ZFYVE16

protein-coding

zinc finger FYVE-type containing 16, the group of Protein phosphatase 1 regulatory subunits|Zinc fingers FYVE-type

Gene summary

This gene encodes an endosomal protein that belongs to the FYVE zinc finger family of proteins. The encoded protein is thought to regulate membrane trafficking in the endosome. This protein functions as a scaffold protein in the transforming growth factor-beta signaling pathway and is involved in positive and negative feedback regulation of the bone morphogenetic protein signaling pathway. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

MANE transcript

NM_001284236.3

Inheritance

—

ClinVar variants

P:1U:202B:21

Top phenotype

Dextrocardia

gnomAD constraint

pLI —, LoF o/e 0.51

Max pathogenic AF

—

Genomic locus

chr5:80,408,013-80,483,379

External References & Databases

Ensembl (ENSG00000039319)

Transcript & Mutation Effects

hg38 • Region Span ~75.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZFYVE16 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 205

not providedTotal: 6

DextrocardiaTotal: 2

Cerebral arteriovenous malformationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001284236.3. 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			2 clinvar	1 clinvar	1 clinvar	4
missense		1 clinvar	194 clinvar	17 clinvar	2 clinvar	214
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	1	202	18	3	224

Highest pathogenic variant AF is 6.8417796e-7

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 42 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001284236.3	RefSeq	NP_001271165.2	17	MANE Select
ENST00000505560.5	Ensembl	ENSP00000426848.1	17	MANE Select
NM_001105251.4	RefSeq	NP_001098721.2	17	Standard
NM_001284237.2	RefSeq	NP_001271166.2	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

TGF-beta signaling pathway - Homo sapiens (human)
Endocytosis - Homo sapiens (human)
TGF-beta Signaling Pathway
Signal Transduction
TGF_beta_Receptor

Biological Process

protein targeting to lysosome
signal transduction
vesicle organization
endosomal transport
regulation of endocytosis

Molecular Function

protein binding
1-phosphatidylinositol binding
phosphatidylinositol-3,4,5-trisphosphate binding
protein transporter activity
metal ion binding

Cellular Component

early endosome
cytosol
early endosome membrane
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000338008
Coding exons: 17
Length: 71338
Individuals with no LoFs: 125677
Homozygous LoFs: 0
Heterozygous LoFs: 64
Defined: 125741
p: 0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.144	757	768	0.985	0.0000357	10179
Missense (PolyPhen)		166	230.28	0.72086		3087
Synonymous	0.841	259	277	0.936	0.0000134	2884
Loss of Function	3.53	31	60.7	0.511	0.00000314	823

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.00051	0.00051	rare
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.00048	0.00042	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in regulating membrane trafficking in the endosomal pathway. Overexpression induces endosome aggregation. Required to target TOM1 to endosomes. {ECO:0000269|PubMed:11546807, ECO:0000269|PubMed:14613930}.;

Recessive Scores

pRec: 0.0976

Intolerance Scores

LoFtool: 0.932
RVIS EVS: 1.21
RVIS percentile EVS: 93.08

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.503

Gene Damage Prediction

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