GENE REFERENCE / HGNC:21576

NHLRC1

NHL repeat containing E3 ubiquitin protein ligase 1

protein-coding gene6p22.3Gene information

What does this gene do?

The NHLRC1 gene provides instructions for making a protein called malin. Although this protein is active in cells throughout the body, it appears to play a critical role in the survival of nerve cells (neurons) in the brain.

Malin is part of the cell machinery that breaks down (degrades) unwanted proteins within cells. The protein tags damaged and excess proteins with a molecule called ubiquitin, which serves as a signal to degrade these proteins. This process, which is known as the ubiquitin-proteasome system, acts as the cell's quality control system by disposing of damaged, misshapen, and excess proteins. This system also regulates the level of proteins involved in several critical cell activities such as the timing of cell division and growth. Malin belongs to a group of proteins in the ubiquitin-proteasome system called E3 protein-ubiquitin ligases.

Malin targets several proteins for degradation, including laforin (which is produced from the EPM2A gene). The interaction between malin and laforin likely plays a critical role in regulating the production of a complex sugar called glycogen. Glycogen is a major source of stored energy in the body. The body stores this sugar in the liver and muscles, breaking it down when it is needed for fuel. Researchers believe that malin and laforin may prevent a potentially damaging buildup of glycogen in tissues that do not normally store this molecule, such as those of the nervous system.

Source: MedlinePlus, National Library of Medicine. Source publication: 2020-08-18. Source review: 2009-07.

ClinGen reviews

ClinGen reviews the evidence linking a particular gene to a condition. Each rating below describes the strength of that link. It does not classify a variant in your DNA file.

Condition	Inheritance	Evidence
Lafora diseaseMONDO:0009697 · Evaluated 2020-03-03	Autosomal recessive	DefinitiveEpilepsy Gene Curation Expert Panel

ClinVar records

These numbers show what has been submitted to ClinVar. They cannot tell you how likely you are to have a condition.

Submitted alleles: 402
Submissions for variants in or overlapping this gene: 637
Submissions explicitly reporting this gene: 615
Alleles reported pathogenic / likely pathogenic: 50
VariationIDs with uncertain significance: 216
VariationIDs with conflicting classifications: 17

The rows count different things: alleles, submissions or VariationIDs. Their categories can overlap, so do not add them together. Pathogenic/likely pathogenic counts exclude structural variants that merely overlap a gene. A dash in the source means “not reported,” not zero.

NCBI produces the gene-summary file each week using counts recorded at the start of the month. The numbers may differ from those on the live ClinVar website. Read the field definitions ↗

View this gene in ClinVar ↗

YOUR DNA FILE

Can your DNA file tell you about NHLRC1?

From a DNA test kit (such as 23andMe, AncestryDNA or MyHeritage). These kits check a fixed list of about 600,000 to 700,000 positions across your whole genome. ClinVar lists 50 alleles in NHLRC1 reported as pathogenic or likely pathogenic. A kit checks only some of these positions, and often none of them.

From whole genome sequencing (a VCF file). Sequencing reads most of your genome. Your file lists the places where your DNA differs from the reference genome. Some regions are hard to sequence, including parts of some genes that have near-identical copies elsewhere, and a VCF file does not record which positions were read well.

If a variant is not in your file, that does not mean you don’t have it.

What BioDecode checks

BioDecode compares every variant in your file with ClinVar, on your own computer. For each match, it shows the ClinVar classification, the review status and the condition it was reported for. Your file is not uploaded.

A ClinVar classification applies to one particular variant and the condition it was reported for. It does not tell you about other variants in NHLRC1.

BioDecode cannot fill gaps in your test, diagnose a condition or replace clinical testing.

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