ZFYVE19

protein-coding

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

Gene summary

Enables phosphatidylinositol-3-phosphate binding activity. Involved in midbody abscission; mitotic cytokinesis checkpoint signaling; and negative regulation of cytokinesis. Located in centrosome; cleavage furrow; and midbody. Implicated in progressive familial intrahepatic cholestasis. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001077268.2

Inheritance

ClinVar variants

P:9U:76B:25

Top phenotype

Cholestasis, progressive familial intrahepatic, 9

gnomAD constraint

pLI —, LoF o/e 0.81

Max pathogenic AF

—

Genomic locus

chr15:40,807,086-40,815,084

External References & Databases

Ensembl (ENSG00000166140)

Transcript & Mutation Effects

hg38 • Region Span ~8.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cholestasis, progressive familial intrahepatic, 9STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030800

Submitter: Labcorp Genetics (formerly Invitae)

cholestasis, progressive familial intrahepatic, 9STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030800

Submitter: PanelApp Australia

cholestasis, progressive familial intrahepatic, 9DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0030800

Submitter: G2P

Clinical Genomic Database (CGD)

Cholestasis, progressive familial intrahepatic, 9AR

Manifestation: Gastrointestinal

Intervention: Gastrointestinal

Rationale: The condition involves sequelae of cholestasis, and medical management (with ursodeoxycholic acid) has been described as beneficial; Liver transplant has been described

Refs: 32737136; 33853651

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZFYVE19 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 80

ZFYVE19-related disorderTotal: 29

Cholestasis, progressive familial intrahepatic, 9Total: 11

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001077268.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				13 clinvar		13
missense	1 clinvar		73 clinvar	12 clinvar		86
nonsense	5 clinvar	1 clinvar				6
start loss						0
frameshift		1 clinvar	2 clinvar			3
splice donor/acceptor (+/-2bp)		1 clinvar	1 clinvar			2
Total	6	3	76	25	0	110

Highest pathogenic variant AF is 0.000029737897

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001077268.2	RefSeq	NP_001070736.1	11	MANE Select
ENST00000355341.8	Ensembl	ENSP00000347498.4	11	MANE Select
NM_001258420.2	RefSeq	NP_001245349.1	10	Standard
NM_001258421.2	RefSeq	NP_001245350.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

abscission
negative regulation of cytokinesis
mitotic cytokinesis checkpoint
cell division

Molecular Function

protein binding
phosphatidylinositol-3-phosphate binding
metal ion binding

Cellular Component

cytoplasm
centrosome
midbody
cleavage furrow
Flemming body

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000355341
Coding exons: 11
Length: 7484
Individuals with no LoFs: 124740
Homozygous LoFs: 0
Heterozygous LoFs: 84
Defined: 124824
p: 0.000337

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.445	251	272	0.924	0.0000153	2989
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000064	rare
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0020	0.0020	notable
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00024	0.00024	rare
South Asian	0.00023	0.00023	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.465

Gene Damage Prediction

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