NECAB1

Summary

NECAB1 (N-terminal EF-hand calcium binding protein 1, HGNC:20983) is a protein-coding gene on chromosome 8q21.3, encoding N-terminal EF-hand calcium-binding protein 1 (Q8N987).

Enables identical protein binding activity. Predicted to be involved in regulation of amyloid precursor protein biosynthetic process. Predicted to act upstream of or within blastocyst hatching. Located in cilium; cytosol; and nucleoplasm.

Source: NCBI Gene 64168 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 46 total
• MANE Select transcript: NM_022351

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20983
Approved symbol	NECAB1
Name	N-terminal EF-hand calcium binding protein 1
Location	8q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000123119
Ensembl biotype	protein_coding
Entrez	64168

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000417640, ENST00000521366, ENST00000521954, ENST00000522729, ENST00000522820, ENST00000523962, ENST00000893035

RefSeq mRNA: 1 — MANE Select: NM_022351 NM_022351

CCDS: CCDS47889

Canonical transcript exons

ENST00000417640 — 13 exons

Exon	Start	End
ENSE00001168901	90951113	90951204
ENSE00001168908	90949807	90949884
ENSE00001676410	90925535	90925656
ENSE00001699948	90917492	90917628
ENSE00001728619	90928223	90928299
ENSE00001777249	90934304	90934357
ENSE00002099407	90791775	90791985
ENSE00002113237	90955487	90959393
ENSE00003527624	90824717	90824825
ENSE00003539531	90881033	90881130
ENSE00003547117	90940786	90940898
ENSE00003590434	90872128	90872153
ENSE00003594831	90801691	90801715

Expression profiles

Bgee: expression breadth ubiquitous, 181 present calls, max score 96.00.

FANTOM5 (CAGE): breadth broad, TPM avg 8.5259 / max 1076.5211, expressed in 362 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89710	5.7209	305
89731	0.9490	136
89707	0.7796	181
89711	0.4725	145
89706	0.1897	123
89720	0.1138	44
89719	0.0915	35
89708	0.0818	46
89709	0.0560	42
89712	0.0368	13

Top tissues by expression

251 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 9	UBERON:0013540	96.00	gold quality
prefrontal cortex	UBERON:0000451	94.78	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.54	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.38	gold quality
anterior cingulate cortex	UBERON:0009835	93.35	gold quality
frontal cortex	UBERON:0001870	92.42	gold quality
right frontal lobe	UBERON:0002810	92.09	gold quality
neocortex	UBERON:0001950	91.83	gold quality
amygdala	UBERON:0001876	90.89	gold quality
spinal cord	UBERON:0002240	90.80	gold quality
cerebral cortex	UBERON:0000956	90.32	gold quality
nucleus accumbens	UBERON:0001882	89.70	gold quality
caudate nucleus	UBERON:0001873	89.17	gold quality
putamen	UBERON:0001874	89.07	gold quality
postcentral gyrus	UBERON:0002581	88.65	gold quality
Brodmann (1909) area 46	UBERON:0006483	88.53	gold quality
Ammon’s horn	UBERON:0001954	88.23	gold quality
superior frontal gyrus	UBERON:0002661	87.96	gold quality
forebrain	UBERON:0001890	87.24	gold quality
temporal lobe	UBERON:0001871	86.55	gold quality
parietal lobe	UBERON:0001872	86.44	gold quality
corpus callosum	UBERON:0002336	86.23	gold quality
hypothalamus	UBERON:0001898	86.16	gold quality
cortical plate	UBERON:0005343	85.49	gold quality
brain	UBERON:0000955	83.11	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.44	gold quality
primary visual cortex	UBERON:0002436	81.70	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	81.45	gold quality
entorhinal cortex	UBERON:0002728	81.34	gold quality
calcaneal tendon	UBERON:0003701	81.19	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	26.78
E-ANND-3	yes	20.00
E-MTAB-7381	no	80.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

193 targeting NECAB1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-568	99.98	69.86	2084
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AJ-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 1)

