VPS4A

Chr 16q23.1

vacuolar protein sorting 4 homolog A

Aliases:: VPS4, VPS4-1, FLJ22197, SKD2, SKD1
MANE:: ENST00000254950.13

OMIM: 609982 ↗NCBI: 27183 ↗Ensembl ↗

Annotations refreshed 10 hours ago.

Predicted protein structure

AlphaFold predicted structure

VPS4A · Q9UN37

v62025-08-01

Predicted Aligned Error matrix for VPS4A — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

85.7/ 100

Confident

437 residues

Confidence breakdown

Very high(≥ 90)59%
Confident(70–90)28%
Low(50–70)8%
Very low(< 50)6%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Bilateral congenital or childhood onset cataracts
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Childhood onset dystonia, chorea or related movement disorder
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Rare anaemia
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
COVID-19 research
Unknown

Disease associations (Open Targets)

cerebellar hypoplasia-intellectual disability-congenital microcephaly-dystonia-anemia-growth retardation syndrome
0.75
viral infectious disease
0.47
HIV infectious disease
0.46
hereditary disease
0.19
breast carcinoma
0.15
cancer
0.09
early-onset non-syndromic cataract
0.09
Posterior polar cataract
0.08
amyotrophic lateral sclerosis
0.08
Total congenital cataract
0.08

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Vacuolar protein sorting-associated protein 4A

Involved in late steps of the endosomal multivesicular bodies (MVB) pathway. Recognizes membrane-associated ESCRT-III assemblies and catalyzes their disassembly, possibly in combination with membrane fission. Redistributes the ESCRT-III components to the cytoplasm for further rounds of MVB sorting. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. It is required for proper accomplishment of various processes including the regulation of endosome size, primary cilium organization, mitotic spindle organization, chromosome segregation, and nuclear envelope sealing and spindle disassembly during anaphase (PubMed:33186545). Involved in cytokinesis: retained at the midbody by ZFYVE19/ANCHR and CHMP4C until abscission checkpoint signaling is terminated at late cytokinesis. It is then released following dephosphorylation of CHMP4C, leading to abscission (PubMed:24814515). VPS4A/B are required for the exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). Critical for normal erythroblast cytokinesis and correct erythropoiesis (PubMed:33186543)