PEDS1

Chr 20

plasmanylethanolamine desaturase 1

Also known as: CarF, KUA, TMEM189

NCBI Gene: 387521 ENSG00000240849 UniProt: A5PLL7 OMIM: 610994

The protein is a plasmanylethanolamine desaturase that catalyzes plasmalogen biosynthesis in the endoplasmic reticulum, producing specialized glycerophospholipids involved in antioxidative and signaling mechanisms. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability and seizures. The gene shows moderate constraint to loss-of-function variants, suggesting some tolerance to complete gene loss.

OMIM ResearchSummary from RefSeq, UniProt

Co-transcription of this gene and the neighboring downstream gene (ubiquitin-conjugating enzyme E2 variant 1) generates a rare read-through transcript, which encodes a fusion protein comprised of sequence sharing identity with each individual gene product. The protein encoded by this individual gene lacks a UEV1 domain but includes three transmembrane regions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2009]

OMIM ResearchGenerating clinical summary…

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 0.008

Z-score 2.65

OE 0.36 (0.20–0.67)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.43Z-score

OE missense 0.53 (0.45–0.62)

112 obs / 211.4 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.36 (0.20–0.67)

0≤0.351.4

Missense OE?0.53 (0.45–0.62)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 7 / 19.7Missense obs/exp: 112 / 211.4Syn Z: -1.18

Background carrier burden — how many people carry a rare variant somewhere in PEDS1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

292 rare PASS variants

Rare truncating (LoF)

1 in 5,400

30 rare PASS variants

Rare synonymous (reference)

1 in 200

165 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PEDS1. 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 180	1 in 6,000
South Asian	~43k	1 in 190	1 in 4,400
Remaining (unassigned)	~30k	1 in 230	1 in 2,100
European (Finnish)	~27k	1 in 660	1 in 5,100
Admixed American	~22k	1 in 200	1 in 4,300
African / African American	~21k	1 in 150	≈ 1 in 4,200
East Asian	~20k	1 in 320	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 1,200	none seen
Middle Eastern	~2,884	1 in 220	≈ 1 in 720

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): 5 of 6 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 6.? see exons ↓