NECAB2

protein-coding

N-terminal EF-hand calcium binding protein 2, the group of N-terminal EF-hand calcium binding proteins|EF-hand domain containing

Gene summary

The protein encoded by this gene is a neuronal calcium-binding protein that binds to and modulates the function of at least two receptors, adenosine A(2A) receptor and metabotropic glutamate receptor type 5. [provided by RefSeq, Jul 2016]

Previous symbols:

EFCBP2

MANE transcript

NM_019065.3

Inheritance

—

ClinVar variants

U:128B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.96

Max pathogenic AF

—

Genomic locus

chr16:83,968,244-84,002,776

External References & Databases

Ensembl (ENSG00000103154)

Transcript & Mutation Effects

hg38 • Region Span ~34.5 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 NECAB2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 129

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_019065.3. 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			2
missense			125 clinvar	3 clinvar		128
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	128	3	0	131

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_019065.3	RefSeq	NP_061938.2	13	MANE Select
ENST00000305202.9	Ensembl	ENSP00000307449.4	13	MANE Select
NM_001329748.1	RefSeq	NP_001316677.1	12	Standard
NM_001329749.2	RefSeq	NP_001316678.1	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of amyloid precursor protein biosynthetic process
positive regulation of adenosine receptor signaling pathway
positive regulation of ERK1 and ERK2 cascade
positive regulation of glutamate receptor signaling pathway
negative regulation of G protein-coupled receptor internalization

Molecular Function

calcium ion binding
protein binding
A2A adenosine receptor binding
type 5 metabotropic glutamate receptor binding

Cellular Component

cytoplasm
plasma membrane
axon
dendrite

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000305202
Coding exons: 13
Length: 34145
Individuals with no LoFs: 125695
Homozygous LoFs: 0
Heterozygous LoFs: 53
Defined: 125748
p: 0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-4.91	390	196	1.99	0.0000121	2496
Missense (PolyPhen)		167	91.304	1.8291		974
Synonymous	-6.92	160	80.9	1.98	0.00000522	752
Loss of Function	0.183	20	20.9	0.957	9.77e-7	253

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00027	0.00027	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00025	0.00025	rare
South Asian	0.00030	0.00029	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May act as a signaling scaffold protein that senses intracellular calcium. Can modulate ligand-induced internalization of ADORA2A and coupling efficiency of mGluR5/GRM5; for both receptors may regulate signaling activity such as promoting MAPK1/3 (ERK1/2) activation. {ECO:0000305|PubMed:17689978, ECO:0000305|PubMed:19694902}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.816
RVIS EVS: -0.13
RVIS percentile EVS: 44.09

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.889

Gene Damage Prediction

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