ENKUR

Summary

ENKUR (enkurin, TRPC channel interacting protein, HGNC:28388) is a protein-coding gene on chromosome 10p12.1, encoding Enkurin (Q8TC29). Adapter that functions to localize a calcium-sensitive signal transduction machinery in sperm to a calcium-permeable ion channel.

This gene encodes a protein that interacts with calmodulin and several transient receptor potential canonical cation channel proteins. The encoded protein may function as an adaptor to localize signal transduction machinery to calcium channels. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 219670 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 160 total
• MANE Select transcript: NM_145010

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28388
Approved symbol	ENKUR
Name	enkurin, TRPC channel interacting protein
Location	10p12.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC26778, enkurin, CFAP106
Ensembl gene	ENSG00000151023
Ensembl biotype	protein_coding
OMIM	611025
Entrez	219670

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

ENST00000331161, ENST00000376363, ENST00000483339, ENST00000496261, ENST00000615958

RefSeq mRNA: 2 — MANE Select: NM_145010 NM_001270383, NM_145010

CCDS: CCDS7146, CCDS73075

Canonical transcript exons

ENST00000331161 — 6 exons

Exon	Start	End
ENSE00001154084	24999401	24999546
ENSE00001311475	24981985	24984376
ENSE00002932410	24990463	24990609
ENSE00002972386	24984736	24984905
ENSE00003561253	24995646	24995869
ENSE00003846310	25015860	25016158

Expression profiles

Bgee: expression breadth ubiquitous, 157 present calls, max score 95.54.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3035 / max 108.5483, expressed in 276 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
108711	1.1788	226
108714	0.1053	46
108713	0.0195	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	95.54	gold quality
right uterine tube	UBERON:0001302	94.56	gold quality
monocyte	CL:0000576	94.01	gold quality
bronchus	UBERON:0002185	93.28	gold quality
leukocyte	CL:0000738	92.49	gold quality
oviduct epithelium	UBERON:0004804	90.71	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.10	gold quality
ventricular zone	UBERON:0003053	88.40	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.88	gold quality
mucosa of paranasal sinus	UBERON:0005030	84.75	gold quality
bone marrow cell	CL:0002092	84.48	gold quality
fallopian tube	UBERON:0003889	82.01	gold quality
hypothalamus	UBERON:0001898	80.94	gold quality
caudate nucleus	UBERON:0001873	80.15	gold quality
ganglionic eminence	UBERON:0004023	79.93	gold quality
putamen	UBERON:0001874	78.52	gold quality
nucleus accumbens	UBERON:0001882	78.43	gold quality
colonic epithelium	UBERON:0000397	78.26	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.89	gold quality
amygdala	UBERON:0001876	76.67	gold quality
anterior cingulate cortex	UBERON:0009835	76.48	gold quality
prefrontal cortex	UBERON:0000451	75.42	gold quality
right frontal lobe	UBERON:0002810	75.32	gold quality
spinal cord	UBERON:0002240	75.01	gold quality
adenohypophysis	UBERON:0002196	74.91	gold quality
Brodmann (1909) area 9	UBERON:0013540	74.72	gold quality
substantia nigra	UBERON:0002038	73.53	gold quality
pituitary gland	UBERON:0000007	73.33	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	72.42	gold quality
granulocyte	CL:0000094	72.26	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	419.82
E-CURD-114	yes	61.06
E-MTAB-10287	yes	26.19
E-HCAD-1	yes	25.99
E-GEOD-130148	yes	12.75
E-ANND-3	yes	9.99
E-MTAB-7249	no	48.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

117 targeting ENKUR, 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-3613-3P	100.00	76.36	7965
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 4)

• Data suggest that enkurin is an adaptor that functions to localize a Ca2+ sensitive signal transduction machinery in sperm to a Ca2+-permeable ion channel [enkurin] (PMID:15385169)
• Decreased ENKUR expression is associated with Colorectal Cancer. (PMID:30947633)
• ENKUR expression induced by chemically synthesized cinobufotalin suppresses malignant activities of hepatocellular carcinoma by modulating beta-catenin/c-Jun/MYH9/USP7/c-Myc axis. (PMID:35414777)
• Enkurin: a novel marker for myeloproliferative neoplasms from platelet, megakaryocyte, and whole blood specimens. (PMID:37315179)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	enkur	ENSDARG00000031248
mus_musculus	Enkur	ENSMUSG00000026679
rattus_norvegicus	Enkur	ENSRNOG00000018631
drosophila_melanogaster	CG16984	FBGN0062517

Paralogs (1): ENKD1 (ENSG00000124074)

Protein

Protein identifiers

Enkurin — Q8TC29 (reviewed: Q8TC29)

All UniProt accessions (4): Q8TC29, A0A087WUX1, L7N489, Q5VV23

UniProt curated annotations — full annotation on UniProt →

Function. Adapter that functions to localize a calcium-sensitive signal transduction machinery in sperm to a calcium-permeable ion channel. Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.

Subunit / interactions. Microtubule inner protein component of sperm flagellar doublet microtubules. Binds calmodulin via its IQ domain. Interacts with TRPC1, TRPC2, TRPC5, but not TRPC3. Interacts with CFAP45.

Subcellular location. Cytoplasm. Cytoskeleton. Cilium axoneme. Flagellum axoneme.

Tissue specificity. Expressed in airway epithelial cells.

Domain organisation. The IQ motif is involved in calmodulin binding.

RefSeq proteins (2): NP_001257312, NP_659447* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027012	Enkurin_dom	Domain
IPR052102	Enkurin_domain-protein	Family

Pfam: PF13864

UniProt features (5 total): domain 2, chain 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7UNG	ELECTRON MICROSCOPY	3.6
8J07	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TC29-F1	87.24	0.44

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 117 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, GOCC_SECRETORY_GRANULE, EFC_Q6, GOBP_SPECIFICATION_OF_SYMMETRY, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, RFX1_02, chr10p12, GOCC_CYTOPLASMIC_REGION, GOCC_SECRETORY_VESICLE, GOCC_MOTILE_CILIUM, GOCC_SPERM_PRINCIPAL_PIECE, GOCC_SPERM_MIDPIECE, GOCC_ACROSOMAL_VESICLE

GO Biological Process (2): flagellated sperm motility (GO:0030317), establishment of left/right asymmetry (GO:0061966)

GO Molecular Function (3): calmodulin binding (GO:0005516), SH3 domain binding (GO:0017124), protein binding (GO:0005515)

GO Cellular Component (13): acrosomal vesicle (GO:0001669), axonemal microtubule (GO:0005879), sperm flagellum (GO:0036126), sperm principal piece (GO:0097228), 9+0 motile cilium (GO:0097728), 9+2 motile cilium (GO:0097729), axonemal B tubule inner sheath (GO:0160112), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), microtubule cytoskeleton (GO:0015630), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
motile cilium	2
inner dynein arm	2
outer dynein arm	2
axonemal doublet microtubule	2
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
determination of left/right symmetry	1
protein binding	1
protein domain specific binding	1
binding	1
secretory granule	1
cytoplasmic microtubule	1
axoneme	1
9+2 motile cilium	1
sperm flagellum	1
radial spoke	1
axonemal central pair	1
A axonemal microtubule	1
axonemal microtubule doublet inner sheath	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
cytoskeleton	1
cilium	1

Protein interactions and networks

STRING

1217 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENKUR	TRPC5	Q9UL62	834
ENKUR	CALM1	P02593	782
ENKUR	CALML6	Q8TD86	778
ENKUR	CALML3	P27482	778
ENKUR	CALML4	Q96GE6	778
ENKUR	CALML5	Q9NZT1	778
ENKUR	TRPC1	P48995	635
ENKUR	PACRG	Q96M98	509
ENKUR	PIK3R1	P27986	490
ENKUR	PLAC8L1	A1L4L8	452
ENKUR	CLGN	O14967	443
ENKUR	CABS1	Q96KC9	431
ENKUR	IQUB	Q8NA54	423
ENKUR	FAM81B	Q96LP2	420
ENKUR	SESTD1	Q86VW0	420

IntAct

58 interactions, top by confidence:

A	B	Type	Score
ENKUR	CFAP45	psi-mi:“MI:0915”(physical association)	0.560
ENKUR	APBB2	psi-mi:“MI:0915”(physical association)	0.560
ENKUR	DCTN1	psi-mi:“MI:0915”(physical association)	0.560
ENKUR		psi-mi:“MI:0915”(physical association)	0.560
PRKN	ENKUR	psi-mi:“MI:0915”(physical association)	0.560
ENKUR	PMP22	psi-mi:“MI:0915”(physical association)	0.560
ENKUR	PRPH	psi-mi:“MI:0915”(physical association)	0.560
ENKUR	UCHL1	psi-mi:“MI:0915”(physical association)	0.560
ENKUR	HTRA2	psi-mi:“MI:0915”(physical association)	0.560
SOD1	ENKUR	psi-mi:“MI:0915”(physical association)	0.560
SNCA	ENKUR	psi-mi:“MI:0915”(physical association)	0.560
HTT	ENKUR	psi-mi:“MI:0915”(physical association)	0.560
ATXN1	ENKUR	psi-mi:“MI:0915”(physical association)	0.560
TARDBP	ENKUR	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (26): ENKUR (Reconstituted Complex), ENKUR (Reconstituted Complex), ENKUR (Affinity Capture-Western), ENKUR (Reconstituted Complex), ENKUR (Reconstituted Complex), ENKUR (Reconstituted Complex), CFAP45 (Two-hybrid), ENKUR (Proximity Label-MS), MYH9 (Affinity Capture-Western), ENKUR (Affinity Capture-Western), CTNNB1 (Affinity Capture-Western), S (Reconstituted Complex), CTNNB1 (Affinity Capture-Western), ENKUR (Affinity Capture-Western), MYH9 (Affinity Capture-Western)

ESM2 similar proteins: A0A1B0GVH7, A0A4X1TZW7, A0A5F8MPE6, E1B836, E1C760, E7EXT2, F7AEX0, O74370, O95391, P21374, P51950, Q20716, Q24276, Q24740, Q28E45, Q2F5J3, Q2KI00, Q3B820, Q3KQD1, Q3TGF2, Q3ZBE5, Q45GW3, Q4R4P2, Q502W7, Q569B9, Q5EAW4, Q5RHY1, Q5U4F3, Q5XI37, Q5XIN9, Q5ZIG2, Q69ZQ2, Q6SP97, Q7L590, Q80ZG5, Q8BHJ9, Q8BRC6, Q8CDN8, Q8NCR3, Q8TC29

Diamond homologs: A0A4X1TZW7, E1B836, Q6SP97, Q8TC29

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 15 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of apoptotic process	6	22.7×	6e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	143
Likely benign	11
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1240 predictions. Top by Δscore:

Variant	Effect	Δscore
10:24984734:A:AC	donor_gain	1.0000
10:24984735:C:CC	donor_gain	1.0000
10:24984738:A:AC	donor_gain	1.0000
10:24990458:CACA:C	donor_loss	1.0000
10:24990459:ACAC:A	donor_loss	1.0000
10:24990461:A:T	donor_loss	1.0000
10:24990462:C:CT	donor_loss	1.0000
10:24990477:C:A	donor_gain	1.0000
10:24990605:TAATC:T	acceptor_gain	1.0000
10:24990608:TC:T	acceptor_gain	1.0000
10:24990609:CC:C	acceptor_gain	1.0000
10:24990610:CTAAA:C	acceptor_loss	1.0000
10:24990611:T:A	acceptor_loss	1.0000
10:24990621:T:C	acceptor_gain	1.0000
10:24995663:TTGGA:T	donor_gain	1.0000
10:24995865:TTTTT:T	acceptor_gain	1.0000
10:24995867:TTT:T	acceptor_gain	1.0000
10:24995870:C:CC	acceptor_gain	1.0000
10:24999399:A:AC	donor_gain	1.0000
10:24999400:C:CC	donor_gain	1.0000
10:25021740:A:AG	acceptor_gain	1.0000
10:25021741:G:GG	acceptor_gain	1.0000
10:25021909:G:GG	donor_gain	1.0000
10:24984738:ATTGG:A	donor_gain	0.9900
10:24984739:T:C	donor_gain	0.9900
10:24984772:ATG:A	donor_gain	0.9900
10:24990606:AATC:A	acceptor_gain	0.9900
10:24990607:ATC:A	acceptor_gain	0.9900
10:24990610:C:CC	acceptor_gain	0.9900
10:24990610:C:T	acceptor_gain	0.9900

AlphaMissense

1718 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:24984867:G:C	F211L	0.989
10:24984867:G:T	F211L	0.989
10:24984869:A:G	F211L	0.989
10:24984819:C:A	K227N	0.986
10:24984819:C:G	K227N	0.986
10:24984901:A:G	L200P	0.983
10:24984790:A:G	L237P	0.981
10:24984811:A:G	L230P	0.975
10:24990575:C:G	R161P	0.975
10:24984799:A:G	M234T	0.967
10:24984868:A:G	F211S	0.960
10:24984853:A:T	V216D	0.956
10:24999438:G:C	F62L	0.952
10:24999438:G:T	F62L	0.952
10:24999440:A:G	F62L	0.952
10:24995671:A:G	L141P	0.951
10:24984859:A:G	L214P	0.950
10:24984888:C:A	W204C	0.948
10:24984888:C:G	W204C	0.948
10:24984823:C:G	R226P	0.947
10:24984897:T:A	K201N	0.946
10:24984897:T:G	K201N	0.946
10:24995716:A:T	V126D	0.943
10:24984863:A:G	S213P	0.941
10:24999476:C:G	G50R	0.939
10:24999476:C:T	G50R	0.939
10:24995778:A:C	F105L	0.937
10:24995778:A:T	F105L	0.937
10:24995780:A:G	F105L	0.937
10:24984821:T:C	K227E	0.936

dbSNP variants (sampled 300 via entrez): RS1000037406 (10:25015862 A>G), RS1000039019 (10:25015986 T>C), RS1000046400 (10:25007141 A>T), RS1000144010 (10:25050436 T>A), RS1000177235 (10:25055887 A>G), RS1000257642 (10:25056423 C>G,T), RS1000286167 (10:25035097 G>A,C,T), RS1000300998 (10:25012962 G>A), RS1000329746 (10:25061522 T>C), RS1000401488 (10:25062203 T>C), RS1000432409 (10:25061899 T>C), RS1000448046 (10:25030429 A>G), RS1000467546 (10:25007735 C>T), RS1000629391 (10:25056654 G>A), RS1000630912 (10:25031110 C>G)

Disease associations

OMIM: gene MIM:611025 | 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
GCST002875_1	Diisocyanate-induced asthma	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
arsenite	increases methylation	1
sodium arsenite	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Air Pollutants, Occupational	increases expression	1
Benzo(a)pyrene	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Malathion	increases expression	1
Methotrexate	increases expression	1
Nickel	increases expression	1
Oxygen	increases expression	1
Smoke	increases expression, increases abundance	1
Tobacco Smoke Pollution	affects expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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