ERMAP

Summary

ERMAP (erythroblast membrane associated protein (Scianna blood group), HGNC:15743) is a protein-coding gene on chromosome 1p34.2, encoding Erythroid membrane-associated protein (Q96PL5). Possible role as a cell-adhesion or receptor molecule of erythroid cells.

The protein encoded by this gene is a cell surface transmembrane protein that may act as an erythroid cell receptor, possibly as a mediator of cell adhesion. Polymorphisms in this gene are responsible for the Scianna/Radin blood group system. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 114625 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 82 total — 1 pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001017922

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15743
Approved symbol	ERMAP
Name	erythroblast membrane associated protein (Scianna blood group)
Location	1p34.2
Locus type	gene with protein product
Status	Approved
Aliases	BTN5
Ensembl gene	ENSG00000164010
Ensembl biotype	protein_coding
OMIM	609017
Entrez	114625

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 16 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000328249, ENST00000372514, ENST00000372517, ENST00000470938, ENST00000487556, ENST00000642150, ENST00000643061, ENST00000645239, ENST00000647120, ENST00000881413, ENST00000881414, ENST00000881415, ENST00000881416, ENST00000881417, ENST00000881418, ENST00000881419, ENST00000881420, ENST00000968886, ENST00000968887, ENST00000968888, ENST00000968889, ENST00000968890

RefSeq mRNA: 2 — MANE Select: NM_001017922 NM_001017922, NM_018538

CCDS: CCDS475

Canonical transcript exons

ENST00000372517 — 12 exons

Exon	Start	End
ENSE00001143920	42835732	42835764
ENSE00001252486	42830768	42831115
ENSE00001358815	42830444	42830533
ENSE00001434201	42825623	42825738
ENSE00003468772	42840152	42840178
ENSE00003477127	42840033	42840053
ENSE00003606936	42838901	42838921
ENSE00003617143	42840270	42840296
ENSE00003645818	42835038	42835154
ENSE00003656764	42837158	42837190
ENSE00003686058	42842517	42844991
ENSE00003822746	42817122	42817253

Expression profiles

Bgee: expression breadth ubiquitous, 199 present calls, max score 87.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.5488 / max 452.5441, expressed in 1743 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2475	4.8946	1722
2479	0.9534	82
2477	0.4335	58
2478	0.1747	51
2476	0.0926	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	87.16	gold quality
mononuclear cell	CL:0000842	86.82	gold quality
tendon of biceps brachii	UBERON:0008188	86.52	silver quality
leukocyte	CL:0000738	86.51	gold quality
right adrenal gland cortex	UBERON:0035827	85.42	gold quality
right adrenal gland	UBERON:0001233	84.77	gold quality
right lobe of liver	UBERON:0001114	84.60	gold quality
stromal cell of endometrium	CL:0002255	84.49	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.77	gold quality
granulocyte	CL:0000094	83.69	gold quality
left adrenal gland	UBERON:0001234	83.68	gold quality
trabecular bone tissue	UBERON:0002483	83.27	gold quality
left adrenal gland cortex	UBERON:0035825	83.15	gold quality
adrenal tissue	UBERON:0018303	82.90	gold quality
body of pancreas	UBERON:0001150	82.88	gold quality
rectum	UBERON:0001052	82.64	gold quality
bone marrow	UBERON:0002371	82.29	gold quality
tendon	UBERON:0000043	82.26	gold quality
adrenal gland	UBERON:0002369	82.23	gold quality
adrenal cortex	UBERON:0001235	82.20	gold quality
adenohypophysis	UBERON:0002196	82.14	gold quality
pituitary gland	UBERON:0000007	81.96	gold quality
left lobe of thyroid gland	UBERON:0001120	81.62	gold quality
gall bladder	UBERON:0002110	81.61	gold quality
pancreas	UBERON:0001264	81.42	gold quality
mucosa of stomach	UBERON:0001199	81.07	gold quality
calcaneal tendon	UBERON:0003701	80.97	gold quality
metanephros cortex	UBERON:0010533	80.90	gold quality
thyroid gland	UBERON:0002046	80.80	gold quality
islet of Langerhans	UBERON:0000006	80.58	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	45.05
E-ANND-3	yes	4.54
E-MTAB-9067	no	4.38

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRX1

miRNA regulators (miRDB)

78 targeting ERMAP, 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-1193	100.00	65.93	529
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-670-5P	99.67	69.94	1565

Literature-anchored findings (GeneRIF, showing 8)

