PPFIA1

protein-coding

PTPRF interacting protein alpha 1, the group of MicroRNA protein coding host genes|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. This protein binds to the intracellular membrane-distal phosphatase domain of tyrosine phosphatase LAR, and appears to localize LAR to cell focal adhesions. This interaction may regulate the disassembly of focal adhesion and thus help orchestrate cell-matrix interactions. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

MANE transcript

NM_003626.5

Inheritance

—

ClinVar variants

U:209B:37

Top phenotype

PPFIA1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.01

Max pathogenic AF

—

Genomic locus

chr11:70,270,690-70,385,312

External References & Databases

Ensembl (ENSG00000131626)

Transcript & Mutation Effects

hg38 • Region Span ~114.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PPFIA1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 180

not providedTotal: 27

PPFIA1-related disorderTotal: 22

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003626.5. 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			5 clinvar	29 clinvar	3 clinvar	37
missense			192 clinvar	4 clinvar	1 clinvar	197
nonsense			3 clinvar			3
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	209	33	4	246

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 74 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003626.5	RefSeq	NP_003617.1	26	MANE Select
ENST00000253925.12	Ensembl	ENSP00000253925.7	26	MANE Select
NM_001378006.1	RefSeq	NP_001364935.1	30	Standard
NM_177423.3	RefSeq	NP_803172.1	25	Standard

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

cell-matrix adhesion
signal transduction
negative regulation of stress fiber assembly
negative regulation of protein localization to plasma membrane

Molecular Function

protein binding

Cellular Component

cytoplasm
cytosol
focal adhesion
presynaptic active zone

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000253925
Coding exons: 26
Length: 113704
Individuals with no LoFs: 125741
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125748
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.06	618	697	0.887	0.0000413	7899
Missense (PolyPhen)		172	247.61	0.69463		2771
Synonymous	0.828	249	266	0.935	0.0000167	2301
Loss of Function	7.69	1	70.8	0.0141	0.00000421	760

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
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	0.000065	0.000033	rare
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:7796809}.;

Recessive Scores

pRec: 0.112

Intolerance Scores

LoFtool: 0.233
RVIS EVS: -1.68
RVIS percentile EVS: 2.69

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.771

Gene Damage Prediction

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