NOL3

nucleolar protein 3, the group of Caspase recruitment domain containing

Basic information

Region (hg38): 16:67170154-67175737

Links

ENSG00000140939 ∙ NCBI:8996 ∙ OMIM:605235 ∙ HGNC:7869 ∙ Uniprot:O60936 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• myoclonus, familial, 1 (Limited), mode of inheritance: AD
• myoclonus, familial (Supportive), mode of inheritance: AD
• myoclonus, familial, 1 (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myoclonus, familial,1	AD	General	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	Neurologic	22926851
The condition may be exacerbated by alcohol, and alleviated by medical treatment (eg, with clonazepam)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NOL3 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NOL3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	3	1	5
missense			18	3		21
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1	2	2	5
Total	0	0	21	8	3

Variants in NOL3

This is a list of pathogenic ClinVar variants found in the NOL3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-67174004-C-T		not specified	Uncertain significance (Nov 20, 2023)
16-67174030-C-T		NOL3-related disorder	Benign (Sep 06, 2019)
16-67174148-C-T		not specified	Likely benign (Oct 06, 2023)
16-67174166-G-T		NOL3-related disorder	Likely benign (Jul 11, 2023)
16-67174199-G-A		not specified	Likely benign (Mar 11, 2024)
16-67174230-G-C		Myoclonus, familial, 1	Uncertain significance (Apr 01, 2020)
16-67174237-T-C			Uncertain significance (Oct 08, 2023)
16-67174244-G-A		NOL3-related disorder	Benign (Jul 15, 2019)
16-67174245-G-T		NOL3-related disorder	Likely benign (Feb 23, 2022)
16-67174264-A-G		not specified	Uncertain significance (Jun 13, 2022)
16-67174264-A-T		not specified	Uncertain significance (Oct 05, 2023)
16-67174323-C-A		not specified	Uncertain significance (May 18, 2023)
16-67174348-G-A		not specified	Uncertain significance (Apr 09, 2024)
16-67174351-T-C		not specified	Uncertain significance (Aug 08, 2022)
16-67174368-G-A		not specified	Uncertain significance (Aug 28, 2023)
16-67174396-T-A		not specified	Uncertain significance (Feb 07, 2024)
16-67174622-C-A		not specified	Uncertain significance (Aug 08, 2023)
16-67174656-G-A			Likely benign (Feb 12, 2018)
16-67174658-C-A		not specified	Uncertain significance (May 28, 2023)
16-67174667-G-C		not specified	Conflicting classifications of pathogenicity (Apr 07, 2022)
16-67174675-C-T		not specified	Uncertain significance (Oct 20, 2021)
16-67174708-C-A		Myoclonus, familial, 1	Uncertain significance (Nov 17, 2018)
16-67174733-C-G		NOL3-related disorder	Likely benign (Sep 11, 2019)
16-67174755-G-A		not specified	Likely benign (Jun 04, 2024)
16-67174756-C-A		not specified	Likely benign (Jun 04, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NOL3	protein_coding	protein_coding	ENST00000568146	3	5587

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000199	0.500	124520	1	171	124692	0.000690

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.129	131	127	1.03	0.00000679	1358
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000437	0.000437
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00140	0.00137
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00117	0.00116

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.0849
• hipred: N
• hipred_score: 0.461
• ghis: 0.503

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Nol3
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); respiratory system phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: response to hypoxia;blood vessel remodeling;response to ischemia;mRNA splice site selection;RNA splicing;cardiac muscle cell apoptotic process;negative regulation of cardiac muscle cell apoptotic process;negative regulation of tumor necrosis factor-mediated signaling pathway;negative regulation of muscle atrophy;release of sequestered calcium ion into cytosol by sarcoplasmic reticulum;response to injury involved in regulation of muscle adaptation;negative regulation of apoptotic process;protein complex oligomerization;negative regulation of necrotic cell death;negative regulation of release of cytochrome c from mitochondria;intrinsic apoptotic signaling pathway;regulation of NIK/NF-kappaB signaling;negative regulation of mitochondrial membrane permeability involved in apoptotic process;negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway;negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway;inhibition of cysteine-type endopeptidase activity involved in apoptotic process;negative regulation of extrinsic apoptotic signaling pathway
• Cellular component: nucleolus;mitochondrion;cytosol;membrane;sarcoplasmic reticulum
• Molecular function: RNA binding;death receptor binding;calcium ion binding;protein binding;death effector domain binding;identical protein binding;cysteine-type endopeptidase inhibitor activity involved in apoptotic process;caspase binding