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.

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.

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			26	7		33
nonsense		1				1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			9	4		13
Total	0	1	35	11	0

Variants in ZFYVE19

This is a list of pathogenic ClinVar variants found in the ZFYVE19 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-40807356-C-A			Likely benign (May 27, 2022)
15-40807361-G-A			Likely benign (May 15, 2023)
15-40807371-C-G		not specified	Uncertain significance (Nov 06, 2023)
15-40807379-G-T			Uncertain significance (Aug 16, 2022)
15-40807379-GC-TT			Uncertain significance (Jun 29, 2023)
15-40807388-T-G			Uncertain significance (Oct 04, 2022)
15-40807393-A-C			Uncertain significance (Feb 20, 2022)
15-40807398-C-T			Uncertain significance (Nov 23, 2022)
15-40807402-C-T			Likely benign (May 22, 2023)
15-40807404-G-A			Likely benign (Aug 24, 2022)
15-40807424-A-G			Uncertain significance (Nov 29, 2022)
15-40807429-C-G			Uncertain significance (Oct 04, 2022)
15-40807430-T-G			Uncertain significance (Jan 11, 2022)
15-40807599-G-A		not specified	Uncertain significance (Oct 16, 2023)
15-40807615-C-G		not specified	Uncertain significance (Jul 30, 2023)
15-40807696-G-A		not specified	Uncertain significance (Oct 29, 2021)
15-40807714-G-A		not specified	Uncertain significance (Jan 29, 2024)
15-40807728-G-A		not specified	Uncertain significance (Apr 18, 2023)
15-40807792-A-T		not specified	Uncertain significance (Aug 16, 2021)
15-40807815-A-G		Cholestasis, progressive familial intrahepatic, 9	Pathogenic (Apr 27, 2022)
15-40807842-G-A		not specified	Uncertain significance (Feb 28, 2023)
15-40809153-C-G		Cholestasis, progressive familial intrahepatic, 9	Pathogenic (Apr 27, 2022)
15-40809177-C-T		not specified	Likely benign (Apr 17, 2023)
15-40809213-G-A		Cholestasis, progressive familial intrahepatic, 9	Uncertain significance (Mar 25, 2024)
15-40809218-C-T		Cholestasis, progressive familial intrahepatic, 9	Pathogenic (Apr 27, 2022)

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