Seroatlas · Human Serome Atlas

KLHL12

Kelch-like protein 12

Also known as: C3IP1, KLH12_HUMAN

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

Protein identityUniProt · HPA

UniProt accession: Q53G59
Gene: KLHL12
Ensembl: ENSG00000117153
Chromosome: 1
Canonical length: 568 aa
Protein class: Predicted intracellular proteins
Subcellular location: Vesicles,Centriolar satellite

OverviewNCBI Gene

This gene encodes a member of the KLHL (Kelch-like) family of proteins. This protein has been identified as an autoantigen in the autoimmune disease Sjogren's syndrome and as a potential biomarker in primary biliary cirrhosis. This protein may act as a substrate adaptor of the Cullin-3 ubiquitin ligase complex to promote substrate-specific ubiquitylation. Ubiquitylation by this complex has been shown to regulate the Wnt signaling pathway as well as COPII vesicle coat size. A pseudogene has been identified on chromosome 22. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

Canonical amino-acid sequenceUniProt

568 residues, UniProt reviewed canonical sequence.

>Q53G59|KLHL12
     1  MGGIMAPKDI MTNTHAKSIL NSMNSLRKSN TLCDVTLRVE QKDFPAHRIV LAACSDYFCA
    61  MFTSELSEKG KPYVDIQGLT ASTMEILLDF VYTETVHVTV ENVQELLPAA CLLQLKGVKQ
   121  ACCEFLESQL DPSNCLGIRD FAETHNCVDL MQAAEVFSQK HFPEVVQHEE FILLSQGEVE
   181  KLIKCDEIQV DSEEPVFEAV INWVKHAKKE REESLPNLLQ YVRMPLLTPR YITDVIDAEP
   241  FIRCSLQCRD LVDEAKKFHL RPELRSQMQG PRTRARLGAN EVLLVVGGFG SQQSPIDVVE
   301  KYDPKTQEWS FLPSITRKRR YVASVSLHDR IYVIGGYDGR SRLSSVECLD YTADEDGVWY
   361  SVAPMNVRRG LAGATTLGDM IYVSGGFDGS RRHTSMERYD PNIDQWSMLG DMQTAREGAG
   421  LVVASGVIYC LGGYDGLNIL NSVEKYDPHT GHWTNVTPMA TKRSGAGVAL LNDHIYVVGG
   481  FDGTAHLSSV EAYNIRTDSW TTVTSMTTPR CYVGATVLRG RLYAIAGYDG NSLLSSIECY
   541  DPIIDSWEVV TSMGTQRCDA GVCVLREK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against KLHL12 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): 0.25
Highest tissue expression: 42 nTPM

Expression across tissuesHPA

Tissue

testis: 42 nTPM
retina: 23 nTPM
rectum: 22 nTPM
epididymis: 21 nTPM
tonsil: 21 nTPM
hypothalamus: 21 nTPM

Single-cell type

early spermatids: 147 nCPM
late spermatids: 119 nCPM
late primary spermatocytes: 104 nCPM
differentiating spermatogonia: 48 nCPM
undifferentiated spermatogonia: 47 nCPM
sertoli cells: 43 nCPM

Immune cell

eosinophil: 16 nTPM
non-classical monocyte: 13 nTPM
intermediate monocyte: 12 nTPM
T-reg: 11 nTPM
myeloid DC: 11 nTPM
MAIT T-cell: 10 nTPM

Brain region

hypothalamus: 34 nTPM
pons: 30 nTPM
cerebral cortex: 29 nTPM
midbrain: 28 nTPM
thalamus: 27 nTPM
basal ganglia: 27 nTPM

ReferencesPubMed · IEDB

Publications for KLHL12 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Reference: AutoantibodyPubMed

5 publications

Autoantibodies Against Proteins Previously Associated With Autoimmunity in Adult and Pediatric Patients With COVID-19 and Children With MIS-C.
2022 · Front Immunol · RCR 2.7 · 32 citations
Novel Anti-Hexokinase 1 Antibodies Are Associated With Poor Prognosis in Patients With Primary Biliary Cholangitis.
2020 · Am J Gastroenterol · RCR 1.7 · 27 citations
Diagnostic and Clinical Value of Specific Autoantibodies against Kelch-like 12 Peptide and Nuclear Envelope Proteins in Patients with Primary Biliary Cholangitis.
2022 · Biomedicines · RCR 1.4 · 12 citations
Identification of specific autoantigens in Sjögren's syndrome by SEREX.
2005 · Immunology · RCR 1.2 · 61 citations
Detection of anti-kelch-like 12 and anti-hexokinase 1 antibodies in primary biliary cholangitis patients in China.
2021 · Rev Esp Enferm Dig · RCR 0.7 · 9 citations

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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): 0.52
gnomAD pLI: 0.03
gnomAD missense Z: 2.83
DepMap mean gene effect: -0.15
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 14% 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 KLHL12 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 KLHL12 as an antibody target. Whether an autoantibody or antibody against KLHL12 could matter depends on whether native KLHL12 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

KLHL12 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.

Source-annotated serology context

The source annotations explicitly mention antibody, autoantibody, autoantigen, or autoimmune context. This is biological context, not study-specific reactivity.

This protein has been identified as an autoantigen in the autoimmune disease Sjogren's syndrome and as a potential biomarker in primary biliary cirrhosis.

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