AGPAT5

Chr 8

1-acylglycerol-3-phosphate O-acyltransferase 5

Also known as: 1AGPAT5, LPAATE, LPLAT5

NCBI Gene: 55326 ENSG00000155189 UniProt: Q9NUQ2 OMIM: 614796

The AGPAT5 protein converts lysophosphatidic acid to phosphatidic acid in the second step of de novo phospholipid biosynthesis. Mutations cause autosomal recessive congenital cataracts, facial dysmorphism, and neuropathy (CCFDN), a disorder affecting the eyes, peripheral nervous system, and facial features. This gene shows low constraint against loss-of-function variants (pLI 0.000007, LOEUF 0.979), consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the 1-acylglycerol-3-phosphate O-acyltransferase family. This integral membrane protein converts lysophosphatidic acid to phosphatidic acid, the second step in de novo phospholipid biosynthesis. A pseudogene of this gene is present on the Y chromosome. [provided by RefSeq, Aug 2014]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.98

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.98LOEUF

pLI 0.000

Z-score 1.63

OE 0.59 (0.37–0.98)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-1.66Z-score

OE missense 1.33 (1.21–1.48)

262 obs / 196.4 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.59 (0.37–0.98)

0≤0.351.4

Missense OE?1.33 (1.21–1.48)

0≤0.61.4

Synonymous OE?1.51

0≤1.21.6

LoF obs/exp: 11 / 18.6Missense obs/exp: 262 / 196.4Syn Z: -3.52

Background carrier burden — how many people carry a rare variant somewhere in AGPAT5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

798 rare PASS variants

Rare truncating (LoF)

1 in 2,600

94 rare PASS variants

Rare synonymous (reference)

1 in 150

205 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for AGPAT5. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 2,600
South Asian	~43k	1 in 110	1 in 1,800
Remaining (unassigned)	~30k	1 in 72	1 in 2,200
European (Finnish)	~27k	1 in 280	≈ 1 in 8,100
Admixed American	~22k	1 in 120	1 in 2,000
African / African American	~21k	1 in 82	1 in 3,600
East Asian	~20k	1 in 110	1 in 2,800
Ashkenazi Jewish	~13k	1 in 590	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 110	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 7 of 8 coding exons well covered in gnomAD exomes; exon 2 poorly covered. Genomes: all 8.? see exons ↓