GK

Summary

GK (glycerol kinase, HGNC:4289) is a protein-coding gene on chromosome Xp21.2, encoding Glycerol kinase (P32189). Kinase that plays a key role in glycerol metabolism, catalyzing its phosphorylation to produce sn-glycerol 3-phosphate. It is haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene belongs to the FGGY kinase family. This protein is a key enzyme in the regulation of glycerol uptake and metabolism. It catalyzes the phosphorylation of glycerol by ATP, yielding ADP and glycerol-3-phosphate. Mutations in this gene are associated with glycerol kinase deficiency (GKD). Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2710 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inborn glycerol kinase deficiency (Definitive, ClinGen)
• GWAS associations: 1
• Clinical variants (ClinVar): 241 total — 14 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 38
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001205019

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4289
Approved symbol	GK
Name	glycerol kinase
Location	Xp21.2
Locus type	gene with protein product
Status	Approved
Aliases	GK1, GKD
Ensembl gene	ENSG00000198814
Ensembl biotype	protein_coding
OMIM	300474
Entrez	2710

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 26 protein_coding, 5 nonsense_mediated_decay

ENST00000378938, ENST00000378941, ENST00000378943, ENST00000378945, ENST00000378946, ENST00000427190, ENST00000471362, ENST00000479048, ENST00000481024, ENST00000487652, ENST00000488296, ENST00000692461, ENST00000896883, ENST00000896884, ENST00000896885, ENST00000896886, ENST00000896887, ENST00000896888, ENST00000896889, ENST00000896890, ENST00000896891, ENST00000896892, ENST00000896893, ENST00000896894, ENST00000896895, ENST00000929977, ENST00000929978, ENST00000945035, ENST00000945036, ENST00000945037, ENST00000945038

RefSeq mRNA: 5 — MANE Select: NM_001205019 NM_000167, NM_001128127, NM_001205019, NM_001399987, NM_203391

CCDS: CCDS14225, CCDS35224, CCDS48090, CCDS75963

Canonical transcript exons

ENST00000427190 — 21 exons

Exon	Start	End
ENSE00003463249	30728732	30731462
ENSE00003488122	30720011	30720095
ENSE00003493144	30724101	30724181
ENSE00003537420	30700838	30700905
ENSE00003547561	30691123	30691199
ENSE00003553974	30720621	30720741
ENSE00003589236	30707556	30707598
ENSE00003603436	30700414	30700449
ENSE00003605546	30720852	30720995
ENSE00003609402	30727466	30727552
ENSE00003625630	30718538	30718616
ENSE00003642580	30708054	30708134
ENSE00003653081	30697732	30697749
ENSE00003668133	30694400	30694537
ENSE00003683423	30719419	30719515
ENSE00003684622	30677375	30677452
ENSE00003692299	30696617	30696683
ENSE00003712472	30668012	30668118
ENSE00003715673	30696042	30696151
ENSE00003728560	30665511	30665584
ENSE00003904663	30653423	30653615

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 94.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.4650 / max 277.2442, expressed in 1166 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
195859	4.0108	1132
209645	0.2511	91
195860	0.2032	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	94.40	gold quality
adrenal tissue	UBERON:0018303	94.14	gold quality
duodenum	UBERON:0002114	93.94	gold quality
buccal mucosa cell	CL:0002336	93.70	gold quality
nephron tubule	UBERON:0001231	93.70	gold quality
monocyte	CL:0000576	92.78	gold quality
mononuclear cell	CL:0000842	92.52	gold quality
leukocyte	CL:0000738	92.00	gold quality
right lobe of liver	UBERON:0001114	91.62	gold quality
blood	UBERON:0000178	91.00	gold quality
stromal cell of endometrium	CL:0002255	90.62	gold quality
kidney epithelium	UBERON:0004819	90.16	gold quality
liver	UBERON:0002107	89.71	gold quality
adult mammalian kidney	UBERON:0000082	89.62	gold quality
kidney	UBERON:0002113	88.85	gold quality
nasal cavity epithelium	UBERON:0005384	88.65	gold quality
gall bladder	UBERON:0002110	88.48	gold quality
upper lobe of left lung	UBERON:0008952	87.36	gold quality
vermiform appendix	UBERON:0001154	86.97	gold quality
metanephric glomerulus	UBERON:0004736	86.67	gold quality
upper lobe of lung	UBERON:0008948	86.61	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.58	gold quality
renal glomerulus	UBERON:0000074	86.52	gold quality
islet of Langerhans	UBERON:0000006	85.80	gold quality
right lung	UBERON:0002167	85.72	gold quality
epithelium of bronchus	UBERON:0002031	85.70	gold quality
bronchial epithelial cell	CL:0002328	85.45	gold quality
cortex of kidney	UBERON:0001225	85.45	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.21	gold quality
bronchus	UBERON:0002185	85.03	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-97	yes	950.12
E-HCAD-10	yes	35.95
E-HCAD-29	no	843.38
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESRRA, FOXC1, FOXO1, HIF1A, HNF4A, NEUROD1, PDX1, PPARA, PPARG, PREB, RXRA, SREBF1, TCF3, USF1, USF2

miRNA regulators (miRDB)

93 targeting GK, 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-3163	100.00	77.23	8605
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-579-3P	99.86	71.66	3628

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 9)

• missense mutations and deletions in glycerol kinase is associated with persistent hypertriglyceridemia (PMID:12636049)
• a functional HNF-4alpha binding site in the first 500 bp of the 5(’) upstream region is important for increased levels of glycerol kinase expression (PMID:14654354)
• Comparison of expression patterns, as well as enzymatic characteristics and subcellular localization of alternatively spliced glycerol kinase isoforms. (PMID:15845384)
• Results suggest that influences on RNA processing and protein stability represent modifiers of the glycerol kinase deficiency phenotype. (PMID:16549535)
• Two siblings with the contiguous X-linked gene deletion syndrome, complex glycerol kinase deficiency, are described. The elder sibling demonstrates the difficulties diagnosing this rare condition. (PMID:20110216)
• Both patients were found to have Xp21.2 deletions involving all coding seqeunces of the glycerol kinase (GK) gene. (PMID:27087023)
• Glycerol kinase enhances hepatic lipid metabolism by repressing nuclear receptor subfamily 4 group A1 in the nucleus. (PMID:31813231)
• Expression and characterisation of human glycerol kinase: the role of solubilising agents and molecular chaperones. (PMID:37021775)
• Glycerol kinase enzyme is a prognostic predictor in esophageal carcinoma and is associated with immune cell infiltration. (PMID:38365953)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	GK2	ENSDARG00000053456
mus_musculus	Gk	ENSMUSG00000025059
rattus_norvegicus	Gk	ENSRNOG00000034116
drosophila_melanogaster	CG8298	FBGN0033673
drosophila_melanogaster	Gk2	FBGN0035266
caenorhabditis_elegans		WBGENE00020007

Paralogs (6): XYLB (ENSG00000093217), FGGY (ENSG00000172456), GK5 (ENSG00000175066), GK2 (ENSG00000196475), SHPK (ENSG00000197417), GK3 (ENSG00000229894)

Protein

Protein identifiers

Glycerol kinase — P32189 (reviewed: P32189)

Alternative names: ATP:glycerol 3-phosphotransferase

All UniProt accessions (9): P32189, A0A8I5KXY7, A6NP46, F8WBI8, F8WC39, F8WDA9, F8WF44, H7BYD2, H7C5F6

UniProt curated annotations — full annotation on UniProt →

Function. Kinase that plays a key role in glycerol metabolism, catalyzing its phosphorylation to produce sn-glycerol 3-phosphate. Sn-glycerol 3-phosphate is a crucial intermediate in various metabolic pathways, such as the synthesis of glycerolipids and triglycerides, glycogenesis, glycolysis and gluconeogenesis.

Subcellular location. Mitochondrion outer membrane. Nucleus. Cytoplasm. Cytosol Mitochondrion outer membrane. Nucleus Cytoplasm. Cytosol.

Tissue specificity. Widely expressed in fetal and adult tissues. Widely expressed in fetal and adult tissues. The sole isoform expressed in adult liver and kidney.

Disease relevance. Glycerol kinase deficiency (GKD) [MIM:307030] A metabolic disorder manifesting as 3 clinically distinct forms: infantile, juvenile, and adult. The infantile form is the most severe and is associated with severe developmental delay and adrenal insufficiency. Patients with the adult form have no symptoms and are often detected fortuitously. GKD results in hyperglycerolemia, a condition characterized by the accumulation of glycerol in the blood and urine. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Potassium and magnesium-dependent.

