PPFIA3

protein-coding

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

Gene summary

The protein encoded by this gene is a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family. Liprins interact with members of LAR family of transmembrane protein tyrosine phosphatases, which are known to be important for axon guidance and mammary gland development. Liprin family protein has been shown to localize phosphatase LAR to cell focal adhesions and may be involved in the molecular organization of presynaptic active zones. [provided by RefSeq, Jul 2008]

MANE transcript

NM_003660.4

Inheritance

ClinVar variants

P:25U:178B:17

Top phenotype

PPFIA3-related neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chr19:49,119,544-49,151,026

External References & Databases

Ensembl (ENSG00000177380)

Transcript & Mutation Effects

hg38 • Region Span ~31.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

PPFIA3-related neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:1040014

Submitter: PanelApp Australia

complex neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

PPFIA3-related neurodevelopmental disorderMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:1040014

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PPFIA3 variants in ClinVar

11 Conditions Cataloged

not providedTotal: 120

Inborn genetic diseasesTotal: 90

PPFIA3-related disorderTotal: 11

PAUL-CHAO NEURODEVELOPMENTAL SYNDROMETotal: 8

PPFIA3-associated neurodevelopmental disorderTotal: 2

Neurodevelopmental delayTotal: 2

PPFIA3-related disordersTotal: 1

PPFIA3-related neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003660.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				14 clinvar	1 clinvar	15
missense	2 clinvar	10 clinvar	165 clinvar	2 clinvar		179
nonsense	2 clinvar	2 clinvar	5 clinvar			9
start loss						0
frameshift	2 clinvar	5 clinvar	4 clinvar			11
splice donor/acceptor (+/-2bp)		2 clinvar	4 clinvar			6
Total	6	19	178	16	1	220

Highest pathogenic variant AF is 0.0000051341103

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003660.4	RefSeq	NP_003651.1	28	MANE Select
ENST00000334186.9	Ensembl	ENSP00000335614.3	28	MANE Select
ENST00000602351.5	Ensembl	ENSP00000473622.1	27	Standard
ENST00000602509.5	Ensembl	ENSP00000473621.1	3	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ppfia3	Danio rerio	Structure: intersegmental vessel Quality: malformed abnormal

Gene / Model

Organism

Observed Phenotype

ppfia3

Danio rerio

Structure: intersegmental vessel

Quality: malformed

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neuronal System
Glutamate Neurotransmitter Release Cycle
Dopamine Neurotransmitter Release Cycle
Acetylcholine Neurotransmitter Release Cycle
Neurotransmitter release cycle

Biological Process

neurotransmitter secretion
synaptic vesicle docking
regulation of short-term neuronal synaptic plasticity

Molecular Function

protein binding

Cellular Component

acrosomal vesicle
cytosol
presynaptic active zone
presynaptic active zone cytoplasmic component
epididymosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000334186
Coding exons: 28
Length: 31638
Individuals with no LoFs: 125731
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125735
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	5.49	311	727	0.428	0.0000436	7622
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.111

Intolerance Scores

LoFtool: 0.0112
RVIS EVS: -1.06
RVIS percentile EVS: 7.48

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.927

Gene Damage Prediction

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