PFN3

Chr 5

profilin 3

Also known as: profilin-3

The protein binds to actin and regulates cytoskeletal structure by slightly reducing actin polymerization, and also binds to various phospholipids and may function in spermatogenesis. Mutations cause autosomal recessive neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy. The gene shows moderate tolerance to loss-of-function variants (pLI 0.50, LOEUF 1.37).

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
57
P/LP submissions
0%
P/LP missense
1.37
LOEUF
Mechanism
Clinical SummaryPFN3
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.50) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
55 unique Pathogenic / Likely Pathogenic· 38 VUS of 96 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
1.37LOEUF
pLI 0.501
Z-score 1.29
OE 0.00 (0.001.37)
Moderately constrained

Highly tolerant — LoF variants common in population

Missense Constraint
0.48Z-score
OE missense 0.86 (0.721.03)
85 obs / 98.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.001.37)
00.351.4
Missense OE0.86 (0.721.03)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 0 / 1.9Missense obs/exp: 85 / 98.4Syn Z: 0.24

ClinVar Variant Classifications

96 submitted variants in ClinVar

Classification Summary

Pathogenic50
Likely Pathogenic5
VUS38
Likely Benign3
50
Pathogenic
5
Likely Pathogenic
38
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
50
0
50
Likely Pathogenic
0
0
5
0
5
VUS
0
27
11
0
38
Likely Benign
0
2
1
0
3
Benign
0
0
0
0
0
Total02967096

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

View in ClinVar →

Protein Context — Lollipop Plot

PFN3 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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