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 (4)

UniProt ID	Names	Canonical?
P32189-3	3, GK+EX18	yes
P32189-1	1
P32189-2	2
P32189-4	4, GK-EX18

RefSeq proteins (5): NP_000158, NP_001121599, NP_001191948, NP_001386916, NP_976325 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000577	Carb_kinase_FGGY	Family
IPR005999	Glycerol_kin	Family
IPR018483	Carb_kinase_FGGY_CS	Conserved_site
IPR018484	FGGY_N	Domain
IPR018485	FGGY_C	Domain
IPR042018	GK1-3_metazoan-type	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 (35 total): binding site 23, sequence variant 8, splice variant 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P32189-F1	92.01	0.83

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 (23): 95; 95; 148; 148; 252; 265; 265; 266; 287; 287; 20; 332 …

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-75109	Triglyceride biosynthesis

MSigDB gene sets: 389 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, MULLIGHAN_NPM1_SIGNATURE_3_UP, MODY_HIPPOCAMPUS_POSTNATAL, PAX4_01, RORA1_01, BROWNE_HCMV_INFECTION_8HR_UP, FISCHER_G1_S_CELL_CYCLE, GOLDRATH_IMMUNE_MEMORY, GOBP_POLYOL_METABOLIC_PROCESS, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, GOBP_POLYOL_CATABOLIC_PROCESS, CREBP1_Q2, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, BROWNE_HCMV_INFECTION_16HR_UP, TGACCTY_ERR1_Q2

GO Biological Process (7): glycerol metabolic process (GO:0006071), triglyceride metabolic process (GO:0006641), triglyceride biosynthetic process (GO:0019432), glycerol catabolic process (GO:0019563), glycerol-3-phosphate biosynthetic process (GO:0046167), carbohydrate metabolic process (GO:0005975), glycerol-3-phosphate metabolic process (GO:0006072)

GO Molecular Function (8): glycerol kinase activity (GO:0004370), ATP binding (GO:0005524), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), phosphotransferase activity, alcohol group as acceptor (GO:0016773)

GO Cellular Component (7): nucleus (GO:0005634), mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), cytosol (GO:0005829), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Triglyceride metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

2128 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GK	VDAC3	Q9Y277	960
GK	VDAC1	P21796	944
GK	VDAC2	P45880	817
GK	LPL	P06858	786
GK	AQP9	O43315	759
GK	NR0B1	P51843	745
GK	AQP3	Q92482	721
GK	TPI1	P00938	690
GK	GUK1	Q16774	683
GK	PXDN	Q92626	655
GK	PXDNL	A1KZ92	655
GK	PC	P11498	630
GK	CS	O75390	629
GK	CEL	P19835	609
GK	PPARA	Q07869	599

IntAct

76 interactions, top by confidence:

A	B	Type	Score
GK	GK2	psi-mi:“MI:0915”(physical association)	0.590
GK2	GK	psi-mi:“MI:0915”(physical association)	0.590
NR4A1	GK	psi-mi:“MI:0915”(physical association)	0.580
GK	NR4A1	psi-mi:“MI:0915”(physical association)	0.580
VDAC1	HK1	psi-mi:“MI:0914”(association)	0.560
VSIG4	TCAF2	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
SLC2A12	METTL15	psi-mi:“MI:0914”(association)	0.530
PDCD1	RTL8C	psi-mi:“MI:0914”(association)	0.530
SYP	APBB1	psi-mi:“MI:0914”(association)	0.530
TNF	B4GALT5	psi-mi:“MI:0914”(association)	0.530
MFSD4A	HIP1R	psi-mi:“MI:0914”(association)	0.530
PTGIR	TMEM63A	psi-mi:“MI:0914”(association)	0.530
GHITM	CCNB2	psi-mi:“MI:0914”(association)	0.530
RSPRY1	NEFL	psi-mi:“MI:0914”(association)	0.530
SLCO1B3	LGALS3	psi-mi:“MI:0914”(association)	0.530
GK	AOX1	psi-mi:“MI:0915”(physical association)	0.370
GK	APCS	psi-mi:“MI:0915”(physical association)	0.370
GK	CYP3A4	psi-mi:“MI:0915”(physical association)	0.370
EIF4G1	GK	psi-mi:“MI:0915”(physical association)	0.370
GPD1	GK	psi-mi:“MI:0915”(physical association)	0.370
GK	RXRA	psi-mi:“MI:0915”(physical association)	0.370
GK	IPO13	psi-mi:“MI:0915”(physical association)	0.370
FBXO28	GK	psi-mi:“MI:0915”(physical association)	0.370
GK	OPLAH	psi-mi:“MI:0915”(physical association)	0.370
CLPTM1L	GK	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (154): GK (Affinity Capture-MS), GK (Affinity Capture-MS), GK (Affinity Capture-MS), GK (Affinity Capture-MS), GK (Affinity Capture-MS), GK (Affinity Capture-MS), GK (Affinity Capture-MS), GK (Affinity Capture-MS), GK (Affinity Capture-MS), GK (Affinity Capture-MS), GK (Affinity Capture-MS), GK (Affinity Capture-MS), GK (Co-fractionation), GK (Affinity Capture-MS), GK3P (Affinity Capture-MS)

ESM2 similar proteins: A2AKQ0, A2VE55, A5GFZ5, C9WPN6, F1QGW6, F6RQL9, O60762, O70152, O77676, P00516, P0C605, P20461, P32189, P35250, P37273, P41091, P53033, P81795, Q05B83, Q0IID9, Q13126, Q13976, Q14409, Q15B89, Q1JQ93, Q2KHU8, Q2KJ61, Q2TBV5, Q2VIR3, Q3MHF7, Q5HZM6, Q5MB13, Q5R797, Q5RDC9, Q5RIC0, Q5ZHS1, Q5ZMS3, Q63060, Q641W4, Q64516

Diamond homologs: A0KAA1, A0KIT3, A1R6X6, A1TGD7, A3QIN4, A4FNR2, A4JHM8, A4SPA7, A4T5Y1, A5CS23, A5G146, A5U920, A5UU55, A5VE44, A5VZG7, A6M1Y8, A6WIC0, A6WXV2, A8F679, A8FQ89, A8H995, A8I8V7, A9AFH2, A9KY18, A9W8T7, A9WJ21, A9WS93, B0K643, B0KUG0, B0RMN0, B0TQM6, B1JY43, B1KKY8, B1LWN6, B1MFT1, B1YWB2, B1ZGW7, B2IE09, B2SYH7, B7KN92

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
FOXO1	“down-regulates quantity by repression”	GK	“transcriptional regulation”
HNF4A	“up-regulates quantity by expression”	GK	“transcriptional regulation”
FOXO	“down-regulates quantity by repression”	GK	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 109 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
Transport of vitamins, nucleosides, and related molecules	6	23.6×	5e-05
SLC-mediated transmembrane transport	10	8.6×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	10
Uncertain significance	42
Likely benign	10
Benign	31

Top pathogenic / likely-pathogenic (24)

Variant ID	HGVS	Classification
10941	NM_001205019.2(GK):c.553-1G>C	Pathogenic
10942	NC_000023.11:g.(30720096_30720620)_(30720742_30720851)del	Pathogenic
10943	NM_001205019.2(GK):c.1337A>T (p.Asp446Val)	Pathogenic
10944	NC_000023.11:g.(30700906_30707555)(30728743?)del	Pathogenic
10945	NM_001205019.2(GK):c.1255C>T (p.Arg419Ter)	Pathogenic
10946	NM_001205019.2(GK):c.1525T>C (p.Trp509Arg)	Pathogenic
10947	NM_001128127.3(GK):c.338-52_338-51insAluY	Pathogenic
1205628	NM_001205019.2(GK):c.851+1G>A	Pathogenic
1685851	NM_001205019.2(GK):c.259+1255G>A	Pathogenic
2712717	NM_001205019.2(GK):c.373_374del (p.Ser125_Leu126insTer)	Pathogenic
3248635	NM_001205019.2(GK):c.542G>A (p.Trp181Ter)	Pathogenic
379569	NM_001205019.2(GK):c.514C>T (p.Arg172Ter)	Pathogenic
379913	NM_001205019.2(GK):c.259+2T>C	Pathogenic
426447	NM_001205019.2(GK):c.907_908insC (p.Asp303fs)	Pathogenic
2631112	NM_001205019.2(GK):c.89C>A (p.Ser30Ter)	Likely pathogenic
3100021	NM_001205019.2(GK):c.1144G>A (p.Ala382Thr)	Likely pathogenic
3238767	NM_001205019.2(GK):c.443dup (p.Tyr148Ter)	Likely pathogenic
3252691	NM_001205019.2(GK):c.1232G>A (p.Arg411Gln)	Likely pathogenic
3903432	NM_001205019.2(GK):c.662+1G>T	Likely pathogenic
4029976	NM_001205019.2(GK):c.1236+2T>C	Likely pathogenic
4263940	NM_001205019.2(GK):c.1151+1G>T	Likely pathogenic
817092	NM_001205019.2(GK):c.385del (p.Arg129fs)	Likely pathogenic
872759	NM_001205019.2(GK):c.553-2A>G	Likely pathogenic
986037	NM_001205019.2(GK):c.152+1G>C	Likely pathogenic

SpliceAI

3580 predictions. Top by Δscore:

Variant	Effect	Δscore
X:30665505:TTTCA:T	acceptor_loss	1.0000
X:30665507:TCAGG:T	acceptor_loss	1.0000
X:30665508:CA:C	acceptor_loss	1.0000
X:30665509:A:AT	acceptor_loss	1.0000
X:30665510:G:A	acceptor_loss	1.0000
X:30665580:GAAGG:G	donor_gain	1.0000
X:30665582:AGGGT:A	donor_loss	1.0000
X:30665583:GG:G	donor_gain	1.0000
X:30665584:GG:G	donor_gain	1.0000
X:30665584:GGTA:G	donor_loss	1.0000
X:30665585:G:GC	donor_loss	1.0000
X:30665585:G:GG	donor_gain	1.0000
X:30665586:T:A	donor_loss	1.0000
X:30668010:AGATG:A	acceptor_gain	1.0000
X:30668011:GATGG:G	acceptor_gain	1.0000
X:30691121:A:AG	acceptor_gain	1.0000
X:30691121:AGTGT:A	acceptor_gain	1.0000
X:30691122:G:GG	acceptor_gain	1.0000
X:30691122:GT:G	acceptor_gain	1.0000
X:30691122:GTGT:G	acceptor_gain	1.0000
X:30691122:GTGTG:G	acceptor_gain	1.0000
X:30694398:A:AG	acceptor_gain	1.0000
X:30694399:G:GA	acceptor_gain	1.0000
X:30696038:CTA:C	acceptor_loss	1.0000
X:30696039:TA:T	acceptor_loss	1.0000
X:30696040:A:AG	acceptor_gain	1.0000
X:30696040:A:C	acceptor_loss	1.0000
X:30696041:G:GG	acceptor_gain	1.0000
X:30696041:GA:G	acceptor_gain	1.0000
X:30696148:GCGA:G	donor_gain	1.0000

AlphaMissense

3671 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:30707572:T:C	F290L	1.000
X:30707574:C:A	F290L	1.000
X:30707574:C:G	F290L	1.000
X:30653580:G:C	A15P	0.999
X:30653608:G:C	R24P	0.999
X:30665514:T:C	F28L	0.999
X:30665515:T:C	F28S	0.999
X:30665516:C:A	F28L	0.999
X:30665516:C:G	F28L	0.999
X:30668060:T:G	C67W	0.999
X:30677413:T:A	W100R	0.999
X:30677413:T:C	W100R	0.999
X:30691125:T:A	W114R	0.999
X:30691125:T:C	W114R	0.999
X:30707561:G:A	G286E	0.999
X:30718571:T:A	W337R	0.999
X:30718571:T:C	W337R	0.999
X:30719464:T:A	V367D	0.999
X:30720072:G:C	A405P	0.999
X:30653578:G:A	G14E	0.998
X:30653592:G:C	G19R	0.998
X:30665512:T:A	V27D	0.998
X:30668059:G:A	C67Y	0.998
X:30677399:A:T	E95V	0.998
X:30691138:G:C	R118T	0.998
X:30694433:A:C	S150R	0.998
X:30694435:T:A	S150R	0.998
X:30694435:T:G	S150R	0.998
X:30696100:G:C	R204T	0.998
X:30696100:G:T	R204M	0.998

