NECAP1

NECAP endocytosis associated 1

Basic information

Region (hg38): 12:8076939-8097881

Links

ENSG00000089818NCBI:25977OMIM:611623HGNC:24539Uniprot:Q8NC96AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • developmental and epileptic encephalopathy, 21 (Moderate), mode of inheritance: AR
  • undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
  • developmental and epileptic encephalopathy, 21 (Strong), mode of inheritance: AR
  • genetic developmental and epileptic encephalopathy (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Developmental and epileptic encephalopathy 21ARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic24399846; 30525121; 30626896
As with other conditions involving seizures, optimal seizure control is beneficial, and awareness of genetic causes may help with medication selection

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NECAP1 gene.

  • Developmental_and_epileptic_encephalopathy,_21 (181 variants)
  • Inborn_genetic_diseases (19 variants)
  • not_provided (16 variants)
  • NECAP1-related_disorder (7 variants)
  • not_specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NECAP1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015509.4. 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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
44
clinvar
46
missense
92
clinvar
2
clinvar
94
nonsense
2
clinvar
2
start loss
0
frameshift
2
clinvar
1
clinvar
3
splice donor/acceptor (+/-2bp)
1
clinvar
1
Total 3 3 94 46 0

Highest pathogenic variant AF is 0.00000309785

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
NECAP1protein_codingprotein_codingENST00000339754 815561
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.1260.870125738091257470.0000358
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.401101600.6880.000008481779
Missense in Polyphen2748.3150.55883561
Synonymous1.084858.50.8200.00000303556
Loss of Function2.48414.00.2856.78e-7163

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001860.000186
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.00004640.0000462
European (Non-Finnish)0.00002640.0000264
Middle Eastern0.000.00
South Asian0.00003340.0000327
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Involved in endocytosis. {ECO:0000250}.;
Disease
DISEASE: Epileptic encephalopathy, early infantile, 21 (EIEE21) [MIM:615833]: A severe disease characterized by intractable seizures, profound global developmental delay, and persistent severe axial hypotonia as well as appendicular hypertonia. {ECO:0000269|PubMed:24399846}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Golgi Associated Vesicle Biogenesis;Clathrin derived vesicle budding;trans-Golgi Network Vesicle Budding;Vesicle-mediated transport;Membrane Trafficking;Clathrin-mediated endocytosis;Cargo recognition for clathrin-mediated endocytosis (Consensus)

Intolerance Scores

loftool
rvis_EVS
-0.1
rvis_percentile_EVS
46.49

Haploinsufficiency Scores

pHI
0.247
hipred
Y
hipred_score
0.543
ghis
0.591

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.840

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Necap1
Phenotype

Gene ontology

Biological process
endocytosis;protein transport;membrane organization
Cellular component
cytosol;plasma membrane;clathrin-coated pit;clathrin vesicle coat
Molecular function