Seroatlas · Human Serome Atlas

KLHL3

Kelch-like protein 3

Also known as: KIAA1129, KLHL3_HUMAN

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

Protein identityUniProt · HPA

UniProt accession
Q9UH77
Gene
KLHL3
Ensembl
ENSG00000146021
Chromosome
5
Canonical length
587 aa
Protein class
Disease related genes, Human disease related genes, Potential drug targets, Predicted intracellular proteins, Transporters
Quaternary structure
Homodimer

OverviewNCBI Gene

This gene is ubiquitously expressed and encodes a full-length protein which has an N-terminal BTB domain followed by a BACK domain and six kelch-like repeats in the C-terminus. These kelch-like repeats promote substrate ubiquitination of bound proteins via interaction of the BTB domain with the CUL3 (cullin 3) component of a cullin-RING E3 ubiquitin ligase (CRL) complex. Muatations in this gene cause pseudohypoaldosteronism type IID (PHA2D); a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Mar 2012]

Canonical amino-acid sequenceUniProt

587 residues, UniProt reviewed canonical sequence.

>Q9UH77|KLHL3
     1  MEGESVKLSS QTLIQAGDDE KNQRTITVNP AHMGKAFKVM NELRSKQLLC DVMIVAEDVE
    61  IEAHRVVLAA CSPYFCAMFT GDMSESKAKK IEIKDVDGQT LSKLIDYIYT AEIEVTEENV
   121  QVLLPAASLL QLMDVRQNCC DFLQSQLHPT NCLGIRAFAD VHTCTDLLQQ ANAYAEQHFP
   181  EVMLGEEFLS LSLDQVCSLI SSDKLTVSSE EKVFEAVISW INYEKETRLE HMAKLMEHVR
   241  LPLLPRDYLV QTVEEEALIK NNNTCKDFLI EAMKYHLLPL DQRLLIKNPR TKPRTPVSLP
   301  KVMIVVGGQA PKAIRSVECY DFEEDRWDQI AELPSRRCRA GVVFMAGHVY AVGGFNGSLR
   361  VRTVDVYDGV KDQWTSIASM QERRSTLGAA VLNDLLYAVG GFDGSTGLAS VEAYSYKTNE
   421  WFFVAPMNTR RSSVGVGVVE GKLYAVGGYD GASRQCLSTV EQYNPATNEW IYVADMSTRR
   481  SGAGVGVLSG QLYATGGHDG PLVRKSVEVY DPGTNTWKQV ADMNMCRRNA GVCAVNGLLY
   541  VVGGDDGSCN LASVEYYNPV TDKWTLLPTN MSTGRSYAGV AVIHKSL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against KLHL3 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
45 nTPM

Expression across tissuesHPA

Tissue

  • cerebellum: 45 nTPM
  • heart muscle: 16 nTPM
  • thyroid gland: 8.8 nTPM
  • basal ganglia: 8.3 nTPM
  • kidney: 8.2 nTPM
  • pituitary gland: 8.1 nTPM

Single-cell type

  • distal convoluted tubule cells: 669 nCPM
  • cardiomyocytes: 181 nCPM
  • brain excitatory neurons: 159 nCPM
  • renal connecting tubule cells: 149 nCPM
  • retinal pigment epithelial cells: 124 nCPM
  • brain inhibitory neurons: 117 nCPM

Immune cell

  • memory CD4 T-cell: 0.9 nTPM
  • naive CD4 T-cell: 0.9 nTPM
  • NK-cell: 0.7 nTPM
  • eosinophil: 0.5 nTPM
  • naive CD8 T-cell: 0.5 nTPM
  • plasmacytoid DC: 0.4 nTPM

Brain region

  • cerebellum: 58 nTPM
  • white matter: 28 nTPM
  • basal ganglia: 23 nTPM
  • hippocampal formation: 22 nTPM
  • cerebral cortex: 21 nTPM
  • amygdala: 20 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about KLHL3.

Disease | AllUniProt

Conditions KLHL3 is implicated in, by any mechanism.

Disease | GeneticClinVar

29 pathogenic / likely-pathogenic of 407 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

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)
0.34
gnomAD pLI
0.94
gnomAD missense Z
2.99
DepMap mean gene effect
-0.11
DepMap dependency class
none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of KLHL3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads KLHL3 as an antibody target. Whether an autoantibody or antibody against KLHL3 could matter depends on whether native KLHL3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

KLHL3 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 KLHL3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/KLHL3. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

© 2026 · Seroatlas, Discover Oregon LLC · Terms of use

Loading the interactive Seroatlas protein explorer...