dbSNP variants (sampled 300 via entrez): RS1000050265 (X:30673294 T>A), RS1000054099 (X:30705012 A>G), RS1000122235 (X:30701454 C>G,T), RS1000199206 (X:30674935 T>C), RS1000223385 (X:30652282 A>C), RS1000261453 (X:30658612 G>A), RS1000312355 (X:30676070 T>A), RS1000405258 (X:30703798 T>A), RS1000455238 (X:30663104 A>C,G), RS1000528699 (X:30653477 C>A,T), RS1000599822 (X:30707510 G>A), RS1000639740 (X:30654395 A>G), RS1000699929 (X:30652737 G>A), RS1000756097 (X:30665209 T>A), RS1000788569 (X:30665791 A>T)

Disease associations

OMIM: gene MIM:300474 | disease phenotypes: MIM:307030

GenCC curated gene-disease

Disease	Classification	Inheritance
inborn glycerol kinase deficiency	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
inborn glycerol kinase deficiency	Definitive	XL

Mondo (1): inborn glycerol kinase deficiency (MONDO:0010613)

Orphanet (2): Glycerol kinase deficiency (Orphanet:308993), Isolated glycerol kinase deficiency (Orphanet:408)

HPO phenotypes

38 total (30 of 38 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000316	Hypertelorism
HP:0000369	Low-set ears
HP:0000486	Strabismus
HP:0000846	Adrenal insufficiency
HP:0000939	Osteoporosis
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001254	Lethargy
HP:0001259	Coma
HP:0001263	Global developmental delay
HP:0001419	X-linked recessive inheritance
HP:0001510	Growth delay
HP:0001518	Small for gestational age
HP:0001942	Metabolic acidosis
HP:0001943	Hypoglycemia
HP:0001993	Ketoacidosis
HP:0002007	Frontal bossing
HP:0002013	Vomiting
HP:0002018	Nausea
HP:0002151	Increased circulating lactate concentration
HP:0002155	Hypertriglyceridemia
HP:0002572	Episodic vomiting
HP:0002714	Downturned corners of mouth
HP:0002756	Pathologic fracture
HP:0003198	Myopathy
HP:0003326	Myalgia
HP:0003560	Muscular dystrophy
HP:0003581	Adult onset
HP:0003621	Juvenile onset

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000789_3	Cardiovascular risk factors (age interaction)	1.000000e-07

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0008007	age at assessment

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2300 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	4
Valproic Acid	increases expression, decreases expression, increases methylation, affects cotreatment	4
Cyclosporine	affects expression, increases expression, affects cotreatment	4
Tetrachlorodibenzodioxin	decreases expression, increases expression	3
bisphenol A	affects expression, increases expression	2
perfluorooctanoic acid	increases expression	2
perfluorooctane sulfonic acid	increases expression	2
Acetaminophen	decreases expression, affects cotreatment	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Estradiol	affects expression, affects cotreatment, decreases expression	2
Cadmium Chloride	increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
moringin	affects cotreatment, increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
trichostatin A	affects expression	1
dimethylselenide	increases expression, increases oxidation	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
sulindac sulfide	increases expression	1
benzo(e)pyrene	increases methylation	1
cupric chloride	increases expression	1
hydroquinone	increases expression	1
ciglitazone	affects binding, increases expression	1
nefazodone	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4700054	Binding	Binding affinity to GLPK in human K562 cells at 1 mM incubated for 2 hrs by LC-MS/MS analysis based pull down assay relative to control	Understanding the mechanism of action of pyrrolo[3,2-b]quinoxaline-derivatives as kinase inhibitors — RSC Med Chem

Cellosaurus cell lines

9 cell lines: 9 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A5PG	GM25168	Transformed cell line	Male
CVCL_B2XQ	Abcam HEK293T GK KO	Transformed cell line	Female
CVCL_D2YL	GM25201	Transformed cell line	Male
CVCL_HL35	GM25162	Transformed cell line	Male
CVCL_HL36	GM25163	Transformed cell line	Male
CVCL_HL37	GM25169	Transformed cell line	Male
CVCL_HL38	GM25234	Transformed cell line	Male
CVCL_VJ10	GM25196	Transformed cell line	Male
CVCL_VJ11	GM25198	Transformed cell line	Male

Clinical trials (associated diseases)

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