NECAP2

protein-coding

NECAP endocytosis associated 2

Gene summary

This gene likely encodes a member of the adaptin-ear-binding coat-associated protein family. Studies of a similar protein in rat suggest a role in clathrin-mediated endocytosis. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2009]

MANE transcript

NM_018090.5

Inheritance

—

ClinVar variants

U:42B:1

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.93

Max pathogenic AF

—

Genomic locus

chr1:16,440,721-16,460,078

External References & Databases

Ensembl (ENSG00000157191)

Transcript & Mutation Effects

hg38 • Region Span ~19.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NECAP2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 36

not providedTotal: 1

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018090.5. 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			2 clinvar		1 clinvar	3
missense			39 clinvar			39
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	42	0	1	43

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 40 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018090.5	RefSeq	NP_060560.1	8	MANE Select
ENST00000337132.10	Ensembl	ENSP00000338746.5	8	MANE Select
NM_001145277.2	RefSeq	NP_001138749.1	7	Standard
NM_001145278.2	RefSeq	NP_001138750.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vesicle-mediated transport
Membrane Trafficking
Clathrin-mediated endocytosis
Cargo recognition for clathrin-mediated endocytosis

Biological Process

endocytosis
protein transport

Cellular Component

plasma membrane
clathrin-coated pit
clathrin vesicle coat

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000443980
Coding exons: 7
Length: 19407
Individuals with no LoFs: 125705
Homozygous LoFs: 0
Heterozygous LoFs: 42
Defined: 125747
p: 0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.270	150	160	0.940	0.00000884	1758
Missense (PolyPhen)		38	42.755	0.88879		499
Synonymous	-0.614	73	66.6	1.10	0.00000398	565
Loss of Function	0.253	14	15.1	0.930	8.97e-7	147

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0.00026	0.00026	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in endocytosis. {ECO:0000250}.;

Recessive Scores

pRec: 0.0975

Intolerance Scores

LoFtool: 0.973
RVIS EVS: 0.64
RVIS percentile EVS: 83.9

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.813

Gene Damage Prediction

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