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…

MultiplemechanismLOEUF 1.67

Clinical Summary— PLET1

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

22 VUS of 27 total submissions

Explore recent and relevant literature in Research Assistant →

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

This gene — mechanism propensity

0.6161th %ile

GOF

0.6541th %ile

LOF

0.2777th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

27 submitted variants in ClinVar

ClinVar

Classification Summary

VUS22

Likely Benign5

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	22	22
Likely Benign	5	5
Benign	0	0
Total	27	27

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 18) ClinVar copy-number / structural variants overlap PLET1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →