Seroatlas · Human Serome Atlas

DENND3

DENN domain-containing protein 3

Also known as: DEND3_HUMAN, KIAA0870

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: A2RUS2
Gene: DENND3
Ensembl: ENSG00000105339
Chromosome: 8
Canonical length: 1198 aa
Protein class: Predicted intracellular proteins, Predicted membrane proteins
Subcellular location: Vesicles,Cytosol

OverviewNCBI Gene

Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in endosome to lysosome transport; protein catabolic process; and regulation of Rab protein signal transduction. Predicted to be located in cytosol. Predicted to be active in cytoplasmic vesicle. [provided by Alliance of Genome Resources, Jul 2025]

Canonical amino-acid sequenceUniProt

1198 residues, UniProt reviewed canonical sequence.

>A2RUS2|DENND3
     1  MRSLRKKREK PRPEQWKGLP GPPRAPEPED VAVPGGVDLL TLPQLCFPGG VCVATEPKED
    61  CVHFLVLTDV CGNRTYGVVA QYYRPLHDEY CFYNGKTHRE CPGCFVPFAV CVVSRFPYYN
   121  SLKDCLSCLL ALLKPCKDFE VDSHIKDFAA KLSLIPSPPP GPLHLVFNMK SLQIVLPARA
   181  DPESPILDLD LHLPLLCFRP EKVLQILTCI LTEQRIVFFS SDWALLTLVT ECFMAYLYPL
   241  QWQHPFVPIL SDQMLDFVMA PTSFLMGCHL DHFEEVSKEA DGLVLINIDH GSITYSKSTD
   301  DNVDIPDVPL LAAQTFIQRV QSLQLHHELH AAHLLSSTDL KEGRAHRRSW QQKLNCQIQQ
   361  TTLQLLVSIF RDVKNHLNYE HRVFNSEEFL KTRAPGDHQF YKQVLDTYMF HSFLKARLNR
   421  RMDAFAQMDL DTQSEEDRIN GMLLSPRRPT VEKRASRKSS HLHVTHRRMV VSMPNLQDIA
   481  MPELAPRNSS LRLTDTAGCR GSSAVLNVTP KSPYTFKIPE IHFPLESKCV QAYHAHFVSM
   541  LSEAMCFLAP DNSLLLARYL YLRGLVYLMQ GQLLNALLDF QNLYKTDIRI FPTDLVKRTV
   601  ESMSAPEWEG AEQAPELMRL ISEILDKPHE ASKLDDHVKK FKLPKKHMQL GDFMKRVQES
   661  GIVKDASIIH RLFEALTVGQ EKQIDPETFK DFYNCWKETE AEAQEVSLPW LVMEHLDKNE
   721  CVCKLSSSVK TNLGVGKIAM TQKRLFLLTE GRPGYLEIST FRNIEEVRRT TTTFLLRRIP
   781  TLKIRVASKK EVFEANLKTE CDLWHLMVKE MWAGKKLADD HKDPHYVQQA LTNVLLMDAV
   841  VGTLQSPGAI YAASKLSYFD KMSNEMPMTL PETTLETLKH KINPSAGEAF PQAVDVLLYT
   901  PGHLDPAEKV EDAHPKLWCA LSEGKVTVFN ASSWTIHQHS FKVGTAKVNC MVMADQNQVW
   961  VGSEDSVIYI INVHSMSCNK QLTAHCSSVT DLIVQDGQEA PSNVYSCSMD GMVLVWNVST
  1021  LQVTSRFQLP RGGLTSIRLH GGRLWCCTGN SIMVMKMNGS LHQELKIEEN FKDTSTSFLA
  1081  FQLLPEEEQL WAACAGRSEV YIWSLKDLAQ PPQRVPLEDC SEINCMIRVK KQVWVGSRGL
  1141  GQGTPKGKIY VIDAERKTVE KELVAHMDTV RTLCSAEDRY VLSGSGREEG KVAIWKGE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against DENND3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.28
Highest tissue expression: 101 nTPM

Expression across tissuesHPA

Tissue

bone marrow: 101 nTPM
lung: 55 nTPM
blood vessel: 48 nTPM
spleen: 42 nTPM
adipose tissue: 41 nTPM
colon: 35 nTPM

Single-cell type

neutrophils: 805 nCPM
microglia: 303 nCPM
alveolar cells type 1: 302 nCPM
neutrophil progenitors: 272 nCPM
epicardial cells: 198 nCPM
monocytes: 136 nCPM

Immune cell

neutrophil: 41 nTPM
eosinophil: 35 nTPM
basophil: 25 nTPM
non-classical monocyte: 10 nTPM
intermediate monocyte: 8.1 nTPM
classical monocyte: 5.4 nTPM

Brain region

medulla oblongata: 83 nTPM
white matter: 77 nTPM
cerebral cortex: 71 nTPM
pons: 65 nTPM
midbrain: 64 nTPM
spinal cord: 59 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about DENND3.

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 234 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Hirschsprung disease, susceptibility to, 1

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.66
gnomAD pLI: 0
gnomAD missense Z: 2.37
DepMap mean gene effect: 0
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

guanyl-nucleotide exchange factor activity

Cellular components

Protein domainsUniProt · Pfam · InterPro

cDENN domain
WD40 repeat
dDENN domain
WD40/YVTN repeat-like-containing domain superfamily
WD40-repeat-containing domain superfamily
Tripartite DENN domain
DENN domain, C-terminal lobe
DENN Domain-Containing GEFs
WD domain, G-beta repeat
DENN (AEX-3) domain
DENND3-like, TPR repeats
DENND3-like, TPR repeats

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads DENND3 as an antibody target. Whether an autoantibody or antibody against DENND3 could matter depends on whether native DENND3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

DENND3 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label DENND3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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