AGK

Chr 7AR

acylglycerol kinase

Also known as: CATC5, CTRCT38, MTDPS10, MULK

NCBI Gene: 55750ENSG00000006530UniProt: Q53H12

The protein encoded by this gene is a mitochondrial membrane protein involved in lipid and glycerolipid metabolism. The encoded protein is a lipid kinase that catalyzes the formation of phosphatidic and lysophosphatidic acids. Defects in this gene have been associated with mitochondrial DNA depletion syndrome 10. [provided by RefSeq, Feb 2012]

Primary Disease Associations & Inheritance

Cataract 38, autosomal recessiveMIM #614691
AR
Sengers syndromeMIM #212350
AR
UniProtMitochondrial DNA depletion syndrome 10
258
ClinVar variants
59
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— AGK
🧬
Gene-Disease Validity (ClinGen)
mitochondrial disease · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
59 Pathogenic / Likely Pathogenic· 89 VUS of 258 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.88LOEUF
pLI 0.000
Z-score 2.08
OE 0.59 (0.41–0.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.76Z-score
OE missense 0.86 (0.76–0.97)
196 obs / 228.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.59 (0.41–0.88)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.76–0.97)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91
0≤1.21.6
LoF obs/exp: 18 / 30.4Missense obs/exp: 196 / 228.1Syn Z: 0.67

ClinVar Variant Classifications

258 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic50
Likely Pathogenic9
VUS89
Likely Benign87
Benign8
Conflicting15
50
Pathogenic
9
Likely Pathogenic
89
VUS
87
Likely Benign
8
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
1
42
0
50
Likely Pathogenic
3
0
6
0
9
VUS
1
72
14
2
89
Likely Benign
1
4
45
37
87
Benign
0
0
8
0
8
Conflicting
—15
Total127711539258

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

AGK · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

AGK-related Sengers syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
ACYLGLYCEROL KINASE; AGK
MIM #610345 · *

Cataract 38, autosomal recessive

MIM #614691

Molecular basis of disorder known

Autosomal recessive

Sengers syndrome

MIM #212350

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — AGK
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Mitochondrial DNA maintenance defects.
El-Hattab AW et al.·Biochim Biophys Acta Mol Basis Dis
2017Review
Sengers syndrome and AGK-related disorders - Minireview of phenotypic variability and clinical outcomes in molecularly confirmed cases.
Wu CW et al.·Mol Genet Metab
2023Review
Protective effects of Gypenoside XVII against cerebral ischemia/reperfusion injury via SIRT1-FOXO3A- and Hif1a-BNIP3-mediated mitochondrial autophagy.
Xie W et al.·J Transl Med
2022
A novel AGK splicing mutation in a patient with Sengers syndrome and left ventricular non-compaction cardiomyopathy.
Fan P et al.·Pediatr Res
2023
Identification of fusions with potential clinical significance in melanoma.
Moran JMT et al.·Mod Pathol
2022
Sengers syndrome: six novel AGK mutations in seven new families and review of the phenotypic and mutational spectrum of 29 patients.
Haghighi A et al.·Orphanet J Rare Dis
2014Review
MEK inhibitors for the treatment of immunotherapy-resistant, AGK-BRAF fusion advanced acral melanoma: a case report and literature review.
Zhang Y et al.·J Cancer Res Clin Oncol
2025Review
AGK enhances angiogenesis and inhibits apoptosis via activation of the NF-κB signaling pathway in hepatocellular carcinoma.
Cui Y et al.·Oncotarget
2014
Inborn errors of metabolism in the biosynthesis and remodelling of phospholipids.
Wortmann SB et al.·J Inherit Metab Dis
2015Review
Novel c.221+1dup pathogenic variant in AGK gene linked to Sengers syndrome.
Galloway M et al.·Neuromuscul Disord
2025Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools