PPFIA3

PTPRF interacting protein alpha 3, the group of Sterile alpha motif domain containing

Basic information

Region (hg38): 19:49119543-49151026

Links

ENSG00000177380 ∙ NCBI:8541 ∙ OMIM:603144 ∙ HGNC:9247 ∙ Uniprot:O75145 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PPFIA3 gene.

• Inborn genetic diseases (20 variants)
• not provided (9 variants)
• Neurodevelopmental delay (2 variants)
• not specified (1 variants)
• PPFIA3-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPFIA3 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		1
missense	2	3	22		1	28
nonsense						0
start loss						0
frameshift		1	2			3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	2	4	24	1	1

Variants in PPFIA3

This is a list of pathogenic ClinVar variants found in the PPFIA3 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-49127988-C-T			Pathogenic (Feb 17, 2023)
19-49127991-G-A		PPFIA3-related disorder	Likely pathogenic (Oct 09, 2023)
19-49128001-T-A		not specified	Uncertain significance (May 04, 2022)
19-49128112-A-C			Uncertain significance (Feb 17, 2023)
19-49128114-G-A		PPFIA3-related disorder	Likely pathogenic (Oct 09, 2023)
19-49128386-A-G		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
19-49128420-G-C		Inborn genetic diseases	Uncertain significance (Oct 03, 2022)
19-49128435-T-G		Inborn genetic diseases	Uncertain significance (Feb 06, 2023)
19-49128453-A-T		Inborn genetic diseases	Uncertain significance (Feb 15, 2023)
19-49128886-C-G		Inborn genetic diseases	Uncertain significance (Jan 30, 2024)
19-49129993-ACT-A		PPFIA3-associated neurodevelopmental disorder	Likely pathogenic (Feb 12, 2024)
19-49130023-C-G		Inborn genetic diseases	Uncertain significance (Feb 03, 2022)
19-49130055-T-G		Inborn genetic diseases	Uncertain significance (Dec 28, 2023)
19-49130418-G-A		Inborn genetic diseases	Uncertain significance (Mar 22, 2023)
19-49130418-G-C		Inborn genetic diseases	Uncertain significance (Dec 07, 2021)
19-49130420-C-T		Inborn genetic diseases	Uncertain significance (Nov 15, 2021)
19-49130459-G-A		Inborn genetic diseases	Uncertain significance (May 31, 2022)
19-49133064-G-T		PPFIA3-related disorder	Likely pathogenic (Oct 09, 2023)
19-49133085-C-G		Inborn genetic diseases	Uncertain significance (Dec 20, 2023)
19-49133099-C-G		Inborn genetic diseases	Uncertain significance (Nov 17, 2022)
19-49133336-G-A		Inborn genetic diseases	Uncertain significance (Jan 24, 2023)
19-49133367-A-G		Inborn genetic diseases	Uncertain significance (Jan 30, 2024)
19-49133843-G-C		Inborn genetic diseases	Uncertain significance (Mar 11, 2024)
19-49133877-C-T		PPFIA3-related disorder	Pathogenic (-)
19-49134073-C-T		PPFIA3-related disorder	Likely pathogenic (Jan 30, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PPFIA3	protein_coding	protein_coding	ENST00000334186	28	31638

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	9.91e-9	125731	0	4	125735	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.49	311	727	0.428	0.0000436	7622
Missense in Polyphen		84	277.74	0.30244		2748
Synonymous	1.42	272	304	0.896	0.0000172	2470
Loss of Function	7.07	3	64.1	0.0468	0.00000318	715

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000274	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May regulate the disassembly of focal adhesions. May localize receptor-like tyrosine phosphatases type 2A at specific sites on the plasma membrane, possibly regulating their interaction with the extracellular environment and their association with substrates. {ECO:0000269|PubMed:9624153}.
• Pathway: Neuronal System;Glutamate Neurotransmitter Release Cycle;Dopamine Neurotransmitter Release Cycle;Acetylcholine Neurotransmitter Release Cycle;Neurotransmitter release cycle;Receptor-type tyrosine-protein phosphatases;Transmission across Chemical Synapses;Protein-protein interactions at synapses;Serotonin Neurotransmitter Release Cycle;Norepinephrine Neurotransmitter Release Cycle (Consensus)

Recessive Scores

• pRec: 0.111

Intolerance Scores

• loftool: 0.0112
• rvis_EVS: -1.06
• rvis_percentile_EVS: 7.48

Haploinsufficiency Scores

• pHI: 0.160
• hipred: Y
• hipred_score: 0.743
• ghis: 0.553

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.927

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ppfia3

Zebrafish Information Network

• Gene name: ppfia3
• Affected structure: intersegmental vessel
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: neurotransmitter secretion;synaptic vesicle docking;regulation of short-term neuronal synaptic plasticity
• Cellular component: acrosomal vesicle;cytosol;presynaptic active zone;presynaptic active zone cytoplasmic component;epididymosome;glutamatergic synapse
• Molecular function: protein binding