• Study suggests that the phenotypic segregation of Neuronal calcium-binding protein 1 and -2 (NECAB1 and -2) to respective excitatory and inhibitory spinal systems can underpin functional modalities in determining the fidelity of synaptic neurotransmission and neuronal responsiveness, and might bear translational relevance to humans. (PMID:26843217)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	necab1	ENSDARG00000056566
mus_musculus	Necab1	ENSMUSG00000040536
rattus_norvegicus	Necab1	ENSRNOG00000066027

Paralogs (2): NECAB2 (ENSG00000103154), NECAB3 (ENSG00000125967)

Protein

Protein identifiers

N-terminal EF-hand calcium-binding protein 1 — Q8N987 (reviewed: Q8N987)

Alternative names: Neuronal calcium-binding protein 1

All UniProt accessions (1): Q8N987

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with STX1. May interact with CPNE6.

Subcellular location. Cytoplasm.

Tissue specificity. Expressed in brain (at protein level).

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N987-1	1	yes
Q8N987-2	2

RefSeq proteins (1): NP_071746* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR007138	ABM_dom	Domain
IPR011008	Dimeric_a/b-barrel	Homologous_superfamily
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR039862	NECAB1/2/3	Family

Pfam: PF03992

UniProt features (19 total): binding site 5, domain 3, modified residue 3, sequence conflict 2, coiled-coil region 2, chain 1, splice variant 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N987-F1	79.61	0.59

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 43; 45; 50; 39; 41

Post-translational modifications (3): 4, 192, 197

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 98 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOZGIT_ESR1_TARGETS_DN, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_REGULATION_OF_GLYCOPROTEIN_METABOLIC_PROCESS, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, WANG_LMO4_TARGETS_DN, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_BLASTOCYST_DEVELOPMENT, ATTCTTT_MIR186, NIKOLSKY_BREAST_CANCER_8Q12_Q22_AMPLICON, BERTUCCI_INVASIVE_CARCINOMA_DUCTAL_VS_LOBULAR_DN, GOBP_AMYLOID_PRECURSOR_PROTEIN_METABOLIC_PROCESS, GOBP_EMBRYO_DEVELOPMENT, GOBP_GLYCOPROTEIN_METABOLIC_PROCESS

GO Biological Process (2): blastocyst hatching (GO:0001835), regulation of amyloid precursor protein biosynthetic process (GO:0042984)

GO Molecular Function (4): calcium ion binding (GO:0005509), identical protein binding (GO:0042802), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cilium (GO:0005929)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
blastocyst development	1
hatching	1
regulation of glycoprotein biosynthetic process	1
amyloid precursor protein biosynthetic process	1
metal ion binding	1
protein binding	1
binding	1
cation binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

1433 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NECAB1	SYT1	P21579	493
NECAB1	H3BUI4	H3BUI4	434
NECAB1	KRTAP10-4	P60372	417
NECAB1	WDR90	Q96KV7	399
NECAB1	EFCC1	Q9HA90	398
NECAB1	CALB1	P05937	394
NECAB1	EFR3A	Q14156	386
NECAB1	CALB2	P22676	386
NECAB1	KLHL32	Q96NJ5	385
NECAB1	ZNF221	Q9UK13	370
NECAB1	MTCL3	Q5TF21	370
NECAB1	CHODL	Q9H9P2	364
NECAB1	A0A0A0MSP3	A0A0A0MSP3	360
NECAB1	CTXN1	P60606	351
NECAB1	SCNN1A	P37088	351
NECAB1	CCDC24	Q8N4L8	351

IntAct

75 interactions, top by confidence:

A	B	Type	Score
NECAB1	NECAB1	psi-mi:“MI:0915”(physical association)	0.630
NECAB1	DISC1	psi-mi:“MI:0915”(physical association)	0.560
NECAB1	CPNE4	psi-mi:“MI:0915”(physical association)	0.560
CDC37	NECAB1	psi-mi:“MI:0915”(physical association)	0.560
CPNE8	NECAB1	psi-mi:“MI:0915”(physical association)	0.560
NECAB1	AP1M1	psi-mi:“MI:0915”(physical association)	0.560
ATOX1	NECAB1	psi-mi:“MI:0915”(physical association)	0.560
TCEA2	NECAB1	psi-mi:“MI:0915”(physical association)	0.560
NECAB1	CPNE7	psi-mi:“MI:0915”(physical association)	0.560
BHLHA9	NECAB1	psi-mi:“MI:0915”(physical association)	0.560
NECAB2	NECAB1	psi-mi:“MI:0915”(physical association)	0.560
	NECAB1	psi-mi:“MI:0915”(physical association)	0.560
BRPF1	NECAB1	psi-mi:“MI:0915”(physical association)	0.560
TCEANC	NECAB1	psi-mi:“MI:0915”(physical association)	0.560
NECAB1	LNX1	psi-mi:“MI:0915”(physical association)	0.560
NECAB1	SNX11	psi-mi:“MI:0915”(physical association)	0.560
PAX4	NECAB1	psi-mi:“MI:0915”(physical association)	0.560
NECAB1	MORF4L1	psi-mi:“MI:0915”(physical association)	0.560
NECAB1	CCDC6	psi-mi:“MI:0914”(association)	0.530
BMP2K	NECAB1	psi-mi:“MI:0915”(physical association)	0.490
NECAB1	DAPK1	psi-mi:“MI:0407”(direct interaction)	0.440
PRNP	CARNS1	psi-mi:“MI:0914”(association)	0.350
PRNP	WDR91	psi-mi:“MI:0914”(association)	0.350
IP6K3	PROZ	psi-mi:“MI:0914”(association)	0.350

BioGRID (44): NECAB3 (Affinity Capture-MS), NECAB2 (Affinity Capture-MS), CIRH1A (Affinity Capture-MS), NECAB1 (Affinity Capture-MS), KANSL2 (Affinity Capture-MS), MPRIP (Affinity Capture-MS), RNF138 (Affinity Capture-MS), MCRS1 (Affinity Capture-MS), CCDC6 (Affinity Capture-MS), RAI14 (Affinity Capture-MS), NECAB1 (Reconstituted Complex), NECAB1 (Co-fractionation), TOMM22 (Co-fractionation), NECAB1 (Two-hybrid), NECAB1 (Two-hybrid)

ESM2 similar proteins: A2AWP8, A2RRU4, A2SXS5, A2VDW6, A6QM06, D4A6L0, E1BBQ2, F1LQY6, O00255, O88559, O94827, P49797, P97260, Q0P5I0, Q12770, Q29RM4, Q2KJ58, Q3B7L5, Q496Y0, Q5MNU5, Q5R467, Q5R5M3, Q66H91, Q66T02, Q68FF6, Q69Z89, Q6GQT6, Q6RFZ7, Q76JQ2, Q7Z6G3, Q8BG18, Q8C190, Q8C419, Q8CEG5, Q8HXH0, Q8N987, Q8QZS3, Q8TBN0, Q8VDV3, Q91ZP9

Diamond homologs: A2VDW6, F1LQY6, Q5R467, Q7Z6G3, Q8BG18, Q8N987, Q91ZP9, Q96P71, Q9D6J4, Q9ESB5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

46 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3075 predictions. Top by Δscore:

