PIKFYVE

phosphoinositide kinase, FYVE-type zinc finger containing, the group of Zinc fingers FYVE-type

Basic information

Region (hg38): 2:208266255-208358746

Previous symbols: [ "PIP5K3" ]

Links

ENSG00000115020 ∙ NCBI:200576 ∙ OMIM:609414 ∙ HGNC:23785 ∙ Uniprot:Q9Y2I7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• fleck corneal dystrophy (Strong), mode of inheritance: AD
• fleck corneal dystrophy (Supportive), mode of inheritance: AD
• fleck corneal dystrophy (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Corneal fleck dystrophy	AD	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	Ophthalmologic	15902656; 23288988; 26396486

ClinVar

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

• Fleck corneal dystrophy (2 variants)
• not provided (2 variants)
• PIKFYVE-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PIKFYVE 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			6	16	27	49
missense			96	12	19	127
nonsense	3	5	2			10
start loss						0
frameshift	2	1				3
inframe indel			1			1
splice donor/acceptor (+/-2bp)		3				3
splice region			4	4	4	12
non coding			47	7	39	93
Total	5	9	152	35	85

Highest pathogenic variant AF is 0.00000657

Variants in PIKFYVE

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

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

Position	Type	Phenotype	Significance	ClinVar
2-208266259-A-T		Fleck corneal dystrophy	Likely benign (Jun 14, 2016)
2-208266265-A-G		Fleck corneal dystrophy	Benign (Jun 14, 2016)
2-208266268-A-T		Fleck corneal dystrophy	Uncertain significance (Jan 13, 2018)
2-208266272-A-T		Fleck corneal dystrophy	Uncertain significance (Jan 12, 2018)
2-208266291-C-T		Fleck corneal dystrophy	Benign (Jan 13, 2018)
2-208266420-G-A		Fleck corneal dystrophy	Likely benign (Apr 27, 2017)
2-208271539-C-T		Inborn genetic diseases	Uncertain significance (Mar 06, 2023)
2-208271544-C-T		Fleck corneal dystrophy	Uncertain significance (Jan 12, 2018)
2-208271556-T-C		Fleck corneal dystrophy	Uncertain significance (Jan 13, 2018)
2-208271573-T-A			Likely benign (May 24, 2022)
2-208271583-A-C		Fleck corneal dystrophy • Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 27, 2023)
2-208273573-C-T		Fleck corneal dystrophy	Benign (Jan 22, 2024)
2-208273589-G-A			Likely benign (Jul 01, 2022)
2-208273644-A-T			Benign (May 02, 2023)
2-208273646-C-A		Fleck corneal dystrophy	Uncertain significance (Jan 13, 2018)
2-208273653-C-T			Uncertain significance (Sep 27, 2022)
2-208273668-T-G			Uncertain significance (Jan 01, 2024)
2-208273690-A-G		Fleck corneal dystrophy	Benign (Oct 11, 2023)
2-208273703-G-A		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
2-208273718-C-T		Fleck corneal dystrophy • Inborn genetic diseases	Uncertain significance (May 31, 2023)
2-208273719-G-A		Fleck corneal dystrophy	Uncertain significance (May 20, 2023)
2-208273734-G-A			Likely pathogenic (Nov 27, 2019)
2-208276765-G-A		Inborn genetic diseases	Uncertain significance (Dec 20, 2022)
2-208276799-G-A		Inborn genetic diseases	Uncertain significance (Dec 04, 2024)
2-208277621-C-T		PIKFYVE-related disorder • Inborn genetic diseases	Uncertain significance (Dec 07, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PIKFYVE	protein_coding	protein_coding	ENST00000264380	41	92485

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000111	1.00	125660	0	88	125748	0.000350

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.05	928	1.12e+3	0.828	0.0000598	13870
Missense in Polyphen		289	436.58	0.66196		5297
Synonymous	0.118	392	395	0.992	0.0000209	3949
Loss of Function	7.15	35	119	0.294	0.00000711	1347

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00150	0.00143
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000490	0.000489
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000361	0.000360
Middle Eastern	0.000490	0.000489
South Asian	0.0000980	0.0000980
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The PI(3,5)P2 regulatory complex regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Catalyzes the phosphorylation of phosphatidylinositol 3-phosphate on the fifth hydroxyl of the myo- inositol ring, to form phosphatidylinositol 3,5-bisphosphate. Required for endocytic-vacuolar pathway and nuclear migration. Plays a role in the biogenesis of endosome carrier vesicles (ECV)/ multivesicular bodies (MVB) transport intermediates from early endosomes. {ECO:0000269|PubMed:17556371}.
• Disease: DISEASE: Corneal dystrophy, fleck (CFD) [MIM:121850]: A form of stromal corneal dystrophy characterized by numerous small white flecks scattered in all levels of the stroma, with configurations varying from semicircular to wreath-like, curvilinear, or punctate. Although CFD may occasionally cause mild photophobia, patients are typically asymptomatic and have normal vision. {ECO:0000269|PubMed:15902656}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Inositol phosphate metabolism - Homo sapiens (human);Phagosome - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Phosphatidylinositol signaling system - Homo sapiens (human);Phosphatidylinositol Phosphate Metabolism;Joubert syndrome;Inositol Metabolism;Metabolism of lipids;Metabolism;3-phosphoinositide biosynthesis;superpathway of inositol phosphate compounds;Synthesis of PIPs at the Golgi membrane;Synthesis of PIPs at the early endosome membrane;Synthesis of PIPs at the late endosome membrane;PI Metabolism;Phospholipid metabolism (Consensus)

Recessive Scores

• pRec: 0.432

Intolerance Scores

• loftool: 0.350
• rvis_EVS: -1.4
• rvis_percentile_EVS: 4.16

Haploinsufficiency Scores

• pHI: 0.401
• hipred: Y
• hipred_score: 0.652
• ghis: 0.632

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.986

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Pikfyve
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); pigmentation phenotype; embryo phenotype

Gene ontology

• Biological process: phosphatidylinositol biosynthetic process;receptor-mediated endocytosis;myelin assembly;protein localization to nucleus;intracellular signal transduction;phosphatidylinositol-3-phosphate biosynthetic process;retrograde transport, endosome to Golgi;phosphatidylinositol phosphorylation;phosphatidylinositol 5-phosphate metabolic process;regulation of autophagosome assembly
• Cellular component: Golgi membrane;cytosol;cell-cell junction;endosome membrane;vesicle membrane;early endosome membrane;late endosome membrane;membrane raft;perinuclear region of cytoplasm
• Molecular function: 1-phosphatidylinositol-3-phosphate 5-kinase activity;protein binding;ATP binding;zinc ion binding;1-phosphatidylinositol-4-phosphate 5-kinase activity;phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity