EIF3CL

Summary

EIF3CL (eukaryotic translation initiation factor 3 subunit C like, HGNC:26347) is a protein-coding gene on chromosome 16p12.1, encoding Eukaryotic translation initiation factor 3 subunit C-like protein (B5ME19). Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis.

The protein encoded by this gene is a core subunit of the eukaryotic translation initiation factor 3 (eIF3) complex. The encoded protein is nearly identical to another protein, eIF3c, from a related gene. The eIF3 complex binds the 40S ribosome and mRNAs to enable translation initiation. Several transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 728689 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 12 total
• MANE Select transcript: NM_001317857

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26347
Approved symbol	EIF3CL
Name	eukaryotic translation initiation factor 3 subunit C like
Location	16p12.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000205609
Ensembl biotype	protein_coding
Entrez	728689

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000380876, ENST00000398944, ENST00000864343, ENST00000918077, ENST00000918078, ENST00000962381, ENST00000962382, ENST00000962383

RefSeq mRNA: 3 — MANE Select: NM_001317857 NM_001099661, NM_001317856, NM_001317857

CCDS: CCDS42136

Canonical transcript exons

ENST00000380876 — 21 exons

Exon	Start	End
ENSE00001602876	28391980	28392142
ENSE00001622183	28400615	28400669
ENSE00001631040	28388508	28388698
ENSE00001636926	28380292	28380379
ENSE00001666906	28401539	28401604
ENSE00001679591	28388058	28388282
ENSE00001697307	28383118	28383481
ENSE00001709881	28391752	28391855
ENSE00001712108	28380468	28380533
ENSE00001718695	28400377	28400486
ENSE00001722268	28379976	28380138
ENSE00001735371	28399871	28399998
ENSE00001736622	28401207	28401396
ENSE00001755465	28390840	28390981
ENSE00001759897	28380632	28380791
ENSE00001761111	28390520	28390645
ENSE00001776765	28400859	28400984
ENSE00001790058	28390291	28390384
ENSE00001849218	28403787	28403841
ENSE00001940731	28379715	28379880
ENSE00002367001	28403518	28403648

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 92.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.6456 / max 201.7010, expressed in 1810 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153386	24.6456	1810

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	92.94	gold quality
lower esophagus mucosa	UBERON:0035834	87.00	gold quality
heart left ventricle	UBERON:0002084	85.92	gold quality
mucosa of transverse colon	UBERON:0004991	84.90	gold quality
colonic epithelium	UBERON:0000397	84.08	gold quality
right atrium auricular region	UBERON:0006631	84.07	gold quality
heart	UBERON:0000948	83.67	gold quality
skeletal muscle tissue	UBERON:0001134	83.27	gold quality
gastrocnemius	UBERON:0001388	83.00	gold quality
anterior cingulate cortex	UBERON:0009835	82.91	gold quality
Ammon’s horn	UBERON:0001954	82.65	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.43	gold quality
right frontal lobe	UBERON:0002810	82.36	gold quality
putamen	UBERON:0001874	81.94	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.90	gold quality
amygdala	UBERON:0001876	81.63	gold quality
muscle of leg	UBERON:0001383	81.56	gold quality
stromal cell of endometrium	CL:0002255	81.53	gold quality
temporal lobe	UBERON:0001871	81.52	gold quality
right hemisphere of cerebellum	UBERON:0014890	80.96	gold quality
nucleus accumbens	UBERON:0001882	80.68	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.68	gold quality
cerebellar hemisphere	UBERON:0002245	80.58	gold quality
cerebral cortex	UBERON:0000956	80.48	gold quality
primary visual cortex	UBERON:0002436	80.46	gold quality
right lobe of liver	UBERON:0001114	80.34	gold quality
muscle tissue	UBERON:0002385	80.33	gold quality
substantia nigra	UBERON:0002038	80.32	gold quality
brain	UBERON:0000955	80.30	gold quality
hypothalamus	UBERON:0001898	80.18	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	18.24
E-MTAB-8060	no	554.92
E-CURD-53	no	511.71
E-MTAB-7008	no	81.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting EIF3CL, 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-3617-3P	99.98	67.86	918
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-1228-3P	99.00	66.53	857
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-1199-5P	98.44	66.51	829
HSA-MIR-6751-3P	98.44	66.35	835
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-4759	97.39	65.86	608
HSA-MIR-134-5P	97.11	66.52	976
HSA-MIR-3118	97.11	66.58	984
HSA-MIR-921	97.09	66.45	562
HSA-MIR-215-3P	97.02	68.01	1209
HSA-MIR-6759-3P	96.94	68.31	823
HSA-MIR-34A-3P	96.80	67.70	805
HSA-MIR-6854-5P	96.77	65.96	848
HSA-MIR-6857-3P	96.70	65.43	915
HSA-MIR-3117-3P	95.96	67.82	473
HSA-MIR-8083	95.93	67.55	694

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	eif3c	ENSDARG00000016443
mus_musculus	Eif3c	ENSMUSG00000030738
rattus_norvegicus	Eif3c	ENSRNOG00000018761
drosophila_melanogaster	eIF3c	FBGN0034258
caenorhabditis_elegans	eif-3.C	WBGENE00001226

Paralogs (1): EIF3C (ENSG00000184110)

Protein

Protein identifiers

Eukaryotic translation initiation factor 3 subunit C-like protein — B5ME19 (reviewed: B5ME19)

All UniProt accessions (1): B5ME19

UniProt curated annotations — full annotation on UniProt →

Function. Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression.

Subunit / interactions. Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex interacts with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation leads to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3.

Subcellular location. Cytoplasm.

Post-translational modifications. Phosphorylated. Phosphorylation is enhanced upon serum stimulation.

Similarity. Belongs to the eIF-3 subunit C family.

RefSeq proteins (3): NP_001093131, NP_001304785, NP_001304786* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000717	PCI_dom	Domain
IPR008905	EIF3C_N_dom	Domain
IPR027516	EIF3C	Family
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR058999	EIF3CL_C	Domain

Pfam: PF01399, PF05470, PF26569

UniProt features (29 total): modified residue 15, compositionally biased region 8, region of interest 4, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-B5ME19-F1	74.11	0.27

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 (15): 9, 11, 13, 15, 16, 18, 39, 99, 166, 178, 181, 182, 525, 644, 910

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 29 (showing top): GOBP_CYTOPLASMIC_TRANSLATION, GOBP_TRANSLATIONAL_INITIATION, GOCC_EUKARYOTIC_TRANSLATION_INITIATION_FACTOR_3_COMPLEX, GOMF_TRANSLATION_INITIATION_FACTOR_ACTIVITY, GOBP_TRANSLATION, GOBP_CYTOPLASMIC_TRANSLATIONAL_INITIATION, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, LINDVALL_IMMORTALIZED_BY_TERT_UP, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, chr16p12, GOCC_RIBONUCLEOPROTEIN_COMPLEX, GOCC_CYTOSOLIC_TRANSLATION_PREINITIATION_COMPLEX, GOMF_TRANSLATION_INITIATION_FACTOR_BINDING, E2F3_UP.V1_DN, SRC_UP.V1_DN

GO Biological Process (4): formation of cytoplasmic translation initiation complex (GO:0001732), translational initiation (GO:0006413), cytoplasmic translational initiation (GO:0002183), translation (GO:0006412)

GO Molecular Function (4): RNA binding (GO:0003723), translation initiation factor activity (GO:0003743), translation initiation factor binding (GO:0031369), protein binding (GO:0005515)

GO Cellular Component (4): eukaryotic translation initiation factor 3 complex (GO:0005852), eukaryotic 43S preinitiation complex (GO:0016282), eukaryotic 48S preinitiation complex (GO:0033290), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translational initiation	3
cytosolic small ribosomal subunit	2
cytosolic translation preinitiation complex	2
cytoplasmic translational initiation	1
protein-RNA complex assembly	1
formation of translation initiation ternary complex	1
translation	1
metabolic process	1
cytoplasmic translation	1
peptidyltransferase activity	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
nucleic acid binding	1
translation factor activity	1
protein binding	1
binding	1
cytoplasm	1
protein-containing complex	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1577 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EIF3CL	SOWAHD	A6NJG2	518
EIF3CL	EIF3D	O15371	507
EIF3CL	TUFM	P49411	497
EIF3CL	RABEP2	Q9H5N1	496
EIF3CL	EIF3F	O00303	490
EIF3CL	EIF3K	Q9UBQ5	458
EIF3CL	EIF2S2	P20042	458
EIF3CL	EIF3M	Q7L2H7	458
EIF3CL	EIF3L	Q9Y262	457
EIF3CL	EIF3G	O75821	454
EIF3CL	NPIPB9	F8W1W9	451
EIF3CL	LRRC47	Q8N1G4	449
EIF3CL	EIF3I	Q13347	447
EIF3CL	EIF3J	O75822	443
EIF3CL	EIF3A	Q14152	443

IntAct

66 interactions, top by confidence:

A	B	Type	Score
EIF3CL	EIF3H	psi-mi:“MI:0915”(physical association)	0.670
EIF3H	EIF3CL	psi-mi:“MI:0914”(association)	0.670
EIF3F	EIF3CL	psi-mi:“MI:0914”(association)	0.640
EIF3I	EIF3CL	psi-mi:“MI:0914”(association)	0.640
EIF3M	EIF3CL	psi-mi:“MI:0914”(association)	0.640
EIF3E	EIF3CL	psi-mi:“MI:0914”(association)	0.530
EIF3L	EIF3CL	psi-mi:“MI:0914”(association)	0.530
EIF3CL	H1-5	psi-mi:“MI:0915”(physical association)	0.400
STK4	EIF3CL	psi-mi:“MI:0914”(association)	0.350
OCRL	EIF3CL	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
RAB5A	EIF3CL	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
BMI1	HMGB1P1	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
RAF1	EIF3CL	psi-mi:“MI:0914”(association)	0.350

BioGRID (156): EIF3CL (Affinity Capture-MS), EIF3CL (Affinity Capture-MS), EIF3CL (Affinity Capture-MS), EIF3CL (Affinity Capture-MS), EIF3B (Co-fractionation), EIF3CL (Co-fractionation), EIF3CL (Co-fractionation), EIF3CL (Co-fractionation), EIF3CL (Co-fractionation), EIF3CL (Co-fractionation), EIF3CL (Co-fractionation), EIF3CL (Co-fractionation), EIF3D (Co-fractionation), EIF3G (Co-fractionation), EIF3CL (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3P7X4, A7S641, A8WG88, A9ULY7, B0R034, B0W6N3, B5DFC8, B5ME19, D6WIX5, E7EXT2, F7AEX0, O60308, O95202, P0C204, P45433, P53569, Q03701, Q0VA06, Q173M7, Q1L987, Q28HX4, Q3SYW6, Q3ZC50, Q4QR58, Q5RAT8, Q5RCI4, Q5U2X6, Q5XGZ8, Q5XIN6, Q5ZK33, Q66I12, Q6AZI2, Q6IVW0, Q6P1V4, Q6PFQ2, Q6PGY6, Q7PGE8, Q7SYB2, Q8BZN6, Q8R1B4

Diamond homologs: A1C987, A1D9P1, A1ZAX1, A3GGB4, A4QSX4, A5DPQ5, A5E3Q2, A6S043, A6ZN26, A7E471, A7TML4, A8WWU0, B0W0S3, B0YEH1, B3MIF1, B3NML0, B4GIB1, B4HMY3, B4J789, B4KN00, B4LNA1, B4MRZ8, B4P562, B5DFC8, B5ME19, O02328, O14164, O49160, P0CN46, P0CN47, P32497, Q0CVT0, Q0V1H5, Q0ZB76, Q17Q06, Q1DP77, Q28Z41, Q2H731, Q2U0Q9, Q3SYW6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 55 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Formation of the ternary complex, and subsequently, the 43S complex	11	56.4×	3e-15
Ribosomal scanning and start codon recognition	12	54.4×	3e-16
Translation initiation complex formation	11	49.9×	6e-15
GTP hydrolysis and joining of the 60S ribosomal subunit	13	31.0×	6e-15
Formation of a pool of free 40S subunits	11	29.3×	2e-12
L13a-mediated translational silencing of Ceruloplasmin expression	12	28.9×	2e-13

GO biological processes:

GO term	Partners	Fold	FDR
formation of cytoplasmic translation initiation complex	11	247.2×	3e-23
translational initiation	11	78.9×	2e-16
regulation of translational initiation	6	56.2×	1e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	12
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2521 predictions. Top by Δscore:

Variant	Effect	Δscore
16:28379881:C:CC	acceptor_gain	1.0000
16:28379883:G:C	acceptor_gain	1.0000
16:28379894:A:AC	acceptor_gain	1.0000
16:28379894:A:C	acceptor_gain	1.0000
16:28379972:TCA:T	donor_loss	1.0000
16:28379973:CACC:C	donor_loss	1.0000
16:28379974:A:AC	donor_gain	1.0000
16:28379974:AC:A	donor_gain	1.0000
16:28379974:ACCT:A	donor_gain	1.0000
16:28379975:C:CA	donor_gain	1.0000
16:28379975:CC:C	donor_gain	1.0000
16:28379975:CCT:C	donor_gain	1.0000
16:28379975:CCTC:C	donor_gain	1.0000
16:28379975:CCTCG:C	donor_gain	1.0000
16:28380134:GAGGC:G	acceptor_gain	1.0000
16:28380135:AGGC:A	acceptor_gain	1.0000
16:28380136:GGC:G	acceptor_gain	1.0000
16:28380137:GC:G	acceptor_gain	1.0000
16:28380138:CC:C	acceptor_gain	1.0000
16:28380139:C:CA	acceptor_loss	1.0000
16:28380139:C:CC	acceptor_gain	1.0000
16:28380139:C:T	acceptor_gain	1.0000
16:28380140:T:A	acceptor_loss	1.0000
16:28380144:A:T	acceptor_gain	1.0000
16:28380147:C:CT	acceptor_gain	1.0000
16:28380150:C:CT	acceptor_gain	1.0000
16:28380150:C:T	acceptor_gain	1.0000
16:28380151:A:T	acceptor_gain	1.0000
16:28380155:C:CT	acceptor_gain	1.0000
16:28380156:A:T	acceptor_gain	1.0000

AlphaMissense

6072 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:28380501:A:G	L793P	1.000
16:28380513:A:G	L789P	1.000
16:28380676:C:A	W767C	1.000
16:28380676:C:G	W767C	1.000
16:28380677:C:G	W767S	1.000
16:28380678:A:G	W767R	1.000
16:28380678:A:T	W767R	1.000
16:28380718:A:C	C753W	1.000
16:28380719:C:T	C753Y	1.000
16:28380729:A:G	W750R	1.000
16:28380729:A:T	W750R	1.000
16:28380753:A:G	S742P	1.000
16:28380755:G:T	A741D	1.000
16:28380756:C:G	A741P	1.000
16:28383147:A:G	L719P	1.000
16:28383158:G:C	F715L	1.000
16:28383158:G:T	F715L	1.000
16:28383159:A:C	F715C	1.000
16:28383159:A:G	F715S	1.000
16:28383160:A:G	F715L	1.000
16:28383164:C:A	K713N	1.000
16:28383164:C:G	K713N	1.000
16:28383166:T:C	K713E	1.000
16:28383167:G:C	S712R	1.000
16:28383167:G:T	S712R	1.000
16:28383169:T:G	S712R	1.000
16:28383220:C:T	E695K	1.000
16:28383225:A:G	L693P	1.000
16:28383231:G:T	A691D	1.000
16:28383232:C:G	A691P	1.000

dbSNP variants (sampled 300 via entrez): RS1000148590 (16:28382489 CCA>C), RS1000410100 (16:28428286 G>A,C), RS1000560068 (16:28412119 G>A), RS1000592727 (16:28411315 T>A), RS1000840889 (16:28427512 T>G), RS1001908574 (16:28427172 C>T), RS1001925069 (16:28426801 G>A), RS1002105067 (16:28410910 G>A), RS1002268117 (16:28410580 G>A), RS1002867940 (16:28396872 C>G), RS1002900237 (16:28423134 C>G,T), RS1002928103 (16:28422570 A>C), RS1003494382 (16:28402451 G>A,T), RS1004361407 (16:28413085 T>C), RS1004969234 (16:28379082 C>G,T)

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

5 associations (top):

Study	Trait	p-value
GCST002598_62	Educational attainment	1.000000e-06
GCST004131_83	Inflammatory bowel disease	2.000000e-12
GCST004132_69	Crohn’s disease	3.000000e-10
GCST010133_15	Lamb consumption	3.000000e-08
GCST010703_152	Brain morphology (MOSTest)	3.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004784	self reported educational attainment
EFO:0008111	diet measurement
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

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

Chemical	Actions (top 5)	PubMed papers
Diethylhexyl Phthalate	affects cotreatment, affects expression, increases expression	2
bisphenol A	decreases expression	1
lead acetate	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, increases expression, affects cotreatment, decreases expression	1
tetrachlorodian	increases expression	1
abrine	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Benztropine	affects cotreatment, decreases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	increases expression	1
Colforsin	affects cotreatment, affects expression	1
Furaldehyde	affects cotreatment, decreases expression, affects localization, increases expression	1
Smoke	decreases expression	1
Sodium Chloride	affects cotreatment, decreases expression, affects localization, increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Valproic Acid	decreases expression	1
Cyclosporine	increases methylation	1
Aflatoxin M1	increases expression	1

Clinical trials (associated diseases)

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