NECAP1

NECAP endocytosis associated 1

Basic information

Region (hg38): 12:8076939-8097881

Links

ENSG00000089818 ∙ NCBI:25977 ∙ OMIM:611623 ∙ HGNC:24539 ∙ Uniprot:Q8NC96 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Developmental and epileptic encephalopathy 21	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	Neurologic	24399846; 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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	44		46
missense			92	2		94
nonsense		2				2
start loss						0
frameshift	2	1				3
splice donor/acceptor (+/-2bp)	1					1
Total	3	3	94	46	0

Highest pathogenic variant AF is 0.00000309785

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NECAP1	protein_coding	protein_coding	ENST00000339754	8	15561

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.126	0.870	125738	0	9	125747	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.40	110	160	0.688	0.00000848	1779
Missense in Polyphen		27	48.315	0.55883		561
Synonymous	1.08	48	58.5	0.820	0.00000303	556
Loss of Function	2.48	4	14.0	0.285	6.78e-7	163

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000186	0.000186
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000334	0.0000327
Other	0.00	0.00

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

• 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

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

Mouse Genome Informatics

• Gene name: Necap1

Gene ontology

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