PLEKHF1

pleckstrin homology and FYVE domain containing 1, the group of Zinc fingers FYVE-type|Pleckstrin homology domain containing

Basic information

Region (hg38): 19:29665459-29675477

Links

ENSG00000166289 ∙ NCBI:79156 ∙ OMIM:615200 ∙ HGNC:20764 ∙ Uniprot:Q96S99 ∙ 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 PLEKHF1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PLEKHF1 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	3	4
missense			28	1	1	30
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	28	2	4

Variants in PLEKHF1

This is a list of pathogenic ClinVar variants found in the PLEKHF1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-29673860-C-A		not specified	Uncertain significance (Dec 21, 2023)
19-29673860-C-G		not specified	Uncertain significance (May 18, 2023)
19-29673871-A-G		not specified	Uncertain significance (Feb 11, 2025)
19-29673890-A-G			Benign (Jun 01, 2023)
19-29673896-G-T		not specified	Uncertain significance (May 02, 2024)
19-29673913-C-T		not specified	Uncertain significance (Sep 22, 2023)
19-29673928-C-T		not specified	Uncertain significance (May 03, 2023)
19-29673940-G-C		not specified	Uncertain significance (Jan 20, 2025)
19-29673940-G-T		not specified	Uncertain significance (Feb 13, 2025)
19-29673978-C-T		not specified	Uncertain significance (Jan 09, 2025)
19-29673981-A-G		not specified	Uncertain significance (Dec 19, 2023)
19-29674009-T-C		not specified	Uncertain significance (Sep 27, 2024)
19-29674053-C-G		not specified	Uncertain significance (Oct 25, 2022)
19-29674071-C-A		not specified	Uncertain significance (Jan 22, 2024)
19-29674083-C-T			Benign (May 16, 2018)
19-29674185-G-A		not specified	Likely benign (Nov 24, 2024)
19-29674227-G-T		not specified	Uncertain significance (Aug 12, 2021)
19-29674234-G-A		not specified	Uncertain significance (Jan 01, 2025)
19-29674258-C-T		not specified	Uncertain significance (Oct 05, 2022)
19-29674275-G-A		not specified	Uncertain significance (Jan 27, 2025)
19-29674277-G-A			Benign (Apr 05, 2018)
19-29674299-G-A		not specified	Uncertain significance (Nov 17, 2022)
19-29674302-A-T		not specified	Uncertain significance (Jul 26, 2022)
19-29674305-G-A		not specified	Uncertain significance (Jan 24, 2023)
19-29674389-G-C		not specified	Uncertain significance (May 28, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PLEKHF1	protein_coding	protein_coding	ENST00000436066	1	10402

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0125	0.866	125681	0	17	125698	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.189	193	201	0.962	0.0000153	1778
Missense in Polyphen		86	101.05	0.8511		858
Synonymous	1.28	82	98.1	0.835	0.00000817	575
Loss of Function	1.28	4	7.86	0.509	4.24e-7	78

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000905	0.0000905
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000124	0.000123
Middle Eastern	0.00	0.00
South Asian	0.0000328	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May induce apoptosis through the lysosomal-mitochondrial pathway. Translocates to the lysosome initiating the permeabilization of lysosomal membrane (LMP) and resulting in the release of CTSD and CTSL to the cytoplasm. Triggers the caspase- independent apoptosis by altering mitochondrial membrane permeabilization (MMP) resulting in the release of PDCD8. {ECO:0000269|PubMed:16188880}.

Recessive Scores

• pRec: 0.135

Intolerance Scores

• loftool: 0.224
• rvis_EVS: -0.56
• rvis_percentile_EVS: 19.31

Haploinsufficiency Scores

• pHI: 0.0469
• hipred: Y
• hipred_score: 0.546
• ghis: 0.540

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.728

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Plekhf1

Gene ontology

• Biological process: apoptotic process;endosome organization;positive regulation of autophagy;vesicle organization;protein localization to plasma membrane;positive regulation of intrinsic apoptotic signaling pathway
• Cellular component: nucleus;lysosome;lysosomal membrane;endosome;endosome membrane;perinuclear region of cytoplasm
• Molecular function: protein binding;phosphatidylinositol-5-phosphate binding;phosphatidylinositol-3-phosphate binding;phosphatidylinositol binding;metal ion binding;phosphatidylinositol-4-phosphate binding