PSTPIP1

proline-serine-threonine phosphatase interacting protein 1, the group of F-BAR domain containing

Basic information

Region (hg38): 15:76993359-77037475

Links

ENSG00000140368

∙ NCBI:9051 ∙ OMIM:606347 ∙ HGNC:9580 ∙ Uniprot:O43586 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

pyogenic arthritis-pyoderma gangrenosum-acne syndrome (Strong), mode of inheritance: AD
pyogenic arthritis-pyoderma gangrenosum-acne syndrome (Supportive), mode of inheritance: AD
recurrent infections-inflammatory syndrome due to zinc metabolism disorder syndrome (Supportive), mode of inheritance: Unknown
pyogenic arthritis-pyoderma gangrenosum-acne syndrome (Definitive), mode of inheritance: AD
autoinflammatory syndrome (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Autoinflammatory syndrome with cytopenia, hyperzincemia, and hypercalprotectinemia; Pyogenic sterile arthritis, pyoderma gangrenosum, and acne;	AD	Allergy/Immunology/Infectious; Dermatologic; Endocrine; Hematologic; Musculoskeletal	Medical treatment (eg, anakinra) can be effective to treat autoimmune manifestations; Cytopenia related to sulfonamide use has been reported	Allergy/Immunology/Infectious; Dermatologic; Endocrine; Musculoskeletal	Autoinflammatory syndrome with cytopenia, hyperzincemia, and hypercalprotectinemia may involve recurrent infections, and awareness may allow preventative measures and early and aggressive treatment of infections; Medical management has been described as beneficial in some individuals; In Pyogenic sterile arthritis, pyoderma gangrenosum, and acne, medical treatment (eg, anakinra) can be effective to treat autoimmune manifestations; Cytopenia related to sulfonamide use has been reported
Allergy/Immunology/Infectious; Pharmacogenomic

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PSTPIP1 gene.

Pyogenic_arthritis-pyoderma_gangrenosum-acne_syndrome (603 variants)
not_provided (151 variants)
Autoinflammatory_syndrome (70 variants)
Inborn_genetic_diseases (64 variants)
not_specified (61 variants)
PSTPIP1-related_disorder (21 variants)
Hyperzincemia_and_hypercalprotectinemia (4 variants)
Behcet_disease (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PSTPIP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003978.5. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			9 clinvar	142 clinvar	1 clinvar	152
missense	5 clinvar		267 clinvar	32 clinvar	1 clinvar	305
nonsense			11 clinvar			11
start loss						0
frameshift		1 clinvar	12 clinvar			13
splice donor/acceptor (+/-2bp)			8 clinvar	1 clinvar	1 clinvar	10
Total	5	1	307	175	3

Highest pathogenic variant AF is 0.0000126206

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PSTPIP1	protein_coding	protein_coding	ENST00000558012	15	43974

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000246	0.996	124457	1	79	124537	0.000321

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.917	215	256	0.839	0.0000167	2652
Missense in Polyphen		48	65.336	0.73467		631
Synonymous	-0.931	121	109	1.11	0.00000770	760
Loss of Function	2.55	14	28.8	0.487	0.00000141	309

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000355	0.000354
Ashkenazi Jewish	0.00	0.00
East Asian	0.000112	0.000111
Finnish	0.000149	0.000139
European (Non-Finnish)	0.000175	0.000168
Middle Eastern	0.000112	0.000111
South Asian	0.00152	0.00147
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Involved in regulation of the actin cytoskeleton. May regulate WAS actin-bundling activity. Bridges the interaction between ABL1 and PTPN18 leading to ABL1 dephosphorylation. May play a role as a scaffold protein between PTPN12 and WAS and allow PTPN12 to dephosphorylate WAS. Has the potential to physically couple CD2 and CD2AP to WAS. Acts downstream of CD2 and CD2AP to recruit WAS to the T-cell:APC contact site so as to promote the actin polymerization required for synapse induction during T-cell activation (By similarity). Down-regulates CD2-stimulated adhesion through the coupling of PTPN12 to CD2. Also has a role in innate immunity and the inflammatory response. Recruited to inflammasomes by MEFV. Induces formation of pyroptosomes, large supramolecular structures composed of oligomerized PYCARD dimers which form prior to inflammatory apoptosis. Binding to MEFV allows MEFV to bind to PYCARD and facilitates pyroptosome formation. Regulates endocytosis and cell migration in neutrophils. {ECO:0000250, ECO:0000269|PubMed:17964261, ECO:0000269|PubMed:18480402, ECO:0000269|PubMed:19109554, ECO:0000269|PubMed:19584923, ECO:0000269|PubMed:9857189}.;
Disease: DISEASE: PAPA syndrome (PAPAS) [MIM:604416]: Characterized by autosomal dominant inheritance of early-onset, primarily affecting skin and joint tissues. Recurring inflammatory episodes lead to accumulation of sterile, pyogenic, neutrophil-rich material within the affected joints, ultimately resulting in significant destruction. {ECO:0000269|PubMed:11971877, ECO:0000269|PubMed:14595024, ECO:0000269|PubMed:22161697}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: NOD-like receptor signaling pathway - Homo sapiens (human);T-Cell antigen Receptor (TCR) Signaling Pathway;The NLRP3 inflammasome;Inflammasomes;Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways;TCR;Innate Immune System;Immune System (Consensus)

Recessive Scores

pRec: 0.172

Intolerance Scores

loftool: 0.794
rvis_EVS: 0.31
rvis_percentile_EVS: 72.71

Haploinsufficiency Scores

pHI: 0.189
hipred: Y
hipred_score: 0.669
ghis: 0.493

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.671

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Pstpip1
Phenotype: immune system phenotype; hematopoietic system phenotype;

Gene ontology

Biological process: endocytosis;inflammatory response;cell adhesion;signal transduction;actin filament polymerization;innate immune response
Cellular component: uropod;cytoplasm;cytosol;cytoskeleton;actin filament;plasma membrane;membrane;lamellipodium;cleavage furrow;perinuclear region of cytoplasm
Molecular function: protein binding;cytoskeletal protein binding;identical protein binding;actin filament binding