NAE1

NEDD8 activating enzyme E1 subunit 1, the group of Ubiquitin like modifier activating enzymes

Basic information

Region (hg38): 16:66802875-66873256

Previous symbols: [ "APPBP1" ]

Links

ENSG00000159593

∙ NCBI:8883 ∙ OMIM:603385 ∙ HGNC:621 ∙ Uniprot:Q13564 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

neurodevelopmental disorder with dysmorphic facies and ischiopubic hypoplasia (Limited), mode of inheritance: AR
neurodevelopmental disorder with dysmorphic facies and ischiopubic hypoplasia (Limited), mode of inheritance: AR
neurodevelopmental disorder with dysmorphic facies and ischiopubic hypoplasia (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with dysmorphic facies and ischiopubic hypoplasia	AR	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	Allergy/Immunology/Infectious; Craniofacial; Musculoskeletal; Neurologic	36608681

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NAE1 gene.

not_specified (62 variants)
Neurodevelopmental_disorder_with_dysmorphic_facies_and_ischiopubic_hypoplasia (6 variants)
not_provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NAE1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003905.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar		2
missense	3 clinvar	1 clinvar	60 clinvar	2 clinvar		66
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	3	1	60	4	0

Highest pathogenic variant AF is 0.00000557702

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NAE1	protein_coding	protein_coding	ENST00000290810	20	70382

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.80e-13	0.800	125697	0	51	125748	0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.09	218	268	0.813	0.0000130	3498
Missense in Polyphen		35	76.376	0.45826		995
Synonymous	1.04	79	91.6	0.862	0.00000456	946
Loss of Function	1.85	26	38.3	0.678	0.00000216	454

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000348	0.000348
Ashkenazi Jewish	0.00104	0.000993
East Asian	0.0000544	0.0000544
Finnish	0.0000471	0.0000462
European (Non-Finnish)	0.000152	0.000149
Middle Eastern	0.0000544	0.0000544
South Asian	0.000287	0.000261
Other	0.00103	0.000978

dbNSFP

Source: dbNSFP

Function: FUNCTION: Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M. Necessary for cell cycle progression through the S-M checkpoint. Overexpression of NAE1 causes apoptosis through deregulation of NEDD8 conjugation. {ECO:0000269|PubMed:10207026, ECO:0000269|PubMed:10722740, ECO:0000269|PubMed:12740388}.;
Pathway: Alzheimer,s disease - Homo sapiens (human);Alzheimers Disease;Post-translational protein modification;Metabolism of proteins;Neddylation (Consensus)

Recessive Scores

pRec: 0.149

Intolerance Scores

loftool: 0.931
rvis_EVS: -0.27
rvis_percentile_EVS: 34.6

Haploinsufficiency Scores

pHI: 0.660
hipred: Y
hipred_score: 0.690
ghis: 0.674

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.854

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Nae1
Phenotype: muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); 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); hematopoietic system phenotype;

Gene ontology

Biological process: signal transduction;protein modification by small protein conjugation;mitotic DNA replication checkpoint;regulation of apoptotic process;regulation of neuron apoptotic process;post-translational protein modification;protein neddylation;neuron apoptotic process
Cellular component: cytoplasm;cytosol;plasma membrane
Molecular function: protein binding;NEDD8 activating enzyme activity;ubiquitin protein ligase binding;protein heterodimerization activity