PFN1

Chr 17

profilin 1

Also known as: ALS18, PDB7

NCBI Gene: 5216 ENSG00000108518 UniProt: P07737

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.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the profilin family of small actin-binding proteins. The encoded protein plays an important role in actin dynamics by regulating actin polymerization in response to extracellular signals. Deletion of this gene is associated with Miller-Dieker syndrome, and the encoded protein may also play a role in Huntington disease. Multiple pseudogenes of this gene are located on chromosome 1. [provided by RefSeq, Jul 2012]

GeneReviews ResearchGenerating clinical summary…

LOEUF 0.69

Clinical Summary— PFN1

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Gene-Disease Validity (ClinGen)

amyotrophic lateral sclerosis type 18 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.73) — some intolerance to loss-of-function variants.

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ClinVar Variants

8 unique Pathogenic / Likely Pathogenic· 42 VUS of 115 total submissions

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Clinical Trials

11 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — PFN1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.00 (0.00–0.69)

0≤0.351.4

Missense OE?0.41 (0.31–0.54)

0≤0.61.4

Synonymous OE?1.30

0≤1.21.6

LoF obs/exp: 0 / 4.4Missense obs/exp: 35 / 85.9Syn Z: -1.40

ClinVar Variant Classifications

115 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic2

VUS42

Likely Benign45

Benign14

Conflicting2

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	4	2	0	6
Likely Pathogenic	1	1	0	0	2
VUS	2	37	3	0	42
Likely Benign	1	1	24	19	45
Benign	0	0	11	3	14
Conflicting	—				2
Total	4	43	40	22	111

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

View in ClinVar →

25 pathogenic / likely-pathogenic (of 39) ClinVar copy-number / structural variants overlap PFN1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

PFN1 · protein map & ClinVar variants

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

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

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GeneReview available — PFN1

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

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

Diabetes MellitusPancreas TransplantationAllograft Rejection

The Norwegian Pancreas Transplantation (PTx) Study

ENROLLING BY INVITATION

NCT01957696Oslo University HospitalStarted 2013-09

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)

Multiple MyelomaAL Amyloidosis

A Phase II Study to Evaluate the Efficacy and Safety of Teclistamab in Combination With Daratumumab (Tec-Dara) in Newly Diagnosed Multiple Myeloma With Concurrent Light Chain Amyloidosis (MM+AL).

RECRUITING

NCT07638683Phase PHASE2Shanghai Zhongshan HospitalStarted 2026-05-22

Teclistamab

Renal Cell CarcinomaAdvancedRecurrent

Neoantigen Peptide Vaccine Plus Pembrolizumab in Renal Cell Carcinoma

NOT YET RECRUITING

NCT07686744Phase PHASE1Jian LinStarted 2026-09-01

Personalized Neoantigen Polyepitope Peptide Vaccine

SepsisCritical IllnessImmunosuppression

Metabolic and Functional Study of γδ T Cells in Critically Ill Patients

NOT YET RECRUITING

NCT07680816Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyStarted 2026-07-15