PLET1

Chr 11

placenta expressed transcript 1

Also known as: C11orf34

NCBI Gene: 349633 ENSG00000188771 UniProt: Q6UQ28 OMIM: 611904

PLET1 encodes a protein that modulates keratinocyte migration and cellular adhesion to matrix proteins during wound healing and promotes wound repair. Mutations cause autosomal recessive congenital hydranencephaly, a severe brain malformation where the cerebral hemispheres are replaced by fluid-filled sacs. The gene shows no constraint against loss-of-function variants in the general population (pLI near 0, LOEUF 1.67), consistent with autosomal recessive inheritance where heterozygous carriers are unaffected.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in negative regulation of cell-matrix adhesion; positive regulation of cell migration; and wound healing, spreading of epidermal cells. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in apical plasma membrane and external side of plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.67

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.67LOEUF

pLI 0.000

Z-score 0.10

OE 0.96 (0.56–1.67)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.84Z-score

OE missense 0.78 (0.65–0.93)

85 obs / 109.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.96 (0.56–1.67)

0≤0.351.4

Missense OE?0.78 (0.65–0.93)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 8 / 8.3Missense obs/exp: 85 / 109.6Syn Z: 0.87

Background carrier burden — how many people carry a rare variant somewhere in PLET1?

gnomAD v4 · ~700k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 350

275 rare PASS variants

Rare truncating (LoF)

1 in 430

50 rare PASS variants

Rare synonymous (reference)

1 in 410

101 rare PASS variants

Rare missense and truncating variants are carried at similar rates in PLET1; this gene does not show strong loss-of-function constraint by this measure. 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)	~540k	1 in 310	1 in 1,400
South Asian	~40k	1 in 220	1 in 840
Remaining (unassigned)	~29k	1 in 310	1 in 240
European (Finnish)	~25k	1 in 1,800	1 in 4,100
African / African American	~21k	1 in 190	1 in 3,500
East Asian	~18k	1 in 170	1 in 1,000
Admixed American	~18k	1 in 220	1 in 260
Ashkenazi Jewish	~13k	1 in 570	≈ 1 in 13,000
Middle Eastern	~2,852	1 in 230	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): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