PFN1

profilin 1, the group of Profilins

Basic information

Region (hg38): 17:4945651-4949061

Links

ENSG00000108518 ∙ NCBI:5216 ∙ OMIM:176610 ∙ HGNC:8881 ∙ Uniprot:P07737 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• amyotrophic lateral sclerosis type 18 (Strong), mode of inheritance: AD
• amyotrophic lateral sclerosis type 18 (Moderate), mode of inheritance: AD
• amyotrophic lateral sclerosis (Supportive), mode of inheritance: AD
• amyotrophic lateral sclerosis type 18 (Strong), mode of inheritance: AD
• amyotrophic lateral sclerosis type 18 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Amyotrophic lateral sclerosis 18	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	22801503; 23141414

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PFN1 gene.

• not provided (56 variants)
• Amyotrophic lateral sclerosis type 18 (6 variants)
• not specified (3 variants)
• Amyotrophic lateral sclerosis (2 variants)
• Neurodegeneration (1 variants)
• Inborn genetic diseases (1 variants)
• PFN1-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PFN1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	9	3	13
missense	1		20	1		22
nonsense						0
start loss						0
frameshift		1	1			2
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1	4		5
non coding				10	7	17
Total	1	1	23	20	10

Variants in PFN1

This is a list of pathogenic ClinVar variants found in the PFN1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-4945893-G-C		PFN1-related disorder	Likely benign (Jan 27, 2023)
17-4945906-C-T			Benign (Dec 05, 2023)
17-4945914-G-A			Uncertain significance (Jun 15, 2023)
17-4945915-C-A			Likely benign (Sep 04, 2023)
17-4945917-G-A			Uncertain significance (Nov 13, 2021)
17-4945919-A-C			Uncertain significance (Jul 23, 2022)
17-4945922-T-G			Uncertain significance (Mar 28, 2021)
17-4945924-G-A		PFN1-related disorder	Benign/Likely benign (Dec 18, 2023)
17-4945954-C-G		Inborn genetic diseases	Uncertain significance (Nov 29, 2023)
17-4945963-G-A		PFN1-related disorder	Likely benign (Dec 13, 2023)
17-4945970-C-A		Amyotrophic lateral sclerosis type 18	Pathogenic (Aug 23, 2012)
17-4945970-CCTT-C			Uncertain significance (Aug 01, 2018)
17-4945971-C-T		Inborn genetic diseases	Uncertain significance (Feb 21, 2024)
17-4945972-T-A		Amyotrophic lateral sclerosis type 18	Likely benign (Aug 28, 2019)
17-4945972-TT-AC		not specified	Conflicting classifications of pathogenicity (Dec 23, 2023)
17-4945973-T-C		Amyotrophic lateral sclerosis type 18 • not specified	Uncertain significance (Mar 06, 2023)
17-4945978-G-A			Uncertain significance (Dec 21, 2021)
17-4945982-A-C		Lower limb muscle weakness	Likely pathogenic (Apr 15, 2016)
17-4945982-A-G		Amyotrophic lateral sclerosis type 18	Pathogenic (Nov 11, 2021)
17-4945989-G-A		not specified • Amyotrophic lateral sclerosis type 18	Benign (Feb 01, 2024)
17-4945996-C-T			Likely benign (Jul 06, 2022)
17-4945999-TGGA-T			Likely benign (Nov 05, 2023)
17-4946004-G-A			Likely benign (Dec 06, 2022)
17-4946010-G-T			Likely benign (Dec 19, 2023)
17-4946010-GAA-G			Likely benign (Aug 09, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PFN1	protein_coding	protein_coding	ENST00000225655	3	3410

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.733	0.257	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.95	35	85.9	0.407	0.00000465	903
Missense in Polyphen		7	17.484	0.40036		232
Synonymous	-1.40	45	34.5	1.30	0.00000179	289
Loss of Function	1.93	0	4.36	0.00	1.84e-7	55

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR. {ECO:0000269|PubMed:18573880}.
• Disease: DISEASE: Amyotrophic lateral sclerosis 18 (ALS18) [MIM:614808]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5- 10% of the cases. {ECO:0000269|PubMed:22801503}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Salmonella infection - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Shigellosis - Homo sapiens (human);Association Between Physico-Chemical Features and Toxicity Associated Pathways;VEGFA-VEGFR2 Signaling Pathway;Regulation of Actin Cytoskeleton;G13 Signaling Pathway;Developmental Biology;Signaling by WNT;Signal Transduction;erk and pi-3 kinase are necessary for collagen binding in corneal epithelia;rho cell motility signaling pathway;RHO GTPases Activate Formins;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;RHO GTPase Effectors;Signaling by Rho GTPases;PCP/CE pathway;EGFR1;Beta-catenin independent WNT signaling;Hemostasis;Signaling by ROBO receptors;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.260

Intolerance Scores

• loftool: 0.175
• rvis_EVS: -0.08
• rvis_percentile_EVS: 47.79

Haploinsufficiency Scores

• pHI: 0.898
• hipred: Y
• hipred_score: 0.665
• ghis: 0.667

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.781

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pfn1
• Phenotype: limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; immune system phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: pfn1
• Affected structure: convergent extension involved in gastrulation
• Phenotype tag: abnormal
• Phenotype quality: disrupted

Gene ontology

• Biological process: neural tube closure;regulation of transcription by RNA polymerase II;positive regulation of epithelial cell migration;actin cytoskeleton organization;regulation of actin filament polymerization;negative regulation of actin filament polymerization;positive regulation of actin filament polymerization;negative regulation of actin filament bundle assembly;positive regulation of actin filament bundle assembly;positive regulation of ATPase activity;protein stabilization;negative regulation of stress fiber assembly;Wnt signaling pathway, planar cell polarity pathway;synapse maturation;modification of postsynaptic actin cytoskeleton;positive regulation of ruffle assembly
• Cellular component: nucleus;cytoplasm;cytosol;cytoskeleton;focal adhesion;cell cortex;membrane;extracellular exosome;blood microparticle;glutamatergic synapse
• Molecular function: adenyl-nucleotide exchange factor activity;RNA binding;actin binding;actin monomer binding;protein binding;phosphatidylinositol-4,5-bisphosphate binding;Rho GTPase binding;cadherin binding;proline-rich region binding