ZFYVE19

zinc finger FYVE-type containing 19, the group of Zinc fingers FYVE-type

Basic information

Region (hg38): 15:40807086-40815084

Links

ENSG00000166140 ∙ NCBI:84936 ∙ OMIM:619635 ∙ HGNC:20758 ∙ Uniprot:Q96K21 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cholestasis, progressive familial intrahepatic, 9 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cholestasis, progressive familial intrahepatic, 9	AR	Gastrointestinal	The condition involves sequelae of cholestasis, and medical management (with ursodeoxycholic acid) has been described as beneficial; Liver transplant has been described	Gastrointestinal	32737136; 33853651

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZFYVE19 gene.

• not_specified (62 variants)
• Cholestasis,_progressive_familial_intrahepatic,_9 (9 variants)
• not_provided (4 variants)
• ZFYVE19-related_disorder (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZFYVE19 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001077268.2. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1		1
missense	1		57	8		66
nonsense	5	1				6
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)		1				1
Total	6	2	57	9	0

Highest pathogenic variant AF is 0.000029737897

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZFYVE19	protein_coding	protein_coding	ENST00000355341	11	7484

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.20e-14	0.142	124740	0	84	124824	0.000337

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.445	251	272	0.924	0.0000153	2989
Missense in Polyphen		62	73.807	0.84003		883
Synonymous	0.135	102	104	0.983	0.00000546	943
Loss of Function	0.942	24	29.5	0.813	0.00000171	281

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000386	0.000386
Ashkenazi Jewish	0.00	0.00
East Asian	0.00201	0.00200
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.000239	0.000238
Middle Eastern	0.00201	0.00200
South Asian	0.000230	0.000229
Other	0.000167	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Key regulator of abscission step in cytokinesis: part of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage. Together with CHMP4C, required to retain abscission-competent VPS4 (VPS4A and/or VPS4B) at the midbody ring until abscission checkpoint signaling is terminated at late cytokinesis. Deactivation of AURKB results in dephosphorylation of CHMP4C followed by its dissociation from ZFYVE19/ANCHR and VPS4 and subsequent abscission. {ECO:0000269|PubMed:24814515}.
• Disease: DISEASE: Note=A chromosomal aberration involving ZFYVE19 is associated with acute myeloblastic leukemia (AML). Translocation t(11;15)(q23;q14) with KMT2A/MLL1 (PubMed:12618766). {ECO:0000269|PubMed:12618766}.

Intolerance Scores

• loftool: 0.737
• rvis_EVS: 1.62
• rvis_percentile_EVS: 96.01

Haploinsufficiency Scores

• pHI: 0.0323
• hipred: N
• hipred_score: 0.170
• ghis: 0.425

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.465

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Zfyve19

Gene ontology

• Biological process: abscission;negative regulation of cytokinesis;mitotic cytokinesis checkpoint;cell division
• Cellular component: cytoplasm;centrosome;midbody;cleavage furrow;Flemming body
• Molecular function: protein binding;phosphatidylinositol-3-phosphate binding;metal ion binding