142170320:CATA:C	donor_loss	1.0000
3:142170322:TACC:T	donor_loss	1.0000
3:142170323:A:T	donor_loss	1.0000
3:142170324:C:CG	donor_loss	1.0000
3:142170324:CCAA:C	donor_gain	1.0000
3:142170454:CTGCC:C	acceptor_gain	1.0000
3:142170457:CC:C	acceptor_gain	1.0000
3:142170458:CC:C	acceptor_gain	1.0000
3:142170458:CCT:C	acceptor_loss	1.0000
3:142170459:C:CA	acceptor_loss	1.0000
3:142170459:C:CC	acceptor_gain	1.0000
3:142171413:ACAT:A	donor_loss	1.0000
3:142171414:CAT:C	donor_loss	1.0000
3:142171415:AT:A	donor_loss	1.0000
3:142171416:TA:T	donor_loss	1.0000
3:142171417:ACCG:A	donor_loss	1.0000
3:142171477:TT:T	acceptor_gain	1.0000
3:142171479:C:CC	acceptor_gain	1.0000
3:142172347:TCATA:T	donor_loss	1.0000
3:142172348:CATA:C	donor_loss	1.0000
3:142172349:ATACC:A	donor_loss	1.0000
3:142172350:TACC:T	donor_loss	1.0000
3:142172351:ACCT:A	donor_loss	1.0000
3:142172352:C:CA	donor_loss	1.0000
3:142172452:GGAGC:G	acceptor_gain	1.0000
3:142172457:C:CC	acceptor_gain	1.0000
3:142172458:T:G	acceptor_loss	1.0000
3:142177477:CATA:C	donor_loss	1.0000
3:142177478:ATAC:A	donor_loss	1.0000
3:142177479:TACCT:T	donor_loss	1.0000

AlphaMissense

3500 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:142182966:A:C	F300L	0.997
3:142182966:A:T	F300L	0.997
3:142182968:A:G	F300L	0.997
3:142204740:T:A	R122S	0.995
3:142204740:T:G	R122S	0.995
3:142177504:A:T	V374D	0.993
3:142181476:A:G	W345R	0.993
3:142181476:A:T	W345R	0.993
3:142204748:C:G	D120H	0.993
3:142204754:A:G	W118R	0.993
3:142204754:A:T	W118R	0.993
3:142213533:A:G	W104R	0.993
3:142213533:A:T	W104R	0.993
3:142204741:C:G	R122T	0.992
3:142172366:A:G	S412P	0.991
3:142172380:C:G	R407P	0.991
3:142181545:A:G	W322R	0.991
3:142181545:A:T	W322R	0.991
3:142204747:T:A	D120V	0.991
3:142204747:T:G	D120A	0.991
3:142181472:G:T	A346D	0.990
3:142183042:T:A	D275V	0.989
3:142186261:A:G	W230R	0.989
3:142186261:A:T	W230R	0.989
3:142186479:A:C	S218R	0.988
3:142186479:A:T	S218R	0.988
3:142186481:T:G	S218R	0.988
3:142170405:A:G	L454P	0.987
3:142187728:A:G	W199R	0.986
3:142187728:A:T	W199R	0.986

dbSNP variants (sampled 300 via entrez): RS1000004815 (3:142182069 G>A), RS1000067798 (3:142188284 C>T), RS1000087489 (3:142195213 T>C), RS1000197648 (3:142218847 T>C), RS1000210995 (3:142220850 A>G), RS1000232643 (3:142176907 C>A,T), RS1000317347 (3:142162735 C>A,G,T), RS1000330021 (3:142188725 A>C), RS1000346928 (3:142182137 C>A), RS1000461320 (3:142195075 G>A), RS1000487338 (3:142189884 C>T), RS1000565668 (3:142161485 T>C), RS1000572250 (3:142220811 A>T), RS1000612101 (3:142183585 C>T), RS1000653802 (3:142183745 C>T)

Disease associations

OMIM: gene MIM:620801 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008158_153	Body mass index	8.000000e-06
GCST010566_3	Benign childhood epilepsy with centro-temporal spikes	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
trichostatin A	affects cotreatment, decreases expression, increases expression	3
bisphenol A	decreases expression	2
triphenyl phosphate	affects expression	1
butyraldehyde	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Amiodarone	increases expression	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	increases expression	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Formaldehyde	decreases expression	1
Nickel	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Testosterone	increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Vanadates	decreases expression	1
Zinc	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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