AGPS

Chr 2AR

alkylglycerone phosphate synthase

Also known as: ADAP-S, ADAS, ADHAPS, ADPS, ALDHPSY, RCDP3

NCBI Gene: 8540 ENSG00000018510 UniProt: O00116 OMIM: 603051

This gene is a member of the FAD-binding oxidoreductase/transferase type 4 family. It encodes a protein that catalyzes the second step of ether lipid biosynthesis in which acyl-dihydroxyacetonephosphate (DHAP) is converted to alkyl-DHAP by the addition of a long chain alcohol and the removal of a long-chain acid anion. The protein is localized to the inner aspect of the peroxisomal membrane and requires FAD as a cofactor. Mutations in this gene have been associated with rhizomelic chondrodysplasia punctata, type 3 and Zellweger syndrome. [provided by RefSeq, Jul 2008]

GeneReviews OMIM Research

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.121 OMIM phenotype

Clinical Summary— AGPS

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Gene-Disease Validity (ClinGen)

alkylglycerone-phosphate synthase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

31 unique Pathogenic / Likely Pathogenic· 207 VUS of 816 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — AGPS

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.12LOEUF

pLI 1.000

Z-score 5.75

OE 0.02 (0.01–0.12)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

3.23Z-score

OE missense 0.52 (0.46–0.59)

186 obs / 357.9 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.02 (0.01–0.12)

0≤0.351.4

Missense OE?0.52 (0.46–0.59)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 1 / 40.5Missense obs/exp: 186 / 357.9Syn Z: 0.15

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveAGPS-related rhizomelic chondrodysplasia punctataLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.3296th %ile

GOF

0.3789th %ile

LOF

0.72top 10%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

816 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8

Likely Pathogenic23

VUS207

Likely Benign469

Benign72

Conflicting18

Pathogenic

Likely Pathogenic

207

VUS

469

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	5	2	1	0	8
Likely Pathogenic	20	2	1	0	23
VUS	3	114	84	6	207
Likely Benign	0	1	210	258	469
Benign	0	0	68	4	72
Conflicting	—				18
Total	28	119	364	268	797

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

View in ClinVar →

32 pathogenic / likely-pathogenic (of 36) ClinVar copy-number / structural variants overlap AGPS — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →