GNPAT

Chr 1AR

glyceronephosphate O-acyltransferase

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

NCBI Gene: 8443 ENSG00000116906 UniProt: O15228 OMIM: 602744

The protein functions as dihydroxyacetonephosphate acyltransferase, catalyzing the first step in plasmalogen biosynthesis within peroxisomal membranes. Mutations cause rhizomelic chondrodysplasia punctata type 2, a severe disorder affecting skeletal development, growth, and neurological function. Inheritance is autosomal recessive.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.421 OMIM phenotype

Clinical Summary— GNPAT

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Gene-Disease Validity (ClinGen)

glyceronephosphate O-acyltransferase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.

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ClinVar Variants

67 unique Pathogenic / Likely Pathogenic· 163 VUS of 591 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

0.67Z-score

OE missense 0.90 (0.82–0.99)

316 obs / 351.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.23 (0.14–0.42)

0≤0.351.4

Missense OE?0.90 (0.82–0.99)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 8 / 34.6Missense obs/exp: 316 / 351.5Syn Z: -0.06

ClinVar Variant Classifications

591 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26

Likely Pathogenic41

VUS163

Likely Benign295

Benign28

Conflicting19

Pathogenic

Likely Pathogenic

163

VUS

295

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	23	1	2	0	26
Likely Pathogenic	39	1	1	0	41
VUS	1	136	20	6	163
Likely Benign	0	6	153	136	295
Benign	0	3	22	3	28
Conflicting	—				19
Total	63	147	198	145	572

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

View in ClinVar →

39 pathogenic / likely-pathogenic (of 48) ClinVar copy-number / structural variants overlap GNPAT — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →