GeneBe

ZFYVE9

protein-coding

zinc finger FYVE-type containing 9, the group of Zinc fingers FYVE-type

Gene summary

This gene encodes a double zinc finger motif-containing protein that participates in the transforming growth factor-beta (TGFB) signalling pathway. The encoded protein interacts directly with SMAD2 and SMAD3, and recruits SMAD2 to the TGFB receptor. There are multiple pseudogenes for this gene on chromosomes 2, 15, and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

Previous symbols:
  • MADHIP

MANE transcript

NM_004799.4

Inheritance

—

ClinVar variants

U:179B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.2

Max pathogenic AF

—

Genomic locus

chr1:52,142,089-52,348,671

External References & Databases

Ensembl (ENSG00000157077)NCBI Gene (9372)OMIM (603755)HGNC:6775GenCCUniProt (O95405)AlphaFoldClinVar (ZFYVE9)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~206.6 kb
Loading mutation effect viewer...

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 ZFYVE9 variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 177
not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004799.4. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
2
clinvar
 3
missense
170
clinvar
9
clinvar
 179
nonsense
0
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
7
clinvar
 7
Total00179110190
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_004799.4RefSeqNP_004790.217MANE Select
ENST00000287727.8EnsemblENSP00000287727.317MANE Select
NM_007324.5RefSeqNP_015563.216Standard
ENST00000357206.6EnsemblENSP00000349737.216Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
zfyve9aDanio rerio

Structure: spinal cord

Quality: process quality

abnormal

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-Ncore
  • TGF-beta Signaling Pathway
  • TGF-beta Receptor Signaling

Biological Process

  • proteolysis
  • endocytosis
  • transforming growth factor beta receptor signaling pathway
  • endosomal transport

Molecular Function

  • protein binding
  • 1-phosphatidylinositol binding
  • serine-type peptidase activity
  • protein domain specific binding
  • metal ion binding

Cellular Component

  • early endosome
  • cytosol
  • early endosome membrane
  • protein-containing complex
  • intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000287727
Coding exons
17
Length
204313
Individuals with no LoFs
125732
Homozygous LoFs
0
Heterozygous LoFs
14
Defined
125746
p
0.0000557
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.806047420.8140.00003589455
Missense (PolyPhen)162295.910.547463833
Synonymous0.8502542720.9340.00001402688
Loss of Function5.571156.00.1960.00000266746

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000630.000062rare
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian0.0000540.000054rare
Finnish00.0absent
European (Non-Finnish)0.0000710.000070rare
South Asian0.0000990.000098rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Early endosomal protein that functions to recruit SMAD2/SMAD3 to intracellular membranes and to the TGF-beta receptor. Plays a significant role in TGF-mediated signaling by regulating the subcellular location of SMAD2 and SMAD3 and modulating the transcriptional activity of the SMAD3/SMAD4 complex. Possibly associated with TGF-beta receptor internalization. {ECO:0000269|PubMed:15356634, ECO:0000269|PubMed:9865696}.;

Intolerance Scores

LoFtool
0.532
RVIS EVS
0.14
RVIS percentile EVS
63.65

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.962

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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