Seroatlas · Human Serome Atlas

NHLRC1

E3 ubiquitin-protein ligase NHLRC1

Also known as: bA204B7.2, EPM2B, NHLC1_HUMAN

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

Protein identityUniProt · HPA

UniProt accession
Q6VVB1
Gene
NHLRC1
Ensembl
ENSG00000187566
Chromosome
6
Canonical length
395 aa
Protein class
Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins
Subcellular location
Nucleoplasm,Cytosol

OverviewNCBI Gene

The protein encoded by this gene is a single subunit E3 ubiquitin ligase. Laforin is polyubiquitinated by the encoded protein. Defects in this intronless gene lead to an accumulation of laforin and onset of Lafora disease, also known as progressive myoclonic epilepsy type 2 (EPM2).[provided by RefSeq, Mar 2010]

Canonical amino-acid sequenceUniProt

395 residues, UniProt reviewed canonical sequence.

>Q6VVB1|NHLRC1
     1  MAAEASESGP ALHELMREAE ISLLECKVCF EKFGHRQQRR PRNLSCGHVV CLACVAALAH
    61  PRTLALECPF CRRACRGCDT SDCLPVLHLI ELLGSALRQS PAAHRAAPSA PGALTCHHTF
   121  GGWGTLVNPT GLALCPKTGR VVVVHDGRRR VKIFDSGGGC AHQFGEKGDA AQDIRYPVDV
   181  TITNDCHVVV TDAGDRSIKV FDFFGQIKLV IGGQFSLPWG VETTPQNGIV VTDAEAGSLH
   241  LLDVDFAEGV LRRTERLQAH LCNPRGVAVS WLTGAIAVLE HPLALGTGVC STRVKVFSSS
   301  MQLVGQVDTF GLSLYFPSKI TASAVTFDHQ GNVIVADTSG PAILCLGKPE EFPVPKPMVT
   361  HGLSHPVALT FTKENSLLVL DTASHSIKVY KVDWG

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NHLRC1 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)
0.27
Highest tissue expression
3.8 nTPM

Expression across tissuesHPA

Tissue

  • liver: 3.8 nTPM
  • skin: 3.6 nTPM
  • basal ganglia: 2.7 nTPM
  • cerebral cortex: 2.6 nTPM
  • epididymis: 2.4 nTPM
  • skeletal muscle: 2.4 nTPM

Single-cell type

  • megakaryocyte-erythroid progenitors: 5 nCPM
  • hepatocytes: 4.5 nCPM
  • pancreatic islet cells: 4.3 nCPM
  • epididymal clear cells: 4.1 nCPM
  • hofbauer cells: 4 nCPM
  • paneth cells: 3.9 nCPM

Immune cell

  • intermediate monocyte: 4.9 nTPM
  • myeloid DC: 4.7 nTPM
  • classical monocyte: 4.4 nTPM
  • memory B-cell: 2.3 nTPM
  • non-classical monocyte: 2.2 nTPM
  • total PBMC: 1.8 nTPM

Brain region

  • white matter: 8.6 nTPM
  • pons: 7 nTPM
  • cerebral cortex: 6.4 nTPM
  • basal ganglia: 6.1 nTPM
  • medulla oblongata: 5.9 nTPM
  • thalamus: 5.5 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NHLRC1.

Disease | AllUniProt

Conditions NHLRC1 is implicated in, by any mechanism.

Disease | GeneticClinVar

50 pathogenic / likely-pathogenic of 380 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)
0.88
gnomAD pLI
0.09
gnomAD missense Z
0.5
DepMap mean gene effect
0.08
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% 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 NHLRC1 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 NHLRC1 as an antibody target. Whether an autoantibody or antibody against NHLRC1 could matter depends on whether native NHLRC1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

NHLRC1 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 NHLRC1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/NHLRC1. 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).

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