NHLRC3

protein-coding

NHL repeat containing 3

Gene summary

This gene encodes a protein containing NCL-1, HT2A and Lin-41 (NHL) family repeats. Mammalian NHL-repeat containing proteins may be involved in a variety of enzymatic processes, including protein modification through ubiquitination. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Aug 2012]

MANE transcript

NM_001012754.4

Inheritance

—

ClinVar variants

U:51B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr13:39,038,306-39,050,109

External References & Databases

Ensembl (ENSG00000188811)

Transcript & Mutation Effects

hg38 • Region Span ~11.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NHLRC3 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 46

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001012754.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			49 clinvar	1 clinvar		50
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	51	1	0	52

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001012754.4	RefSeq	NP_001012772.1	7	MANE Select
ENST00000379600.8	Ensembl	ENSP00000368920.3	7	MANE Select
NM_001017370.3	RefSeq	NP_001017370.1	6	Standard
ENST00000379599.6	Ensembl	ENSP00000368919.2	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neutrophil degranulation
Innate Immune System
Immune System

Biological Process

protein polyubiquitination
proteasome-mediated ubiquitin-dependent protein catabolic process
neutrophil degranulation

Molecular Function

ubiquitin protein ligase activity

Cellular Component

extracellular region
azurophil granule lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000379600
Coding exons: 7
Length: 11804
Individuals with no LoFs: 125656
Homozygous LoFs: 0
Heterozygous LoFs: 92
Defined: 125748
p: 0.000366

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.293	171	182	0.939	0.00000854	2246
Missense (PolyPhen)		55	63.695	0.86349		782
Synonymous	0.546	62	67.7	0.916	0.00000324	691
Loss of Function	1.54	10	16.8	0.595	8.97e-7	189

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00040	0.00040	rare
South Asian	0.0011	0.0011	notable
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0968

Intolerance Scores

LoFtool: 0.326
RVIS EVS: 0.62
RVIS percentile EVS: 83.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.508

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium