ENKD1

Summary

ENKD1 (enkurin domain containing 1, HGNC:25246) is a protein-coding gene on chromosome 16q22.1, encoding Enkurin domain-containing protein 1 (Q9H0I2). Microtubule-binding protein which regulates microtubule organization and stability.

Enables alpha-tubulin binding activity and microtubule binding activity. Involved in establishment of mitotic spindle orientation and non-motile cilium assembly. Located in microtubule cytoskeleton and plasma membrane.

Source: NCBI Gene 84080 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 74 total — 1 pathogenic
• MANE Select transcript: NM_032140

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25246
Approved symbol	ENKD1
Name	enkurin domain containing 1
Location	16q22.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434A1319, FBB11
Ensembl gene	ENSG00000124074
Ensembl biotype	protein_coding
OMIM	621119
Entrez	84080

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000243878, ENST00000602409, ENST00000602415, ENST00000602531, ENST00000602642, ENST00000602644, ENST00000602942, ENST00000857832

RefSeq mRNA: 1 — MANE Select: NM_032140 NM_032140

CCDS: CCDS10844

Canonical transcript exons

ENST00000243878 — 7 exons

Exon	Start	End
ENSE00000844194	67666358	67666750
ENSE00001863371	67662945	67663321
ENSE00003489328	67666071	67666265
ENSE00003627296	67663937	67664062
ENSE00003673205	67663657	67663820
ENSE00003683024	67663420	67663556
ENSE00003728349	67664996	67665168

Expression profiles

Bgee: expression breadth ubiquitous, 228 present calls, max score 97.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.7541 / max 50.0734, expressed in 1704 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157811	6.3827	1650
157812	0.3714	201

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	97.53	gold quality
right uterine tube	UBERON:0001302	96.57	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.32	gold quality
cerebellar hemisphere	UBERON:0002245	96.04	gold quality
cerebellar cortex	UBERON:0002129	95.82	gold quality
right testis	UBERON:0004534	94.78	gold quality
left testis	UBERON:0004533	94.70	gold quality
cerebellum	UBERON:0002037	93.74	gold quality
adenohypophysis	UBERON:0002196	92.92	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.30	gold quality
lower esophagus	UBERON:0013473	92.27	gold quality
metanephros cortex	UBERON:0010533	92.11	gold quality
testis	UBERON:0000473	92.10	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.06	gold quality
pituitary gland	UBERON:0000007	91.80	gold quality
right lobe of thyroid gland	UBERON:0001119	91.80	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	91.63	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.58	gold quality
left lobe of thyroid gland	UBERON:0001120	91.24	gold quality
body of uterus	UBERON:0009853	90.89	gold quality
bronchial epithelial cell	CL:0002328	90.69	gold quality
tibial nerve	UBERON:0001323	90.16	gold quality
thyroid gland	UBERON:0002046	89.99	gold quality
left ovary	UBERON:0002119	89.97	gold quality
right ovary	UBERON:0002118	89.90	gold quality
endocervix	UBERON:0000458	89.82	gold quality
left uterine tube	UBERON:0001303	89.78	gold quality
bronchus	UBERON:0002185	89.68	gold quality
pancreas	UBERON:0001264	89.65	gold quality
mucosa of stomach	UBERON:0001199	89.30	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.06

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting ENKD1, 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-1184	99.99	68.19	1458
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-4252	98.45	66.37	987
HSA-MIR-7156-3P	98.25	67.66	859
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-3121-5P	97.30	66.62	1146
HSA-MIR-514A-3P	96.43	67.77	1048
HSA-MIR-514B-3P	96.43	67.77	1048

Literature-anchored findings (GeneRIF, showing 2)

• Enkurin domain containing 1 (ENKD1) regulates the proliferation, migration and invasion of non-small cell lung cancer cells. (PMID:33724673)
• Upregulation of ENKD1 disrupts cellular homeostasis to promote lymphoma development. (PMID:36960713)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	enkd1	ENSDARG00000043550
mus_musculus	Enkd1	ENSMUSG00000013155
rattus_norvegicus	Enkd1	ENSRNOG00000024364
drosophila_melanogaster	CG11125	FBGN0033174

Paralogs (1): ENKUR (ENSG00000151023)

Protein

Protein identifiers

Enkurin domain-containing protein 1 — Q9H0I2 (reviewed: Q9H0I2)

All UniProt accessions (3): A0A087X0D0, Q9H0I2, R4GN60

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule-binding protein which regulates microtubule organization and stability. Promotes the stability of astral microtubules and facilitates the proper orientation of the mitotic spindle. This allows the oriented division of basal keratinocytes and contributes to epidermal stratification. Required for the assembly of both primary and motile cilia. Destabilizes the interaction between CCP110 and CEP97 by competing with CEP97 for binding to CCP110 which promotes the removal of CCP110 and CEP97 from the mother centriole and allows the initiation of ciliogenesis.

Subunit / interactions. Interacts with alpha-tubulin. Interacts (via central region) with CCP110 (via N-terminal region); competes with CEP97 for binding to CCP110.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Centriole. Cilium basal body. Cell projection. Cilium. Spindle. Spindle pole. Cilium axoneme.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H0I2-1	1	yes
Q9H0I2-2	2

RefSeq proteins (1): NP_115516* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027012	Enkurin_dom	Domain
IPR052102	Enkurin_domain-protein	Family

Pfam: PF13864

UniProt features (13 total): region of interest 5, modified residue 2, splice variant 2, compositionally biased region 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H0I2-F1	77.54	0.39

Functional residue map

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

Post-translational modifications (2): 136, 91

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 128 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, MYOGENIN_Q6, chr16q22, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_SPINDLE_LOCALIZATION, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_ESTABLISHMENT_OF_CELL_POLARITY, GOBP_CILIUM_ORGANIZATION, GOCC_CENTROSOME, GGGNNTTTCC_NFKB_Q6_01, GOBP_ORGANELLE_ASSEMBLY, GOBP_MITOTIC_CELL_CYCLE, GOBP_MOTILE_CILIUM_ASSEMBLY

GO Biological Process (4): establishment of mitotic spindle orientation (GO:0000132), motile cilium assembly (GO:0044458), non-motile cilium assembly (GO:1905515), cell projection organization (GO:0030030)

GO Molecular Function (3): microtubule binding (GO:0008017), alpha-tubulin binding (GO:0043014), protein binding (GO:0005515)

GO Cellular Component (16): spindle pole (GO:0000922), centrosome (GO:0005813), centriole (GO:0005814), cytoplasmic microtubule (GO:0005881), plasma membrane (GO:0005886), cilium (GO:0005929), axoneme (GO:0005930), microtubule cytoskeleton (GO:0015630), ciliary basal body (GO:0036064), ciliary base (GO:0097546), 9+0 non-motile cilium (GO:0097731), cytoplasm (GO:0005737), spindle (GO:0005819), cytoskeleton (GO:0005856), microtubule (GO:0005874), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
microtubule organizing center	3
intracellular membraneless organelle	3
cilium assembly	2
tubulin binding	2
microtubule	2
cytoskeleton	2
cilium	2
microtubule cytoskeleton	2
mitotic cell cycle	1
establishment of mitotic spindle localization	1
establishment of spindle orientation	1
cellular component organization	1
binding	1
spindle	1
centriole	1
cytoplasm	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
ciliary plasm	1
ciliary transition zone	1
ciliary transition fiber	1
non-motile cilium	1
intracellular anatomical structure	1
polymeric cytoskeletal fiber	1

Protein interactions and networks

STRING

538 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENKD1	CLHC1	Q8NHS4	555
ENKD1	TMEM129	A0AVI4	483
ENKD1	CALY	Q9NYX4	475
ENKD1	ANKRD13D	Q6ZTN6	446
ENKD1	GFOD2	Q3B7J2	431
ENKD1	C1orf35	Q9BU76	431
ENKD1	SCRN1	Q12765	417
ENKD1	SLC49A3	Q6UXD7	417
ENKD1	CARD6	Q9BX69	374
ENKD1	DEF8	Q6ZN54	373
ENKD1	DAW1	Q8N136	370
ENKD1	PRM3	Q9NNZ6	370
ENKD1	SERPINB11	Q96P15	368
ENKD1	ANKRD13A	Q8IZ07	366
ENKD1	STAC3	Q96MF2	359

