PFN3

Chr 5

profilin 3

Also known as: profilin-3

NCBI Gene: 345456 ENSG00000196570 UniProt: P60673 OMIM: 612812

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).

OMIM ResearchSummary from RefSeq, UniProt

The product of this gene belongs to the profilin family of proteins. This protein binds to actin and affects the structure of the cytoskeleton. It also may be involved in spermatogenesis. It is a single exon gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOEUF 1.37

Clinical Summary— PFN3

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.50) — some intolerance to loss-of-function variants.

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ClinVar Variants

27 VUS of 29 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

1.37LOEUF

pLI 0.501

Z-score 1.29

OE 0.00 (0.00–1.37)

Moderately constrained

Highly tolerant — LoF variants common in population

Missense Constraint?

0.48Z-score

OE missense 0.86 (0.72–1.03)

85 obs / 98.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.37)

0≤0.351.4

Missense OE?0.86 (0.72–1.03)

0≤0.61.4

Synonymous OE?0.95

0≤1.21.6

LoF obs/exp: 0 / 1.9Missense obs/exp: 85 / 98.4Syn Z: 0.24

ClinVar Variant Classifications

29 submitted variants in ClinVar

ClinVar

Classification Summary

VUS27

Likely Benign2

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	27	27
Likely Benign	2	2
Benign	0	0
Total	29	29

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

View in ClinVar →

57 pathogenic / likely-pathogenic (of 69) ClinVar copy-number / structural variants overlap PFN3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →