RENBP

Summary

RENBP (renin binding protein, HGNC:9959) is a protein-coding gene on chromosome Xq28, encoding N-acylglucosamine 2-epimerase (P51606). Catalyzes the interconversion of N-acetylglucosamine to N-acetylmannosamine.

The gene product inhibits renin activity by forming a dimer with renin, a complex known as high molecular weight renin. The encoded protein contains a leucine zipper domain, which is essential for its dimerization with renin. The gene product can catalyze the interconversion of N-acetylglucosamine to N-acetylmannosamine, indicating that it is a GlcNAc 2-epimerase. Transcript variants utilizing alternative promoters have been described in the literature.

Source: NCBI Gene 5973 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 145 total — 2 pathogenic
• MANE Select transcript: NM_002910

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9959
Approved symbol	RENBP
Name	renin binding protein
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	RNBP, RBP
Ensembl gene	ENSG00000102032
Ensembl biotype	protein_coding
OMIM	312420
Entrez	5973

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 4 protein_coding, 3 nonsense_mediated_decay, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000369997, ENST00000393700, ENST00000423624, ENST00000442361, ENST00000451114, ENST00000457282, ENST00000462086, ENST00000464227, ENST00000471056, ENST00000475904, ENST00000875215

RefSeq mRNA: 1 — MANE Select: NM_002910 NM_002910

CCDS: CCDS14738

Canonical transcript exons

ENST00000393700 — 11 exons

Exon	Start	End
ENSE00001853434	153935269	153935404
ENSE00001943924	153944584	153944643
ENSE00003464729	153941478	153941653
ENSE00003479839	153940102	153940233
ENSE00003493370	153944080	153944155
ENSE00003508862	153943546	153943718
ENSE00003514192	153941950	153942031
ENSE00003562126	153942855	153943079
ENSE00003576022	153935489	153935576
ENSE00003631648	153944309	153944418
ENSE00003686576	153943895	153943970

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 95.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.8151 / max 227.6009, expressed in 1018 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200933	5.8454	924
200934	2.6891	827
200932	0.2806	168

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	95.03	gold quality
spleen	UBERON:0002106	93.86	gold quality
mononuclear cell	CL:0000842	93.85	gold quality
leukocyte	CL:0000738	93.39	gold quality
granulocyte	CL:0000094	91.68	gold quality
right adrenal gland cortex	UBERON:0035827	90.58	gold quality
upper lobe of left lung	UBERON:0008952	89.57	gold quality
right lung	UBERON:0002167	89.40	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.19	gold quality
right adrenal gland	UBERON:0001233	88.80	gold quality
upper lobe of lung	UBERON:0008948	88.68	gold quality
tibial nerve	UBERON:0001323	88.55	gold quality
left adrenal gland cortex	UBERON:0035825	88.09	gold quality
left adrenal gland	UBERON:0001234	87.91	gold quality
right coronary artery	UBERON:0001625	87.16	gold quality
adult mammalian kidney	UBERON:0000082	87.04	gold quality
metanephros cortex	UBERON:0010533	86.99	gold quality
adrenal cortex	UBERON:0001235	86.68	gold quality
tibial artery	UBERON:0007610	86.46	gold quality
popliteal artery	UBERON:0002250	86.45	gold quality
spinal cord	UBERON:0002240	86.17	gold quality
sural nerve	UBERON:0015488	86.14	gold quality
nucleus accumbens	UBERON:0001882	85.89	gold quality
left coronary artery	UBERON:0001626	85.36	gold quality
adrenal gland	UBERON:0002369	85.33	gold quality
muscle layer of sigmoid colon	UBERON:0035805	85.30	gold quality
apex of heart	UBERON:0002098	85.29	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.04	gold quality
caudate nucleus	UBERON:0001873	84.99	gold quality
putamen	UBERON:0001874	84.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	45.49
E-CURD-112	yes	10.31
E-ANND-3	yes	4.40

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• domain structure of RBP (PMID:11926999)
• determination of catabolic role in sialic acid metabolism (PMID:12499362)
• gene and protein expression were selectively activated in left ventricular myocytes from end-stage failing human hearts (PMID:12612874)
• several SNPs and haplotypes of the RnBP gene are associated with either increased or decreased risk of developing essential hypertension. (PMID:23969252)
• rs2269372 in RENBP was associated with risk of schizophrenia in a Han Chinese population. (PMID:24043878)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	renbp	ENSDARG00000008931
mus_musculus	Renbp	ENSMUSG00000031387
rattus_norvegicus	Renbp	ENSRNOG00000054765

Protein

Protein identifiers

N-acylglucosamine 2-epimerase — P51606 (reviewed: P51606)

Alternative names: GlcNAc 2-epimerase, N-acetyl-D-glucosamine 2-epimerase, Renin-binding protein

All UniProt accessions (6): P51606, A6NKZ2, F8WE83, H7C1A7, H7C2G7, H7C317

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the interconversion of N-acetylglucosamine to N-acetylmannosamine. Involved in the N-glycolylneuraminic acid (Neu5Gc) degradation pathway: although human is not able to catalyze formation of Neu5Gc due to the inactive CMAHP enzyme, Neu5Gc is present in food and must be degraded.

Subunit / interactions. Homodimer. Forms a heterodimer with renin and inhibits its activity.

Activity regulation. Inhibited by N-ethylmaleimide, 5,5’-dithiobis-2-nitrobenzoate and iodoacetic acid.

Pathway. Amino-sugar metabolism; N-acetylneuraminate degradation.

Similarity. Belongs to the N-acylglucosamine 2-epimerase family.

Isoforms (3)

UniProt ID	Names	Canonical?
P51606-1	1	yes
P51606-2	2
P51606-3	3

RefSeq proteins (1): NP_002901* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008928	6-hairpin_glycosidase_sf	Homologous_superfamily
IPR010819	AGE/CE	Family
IPR012341	6hp_glycosidase-like_sf	Homologous_superfamily
IPR034116	AGE_dom	Domain

Pfam: PF07221

Enzyme classification (BRENDA):

• EC 5.1.3.8 — N-acylglucosamine 2-epimerase (BRENDA: 16 organisms, 21 substrates, 22 inhibitors, 53 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
N-ACETYL-D-GLUCOSAMINE	3.4–231.9	26
N-ACETYL-D-MANNOSAMINE	1.7–211	26

Catalyzed reactions (Rhea), 1 shown:

• an N-acyl-D-glucosamine = an N-acyl-D-mannosamine (RHEA:19033)

UniProt features (19 total): mutagenesis site 10, splice variant 3, sequence variant 2, chain 1, region of interest 1, sequence conflict 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51606-F1	94.97	0.91

Functional residue map

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

Catalytic / active sites (1): 390 (important for enzyme activity)

Mutagenesis-validated functional residues (10):

Position	Phenotype
114	activity is about 26% of that of the wild-type.
135	activity is similiar to wild-type.
220	activity is similiar to wild-type.
249	activity is similiar to wild-type.
312	activity is similiar to wild-type.
390	loss of enzyme activity.
396	activity is similiar to wild-type.
400	activity is similiar to wild-type.
51	activity is similiar to wild-type.
76	activity is similiar to wild-type.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-446210	Synthesis of UDP-N-acetyl-glucosamine

MSigDB gene sets: 182 (showing top): GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, CAGCTG_AP4_Q5, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GCM_PRKCG, BROWNE_HCMV_INFECTION_48HR_DN, GCM_RING1, GOBP_AMIDE_METABOLIC_PROCESS, GCM_FCGR2B, GOBP_ORGANIC_ACID_CATABOLIC_PROCESS, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_AMINO_SUGAR_CATABOLIC_PROCESS, GOBP_AMINO_SUGAR_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS

GO Biological Process (6): carbohydrate metabolic process (GO:0005975), N-acetylglucosamine metabolic process (GO:0006044), N-acetylmannosamine metabolic process (GO:0006051), regulation of blood pressure (GO:0008217), N-acetylneuraminate catabolic process (GO:0019262), amino sugar metabolic process (GO:0006040)

GO Molecular Function (6): endopeptidase inhibitor activity (GO:0004866), peptidase inhibitor activity (GO:0030414), identical protein binding (GO:0042802), N-acylglucosamine 2-epimerase activity (GO:0050121), protein binding (GO:0005515), isomerase activity (GO:0016853)

GO Cellular Component (2): cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Synthesis of substrates in N-glycan biosythesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
amino sugar metabolic process	2
primary metabolic process	1
blood circulation	1
regulation of biological quality	1
N-acetylneuraminate metabolic process	1
amino sugar catabolic process	1
carboxylic acid catabolic process	1
carbohydrate derivative metabolic process	1
endopeptidase activity	1
peptidase inhibitor activity	1
endopeptidase regulator activity	1
enzyme inhibitor activity	1
peptidase activity	1
peptidase regulator activity	1
protein binding	1
racemase and epimerase activity, acting on carbohydrates and derivatives	1
binding	1
catalytic activity	1
cytoplasm	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

652 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RENBP	REN	P00797	871
RENBP	NAA10	P41227	865
RENBP	AVPR2	P30518	824
RENBP	L1CAM	P32004	814
RENBP	HCFC1	P51610	729
RENBP	AGK	Q53H12	528
RENBP	ESCO1	Q5FWF5	516
RENBP	ESCO2	Q56NI9	515
RENBP	NAGK	Q9UJ70	513
RENBP	ATP6AP2	O75787	488
RENBP	GNE	Q9Y223	471
RENBP	UAP1L1	Q3KQV9	463
RENBP	SLC35A1	P78382	449
RENBP	NANS	Q9NR45	438
RENBP	SPRY3	O43610	434

IntAct

11 interactions, top by confidence:

A	B	Type	Score
RENBP	SCML1	psi-mi:“MI:0915”(physical association)	0.560
RENBP	ZBED1	psi-mi:“MI:0915”(physical association)	0.370
P3H1	KRBA1	psi-mi:“MI:0914”(association)	0.350
HSPE1	LYPLA2	psi-mi:“MI:0914”(association)	0.350
RENBP	SCML1	psi-mi:“MI:0915”(physical association)	0.000
RENBP	pqiB2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): ZBED1 (Two-hybrid), RENBP (Affinity Capture-MS), RENBP (Two-hybrid), RENBP (Affinity Capture-MS), RENBP (Affinity Capture-MS), RENBP (Proximity Label-MS), RENBP (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A077LPS9, A0A0P9JFY5, A0KIF5, A1JP08, A1JRM4, A4SPN8, A4TPM8, A4W7Z0, A4XWE4, A6T655, A7FID4, A7FLL0, A7MEB0, A7MKY0, A8ANI4, A8GAB2, A9QYY2, A9R2Z4, B1JIK2, B2K634, B2U942, B2VIQ9, B3R5F6, B5EIQ6, B5XZW3, C6DCZ0, F2JVT6, O31201, P17560, P29954, P32140, P51606, P51607, P82343, Q0IBR6, Q0K848, Q1C824, Q2KIS1, Q39SM2, Q3ALG7

Diamond homologs: O18921, P17560, P51606, P51607, P82343, Q2KIS1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	35
Likely benign	6
Benign	3

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
3893270	GRCh37/hg19 Xq28(chrX:153168032-153601836)x2	Pathogenic
536593	NC_000023.10:g.(?153128098)(153599633_?)dup	Pathogenic

SpliceAI

1380 predictions. Top by Δscore:

Variant	Effect	Δscore
X:153935503:C:A	donor_gain	1.0000
X:153935577:C:CC	acceptor_gain	1.0000
X:153943086:G:C	acceptor_gain	1.0000
X:153943086:G:GC	acceptor_gain	1.0000
X:153943089:C:CT	acceptor_gain	1.0000
X:153943090:A:T	acceptor_gain	1.0000
X:153943559:T:TA	donor_gain	1.0000
X:153943560:C:A	donor_gain	1.0000
X:153943609:A:AC	donor_gain	1.0000
X:153943610:C:CC	donor_gain	1.0000
X:153943718:CCTG:C	acceptor_loss	1.0000
X:153943719:CTGG:C	acceptor_loss	1.0000
X:153943892:TAC:T	donor_loss	1.0000
X:153943893:A:AC	donor_gain	1.0000
X:153943893:ACCTG:A	donor_gain	1.0000
X:153943894:C:CC	donor_gain	1.0000
X:153943894:CCTG:C	donor_gain	1.0000
X:153943894:CCTGC:C	donor_gain	1.0000
X:153943966:CATAC:C	acceptor_gain	1.0000
X:153943967:ATAC:A	acceptor_gain	1.0000
X:153943968:TAC:T	acceptor_gain	1.0000
X:153943969:AC:A	acceptor_gain	1.0000
X:153943969:ACC:A	acceptor_loss	1.0000
X:153943970:CC:C	acceptor_gain	1.0000
X:153943970:CCT:C	acceptor_loss	1.0000
X:153943971:C:A	acceptor_loss	1.0000
X:153943972:T:A	acceptor_loss	1.0000
X:153943974:CGGGG:C	acceptor_gain	1.0000
X:153943978:G:C	acceptor_gain	1.0000
X:153943978:G:GC	acceptor_gain	1.0000

AlphaMissense

2790 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:153935490:T:A	K388N	0.995
X:153935490:T:G	K388N	0.995
X:153943600:G:C	F136L	0.995
X:153943600:G:T	F136L	0.995
X:153943602:A:G	F136L	0.995
X:153935491:T:A	K388I	0.994
X:153935397:G:C	F391L	0.993
X:153935397:G:T	F391L	0.993
X:153935399:A:G	F391L	0.993
X:153940209:A:G	W324R	0.993
X:153940209:A:T	W324R	0.993
X:153943609:A:C	S133R	0.993
X:153943609:A:T	S133R	0.993
X:153943611:T:G	S133R	0.993
X:153940207:C:A	W324C	0.992
X:153940207:C:G	W324C	0.992
X:153935505:C:A	K383N	0.991
X:153935505:C:G	K383N	0.991
X:153944084:C:G	R70T	0.991
X:153944097:A:G	W66R	0.991
X:153944097:A:T	W66R	0.991
X:153935552:A:G	W368R	0.990
X:153935552:A:T	W368R	0.990
X:153944084:C:A	R70M	0.990
X:153943708:G:C	F100L	0.989
X:153943708:G:T	F100L	0.989
X:153943710:A:G	F100L	0.989
X:153935493:G:C	F387L	0.988
X:153935493:G:T	F387L	0.988
X:153935495:A:G	F387L	0.988

dbSNP variants (sampled 300 via entrez): RS1000447894 (X:153943771 C>T), RS1000757603 (X:153937589 C>T), RS1000986627 (X:153936747 C>T), RS1002014393 (X:153942519 G>A,T), RS1002521125 (X:153946116 G>A,C), RS1004971747 (X:153942597 A>G), RS1005679174 (X:153938492 C>T), RS1005790551 (X:153938081 T>G), RS1005845355 (X:153946356 G>A), RS1006579913 (X:153943277 G>A), RS1007349241 (X:153936399 G>C), RS1007463744 (X:153935989 C>T), RS1007940247 (X:153944701 C>A,G,T), RS1008249707 (X:153941351 C>A), RS1009973185 (X:153943301 G>A)

Disease associations

OMIM: gene MIM:312420 | disease phenotypes: MIM:300260, MIM:300673

GenCC curated gene-disease

Mondo (2): syndromic X-linked intellectual disability Lubs type (MONDO:0010283), severe neonatal-onset encephalopathy with microcephaly (MONDO:0010397)

Orphanet (2): Proximal Xq28 duplication syndrome (Orphanet:1762), MECP2-related severe neonatal encephalopathy (Orphanet:209370)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002190_1	Schizophrenia	4.000000e-08
GCST003155_27	Systemic lupus erythematosus	2.000000e-15

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C566878	Encephalopathy, Neonatal Severe, Due To Mecp2 Mutations (supp.)
C537723	Lubs X-linked mental retardation syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

39 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, increases expression	3
Benzo(a)pyrene	affects methylation	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
sodium arsenate	increases abundance, increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	increases methylation	1
benazol P	affects expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
bisphenol S	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	decreases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Cisplatin	affects expression	1
Dexamethasone	affects cotreatment, increases expression	1
Dibutyl Phthalate	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Hydrogen Peroxide	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methamphetamine	increases expression	1
Methapyrilene	increases methylation	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TI79	HAP1 RENBP (-) 1	Cancer cell line	Male
CVCL_XS21	HAP1 RENBP (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03077308	Not specified	COMPLETED	Rare Diseases Clinical Research Network: Neurophysiological Correlates
NCT06615206	Not specified	RECRUITING	A First-in-Human Clinical Trial to Evaluate the Safety, Tolerability, and Efficacy of a Novel CRISPR RNA-editing Therapy in Patients with Mecp2 Duplication Syndrome, a Rare Orphan Disease (HERO)