PEMT

Chr 17

phosphatidylethanolamine N-methyltransferase

Also known as: PEAMT, PEMPT, PEMT2, PLMT

NCBI Gene: 10400 ENSG00000133027 UniProt: Q9UBM1 OMIM: 602391

The enzyme catalyzes the three sequential methylation steps that convert phosphatidylethanolamine to phosphatidylcholine, an essential membrane phospholipid, and is responsible for approximately 30% of hepatic phosphatidylcholine synthesis. Mutations cause autosomal recessive nonalcoholic fatty liver disease, which can present in childhood and may progress to cirrhosis. The gene shows moderate constraint against loss-of-function variants, reflecting its important but non-essential role given alternative phosphatidylcholine synthesis pathways.

OMIM ResearchSummary from RefSeq, UniProt

Phosphatidylcholine (PC) is the most abundant mammalian phospholipid. This gene encodes an enzyme which converts phosphatidylethanolamine to phosphatidylcholine by sequential methylation in the liver. Another distinct synthetic pathway in nucleated cells converts intracellular choline to phosphatidylcholine by a three-step process. The protein isoforms encoded by this gene localize to the endoplasmic reticulum and mitochondria-associated membranes. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2012]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.67

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.67LOEUF

pLI 0.235

Z-score 2.35

OE 0.26 (0.12–0.67)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.11Z-score

OE missense 1.03 (0.90–1.18)

142 obs / 138.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.26 (0.12–0.67)

0≤0.351.4

Missense OE?1.03 (0.90–1.18)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 3 / 11.6Missense obs/exp: 142 / 138.3Syn Z: -0.19

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

352 rare PASS variants

Rare truncating (LoF)

1 in 3,000

68 rare PASS variants

Rare synonymous (reference)

1 in 240

129 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PEMT. 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 140	1 in 1,900
South Asian	~43k	1 in 130	1 in 440
Remaining (unassigned)	~30k	1 in 85	1 in 2,700
European (Finnish)	~27k	1 in 620	≈ 1 in 27,000
Admixed American	~22k	1 in 120	1 in 2,700
African / African American	~21k	1 in 120	1 in 2,900
East Asian	~20k	1 in 250	1 in 2,400
Ashkenazi Jewish	~13k	1 in 300	none seen
Middle Eastern	~2,884	1 in 80	≈ 1 in 1,400

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): All 7 coding exons well covered in gnomAD exomes and genomes.? see exons ↓