NOL3

protein-coding

nucleolar protein 3, the group of Caspase recruitment domain containing

Gene summary

This gene encodes an anti-apoptotic protein that has been shown to down-regulate the enzyme activities of caspase 2, caspase 8 and tumor protein p53. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

MANE transcript

NM_001276309.3

Inheritance

ClinVar variants

U:46B:23

Top phenotype

Myoclonus, familial,1

gnomAD constraint

pLI —, LoF o/e 0.85

Max pathogenic AF

—

Genomic locus

chr16:67,170,154-67,175,737

External References & Databases

Ensembl (ENSG00000140939)

Transcript & Mutation Effects

hg38 • Region Span ~5.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

myoclonus, familial, 1LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100093

Submitter: Labcorp Genetics (formerly Invitae)

myoclonus, familialSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0013981

Submitter: Orphanet

myoclonus, familial, 1LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100093

Submitter: Ambry Genetics

myoclonus, familial, 1LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0100093

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Myoclonus, familial,1AD

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Comments: The condition may be exacerbated by alcohol, and alleviated by medical treatment (eg, with clonazepam)

Refs: 22926851

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NOL3 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 65

not providedTotal: 9

NOL3-related disorderTotal: 6

Myoclonus, familial, 1Total: 2

Myoclonus, familialTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001276309.3. 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			12 clinvar	9 clinvar		21
missense			32 clinvar	12 clinvar		44
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar	1 clinvar		2
splice donor/acceptor (+/-2bp)				1 clinvar		1
Total	0	0	46	23	0	69

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 85 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001276309.3	RefSeq	NP_001263238.1	3	MANE Select
ENST00000564992.2	Ensembl	ENSP00000457720.2	3	MANE Select
NM_001185057.3	RefSeq	NP_001171986.1	3	Standard
NM_001276307.3	RefSeq	NP_001263236.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

response to hypoxia
blood vessel remodeling
response to ischemia
mRNA splice site selection
RNA splicing

Molecular Function

RNA binding
death receptor binding
calcium ion binding
protein binding
death effector domain binding

Cellular Component

nucleolus
mitochondrion
cytosol
membrane
sarcoplasmic reticulum

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000568146
Coding exons: 3
Length: 5587
Individuals with no LoFs: 124520
Homozygous LoFs: 1
Heterozygous LoFs: 171
Defined: 124692
p: 0.000690

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.129	131	127	1.03	0.00000679	1358
Missense (PolyPhen)		50	45.436	1.1005		529
Synonymous	0.653	55	61.5	0.894	0.00000331	474
Loss of Function	0.374	6	7.07	0.848	3.03e-7	75

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00026	0.00026	rare
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0014	0.0014	notable
South Asian	0	0.0	absent
Other	0.0012	0.0012	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Isoform 1: May be involved in RNA splicing. {ECO:0000269|PubMed:10196175}.;
Disease: DISEASE: Myoclonus, familial cortical (FCM) [MIM:614937]: An autosomal dominant neurologic condition characterized by adult onset of cortical myoclonus manifest as involuntary jerks or movements affecting the face and limbs. Affected individuals can also experience falls without seizure activity or loss of consciousness. {ECO:0000269|PubMed:22926851, ECO:0000269|PubMed:25138476}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.140

Intolerance Scores

LoFtool: 0.516
RVIS EVS: 0.13
RVIS percentile EVS: 62.74

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

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