PLS1

Chr 3AD

plastin 1

Also known as: DFNA76

NCBI Gene: 5357ENSG00000120756UniProt: Q14651

Plastins are a family of actin-binding proteins that are conserved throughout eukaryote evolution and expressed in most tissues of higher eukaryotes. In humans, two ubiquitous plastin isoforms (L and T) have been identified. The protein encoded by this gene is a third distinct plastin isoform, which is specifically expressed at high levels in the small intestine. Alternatively spliced transcript variants varying in the 5' UTR, but encoding the same protein, have been found for this gene. A pseudogene of this gene is found on chromosome 11.[provided by RefSeq, Feb 2010]

Primary Disease Associations & Inheritance

Deafness, autosomal dominant 76MIM #618787
AD
158
ClinVar variants
21
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— PLS1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 97 VUS of 158 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.67LOEUF
pLI 0.000
Z-score 3.05
OE 0.43 (0.28–0.67)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.48Z-score
OE missense 0.77 (0.69–0.85)
252 obs / 327.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.43 (0.28–0.67)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.69–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.87
0≤1.21.6
LoF obs/exp: 14 / 32.8Missense obs/exp: 252 / 327.1Syn Z: 1.16

ClinVar Variant Classifications

158 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic3
VUS97
Likely Benign10
Benign28
Conflicting2
18
Pathogenic
3
Likely Pathogenic
97
VUS
10
Likely Benign
28
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
1
2
0
0
3
VUS
2
86
8
1
97
Likely Benign
0
3
1
6
10
Benign
0
3
23
2
28
Conflicting
—2
Total394509158

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

View in ClinVar →

Protein Context — Lollipop Plot

PLS1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
PLASTIN 1; PLS1
MIM #602734 · *

Deafness, autosomal dominant 76

MIM #618787

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A novel PLS1 c.981+1G>A variant causes autosomal-dominant hereditary hearing loss in a family.
Xu L et al.·Clin Genet
2023
Novel variant p.E269K confirms causative role of PLS1 mutations in autosomal dominant hearing loss.
Diaz-Horta O et al.·Clin Genet
2019
Mendelian non-syndromic and syndromic hearing loss genes contribute to presbycusis.
Cornejo-Sanchez DM et al.·Eur J Hum Genet
2025
Alterations in gray matter volume and associated transcriptomics after electroconvulsive therapy in major depressive disorder.
Liu X et al.·Psychol Med
2025
Imaging Transcriptomics of Brain Functional Alterations in MS and Neuromyelitis Optica Spectrum Disorder.
Li Y et al.·AJNR Am J Neuroradiol
2024Functional
Mutations in PLS1, encoding fimbrin, cause autosomal dominant nonsyndromic hearing loss.
Morgan A et al.·Hum Mutat
2019
Hearing impairment locus heterogeneity and identification of PLS1 as a new autosomal dominant gene in Hungarian Roma.
Schrauwen I et al.·Eur J Hum Genet
2019Clinical trial
Activation of AMPK in platelets promotes the production of offspring.
Zhang T et al.·Platelets
2024
COMT-Polymorphisms Modulated Functional Profile of the Fusiform Face Area Contributes to Face-Specific Recognition Ability.
Wu C et al.·Sci Rep
2020Functional
Conservation of fungal and animal nicotinamide adenine dinucleotide phosphate oxidase complexes.
Scott B·Mol Microbiol
2015
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools