EFCAB7

Summary

EFCAB7 (EF-hand calcium binding domain 7, HGNC:29379) is a protein-coding gene on chromosome 1p31.3, encoding EF-hand calcium-binding domain-containing protein 7 (A8K855). Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling.

Predicted to enable calcium ion binding activity. Predicted to be involved in positive regulation of protein import into nucleus; positive regulation of protein localization to ciliary membrane; and positive regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasmic side of plasma membrane. Predicted to be part of plasma membrane protein complex. Predicted to be active in ciliary membrane.

Source: NCBI Gene 84455 — RefSeq curated summary.

At a glance

• Gene–disease (curated): polydactyly (Moderate, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 84 total
• MANE Select transcript: NM_032437

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29379
Approved symbol	EFCAB7
Name	EF-hand calcium binding domain 7
Location	1p31.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1799, RP4-534K7.1
Ensembl gene	ENSG00000203965
Ensembl biotype	protein_coding
OMIM	617632
Entrez	84455

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 5 protein_coding, 5 protein_coding_CDS_not_defined

ENST00000371088, ENST00000460678, ENST00000461039, ENST00000480886, ENST00000493605, ENST00000496956, ENST00000927137, ENST00000971337, ENST00000971338, ENST00000971339

RefSeq mRNA: 1 — MANE Select: NM_032437 NM_032437

CCDS: CCDS30737

Canonical transcript exons

ENST00000371088 — 14 exons

Exon	Start	End
ENSE00001454324	63555358	63555515
ENSE00001454327	63534095	63534216
ENSE00001454328	63533454	63533649
ENSE00001454329	63532670	63532756
ENSE00001857713	63523525	63523634
ENSE00003475395	63557114	63557247
ENSE00003493180	63551725	63551834
ENSE00003515952	63572442	63572693
ENSE00003581060	63531820	63532031
ENSE00003581343	63561709	63561857
ENSE00003585793	63545916	63546057
ENSE00003599671	63525572	63525759
ENSE00003621790	63571021	63571128
ENSE00003688814	63568310	63568519

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 93.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.6030 / max 258.3651, expressed in 1567 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3176	5.0824	1354
3175	2.7881	1119
3177	1.6043	725
3178	0.0537	16
3179	0.0500	10
3180	0.0245	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	93.74	gold quality
bronchial epithelial cell	CL:0002328	91.75	gold quality
secondary oocyte	CL:0000655	91.56	gold quality
bronchus	UBERON:0002185	90.35	gold quality
cortical plate	UBERON:0005343	89.23	gold quality
ventricular zone	UBERON:0003053	88.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.14	gold quality
calcaneal tendon	UBERON:0003701	87.21	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.74	gold quality
endothelial cell	CL:0000115	86.51	gold quality
ganglionic eminence	UBERON:0004023	85.73	gold quality
tibialis anterior	UBERON:0001385	84.82	silver quality
cerebellar hemisphere	UBERON:0002245	84.13	gold quality
cerebellar cortex	UBERON:0002129	84.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.78	gold quality
right uterine tube	UBERON:0001302	83.71	gold quality
cerebellum	UBERON:0002037	83.35	gold quality
Brodmann (1909) area 46	UBERON:0006483	83.32	gold quality
mucosa of paranasal sinus	UBERON:0005030	82.94	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.32	gold quality
tendon	UBERON:0000043	82.05	gold quality
prefrontal cortex	UBERON:0000451	81.93	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.67	gold quality
adrenal tissue	UBERON:0018303	81.54	gold quality
primary visual cortex	UBERON:0002436	81.09	gold quality
left ovary	UBERON:0002119	80.93	gold quality
Brodmann (1909) area 23	UBERON:0013554	80.92	gold quality
ovary	UBERON:0000992	80.63	gold quality
cardiac muscle of right atrium	UBERON:0003379	80.62	silver quality
neocortex	UBERON:0001950	80.59	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

miRNA regulators (miRDB)

20 targeting EFCAB7, 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-3646	100.00	73.56	5283
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-448	99.79	72.37	2103
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-5571-5P	99.49	66.99	1764
HSA-MIR-8054	99.48	70.81	2084
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-3168	99.08	67.75	1384
HSA-MIR-7153-3P	99.00	65.35	608
HSA-MIR-5585-3P	98.25	67.41	941
HSA-MIR-562	97.66	65.63	698
HSA-MIR-6509-5P	97.39	68.27	969
HSA-MIR-331-5P	96.59	67.94	705

Literature-anchored findings (GeneRIF, showing 2)

• we detected two novel nonsense mutations and a partial deletion of EVC/EVC2 in two Vietnamese families with EvC. Moreover, we found in one family a missense mutation of EFCAB7, a possible modifier gene in EvC and its related disorders. (PMID:26748586)
• Novel mutation in EFCAB7 alters expression and interaction with EVC2 protein. (PMID:29845660)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	efcab7	ENSDARG00000020279
mus_musculus	Efcab7	ENSMUSG00000073791
rattus_norvegicus	Efcab7	ENSRNOG00000009782
drosophila_melanogaster	TpnC4	FBGN0033027
caenorhabditis_elegans		WBGENE00000285
caenorhabditis_elegans		WBGENE00000287
caenorhabditis_elegans	pat-10	WBGENE00003934
caenorhabditis_elegans		WBGENE00006583
caenorhabditis_elegans		WBGENE00008453
caenorhabditis_elegans	F35C12.3	WBGENE00009408
caenorhabditis_elegans		WBGENE00015264

Paralogs (20): CABP7 (ENSG00000100314), CABP5 (ENSG00000105507), CALML4 (ENSG00000129007), CALM2 (ENSG00000143933), CETN2 (ENSG00000147400), CETN3 (ENSG00000153140), CABP1 (ENSG00000157782), CALM3 (ENSG00000160014), CABP2 (ENSG00000167791), CALML6 (ENSG00000169885), EFCAB3 (ENSG00000172421), EFCAB12 (ENSG00000172771), CABP4 (ENSG00000175544), CETN1 (ENSG00000177143), CALML3 (ENSG00000178363), CALML5 (ENSG00000178372), CALN1 (ENSG00000183166), CALM1 (ENSG00000198668), EFCAB2 (ENSG00000203666), EFCAB9 (ENSG00000214360)

Protein

Protein identifiers

EF-hand calcium-binding domain-containing protein 7 — A8K855 (reviewed: A8K855)

All UniProt accessions (1): A8K855

UniProt curated annotations — full annotation on UniProt →

Function. Component of the EvC complex that positively regulates ciliary Hedgehog (Hh) signaling. Required for the localization of the EVC2:EVC subcomplex at the base of primary cilia.

Subunit / interactions. Component of the EvC complex composed of EFCAB7, IQCE, EVC2 and EVC; built from two subcomplexes, EVC2:EVC and EFCAB7:IQCE. Interacts (via EF-hand 1 and 2) with IQCE (via N-terminus); this interaction anchors the EVC-EVC2 complex in a signaling microdomain at the base of cilia and stimulates the Hedgehog (Hh) pathway. Interacts with EVC2 (via N-terminal end). Interacts with EVC.

Subcellular location. Cell projection. Cilium membrane.

Isoforms (2)

UniProt ID	Names	Canonical?
A8K855-1	1	yes
A8K855-2	2

RefSeq proteins (1): NP_115813* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR052266	Miro-EF-hand_domain	Family

Pfam: PF13499

UniProt features (19 total): sequence variant 5, binding site 4, domain 3, modified residue 2, region of interest 2, chain 1, splice variant 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A8K855-F1	80.62	0.45

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 (4): 427; 416; 418; 420

Post-translational modifications (2): 200, 212

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-5635838	Activation of SMO

MSigDB gene sets: 177 (showing top): GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_NUCLEAR_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION_TO_NUCLEUS, GOBP_REGULATION_OF_NUCLEOCYTOPLASMIC_TRANSPORT, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOBP_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_NUCLEOCYTOPLASMIC_TRANSPORT, GOBP_REGULATION_OF_SMOOTHENED_SIGNALING_PATHWAY

GO Biological Process (5): regulation of smoothened signaling pathway (GO:0008589), positive regulation of protein import into nucleus (GO:0042307), positive regulation of transcription by RNA polymerase II (GO:0045944), protein localization to motile cilium (GO:0120229), positive regulation of protein localization to ciliary membrane (GO:1903569)

GO Molecular Function (2): calcium ion binding (GO:0005509), metal ion binding (GO:0046872)

GO Cellular Component (7): cilium (GO:0005929), cytoplasmic side of plasma membrane (GO:0009898), ciliary membrane (GO:0060170), plasma membrane protein complex (GO:0098797), plasma membrane (GO:0005886), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Hedgehog ‘on’ state	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
plasma membrane	2
cellular anatomical structure	2
smoothened signaling pathway	1
regulation of signal transduction	1
protein import into nucleus	1
regulation of protein import into nucleus	1
positive regulation of nucleocytoplasmic transport	1
positive regulation of intracellular protein transport	1
positive regulation of protein localization to nucleus	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
protein localization to cilium	1
protein localization to ciliary membrane	1
positive regulation of protein localization to cilium	1
regulation of protein localization to ciliary membrane	1
positive regulation of protein localization to cell periphery	1
positive regulation of protein localization to membrane	1
metal ion binding	1
cation binding	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoplasmic side of membrane	1
cilium	1
cell projection membrane	1
bounding membrane of organelle	1
membrane protein complex	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1934 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EFCAB7	IQCE	Q6IPM2	943
EFCAB7	EVC2	Q86UK5	805
EFCAB7	CAPN15	O75808	513
EFCAB7	EVC	P57679	484
EFCAB7	EFCAB11	Q9BUY7	481
EFCAB7	CLSTN1	O94985	480
EFCAB7	TTC23	Q5W5X9	454
EFCAB7	EFCC1	Q9HA90	447
EFCAB7	DLG5	Q8TDM6	445
EFCAB7	C14orf119	Q9NWQ9	431
EFCAB7	CACHD1	Q5VU97	426
EFCAB7	CPSF2	Q9P2I0	421
EFCAB7	ALG6	Q9Y672	407
EFCAB7	WDFY1	Q8IWB7	400
EFCAB7	ITGB3BP	Q13352	398

IntAct

20 interactions, top by confidence:

A	B	Type	Score
TTC23L	EFCAB7	psi-mi:“MI:0914”(association)	0.530
EFCAB7	H1-5	psi-mi:“MI:0915”(physical association)	0.400
N	RBM47	psi-mi:“MI:0914”(association)	0.350
YWHAE	DEPDC5	psi-mi:“MI:0914”(association)	0.350
YWHAG	BRAF	psi-mi:“MI:0914”(association)	0.350
MCC	CIBAR1	psi-mi:“MI:0914”(association)	0.350
NRGN	EFCAB7	psi-mi:“MI:0914”(association)	0.350
MYL12B	EFCAB7	psi-mi:“MI:0914”(association)	0.350
SPA17	EFCAB7	psi-mi:“MI:0914”(association)	0.350
RFFL	EFCAB7	psi-mi:“MI:0914”(association)	0.350
AKAP14	EFCAB7	psi-mi:“MI:0914”(association)	0.350
RNF34	UNC119B	psi-mi:“MI:0914”(association)	0.350
TTC23	EFCAB7	psi-mi:“MI:0914”(association)	0.350

BioGRID (30): EFCAB7 (Affinity Capture-MS), EFCAB7 (Affinity Capture-MS), EFCAB7 (Affinity Capture-MS), EFCAB7 (Affinity Capture-MS), EFCAB7 (Affinity Capture-MS), EFCAB7 (Affinity Capture-MS), EFCAB7 (Affinity Capture-MS), EFCAB7 (Affinity Capture-MS), EFCAB7 (Affinity Capture-MS), EFCAB7 (Affinity Capture-MS), EFCAB7 (Synthetic Lethality), HIST1H1B (Proximity Label-MS), EFCAB7 (Affinity Capture-MS), EFCAB7 (Affinity Capture-MS), EFCAB7 (Affinity Capture-MS)

ESM2 similar proteins: A0M8R4, A0M8S5, A0M8U6, A8K855, O00151, P47226, P52944, P60670, Q00PK1, Q07DW1, Q07DX3, Q07DY3, Q07DZ4, Q07E27, Q07E40, Q07E51, Q09YI0, Q09YJ2, Q09YK3, Q09YL5, Q09YN8, Q0E908, Q108U9, Q17QE2, Q2IBA3, Q2IBC3, Q2IBH0, Q2LAP6, Q2QL92, Q2QLA1, Q2QLB2, Q2QLC3, Q2QLE3, Q2QLF4, Q2QLG8, Q2QLH9, Q2YDE9, Q5PXT2, Q5RC52, Q6DIR5

Diamond homologs: A8K855, P04464, P27165, P54680, Q338P8, Q38868, Q40302, Q41420, Q42479, Q6DCF6, Q6NVC5, Q71UH5, Q8VDY4, Q948R0, Q9SU00, A0AVX7, A4GNA8, B5FZ84, C7A276, F4KAK5, G5EDN6, O18757, O43745, O73763, O81223, O81445, P0CM54, P0CM55, P25296, P28470, P29104, P29291, P35332, P35571, P42322, P42324, P42325, P48451, P54213, P61022

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2351 predictions. Top by Δscore:

Variant	Effect	Δscore
1:63525567:A:AG	acceptor_gain	1.0000
1:63525570:A:AG	acceptor_gain	1.0000
1:63525570:AGAAT:A	acceptor_gain	1.0000
1:63525571:G:GA	acceptor_gain	1.0000
1:63525571:GA:G	acceptor_gain	1.0000
1:63525571:GAAT:G	acceptor_gain	1.0000
1:63525571:GAATG:G	acceptor_gain	1.0000
1:63525756:TTAG:T	donor_loss	1.0000
1:63525757:TAGGT:T	donor_loss	1.0000
1:63525758:AGGT:A	donor_loss	1.0000
1:63525759:GGTAA:G	donor_loss	1.0000
1:63525760:G:A	donor_loss	1.0000
1:63525761:T:A	donor_loss	1.0000
1:63532666:TCA:T	acceptor_loss	1.0000
1:63532667:CAGA:C	acceptor_loss	1.0000
1:63532668:A:AG	acceptor_gain	1.0000
1:63532669:G:GA	acceptor_gain	1.0000
1:63532669:GA:G	acceptor_gain	1.0000
1:63532669:GAGA:G	acceptor_gain	1.0000
1:63532757:GTAC:G	donor_loss	1.0000
1:63532758:T:G	donor_loss	1.0000
1:63533452:A:AG	acceptor_gain	1.0000
1:63533453:G:GG	acceptor_gain	1.0000
1:63533453:GTT:G	acceptor_gain	1.0000
1:63533453:GTTTT:G	acceptor_gain	1.0000
1:63551832:G:GT	donor_gain	1.0000
1:63551832:GAA:G	donor_gain	1.0000
1:63556553:G:T	donor_gain	1.0000
1:63557244:AGAGG:A	donor_loss	1.0000
1:63557245:GAG:G	donor_gain	1.0000

AlphaMissense

4187 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:63525699:T:G	Y43D	0.990
1:63557234:G:C	W445C	0.989
1:63557234:G:T	W445C	0.989
1:63557232:T:A	W445R	0.986
1:63557232:T:C	W445R	0.986
1:63561751:T:C	F464S	0.985
1:63525751:T:C	L60P	0.983
1:63531823:T:C	L64P	0.983
1:63531870:T:A	W80R	0.981
1:63531870:T:C	W80R	0.981
1:63561736:T:C	L459P	0.980
1:63531831:G:C	A67P	0.979
1:63545985:T:G	Y292D	0.978
1:63531907:T:C	F92S	0.976
1:63561714:T:C	F452L	0.975
1:63561716:T:A	F452L	0.975
1:63561716:T:G	F452L	0.975
1:63561747:G:A	G463R	0.974
1:63561747:G:C	G463R	0.974
1:63531892:T:C	L87P	0.973
1:63557133:T:C	F412L	0.971
1:63557135:T:A	F412L	0.971
1:63557135:T:G	F412L	0.971
1:63561736:T:A	L459Q	0.969
1:63531897:T:C	F89L	0.968
1:63531899:T:A	F89L	0.968
1:63531899:T:G	F89L	0.968
1:63557167:T:C	L423P	0.968
1:63568310:G:C	A500P	0.968
1:63532012:T:C	L127P	0.967

dbSNP variants (sampled 300 via entrez): RS1000058121 (1:63537312 T>C), RS1000222327 (1:63580765 GT>G), RS1000242096 (1:63568038 G>A), RS1000296826 (1:63553615 G>A,C), RS1000307445 (1:63544809 T>C,G), RS1000369769 (1:63546446 C>T), RS1000507141 (1:63524125 G>A), RS1000509970 (1:63581485 T>C,G), RS1000701355 (1:63545134 G>C,T), RS1000764979 (1:63524056 A>C), RS1000885261 (1:63560498 C>A,T), RS1000907906 (1:63546451 G>A), RS1000989049 (1:63531152 C>A,T), RS1001002570 (1:63565776 G>C), RS1001029063 (1:63539377 C>T)

Disease associations

OMIM: gene MIM:617632 | disease phenotypes: MIM:174200

GenCC curated gene-disease

Disease	Classification	Inheritance
polydactyly	Moderate	Autosomal recessive

Mondo (2): postaxial polydactyly (MONDO:0020927), polydactyly (MONDO:0021003)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002397_633	Mean spheric corpuscular volume	1.000000e-12

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D017689	Polydactyly	C05.660.585.600; C16.131.621.585.600

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation, increases expression	2
Cyclosporine	increases expression	2
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
urushiol	decreases expression	1
triphenyl phosphate	affects expression	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, decreases reaction	1
MT19c compound	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic	affects methylation	1
Calcitriol	increases expression	1
Doxorubicin	affects response to substance	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Lipopolysaccharides	decreases reaction, decreases expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Vinblastine	affects response to substance	1
Zinc	affects cotreatment, increases expression	1
Oxyquinoline	decreases expression	1
Aflatoxin B1	decreases methylation	1
Aflatoxin M1	decreases expression	1
Paclitaxel	affects response to substance	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00001404	Not specified	COMPLETED	Phenotype and Etiology of Pallister-Hall Syndrome
NCT06239064	Not specified	ACTIVE_NOT_RECRUITING	Early Genetic Identification of Obesity