Inborn glycerol kinase deficiency

Summary

Inborn glycerol kinase deficiency (MONDO:0010613) is a disease caused by GK (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: GK (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 18

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	inborn glycerol kinase deficiency
Mondo ID	MONDO:0010613
OMIM	307030
Orphanet	308993
DOID	DOID:0060363
SNOMED CT	124322002
UMLS	C0268418
MedGen	82803
GARD	0021311
Is cancer (heuristic)	no

Also known as: GKD · glycerol kinase deficiency · glycerol kinase deficiency, X-linked recessive · inborn error of glycerol kinase activity · inborn glycerol kinase activity disorder · rare inborn error of glycerol kinase activity

Data availability: 18 ClinVar variants · 4 GenCC gene-disease records.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › inborn glycerol kinase deficiency

Related subtypes (92): thiopurine metabolic disease, hypercalcemia, infantile, hypermanganesemia with dystonia, abdominal obesity-metabolic syndrome, plasma protein metabolism disease, inherited lipid metabolism disorder, lysosomal storage disease, striatonigral degeneration, inborn metal metabolism disorder, inborn vitamin metabolic disorder, chondrocalcinosis 2, Ehlers-Danlos syndrome, spondylodysplastic type, fish eye disease, aromatase excess syndrome, spondyloepiphyseal dysplasia with congenital joint dislocations, hypertriglyceridemia 1, autosomal dominant myoglobinuria, diastrophic dysplasia, hemolytic anemia due to diphosphoglycerate mutase deficiency, multiple epiphyseal dysplasia type 4, atelosteogenesis type II, inherited threoninemia, achondrogenesis type IB, diabetes mellitus, noninsulin-dependent, 1, diabetes mellitus, noninsulin-dependent, 2, renal tubular acidosis, distal, 3, with or without sensorineural hearing loss, diabetes mellitus, noninsulin-dependent, 3, hypercholesterolemia, familial, 4, hypoalphalipoproteinemia, primary, 1, autosomal recessive proximal renal tubular acidosis, diabetes mellitus, noninsulin-dependent, 4, normophosphatemic familial tumoral calcinosis, apolipoprotein c-III deficiency, hypotonia-failure to thrive-microcephaly syndrome, chondrodysplasia with joint dislocations, gPAPP type, gluthathione peroxidase deficiency, congenital microcephaly - severe encephalopathy - progressive cerebral atrophy syndrome, diabetes mellitus, noninsulin-dependent, 5, congenital disorder of glycosylation, monogenic diabetes, 2-hydroxyglutaric aciduria, familial hypoparathyroidism, familial intrahepatic cholestasis, inborn aminoacylase deficiency, disorder of lysosomal-related organelles, inborn disorder of porphyrin metabolism, disorder of metabolite absorption and transport, autosomal dominant proximal renal tubular acidosis, neurodegeneration with brain iron accumulation, ferro-cerebro-cutaneous syndrome, familial hypocalciuric hypercalcemia, hypophosphatasia, hereditary amyloidosis, peroxisomal disease, inborn disorder of amino acid and other organic acid metabolism, inborn carbohydrate metabolic disorder, inborn disorder of energy metabolism, inborn disorder of biogenic amine metabolism and transport, inborn disorder of purine or pyrimidine metabolism, spondyloepimetaphyseal dysplasia, PAPSS2 type, hereditary lipodystrophy, hereditary recurrent myoglobinuria, DNA repair disease, 4-hydroxyphenylacetic aciduria, 5-nucleotidase syndrome, antigen-peptide-transporter 2 deficiency, APO A-i deficiency, cardiomyopathy hypogonadism metabolic anomalies, deficiency of coenzyme q cytochrome c reductase, defective apolipoprotein b-100, sulfide quinone oxidoreductase deficiency, congenital disorder of deglycosylation, hypoalphalipoproteinemia, primary, 2, uridine-cytidineuria, NAD(P)HX dehydratase deficiency, inborn disorder of aspartate family metabolism, weinstein kliman scully syndrome, glycoprotein metabolism disease, inherited thyroid metabolism disease, tumoral calcinosis, hyperphosphatemic, familial, 2, tumoral calcinosis, hyperphosphatemic, familial, 3, combined ApoA-I and ApoC-III deficiency, familial hyperphosphatemic tumoral calcinosis/hyperphosphatemic hyperostosis syndrome, tumoral calcinosis, hyperphosphatemic, familial, 1, Waldenstrom macroglobulinemia, mucopolysaccharidosis or mucopolysaccharidosis-like disorder, disorder of peptide and amine metabolism, CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis, Lane Hamilton syndrome, SQSTM1-related multisystem proteinopathy, hypertriglyceridemia 2, autosomal dominant dopa-responsive dystonia

Subtypes (3): chromosome Xp21 deletion syndrome, glycerol kinase deficiency, infantile form, isolated glycerol kinase deficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

18 retrieved; paginated sample, class counts are floors:

10 pathogenic, 5 uncertain significance, 3 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
10941	NM_001205019.2(GK):c.553-1G>C	GK	Pathogenic	no assertion criteria provided
10942	NC_000023.11:g.(30720096_30720620)_(30720742_30720851)del	GK	Pathogenic	no assertion criteria provided
10943	NM_001205019.2(GK):c.1337A>T (p.Asp446Val)	GK	Pathogenic	no assertion criteria provided
10944	NC_000023.11:g.(30700906_30707555)(30728743?)del	GK	Pathogenic	no assertion criteria provided
10945	NM_001205019.2(GK):c.1255C>T (p.Arg419Ter)	GK	Pathogenic	no assertion criteria provided
10946	NM_001205019.2(GK):c.1525T>C (p.Trp509Arg)	GK	Pathogenic	no assertion criteria provided
10947	NM_001128127.3(GK):c.338-52_338-51insAluY	GK	Pathogenic	no assertion criteria provided
1685851	NM_001205019.2(GK):c.259+1255G>A	GK	Pathogenic	criteria provided, single submitter
3248635	NM_001205019.2(GK):c.542G>A (p.Trp181Ter)	GK	Pathogenic	criteria provided, single submitter
10948	NM_001205019.2(GK):c.880A>G (p.Asn294Asp)	GK-AS1	Pathogenic	no assertion criteria provided
3238767	NM_001205019.2(GK):c.443dup (p.Tyr148Ter)	GK	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3903432	NM_001205019.2(GK):c.662+1G>T	GK	Likely pathogenic	criteria provided, single submitter
986037	NM_001205019.2(GK):c.152+1G>C	GK	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1029689	NM_001205019.2(GK):c.106C>T (p.Leu36Phe)	GK	Uncertain significance	criteria provided, multiple submitters, no conflicts
1679737	NM_001205019.2(GK):c.197A>C (p.Glu66Ala)	GK	Uncertain significance	criteria provided, single submitter
2442213	NM_001205019.2(GK):c.749A>G (p.Lys250Arg)	GK	Uncertain significance	criteria provided, single submitter
2689131	NM_001205019.2(GK):c.683A>C (p.Glu228Ala)	GK	Uncertain significance	criteria provided, single submitter
3376334	NM_001205019.2(GK):c.1406C>T (p.Ala469Val)	GK	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
GK	Definitive	Autosomal recessive	inborn glycerol kinase deficiency	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GK	Orphanet:284411	Glycerol kinase deficiency, juvenile form
GK	Orphanet:284414	Glycerol kinase deficiency, adult form

Cohort genes → proteins

2 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GK	HGNC:4289	ENSG00000198814	P32189	Glycerol kinase	gencc,clinvar
GK-AS1	HGNC:40255	ENSG00000243055		GK antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GK	Glycerol kinase	Kinase that plays a key role in glycerol metabolism, catalyzing its phosphorylation to produce sn-glycerol 3-phosphate.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	1	13.9×	0.142
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GK	Kinase	yes	2.7.1.30	Carb_kinase_FGGY, Glycerol_kin, Carb_kinase_FGGY_CS
GK-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adrenal tissue	1
duodenum	1
jejunal mucosa	1
blood	1
colonic epithelium	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GK	243	ubiquitous	marker	jejunal mucosa, adrenal tissue, duodenum
GK-AS1	130		marker	primordial germ cell in gonad, blood, colonic epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GK	2,358
GK-AS1	0

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GK	P32189	92.01

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Triglyceride biosynthesis	1	671.8×	0.001	GK

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
glycerol-3-phosphate biosynthetic process	1	4213.0×	0.001	GK
glycerol catabolic process	1	2407.4×	0.001	GK
glycerol metabolic process	1	1123.5×	0.001	GK
triglyceride biosynthetic process	1	732.7×	0.002	GK
triglyceride metabolic process	1	443.5×	0.002	GK

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GK	0	0
GK-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
GK	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
GK	2.7.1.30	glycerol kinase

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	GK
E	Difficult family or no structure, no drug	1	GK-AS1

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
GK	2	—
GK-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.