Variant	Effect	Δscore
8:90791983:GAC:G	donor_gain	1.0000
8:90791984:AC:A	donor_gain	1.0000
8:90791984:ACG:A	donor_loss	1.0000
8:90791986:G:GA	donor_loss	1.0000
8:90791986:G:GG	donor_gain	1.0000
8:90791987:T:A	donor_loss	1.0000
8:90801685:TTCCA:T	acceptor_loss	1.0000
8:90801686:TCCAG:T	acceptor_loss	1.0000
8:90801687:CCAG:C	acceptor_loss	1.0000
8:90801688:CAGAT:C	acceptor_loss	1.0000
8:90801689:AGATA:A	acceptor_loss	1.0000
8:90801716:G:GG	donor_gain	1.0000
8:90824706:T:TA	acceptor_gain	1.0000
8:90824711:TTTCA:T	acceptor_loss	1.0000
8:90824712:TTCA:T	acceptor_loss	1.0000
8:90824713:TCAGA:T	acceptor_loss	1.0000
8:90824714:CAG:C	acceptor_loss	1.0000
8:90824715:A:AG	acceptor_gain	1.0000
8:90824715:AG:A	acceptor_loss	1.0000
8:90824715:AGAT:A	acceptor_gain	1.0000
8:90824716:G:GA	acceptor_gain	1.0000
8:90824716:GAT:G	acceptor_gain	1.0000
8:90824716:GATG:G	acceptor_gain	1.0000
8:90824822:C:CG	donor_gain	1.0000
8:90824822:C:G	donor_gain	1.0000
8:90824826:G:GG	donor_gain	1.0000
8:90872119:T:G	acceptor_gain	1.0000
8:90872126:A:AG	acceptor_gain	1.0000
8:90872127:G:GA	acceptor_gain	1.0000
8:90872127:GT:G	acceptor_gain	1.0000

AlphaMissense

2344 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:90824729:T:C	L46S	0.999
8:90881090:T:C	L106P	0.999
8:90801702:A:C	R37S	0.998
8:90801702:A:T	R37S	0.998
8:90824744:T:C	F51S	0.998
8:90917522:T:C	F130L	0.998
8:90917524:C:A	F130L	0.998
8:90917524:C:G	F130L	0.998
8:90917562:T:C	L143P	0.998
8:90917571:T:C	L146P	0.998
8:90928268:T:C	L221P	0.998
8:90951199:T:A	V342D	0.998
8:90801701:G:C	R37T	0.997
8:90824743:T:C	F51L	0.997
8:90824745:C:A	F51L	0.997
8:90824745:C:G	F51L	0.997
8:90881081:T:C	L103P	0.997
8:90917535:T:C	F134S	0.997
8:90940805:G:C	R256P	0.997
8:90949859:T:A	W305R	0.997
8:90949859:T:C	W305R	0.997
8:90955492:T:A	W346R	0.997
8:90955492:T:C	W346R	0.997
8:90824755:T:C	F55L	0.996
8:90824757:T:A	F55L	0.996
8:90824757:T:G	F55L	0.996
8:90824797:T:C	F69L	0.996
8:90824799:C:A	F69L	0.996
8:90824799:C:G	F69L	0.996
8:90917541:T:C	L136S	0.996

dbSNP variants (sampled 300 via entrez): RS1000041604 (8:90804238 G>A), RS1000101798 (8:90946990 C>G), RS1000102138 (8:90895251 A>G), RS1000125843 (8:90837128 C>A), RS1000139746 (8:90949961 G>C), RS1000145336 (8:90848186 G>T), RS1000159832 (8:90943044 T>C), RS1000175212 (8:90895712 G>A), RS1000208059 (8:90920600 A>G), RS1000218059 (8:90935984 G>T), RS1000236853 (8:90886467 T>C), RS1000250686 (8:90826974 G>A,T), RS1000275104 (8:90842781 A>C), RS1000282166 (8:90888823 T>C,G), RS1000331206 (8:90791363 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90000047_160	Age at first sexual intercourse	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009749	age at first sexual intercourse measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs74569896	Efficacy	3	aspirin;clopidogrel	Acute coronary syndrome;Major Adverse Cardiac Events (MACE)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs74569896	NECAB1	3	3.50	1	aspirin;clopidogrel

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
entinostat	increases expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	increases expression	1
bisphenol S	decreases methylation	1
NSC668394	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Catechin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance, affects cotreatment	1
Silicon Dioxide	affects expression	1
Smoke	increases expression	1
Tretinoin	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.