PSTPIP1

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

Basic information

Region (hg38): 15:76993358-77037475

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pyogenic sterile arthritis, pyoderma gangrenosum, and acne	AD	Allergy/Immunology/Infectious; Pharmacogenomic	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	9212761; 11971877; 19673875; 21790734

ClinVar

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

• Pyogenic arthritis-pyoderma gangrenosum-acne syndrome (453 variants)
• not provided (157 variants)
• Autoinflammatory syndrome (72 variants)
• not specified (64 variants)
• Inborn genetic diseases (24 variants)
• Behcet disease (2 variants)
• PSTPIP1-related condition (2 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.

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			6	84	4	94
missense	3		187	20	1	211
nonsense			7	3		10
start loss						0
frameshift		1	9			10
inframe indel						0
splice donor/acceptor (+/-2bp)			3			3
splice region			14	19	3	36
non coding			15	85	54	154
Total	3	1	227	192	59

Variants in PSTPIP1

This is a list of pathogenic ClinVar variants found in the PSTPIP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-76994821-C-T		PSTPIP1-related disorder	Likely benign (Jul 15, 2019)
15-76994970-C-T			Likely benign (Oct 24, 2018)
15-76995138-G-A		Pyogenic arthritis-pyoderma gangrenosum-acne syndrome	Benign (Jan 12, 2018)
15-76995149-G-GCTGC		Pyogenic arthritis-pyoderma gangrenosum-acne syndrome • Autoinflammatory syndrome	Benign/Likely benign (Aug 21, 2019)
15-76995149-G-GCTGCCTGCCTGC		Pyogenic arthritis-pyoderma gangrenosum-acne syndrome	Benign (Aug 21, 2019)
15-76995207-G-A		Pyogenic arthritis-pyoderma gangrenosum-acne syndrome	Uncertain significance (Jan 13, 2018)
15-76995291-G-GGGGCT		Pyogenic arthritis-pyoderma gangrenosum-acne syndrome	Uncertain significance (Jun 14, 2016)
15-76995403-A-T		Pyogenic arthritis-pyoderma gangrenosum-acne syndrome	Benign (Jan 13, 2018)
15-76995415-C-G		PSTPIP1-related disorder	Likely benign (Feb 19, 2019)
15-76995433-C-T		PSTPIP1-related disorder	Likely benign (Feb 19, 2019)
15-76995436-A-T			Benign (Mar 03, 2015)
15-76995448-G-T		PSTPIP1-related disorder	Likely benign (May 06, 2021)
15-76995450-C-T		Pyogenic arthritis-pyoderma gangrenosum-acne syndrome	Benign/Likely benign (Feb 02, 2019)
15-76995451-G-A		Pyogenic arthritis-pyoderma gangrenosum-acne syndrome	Likely benign (Mar 23, 2020)
15-76995454-G-A		Pyogenic arthritis-pyoderma gangrenosum-acne syndrome	Likely benign (Sep 03, 2021)
15-76995457-C-T		Pyogenic arthritis-pyoderma gangrenosum-acne syndrome • PSTPIP1-related disorder	Benign/Likely benign (Sep 28, 2023)
15-76995558-C-T		not specified	Likely benign (Jun 23, 2017)
15-76995573-G-A		PSTPIP1-related disorder	Likely benign (May 04, 2022)
15-76995578-T-C		Pyogenic arthritis-pyoderma gangrenosum-acne syndrome • Autoinflammatory syndrome	Conflicting classifications of pathogenicity (Dec 21, 2023)
15-76995579-G-T		Inborn genetic diseases	Uncertain significance (Jul 25, 2023)
15-76995580-C-T			Uncertain significance (Jul 01, 2016)
15-76995588-G-A		Pyogenic arthritis-pyoderma gangrenosum-acne syndrome	Likely benign (Jul 07, 2023)
15-76995590-A-G		Pyogenic arthritis-pyoderma gangrenosum-acne syndrome	Uncertain significance (May 08, 2022)
15-76995590-A-T		Pyogenic arthritis-pyoderma gangrenosum-acne syndrome	Uncertain significance (Sep 27, 2022)
15-76995595-A-G		Pyogenic arthritis-pyoderma gangrenosum-acne syndrome	Uncertain significance (Jul 06, 2021)

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