PPFIBP1

PPFIA binding protein 1, the group of Sterile alpha motif domain containing

Basic information

Region (hg38): 12:27523431-27695564

Links

ENSG00000110841 ∙ NCBI:8496 ∙ OMIM:603141 ∙ HGNC:9249 ∙ Uniprot:Q86W92 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities (Strong), mode of inheritance: AR
• neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities	AR	General	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	Neurologic	30214071; 35830857

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PPFIBP1 gene.

• Cerebral calcification;Microcephaly;Seizure;Intellectual disability, severe (7 variants)
• Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities (6 variants)
• Microcephaly;Cerebral calcification;Intellectual disability, severe;Seizure (2 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPFIBP1 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						0
missense			56	6	1	63
nonsense	4					4
start loss			1			1
frameshift	3					3
inframe indel						0
splice donor/acceptor (+/-2bp)	2	1				3
splice region						0
non coding	1		2			3
Total	10	1	59	6	1

Highest pathogenic variant AF is 0.0000132

Variants in PPFIBP1

This is a list of pathogenic ClinVar variants found in the PPFIBP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-27634955-C-T		Inborn genetic diseases	Uncertain significance (Jul 06, 2021)
12-27635002-G-A		Inborn genetic diseases	Uncertain significance (Mar 29, 2022)
12-27635011-C-T		Inborn genetic diseases	Uncertain significance (Nov 09, 2021)
12-27635013-TG-T		Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities	Pathogenic (Jul 17, 2023)
12-27635060-G-T		Inborn genetic diseases	Uncertain significance (Oct 28, 2024)
12-27635064-G-C		Inborn genetic diseases	Uncertain significance (Feb 14, 2023)
12-27635084-A-G		Inborn genetic diseases	Uncertain significance (Aug 17, 2021)
12-27646086-G-A		Inborn genetic diseases	Uncertain significance (Aug 05, 2024)
12-27646092-G-A		Inborn genetic diseases	Uncertain significance (Jun 11, 2021)
12-27646095-T-C		Inborn genetic diseases	Uncertain significance (Nov 10, 2022)
12-27646114-G-A		Inborn genetic diseases	Uncertain significance (Oct 05, 2022)
12-27646128-A-G		Inborn genetic diseases	Uncertain significance (Dec 03, 2021)
12-27647727-AG-CC		Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities	Likely pathogenic (Jan 08, 2024)
12-27647757-C-A		Inborn genetic diseases	Uncertain significance (Dec 10, 2024)
12-27647759-C-G		Inborn genetic diseases	Uncertain significance (Dec 10, 2024)
12-27647774-C-T		Cerebral calcification;Intellectual disability, severe;Seizure;Microcephaly • Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities	Pathogenic (Apr 14, 2022)
12-27647805-G-C		Inborn genetic diseases	Uncertain significance (Jul 22, 2024)
12-27647832-T-C		Inborn genetic diseases	Uncertain significance (Dec 14, 2021)
12-27647854-G-C			Likely benign (Oct 01, 2024)
12-27647859-G-T			Likely benign (Oct 01, 2024)
12-27647861-A-T			Likely benign (Dec 01, 2023)
12-27650012-G-C		Inborn genetic diseases	Uncertain significance (Jun 09, 2022)
12-27650025-A-G		Inborn genetic diseases	Uncertain significance (Aug 16, 2021)
12-27654741-A-G		Inborn genetic diseases	Uncertain significance (Aug 05, 2024)
12-27654801-T-A		Inborn genetic diseases	Uncertain significance (May 31, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PPFIBP1	protein_coding	protein_coding	ENST00000318304	27	172134

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.15e-16	0.999	125670	0	78	125748	0.000310

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.745	482	530	0.909	0.0000274	6662
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000883	0.000877
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000370	0.000370
European (Non-Finnish)	0.000312	0.000308
Middle Eastern	0.000109	0.000109
South Asian	0.000364	0.000359
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May regulate the disassembly of focal adhesions. Did not bind receptor-like tyrosine phosphatases type 2A. {ECO:0000269|PubMed:9624153}.
• Pathway: Neuronal System;Receptor-type tyrosine-protein phosphatases;Protein-protein interactions at synapses (Consensus)

Recessive Scores

• pRec: 0.111

Intolerance Scores

• loftool: 0.967
• rvis_EVS: -0.5
• rvis_percentile_EVS: 21.81

Haploinsufficiency Scores

• pHI: 0.662
• hipred: N
• hipred_score: 0.492
• ghis: 0.551

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.695

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ppfibp1

Gene ontology

• Biological process: cell adhesion
• Cellular component: cytosol;plasma membrane;focal adhesion
• Molecular function: cadherin binding