GNPAT

Chr 1AR

glyceronephosphate O-acyltransferase

Also known as: DAP-AT, DAPAT, DHAPAT, RCDP2

NCBI Gene: 8443ENSG00000116906UniProt: O15228

This gene encodes an enzyme located in the peroxisomal membrane which is essential to the synthesis of ether phospholipids. Mutations in this gene are associated with rhizomelic chondrodysplasia punctata. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

Primary Disease Associations & Inheritance

Rhizomelic chondrodysplasia punctata, type 2MIM #222765
AR
636
ClinVar variants
68
Pathogenic / LP
0.30
pLI score
0
Active trials
Clinical Summary— GNPAT
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.
📋
ClinVar Variants
68 Pathogenic / Likely Pathogenic· 124 VUS of 636 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.42LOEUF
pLI 0.304
Z-score 4.19
OE 0.23 (0.14–0.42)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
0.67Z-score
OE missense 0.90 (0.82–0.99)
316 obs / 351.5 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.0.23 (0.14–0.42)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.90 (0.82–0.99)
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.1.01
0≤1.21.6
LoF obs/exp: 8 / 34.6Missense obs/exp: 316 / 351.5Syn Z: -0.06

ClinVar Variant Classifications

636 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic37
VUS124
Likely Benign274
Benign13
Conflicting2
31
Pathogenic
37
Likely Pathogenic
124
VUS
274
Likely Benign
13
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
0
20
0
31
Likely Pathogenic
23
0
14
0
37
VUS
1
113
8
2
124
Likely Benign
0
4
143
127
274
Benign
0
2
11
0
13
Conflicting
—2
Total35119196129481

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

View in ClinVar →

Protein Context — Lollipop Plot

GNPAT · protein map & ClinVar variants

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

Gene2Phenotype Curations

GNPAT-related rhizomelic chondrodysplasia punctata

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeSkeletal
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Rhizomelic chondrodysplasia punctata, type 2

MIM #222765

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Gnpat does not play an essential role in systemic iron homeostasis in murine model.
An P et al.·J Cell Mol Med
2020Functional
Amplification of Glyceronephosphate O-Acyltransferase and Recruitment of USP30 Stabilize DRP1 to Promote Hepatocarcinogenesis.
Gu L et al.·Cancer Res
2018
Reduction of Ether-Type Glycerophospholipids, Plasmalogens, by NF-κB Signal Leading to Microglial Activation.
Hossain MS et al.·J Neurosci
2017
 GNPAT variant (D519G) is not associated with an elevated serum ferritin or iron removed by phlebotomy in patients referred for C282Y-linked hemochromatosis.
Levstik A et al.·Ann Hepatol
2016Cohort
Clinical, biochemical, and molecular characterization of mild (nonclassic) rhizomelic chondrodysplasia punctata.
Fallatah W et al.·J Inherit Metab Dis
2021
A new GNPAT variant of foetal rhizomelic chondrodysplasia punctata.
Cordisco A et al.·Mol Genet Genomic Med
2021Case report
GNPAT p.D519G variant and iron metabolism during oral iron tolerance test.
Rametta R et al.·Hepatology
2017
Disturbed neurotransmitter homeostasis in ether lipid deficiency.
Dorninger F et al.·Hum Mol Genet
2019
Genetic adaptation of skin pigmentation in highland Tibetans.
Yang Z et al.·Proc Natl Acad Sci U S A
2022
Exome sequencing in HFE C282Y homozygous men with extreme phenotypes identifies a GNPAT variant associated with severe iron overload.
McLaren CE et al.·Hepatology
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
GNPAT/USP30 Stabilizes DRP1 Protein to Promote Mitochondrial Fission and Functional Damage in COPD Progression.
Cheng XG et al.·Kaohsiung J Med Sci
2025🔓 Open AccessFunctional
A bovine model of rhizomelic chondrodysplasia punctata caused by a deep intronic splicing variant in the GNPAT gene.
Boulling A et al.·Genet Sel Evol
2025🔓 Open AccessFunctional
CSE triggers ferroptosis via SIRT4-mediated GNPAT deacetylation in the pathogenesis of COPD.
Li C et al.·Respir Res
2023🔓 Open Access
Neonatal rhizomelic chondrodysplasia punctata type 2 caused by a novel homozygous variant in the GNPAT gene.
Sayed J et al.·Clin Case Rep
2023🔓 Open Access
Differential Eye Expression of Xenopus Acyltransferase Gnpat and Its Biochemical Characterization Shed Light on Lipid-Associated Ocular Pathologies.
Bertolesi GE et al.·Invest Ophthalmol Vis Sci
2023🔓 Open Access
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