• ERMAP, a unique member of the B30.2 domain protein family, is expressed in erythroid cells in fetal liver, adult bone marrow, reticulocytes and in circulating erythroblasts in 8-12-week fetal cord blood. (PMID:11549310)
• A human cDNA and gene encoding for human ERMAP is cloned and characterized. The protein is sequenced and its expression analyzed. (PMID:11783959)
• DNA sequencing demonstrates Scianna antigens including Rd are expressed by ERMAP. (PMID:12393480)
• The human ermap gene plays an important role in differentiation and development of erythroid cells. (PMID:18426659)
• the five known probands with the SC*994C>T silencing nucleotide change were from the Pacific Islands. (PMID:24094239)
• Through molecular genotyping we also identified polymorphisms in RhCE, Kell, Duffy, Colton, Lutheran and Scianna loci in donors and patients. (PMID:25582271)
• ERMAP is a B7 family-related molecule that negatively regulates T cell and macrophage responses. (PMID:32620788)
• The ligation between ERMAP, galectin-9 and dectin-2 promotes Kupffer cell phagocytosis and antitumor immunity. (PMID:37813965)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ermap	ENSMUSG00000028644
rattus_norvegicus	Ermap	ENSRNOG00000000335
rattus_norvegicus	Zfp691	ENSRNOG00000007398

Paralogs (15): BTN3A1 (ENSG00000026950), CD276 (ENSG00000103855), BTN3A3 (ENSG00000111801), BTN2A1 (ENSG00000112763), BTNL8 (ENSG00000113303), HHLA2 (ENSG00000114455), BTN2A2 (ENSG00000124508), BTN1A1 (ENSG00000124557), VTCN1 (ENSG00000134258), ICOSLG (ENSG00000160223), BTNL9 (ENSG00000165810), BTNL3 (ENSG00000168903), BTN3A2 (ENSG00000186470), BTNL2 (ENSG00000204290), MOG (ENSG00000204655)

Protein

Protein identifiers

Erythroid membrane-associated protein — Q96PL5 (reviewed: Q96PL5)

Alternative names: Radin blood group antigen, Scianna blood group antigen

All UniProt accessions (3): A0A1C9HIH9, A0A2R8YH65, Q96PL5

UniProt curated annotations — full annotation on UniProt →

Function. Possible role as a cell-adhesion or receptor molecule of erythroid cells.

Subcellular location. Cell membrane. Cytoplasm.

Tissue specificity. Expressed in erythroid-enriched bone marrow (at protein level). Highly expressed in bone marrow and to a lower extent in leukocytes, thymus, lymph node and spleen.

Post-translational modifications. Glycosylated.

Polymorphism. ERMAP is responsible for the Scianna/Radin blood group system which comprises seven different antigens. The Sc1 and Sc2 antigens are resulting from a single variation in position 57; Arg-57 corresponds to the Sc2 antigen and Gly-57 to the Sc1 antigen. The Sc2 antigen is rare with an occurrence of less than 1% in the population while Sc1 is more frequent. Sc3 is not expressed by individuals homozygous for a null allele encoding a truncated protein lacking its extracellular part (Sc-3). The Sc4 antigen corresponding to the previously defined Radin blood group antigen (Rd) is due to a single variation in position 60; Ala-60 corresponds to Sc4/Rd(+), the antigenic form of the protein. Sc4 is found in less than 1% of the population. Sc5/STAR, Sc6/SCER and Sc7/SCAN antigens are due to single variations in positions 47, 81 and 35 respectively. Alloantibodies to the low frequency Sc2 and Sc4 antigens are the cause of hemolytic disease in the newborn.

Similarity. Belongs to the immunoglobulin superfamily. BTN/MOG family.

RefSeq proteins (2): NP_001017922, NP_061008 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001870	B30.2/SPRY	Domain
IPR003599	Ig_sub	Domain
IPR003877	SPRY_dom	Domain
IPR003879	Butyrophylin_SPRY	Domain
IPR006574	PRY	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR043136	B30.2/SPRY_sf	Homologous_superfamily
IPR050143	TRIM/RBCC	Family

Pfam: PF00622, PF07686, PF13765

UniProt features (22 total): sequence variant 11, topological domain 2, domain 2, signal peptide 1, chain 1, sequence conflict 1, transmembrane region 1, modified residue 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PL5-F1	82.22	0.59

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 (1): 418

Disulfide bonds (1): 50–126

Glycosylation sites (1): 132

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 98 (showing top): GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOCC_CELL_SURFACE, GNF2_ANK1, NKX61_01, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, GOBP_REGULATION_OF_IMMUNE_RESPONSE, GOBP_CYTOKINE_PRODUCTION, chr1p34, GNF2_SPTA1, GOBP_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GNF2_PCAF, GOMF_SIGNALING_RECEPTOR_BINDING, GNF2_MAP2K3

GO Biological Process (2): regulation of cytokine production (GO:0001817), T cell receptor signaling pathway (GO:0050852)

GO Molecular Function (2): signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (6): Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
antigen receptor-mediated signaling pathway	1
protein binding	1
binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

782 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERMAP	XDH	P47989	969
ERMAP	PLIN2	Q99541	923
ERMAP	TECR	Q9NZ01	918
ERMAP	MFGE8	Q08431	782
ERMAP	MUC1	P13931	598
ERMAP	LTF	P02788	585
ERMAP	GOT2	P00505	551
ERMAP	MUC15	Q8N387	521
ERMAP	CIDEA	O60543	511
ERMAP	PGM1	P36871	508
ERMAP	AASDH	Q4L235	471
ERMAP	OMG	P23515	470
ERMAP	CD1B	P29016	456
ERMAP	SLC14A1	Q13336	452
ERMAP	SLC4A1	P02730	448

IntAct

19 interactions, top by confidence:

A	B	Type	Score
TMEM14A	ERMAP	psi-mi:“MI:0915”(physical association)	0.560
EMD	ERMAP	psi-mi:“MI:0915”(physical association)	0.560
ERMAP	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.560
LEMD1	ERMAP	psi-mi:“MI:0915”(physical association)	0.560
ERMAP	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
ERMAP	AP3B1	psi-mi:“MI:0914”(association)	0.530
ERMAP	PCNA	psi-mi:“MI:0915”(physical association)	0.370
CFTR	ERMAP	psi-mi:“MI:0915”(physical association)	0.370
ERMAP	NRDC	psi-mi:“MI:0914”(association)	0.350
ERMAP	KRTAP3-3	psi-mi:“MI:0915”(physical association)	0.000
LEMD1	ERMAP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (36): MECOM (Affinity Capture-MS), FAM199X (Affinity Capture-MS), DOCK4 (Affinity Capture-MS), USP34 (Affinity Capture-MS), ELMO2 (Affinity Capture-MS), CWC22 (Affinity Capture-MS), AP3B1 (Affinity Capture-MS), ZC3H18 (Affinity Capture-MS), GEMIN2 (Affinity Capture-MS), AKAP11 (Affinity Capture-MS), CDC73 (Affinity Capture-MS), UBR4 (Affinity Capture-MS), PRKAR1B (Affinity Capture-MS), ERMAP (Synthetic Lethality), ERMAP (Two-hybrid)

ESM2 similar proteins: A0A0E4BZH1, A4QPC6, A7TZE6, A8K4G0, A8MVZ5, O00478, O00481, O00635, O70355, O75677, O75679, P14373, P18892, P19474, P55803, P78410, Q13410, Q1XHU0, Q3ZEE5, Q58DK8, Q5BN31, Q5C8U1, Q5D7H8, Q5D7I0, Q5D7I2, Q5D7I3, Q5D7I5, Q5D7J2, Q5R7W8, Q5R996, Q61885, Q62158, Q62191, Q62556, Q6MFZ5, Q6MG97, Q6UX41, Q6UXE8, Q6UXG8, Q7KYR7

Diamond homologs: A0A0E4BZH1, A4QPC6, A7TZE6, A7TZF0, A7TZF3, A7TZG1, A7TZG3, A7XUX6, A7XUY5, A7XUZ6, A7XV04, A7XV07, A7XV14, A8MVZ5, O00478, O00481, O70355, P18892, P55803, P78410, Q13410, Q16653, Q29ZQ1, Q5R7W8, Q5R960, Q5R996, Q61885, Q62556, Q63345, Q6MG97, Q6UX41, Q6UXE8, Q6UXG8, Q7KYR7, Q7TST0, Q8BJE2, Q8WVV5, Q96KV6, Q96PL5, Q9BGS7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
IRX1	“up-regulates quantity by expression”	ERMAP	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	54
Likely benign	6
Benign	6

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1915	NM_001017922.2(ERMAP):c.307_308del (p.Asp103fs)	Pathogenic

SpliceAI

1942 predictions. Top by Δscore:

Variant	Effect	Δscore
1:42817210:G:GT	donor_gain	1.0000
1:42817251:A:T	donor_gain	1.0000
1:42842515:A:AG	acceptor_gain	1.0000
1:42842515:AGT:A	acceptor_gain	1.0000
1:42842516:G:GG	acceptor_gain	1.0000
1:42842516:GT:G	acceptor_gain	1.0000
1:42842516:GTG:G	acceptor_gain	1.0000
1:42817179:G:GT	donor_gain	0.9900
1:42817249:G:GT	donor_gain	0.9900
1:42817249:GGAGG:G	donor_gain	0.9900
1:42817250:G:GT	donor_gain	0.9900
1:42817250:G:T	donor_gain	0.9900
1:42817252:GG:G	donor_gain	0.9900
1:42817253:GG:G	donor_gain	0.9900
1:42817402:G:GT	donor_gain	0.9900
1:42835730:A:AG	acceptor_gain	0.9900
1:42835731:G:GG	acceptor_gain	0.9900
1:42838978:GGA:G	donor_gain	0.9900
1:42842512:TGCA:T	acceptor_loss	0.9900
1:42842514:CAG:C	acceptor_loss	0.9900
1:42842515:AGTG:A	acceptor_gain	0.9900
1:42842516:G:GT	acceptor_loss	0.9900
1:42842516:GTGG:G	acceptor_gain	0.9900
1:42842516:GTGGC:G	acceptor_gain	0.9900
1:42817250:GAGG:G	donor_gain	0.9800
1:42838979:GA:G	donor_gain	0.9800
1:42817210:G:T	donor_gain	0.9700
1:42827666:G:GT	donor_gain	0.9700
1:42831110:TTGC:T	donor_gain	0.9700
1:42837156:A:AG	acceptor_gain	0.9700

AlphaMissense

3057 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:42842717:T:A	W305R	0.998
1:42842717:T:C	W305R	0.998
1:42842630:T:C	F276L	0.996
1:42842632:T:A	F276L	0.996
1:42842632:T:G	F276L	0.996
1:42842727:G:A	G308E	0.995
1:42842556:T:C	L251P	0.994
1:42842645:A:C	S281R	0.994
1:42842647:C:A	S281R	0.994
1:42842647:C:G	S281R	0.994
1:42842687:T:A	W295R	0.994
1:42842687:T:C	W295R	0.994
1:42842726:G:A	G308R	0.994
1:42842726:G:C	G308R	0.994
1:42842727:G:T	G308V	0.993
1:42842734:T:G	C310W	0.993
1:42842689:G:C	W295C	0.992
1:42842689:G:T	W295C	0.992
1:42830877:G:C	W65C	0.991
1:42830877:G:T	W65C	0.991
1:42842547:A:G	H248R	0.991
1:42842889:T:C	L362P	0.991
1:42842719:G:C	W305C	0.990
1:42842719:G:T	W305C	0.990
1:42842879:G:T	G359W	0.990
1:42831020:T:C	I113T	0.989
1:42842789:T:A	W329R	0.989
1:42842789:T:C	W329R	0.989
1:42842799:G:C	R332P	0.989
1:42842752:G:C	R316S	0.987

dbSNP variants (sampled 300 via entrez): RS1000119763 (1:42817601 C>A,T), RS1000192285 (1:42821343 T>C), RS1000193435 (1:42818031 A>G), RS1000296382 (1:42829380 G>A), RS1000526226 (1:42842642 G>A), RS1000763119 (1:42824964 G>C), RS1000807058 (1:42835874 A>G,T), RS1000892530 (1:42845194 A>G), RS1000941393 (1:42845350 T>C), RS1000977241 (1:42816218 C>A,T), RS1001133127 (1:42823567 T>C), RS1001133713 (1:42826707 T>C), RS1001382542 (1:42832880 G>C,T), RS1001491542 (1:42815510 C>T), RS1001685252 (1:42830143 C>T)

Disease associations

OMIM: gene MIM:609017 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0010701	Abnormal circulating immunoglobulin concentration

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008473_12	Visceral fat	6.000000e-06
GCST90002404_462	Red cell distribution width	1.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	5
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
propionaldehyde	decreases expression	1
trichostatin A	affects expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
belinostat	decreases expression	1
abrine	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation, decreases methylation	1
Aldehydes	decreases expression	1
Arsenic	affects methylation	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Sodium Dodecyl Sulfate	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	increases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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