PFN1

Chr 17

profilin 1

Also known as: ALS18

NCBI Gene: 5216ENSG00000108518UniProt: P07737OMIM: 176610

Profilin 1 binds to actin and regulates actin polymerization, playing a critical role in cytoskeletal dynamics and cellular signaling. Mutations cause amyotrophic lateral sclerosis 18, a motor neuron degenerative disease with autosomal dominant inheritance. The gene shows moderate constraint against loss-of-function variants (pLI 0.73, LOEUF 0.69), and comprehensive clinical information is available in GeneReviews.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOEUF 0.691 OMIM phenotype
Clinical Summary— PFN1
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Gene-Disease Validity (ClinGen)
amyotrophic lateral sclerosis type 18 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.73) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
29 unique Pathogenic / Likely Pathogenic· 55 VUS of 150 total submissions
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Clinical Trials
8 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — PFN1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.69LOEUF
pLI 0.733
Z-score 1.93
OE 0.00 (0.00–0.69)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
1.95Z-score
OE missense 0.41 (0.31–0.54)
35 obs / 85.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.69)
0≤0.351.4
Missense OE0.41 (0.31–0.54)
0≤0.61.4
Synonymous OE1.30
0≤1.21.6
LoF obs/exp: 0 / 4.4Missense obs/exp: 35 / 85.9Syn Z: -1.40

ClinVar Variant Classifications

150 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic4
VUS55
Likely Benign46
Benign14
Conflicting2
25
Pathogenic
4
Likely Pathogenic
55
VUS
46
Likely Benign
14
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
3
22
0
25
Likely Pathogenic
1
1
2
0
4
VUS
2
37
16
0
55
Likely Benign
1
1
25
19
46
Benign
0
0
11
3
14
Conflicting
—2
Total4427622146

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

View in ClinVar →

Protein Context — Lollipop Plot

PFN1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Malnutrition PregnancyMalnutrition in ChildrenMalnutrition (Calorie)

Early Life Malnutrition, Environmental Enteric Dysfunction and Microbiome Trajectories

RECRUITING
NCT07195006University of ZimbabweStarted 2025-01-27
Malnutrition in pregnancy as exposurePoor WASH living conditions as exposure
Early Breast CancerTriple Negative Breast Cancer

Trial for Treatment of High Risk BC With Two Sequences of Neoadjuvant Chemotherapy With Pembrolizumab

NOT YET RECRUITING
NCT06371807Phase PHASE2Fundacao ChampalimaudStarted 2024-07
Pembrolizumab injection
Myelodysplastic Syndrome

Study of an Innovative Therapy Using CAR-T Cells Targeting IL-1RAP in Patients With High-Risk Myelodysplastic Syndromes (MDS

NOT YET RECRUITING
NCT07455500Phase NAUniversity Hospital, GrenobleStarted 2026-05
Bone marrow and blood sampling
ALS

Amyotrophic Lateral Sclerosis (ALS) Families Project

RECRUITING
NCT03865420Columbia UniversityStarted 2018-09-11
Post-Acute COVID-19 Syndrome

A Study of Apabetalone in Subjects With Long -COVID

RECRUITING
NCT06590324Phase PHASE2, PHASE3Resverlogix CorpStarted 2025-04-15
Apabetalone
EndometriosisAdenomyosis

Pain in Endometriosis And the Relation to Lifestyle

RECRUITING
NCT06332560Phase NARadboud University Medical CenterStarted 2024-10-04
Anti-inflammatory diet (DI)Cognitive behavioral therapy (CBT)
Transplantation InfectionKidney Diseases

Molecular Biological and Moleculargenetic Monitoring of Therapy After Kidney Transplantation

RECRUITING
NCT01515605Odense University HospitalStarted 2011-01-01
Diabetes MellitusPancreas TransplantationAllograft Rejection

The Norwegian Pancreas Transplantation (PTx) Study

ENROLLING BY INVITATION
NCT01957696Oslo University HospitalStarted 2013-09
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Comparison between PFN1 and SOD1 mutations in amyotrophic lateral sclerosis.
Corcia P et al.·Eur J Neurol
2023Review
Profilin1 is required for prevention of mitotic catastrophe in murine and human glomerular diseases.
Tian X et al.·J Clin Invest
2023
Integrated single-cell and bulk RNA sequencing reveals immune-related SPP1+ macrophages as a potential strategy for predicting the prognosis and treatment of liver fibrosis and hepatocellular carcinoma.
Li B et al.·Front Immunol
2024
m(6)A Modification of Profilin-1 in Vascular Smooth Muscle Cells Drives Phenotype Switching and Neointimal Hyperplasia via Activation of the p-ANXA2/STAT3 Pathway.
Gao XF et al.·Arterioscler Thromb Vasc Biol
2024
The actin binding protein profilin 1 localizes inside mitochondria and is critical for their function.
Read TA et al.·EMBO Rep
2024
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
F-Box and Leucine-Rich Repeat Protein 4 (FBXL4) Maintains Sarcomere Integrity and Cardiac Function by Enhancing K48-Linked Ubiquitinated Degradation of Profilin-1 (PFN1).
Li X et al.·Adv Sci (Weinh)
2026Open Access
A Missense Mutation in Close Proximity of ALS-linked PFN1 Mutations Causes Only Early-onset Paget Disease of Bone.
Weng R et al.·J Clin Endocrinol Metab
2025Open Access
MAIT Cells with High PFN1 Expression Mediate Immune Activation and Metabolic Reprogramming in Psoriasis.
Wu MN et al.·Clin Cosmet Investig Dermatol
2025Open Access
Metal Ion Nanodepots Orchestrate Neuronal Axon and Dendrite Growth via the Actin-PFN1 Pathway.
Yang Y et al.·ACS Appl Mater Interfaces
2025
Viral-mediated knockdown of Atxn2 attenuates TDP-43 pathology and muscle dysfunction in the PFN1C71G ALS mouse model.
Hawley ZCE et al.·Acta Neuropathol Commun
2025Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients