EFCAB8

Summary

EFCAB8 (EF-hand calcium binding domain 8, HGNC:34532) is a protein-coding gene on chromosome 20q11.21, encoding EF-hand calcium-binding domain-containing protein 8 (A8MWE9).

Predicted to enable calcium ion binding activity.

Source: NCBI Gene 388795 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 3 total — 1 pathogenic
• MANE Select transcript: NM_001143967

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34532
Approved symbol	EFCAB8
Name	EF-hand calcium binding domain 8
Location	20q11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000215529
Ensembl biotype	protein_coding
Entrez	388795

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 2 retained_intron

ENST00000400522, ENST00000524882, ENST00000533479, ENST00000618684

RefSeq mRNA: 1 — MANE Select: NM_001143967 NM_001143967

Canonical transcript exons

ENST00000400522 — 27 exons

Exon	Start	End
ENSE00001543319	32878704	32878807
ENSE00001543320	32875926	32876044
ENSE00001543321	32867582	32867747
ENSE00001556082	32889301	32889406
ENSE00001647096	32912794	32912864
ENSE00001657025	32920078	32920215
ENSE00001664452	32961136	32961845
ENSE00001672924	32863783	32863834
ENSE00001691115	32930398	32930616
ENSE00001694327	32906843	32906994
ENSE00001728712	32911480	32911707
ENSE00001743557	32858923	32859006
ENSE00001751758	32906562	32906629
ENSE00001759410	32931178	32931336
ENSE00001763787	32898493	32898623
ENSE00001768489	32917301	32917505
ENSE00001775463	32896454	32896527
ENSE00001781039	32960063	32960161
ENSE00001784469	32959778	32959982
ENSE00001799883	32893174	32893298
ENSE00003173430	32885505	32885640
ENSE00003208410	32892213	32892297
ENSE00003569932	32918362	32918574
ENSE00003756413	32958421	32958550
ENSE00003757171	32909821	32909931
ENSE00003757404	32943636	32943804
ENSE00003758303	32908275	32908412

Expression profiles

Bgee: expression breadth broad, 100 present calls, max score 77.42.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.52	gold quality
sural nerve	UBERON:0015488	67.49	silver quality
left testis	UBERON:0004533	67.20	gold quality
right testis	UBERON:0004534	66.79	gold quality
testis	UBERON:0000473	66.56	gold quality
blood	UBERON:0000178	65.09	gold quality
granulocyte	CL:0000094	63.48	gold quality
vermiform appendix	UBERON:0001154	52.63	gold quality
spleen	UBERON:0002106	52.18	gold quality
monocyte	CL:0000576	50.64	gold quality
mucosa of stomach	UBERON:0001199	50.41	gold quality
lymph node	UBERON:0000029	50.34	gold quality
leukocyte	CL:0000738	50.06	gold quality
adenohypophysis	UBERON:0002196	49.36	gold quality
pituitary gland	UBERON:0000007	48.99	gold quality
bone marrow	UBERON:0002371	48.60	gold quality
tonsil	UBERON:0002372	48.58	gold quality
upper lobe of left lung	UBERON:0008952	47.84	gold quality
small intestine	UBERON:0002108	47.77	gold quality
gall bladder	UBERON:0002110	47.38	gold quality
left uterine tube	UBERON:0001303	47.37	gold quality
small intestine Peyer’s patch	UBERON:0003454	47.03	gold quality
duodenum	UBERON:0002114	46.95	silver quality
gastrocnemius	UBERON:0001388	46.23	gold quality
urinary bladder	UBERON:0001255	46.18	gold quality
mucosa of transverse colon	UBERON:0004991	46.09	gold quality
left coronary artery	UBERON:0001626	45.83	gold quality
islet of Langerhans	UBERON:0000006	45.55	gold quality
muscle layer of sigmoid colon	UBERON:0035805	45.52	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.52

Regulation

Is transcription factor: no

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Efcab8	ENSMUSG00000044083
rattus_norvegicus	Efcab8	ENSRNOG00000070431
caenorhabditis_elegans		WBGENE00004767

Paralogs (14): WDR54 (ENSG00000005448), FBXW11 (ENSG00000072803), FBXW7 (ENSG00000109670), TRAF7 (ENSG00000131653), FBXW9 (ENSG00000132004), FBXO36 (ENSG00000153832), WDR64 (ENSG00000162843), FBXW12 (ENSG00000164049), BTRC (ENSG00000166167), WDR49 (ENSG00000174776), FBXW8 (ENSG00000174989), PAAF1 (ENSG00000175575), WDR86 (ENSG00000187260), FBXO16 (ENSG00000214050)

Protein

Protein identifiers

EF-hand calcium-binding domain-containing protein 8 — A8MWE9 (reviewed: A8MWE9)

All UniProt accessions (2): A0A096LNH2, A8MWE9

RefSeq proteins (1): NP_001137439* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR051242	WD-EF-hand_domain	Family

UniProt features (3 total): domain 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A8MWE9-F1	69.52	0.17

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 13 (showing top): chr20q11, CBX5_TARGET_GENES, HMGA1_TARGET_GENES, ZNF707_TARGET_GENES, DESCARTES_MAIN_FETAL_LENS_FIBRE_CELLS, DESCARTES_FETAL_EYE_LENS_FIBRE_CELLS, DESCARTES_FETAL_LUNG_CSH1_CSH2_POSITIVE_CELLS, ZSCAN5DP_TARGET_GENES, GSE12507_PDC_CELL_LINE_VS_IMMATUE_T_CELL_LINE_DN, GSE21033_1H_VS_24H_POLYIC_STIM_DC_UP, GSE37533_UNTREATED_VS_PIOGLIZATONE_TREATED_CD4_TCELL_PPARG2_AND_FOXP3_TRASDUCED_UP, GSE33292_DN3_THYMOCYTE_VS_TCF1_KO_TCELL_LYMPHOMA_DN, GOMF_CALCIUM_ION_BINDING

GO Biological Process (0):

GO Molecular Function (2): calcium ion binding (GO:0005509), protein binding (GO:0005515)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metal ion binding	1
binding	1

Protein interactions and networks

STRING

358 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EFCAB8	TEX13D	A0A0J9YY54	506
EFCAB8	A0A2R8Y455	A0A2R8Y455	495
EFCAB8	BPIFB2	Q8N4F0	473
EFCAB8	COMMD7	Q86VX2	469
EFCAB8	MTRNR2L3	P0CJ70	468
EFCAB8	POP1	Q99575	463
EFCAB8	WDR49	Q8IV35	460
EFCAB8	SUN5	Q8TC36	458
EFCAB8	TEKTL1	Q8IYK2	439
EFCAB8	C5orf15	Q8NC54	434
EFCAB8	OR5H2	Q8NGV7	431
EFCAB8	TLCD1	Q96CP7	428
EFCAB8	VSTM2L	Q96N03	398
EFCAB8	CDHR4	A6H8M9	397
EFCAB8	ZNF17	P17021	396

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A2AHC3, A4FU69, A5WUN7, A7E379, A8MWE9, D3Z6S9, D3Z8E6, D3ZSP7, D4AEC2, O43149, O88196, P53804, Q06190, Q06BI3, Q08AD1, Q12923, Q13009, Q13129, Q3UMB5, Q4R8X0, Q5RBH9, Q5SSH7, Q5SW75, Q5T5Y3, Q60610, Q66HC0, Q6DGK9, Q6IRN6, Q6NZK8, Q76I76, Q80VH0, Q80X60, Q86WZ0, Q8C115, Q8C1B1, Q8C9R9, Q8CDN1, Q8ND61, Q8WWI1, Q99J45

Diamond homologs: A8MWE9, Q8C9R9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	0
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1457888	NC_000020.10:g.(?31189994)(34287210_?)del	Pathogenic

SpliceAI

5457 predictions. Top by Δscore:

Variant	Effect	Δscore
20:32875921:T:TA	acceptor_gain	1.0000
20:32875921:TGAA:T	acceptor_loss	1.0000
20:32875922:GAAG:G	acceptor_loss	1.0000
20:32875923:AAGCC:A	acceptor_loss	1.0000
20:32875924:A:AG	acceptor_gain	1.0000
20:32875924:A:T	acceptor_loss	1.0000
20:32875925:G:GG	acceptor_gain	1.0000
20:32875925:G:GT	acceptor_loss	1.0000
20:32877815:GGGCC:G	donor_gain	1.0000
20:32878808:G:GG	donor_gain	1.0000
20:32885639:GG:G	donor_gain	1.0000
20:32885640:GG:G	donor_gain	1.0000
20:32893253:A:AG	donor_gain	1.0000
20:32893254:G:GG	donor_gain	1.0000
20:32898623:GGT:G	donor_loss	1.0000
20:32898624:G:GA	donor_loss	1.0000
20:32898625:T:A	donor_loss	1.0000
20:32907036:G:T	donor_gain	1.0000
20:32908269:CCCCA:C	acceptor_loss	1.0000
20:32908271:CCAGA:C	acceptor_loss	1.0000
20:32908272:CAG:C	acceptor_loss	1.0000
20:32908273:A:AC	acceptor_loss	1.0000
20:32908273:A:AG	acceptor_gain	1.0000
20:32908274:G:GT	acceptor_gain	1.0000
20:32908274:GA:G	acceptor_gain	1.0000
20:32908274:GAAT:G	acceptor_gain	1.0000
20:32908410:TCA:T	donor_gain	1.0000
20:32908413:G:GG	donor_gain	1.0000
20:32917501:AGAGG:A	donor_gain	1.0000
20:32917502:GAGG:G	donor_gain	1.0000

AlphaMissense

8550 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:32875943:T:C	F76L	0.978
20:32875945:C:A	F76L	0.978
20:32875945:C:G	F76L	0.978
20:32876003:T:C	F96L	0.970
20:32876005:T:A	F96L	0.970
20:32876005:T:G	F96L	0.970
20:32875944:T:C	F76S	0.958
20:32876037:T:A	V107D	0.954
20:32878734:T:C	F120L	0.951
20:32878736:C:A	F120L	0.951
20:32878736:C:G	F120L	0.951
20:32876004:T:C	F96S	0.940
20:32867720:T:C	F61L	0.938
20:32867722:T:A	F61L	0.938
20:32867722:T:G	F61L	0.938
20:32876001:T:C	L95P	0.938
20:32876044:G:C	W109C	0.936
20:32876044:G:T	W109C	0.936
20:32876042:T:A	W109R	0.934
20:32876042:T:C	W109R	0.934
20:32876011:G:C	K98N	0.911
20:32876011:G:T	K98N	0.911
20:32876017:C:A	D100E	0.904
20:32876017:C:G	D100E	0.904
20:32878710:T:G	Y112D	0.898
20:32875992:T:C	L92P	0.893
20:32876004:T:G	F96C	0.884
20:32867721:T:G	F61C	0.868
20:32875944:T:G	F76C	0.862
20:32876015:G:C	D100H	0.855

dbSNP variants (sampled 300 via entrez): RS1000007475 (20:32900891 A>G,T), RS1000022421 (20:32949377 C>G), RS1000027549 (20:32925706 G>C), RS1000038437 (20:32949869 G>A), RS1000064053 (20:32904836 A>G), RS1000065205 (20:32909869 A>C,G), RS1000101466 (20:32866565 G>T), RS1000116044 (20:32913232 A>G,T), RS1000132821 (20:32866283 G>C), RS1000155448 (20:32959280 C>T), RS1000218012 (20:32889809 C>G), RS1000249129 (20:32889959 C>T), RS1000256421 (20:32871831 C>A), RS1000265387 (20:32912838 A>G,T), RS1000278959 (20:32928574 A>G)

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

2 associations (top):

Study	Trait	p-value
GCST008152_169	Weight	7.000000e-06
GCST010703_192	Brain morphology (MOSTest)	8.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004338	body weight
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
aflatoxin B2	decreases methylation	1
resorcinol	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Quercetin	increases expression	1
Smoke	decreases expression	1
Thiram	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1
Permethrin	decreases expression	1

Clinical trials (associated diseases)

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