IntAct

718 interactions, top by confidence:

A	B	Type	Score
PNMA2	ENKD1	psi-mi:“MI:0915”(physical association)	0.870
ENKD1	PNMA2	psi-mi:“MI:0915”(physical association)	0.870
ENKD1	MDFI	psi-mi:“MI:0915”(physical association)	0.830
MDFI	ENKD1	psi-mi:“MI:0915”(physical association)	0.830
TRAF2	ENKD1	psi-mi:“MI:0915”(physical association)	0.780
SPSB3	ENKD1	psi-mi:“MI:0915”(physical association)	0.720
CCDC102B	ENKD1	psi-mi:“MI:0915”(physical association)	0.720
ENKD1	CDR2	psi-mi:“MI:0915”(physical association)	0.720
ENKD1	MIPOL1	psi-mi:“MI:0915”(physical association)	0.720
TRIM54	ENKD1	psi-mi:“MI:0915”(physical association)	0.720
ENKD1	SPSB3	psi-mi:“MI:0915”(physical association)	0.720
CDR2	ENKD1	psi-mi:“MI:0915”(physical association)	0.720
ENKD1	TRIM54	psi-mi:“MI:0915”(physical association)	0.720
ENKD1	CCDC102B	psi-mi:“MI:0915”(physical association)	0.720
MIPOL1	ENKD1	psi-mi:“MI:0915”(physical association)	0.720
MKRN3	ENKD1	psi-mi:“MI:0915”(physical association)	0.670
ENKD1	PHC2	psi-mi:“MI:0915”(physical association)	0.670
ENKD1	CEP70	psi-mi:“MI:0915”(physical association)	0.670
CEP70	ENKD1	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (254): ENKD1 (Two-hybrid), ENKD1 (Two-hybrid), ENKD1 (Two-hybrid), ENKD1 (Two-hybrid), ENKD1 (Two-hybrid), ENKD1 (Two-hybrid), ENKD1 (Two-hybrid), ENKD1 (Two-hybrid), ENKD1 (Two-hybrid), ENKD1 (Two-hybrid), ENKD1 (Two-hybrid), ENKD1 (Two-hybrid), ENKD1 (Two-hybrid), ENKD1 (Two-hybrid), SPSB3 (Two-hybrid)

ESM2 similar proteins: A6H7J2, B5G1P1, B5X7E4, E9PRG8, O70279, P53814, P58468, P86346, Q13111, Q13487, Q28IC1, Q2KIL7, Q3T078, Q58CQ0, Q5E9N0, Q5I034, Q5I0E3, Q5ZMG5, Q6CT43, Q751T1, Q758S2, Q75E67, Q7TSV9, Q7ZWE7, Q80VC9, Q80Y56, Q86WX3, Q8C3W1, Q8C6B9, Q8K305, Q8NEG2, Q8WUQ7, Q96C57, Q96DF8, Q96IY1, Q96KC8, Q99L00, Q99PT3, Q9BRJ6, Q9CS00

Diamond homologs: Q3T078, Q7TSV9, Q9H0I2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	62
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
59493	GRCh38/hg38 16q21-22.1(chr16:64311275-68062011)x1	Pathogenic

SpliceAI

961 predictions. Top by Δscore:

Variant	Effect	Δscore
16:67663317:CTGGC:C	acceptor_gain	1.0000
16:67663318:TGGC:T	acceptor_gain	1.0000
16:67663320:GCC:G	acceptor_loss	1.0000
16:67663322:C:CC	acceptor_gain	1.0000
16:67663322:CTAC:C	acceptor_loss	1.0000
16:67663334:C:CT	acceptor_gain	1.0000
16:67663334:C:T	acceptor_gain	1.0000
16:67663335:G:T	acceptor_gain	1.0000
16:67663414:A:AC	donor_gain	1.0000
16:67663415:C:CC	donor_gain	1.0000
16:67663415:CTCA:C	donor_gain	1.0000
16:67663416:TCA:T	donor_loss	1.0000
16:67663417:CACT:C	donor_loss	1.0000
16:67663418:A:AC	donor_gain	1.0000
16:67663418:ACT:A	donor_gain	1.0000
16:67663419:C:CA	donor_gain	1.0000
16:67663419:CT:C	donor_gain	1.0000
16:67663419:CTC:C	donor_gain	1.0000
16:67663419:CTCT:C	donor_gain	1.0000
16:67663419:CTCTG:C	donor_gain	1.0000
16:67663553:CAAG:C	acceptor_gain	1.0000
16:67663554:AAG:A	acceptor_gain	1.0000
16:67663556:GC:G	acceptor_loss	1.0000
16:67663557:C:CC	acceptor_gain	1.0000
16:67663655:A:AC	donor_gain	1.0000
16:67663656:C:CC	donor_gain	1.0000
16:67663656:CTA:C	donor_gain	1.0000
16:67663656:CTAA:C	donor_gain	1.0000
16:67663656:CTAAT:C	donor_gain	1.0000
16:67663668:ATGGC:A	donor_gain	1.0000

AlphaMissense

2210 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:67663179:G:C	F341L	0.979
16:67663179:G:T	F341L	0.979
16:67663181:A:G	F341L	0.979
16:67663211:C:G	A331P	0.975
16:67663797:G:C	F201L	0.964
16:67663797:G:T	F201L	0.964
16:67663799:A:G	F201L	0.964
16:67663464:A:G	M279T	0.959
16:67663197:A:C	F335L	0.958
16:67663197:A:T	F335L	0.958
16:67663199:A:G	F335L	0.958
16:67663428:A:G	L291P	0.942
16:67663554:A:G	L249S	0.941
16:67663309:A:G	L298P	0.931
16:67663198:A:G	F335S	0.925
16:67663228:A:G	L325P	0.922
16:67663437:A:G	L288P	0.922
16:67664024:G:C	F164L	0.917
16:67664024:G:T	F164L	0.917
16:67664026:A:G	F164L	0.917
16:67663449:C:G	R284P	0.914
16:67663545:C:G	R252P	0.914
16:67665129:C:G	R107P	0.914
16:67663240:A:G	L321P	0.913
16:67663180:A:C	F341C	0.912
16:67663297:A:G	L302P	0.904
16:67663180:A:G	F341S	0.900
16:67663474:G:C	H276D	0.898
16:67663201:A:G	I334T	0.887
16:67666408:A:G	I12T	0.884

dbSNP variants (sampled 300 via entrez): RS1002497400 (16:67664480 C>T), RS1002798011 (16:67665023 C>T), RS1003259727 (16:67667385 G>A,C,T), RS1004170418 (16:67668722 G>T), RS1004685099 (16:67667518 C>T), RS1004858158 (16:67662569 C>T), RS1004991220 (16:67667160 C>T), RS1005451035 (16:67663850 C>G), RS1005797462 (16:67666913 C>A,T), RS1005846163 (16:67667176 G>C), RS1006823805 (16:67666240 C>G), RS1006918588 (16:67666575 G>A,T), RS1006956974 (16:67664159 C>T), RS1007107608 (16:67664436 C>A,G), RS1007705936 (16:67663009 C>A,T)

Disease associations

OMIM: gene MIM:621119 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002539_84	Schizophrenia	2.000000e-08
GCST005751_4	Empathy quotient	9.000000e-07
GCST006803_42	Schizophrenia	4.000000e-08
GCST010002_113	Refractive error	2.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009183	empathy measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
jinfukang	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	decreases expression	1
Atrazine	decreases expression	1
Cisplatin	increases expression	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Tunicamycin	increases expression	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	decreases expression	1
Thapsigargin	increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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