PPFIBP1

protein-coding

PPFIA binding protein 1, 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. It has been proposed that liprins are multivalent proteins that form complex structures and act as scaffolds for the recruitment and anchoring of LAR family of tyrosine phosphatases. This protein was found to interact with S100A4, a calcium-binding protein related to tumor invasiveness and metastasis. In vitro experiment demonstrated that the interaction inhibited the phosphorylation of this protein by protein kinase C and protein kinase CK2. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

MANE transcript

NM_003622.4

Inheritance

ClinVar variants

P:17U:150B:17

Top phenotype

Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities

gnomAD constraint

pLI —, LoF o/e 0.57

Max pathogenic AF

—

Genomic locus

chr12:27,523,431-27,695,564

External References & Databases

Ensembl (ENSG00000110841)

Transcript & Mutation Effects

hg38 • Region Span ~172.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with seizures, microcephaly, and brain abnormalitiesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859283

Submitter: Ambry Genetics

neurodevelopmental disorder with seizures, microcephaly, and brain abnormalitiesLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0859283

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with seizures, microcephaly, and brain abnormalitiesSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859283

Submitter: PanelApp Australia

neurodevelopmental disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: G2P

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalitiesAR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 30214071; 35830857

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PPFIBP1 variants in ClinVar

10 Conditions Cataloged

Inborn genetic diseasesTotal: 138

not providedTotal: 18

Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalitiesTotal: 18

not specifiedTotal: 11

Severe intellectual disabilityTotal: 10

SeizureTotal: 10

MicrocephalyTotal: 10

Cerebral calcificationTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003622.4. 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			3 clinvar	8 clinvar		11
missense			136 clinvar	8 clinvar	1 clinvar	145
nonsense	5 clinvar					5
start loss						0
frameshift	4 clinvar	5 clinvar	1 clinvar			10
splice donor/acceptor (+/-2bp)	2 clinvar	1 clinvar	10 clinvar			13
Total	11	6	150	16	1	184

Highest pathogenic variant AF is 0.000019534658

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 167 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003622.4	RefSeq	NP_003613.4	28	MANE Select
ENST00000228425.11	Ensembl	ENSP00000228425.6	28	MANE Select
NM_001198915.2	RefSeq	NP_001185844.1	24	Standard
NM_001198916.2	RefSeq	NP_001185845.2	26	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neuronal System
Receptor-type tyrosine-protein phosphatases
Protein-protein interactions at synapses

Biological Process

cell adhesion

Molecular Function

cadherin binding

Cellular Component

cytosol
plasma membrane
focal adhesion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000318304
Coding exons: 27
Length: 172134
Individuals with no LoFs: 125670
Homozygous LoFs: 0
Heterozygous LoFs: 78
Defined: 125748
p: 0.000310

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.745	482	530	0.909	0.0000274	6662
Missense (PolyPhen)		244	276.92	0.88113		3483
Synonymous	0.921	174	190	0.915	0.00000985	1863
Loss of Function	3.15	35	61.8	0.567	0.00000342	729

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00044	0.00043	rare
Latino/Admixed American	0.00045	0.00043	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.00037	0.00037	rare
European (Non-Finnish)	0.00031	0.00031	rare
South Asian	0.00036	0.00036	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May regulate the disassembly of focal adhesions. Did not bind receptor-like tyrosine phosphatases type 2A. {ECO:0000269|PubMed:9624153}.;

Recessive Scores

pRec: 0.111

Intolerance Scores

LoFtool: 0.967
RVIS EVS: -0.5
RVIS percentile EVS: 21.81

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.695

Gene Damage Prediction

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