GYPE

Summary

GYPE (glycophorin E (MNS blood group), HGNC:4705) is a protein-coding gene on chromosome 4q31.21, encoding Glycophorin-E (P15421). This protein is a minor sialoglycoprotein in human erythrocyte membranes.

The protein encoded by this gene is a sialoglycoprotein and a type I membrane protein. It is a member of a gene family with GPA and GPB genes. This encoded protein might carry the M blood group antigen. GYPA, GYPB, and GYPE are organized in tandem on chromosome 4. This gene might have derived from an ancestral gene common to the GPB gene by gene duplication. Two alternatively spliced transcript variants encoding the same protein have been described for this gene.

Source: NCBI Gene 2996 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 17 total
• MANE Select transcript: NM_198682

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4705
Approved symbol	GYPE
Name	glycophorin E (MNS blood group)
Location	4q31.21
Locus type	gene with protein product
Status	Approved
Aliases	GPE, MNS
Ensembl gene	ENSG00000197465
Ensembl biotype	protein_coding
OMIM	138590
Entrez	2996

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000358615, ENST00000437468, ENST00000506264

RefSeq mRNA: 2 — MANE Select: NM_198682 NM_002102, NM_198682

CCDS: CCDS47138

Canonical transcript exons

ENST00000358615 — 4 exons

Exon	Start	End
ENSE00001257554	143870864	143872252
ENSE00001388347	143876746	143876855
ENSE00001776800	143880411	143880509
ENSE00002479410	143905471	143905559

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 82.04.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5674 / max 280.4157, expressed in 83 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54206	0.5674	83

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	82.04	gold quality
endometrium epithelium	UBERON:0004811	81.50	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.75	gold quality
bone marrow	UBERON:0002371	77.24	gold quality
paraflocculus	UBERON:0005351	74.41	gold quality
frontal pole	UBERON:0002795	72.40	silver quality
middle frontal gyrus	UBERON:0002702	72.27	silver quality
spleen	UBERON:0002106	69.38	gold quality
thoracic aorta	UBERON:0001515	68.78	gold quality
ascending aorta	UBERON:0001496	68.70	gold quality
descending thoracic aorta	UBERON:0002345	68.32	gold quality
buccal mucosa cell	CL:0002336	67.49	silver quality
aorta	UBERON:0000947	66.96	gold quality
calcaneal tendon	UBERON:0003701	66.19	gold quality
tibial artery	UBERON:0007610	65.89	gold quality
popliteal artery	UBERON:0002250	65.87	gold quality
bone marrow cell	CL:0002092	65.63	gold quality
left coronary artery	UBERON:0001626	65.55	gold quality
adrenal tissue	UBERON:0018303	65.49	gold quality
cerebellar vermis	UBERON:0004720	64.71	silver quality
right atrium auricular region	UBERON:0006631	64.67	gold quality
right coronary artery	UBERON:0001625	64.54	gold quality
blood	UBERON:0000178	64.21	gold quality
coronary artery	UBERON:0001621	64.10	gold quality
cardiac atrium	UBERON:0002081	63.40	gold quality
Brodmann (1909) area 10	UBERON:0013541	62.81	gold quality
subcutaneous adipose tissue	UBERON:0002190	62.50	gold quality
lymph node	UBERON:0000029	61.66	gold quality
vermiform appendix	UBERON:0001154	61.27	gold quality
stromal cell of endometrium	CL:0002255	61.26	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	662.24
E-CURD-112	yes	40.79
E-MTAB-9388	yes	9.44
E-HCAD-9	yes	5.61
E-MTAB-9067	yes	4.91
E-ANND-3	yes	3.96
E-HCAD-10	no	2.58

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting GYPE, 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-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-6832-5P	99.58	64.82	1132
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-3925-5P	99.21	67.90	1466
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-4773	98.35	67.30	1710
HSA-MIR-645	97.28	66.30	486

Literature-anchored findings (GeneRIF, showing 2)

• Novel hybrid genes and a splice site mutation encoding the St(a) antigen among Japanese blood donors. (PMID:32394466)
• Structural variation of the malaria-associated human glycophorin A-B-E region. (PMID:32600246)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gypa	ENSMUSG00000051839

Paralogs (2): GYPA (ENSG00000170180), GYPB (ENSG00000250361)

Protein

Protein identifiers

Glycophorin-E — P15421 (reviewed: P15421)

All UniProt accessions (2): E9PCN6, P15421

UniProt curated annotations — full annotation on UniProt →

Function. This protein is a minor sialoglycoprotein in human erythrocyte membranes.

Subcellular location. Membrane.

Tissue specificity. Erythrocytes.

Post-translational modifications. The N-terminal extracellular domain is heavily glycosylated on serine and threonine residues.

Similarity. Belongs to the glycophorin-A family.

RefSeq proteins (2): NP_002093, NP_941391* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001195	Glycophorin	Family

UniProt features (7 total): topological domain 2, sequence variant 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P15421-F1	70.71	0.00

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 67 (showing top): MODULE_64, GNF2_ANK1, GNF2_SPTA1, GNF2_PCAF, GNF2_MAP2K3, MODULE_539, MODULE_23, GNF2_RAD23A, GNF2_TAL1, KIM_BIPOLAR_DISORDER_OLIGODENDROCYTE_DENSITY_CORR_DN, ALK_DN.V1_DN, CHAMP1_TARGET_GENES, DACH1_TARGET_GENES, E2F5_TARGET_GENES, PHB2_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

640 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GYPE	GYPC	P04921	895
GYPE	FREM3	P0C091	729
GYPE	CD36	P16671	641
GYPE	SCARB2	Q14108	633
GYPE	HBB	P02023	629
GYPE	ACKR1	Q16570	628
GYPE	AHSP	Q9NZD4	627
GYPE	HBE1	P02100	626
GYPE	SCARB1	Q8WTV0	608
GYPE	PVALB	P20472	604
GYPE	SLC4A1	P02730	585
GYPE	DRD2	P14416	583
GYPE	PDYN	P01213	582
GYPE	TAC1	P20366	580
GYPE	DRD1	P21728	570
GYPE	NPAS1	Q99742	570

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A146B485, A0A146B5A4, A0A158RFT4, A0A1B0GWG4, E2J6T4, F5HB98, F5HC14, F5HGU6, F5HHQ0, F5HHS3, G5EEV9, O55653, P02724, P02727, P03224, P06028, P0DQV0, P11320, P11450, P15421, P16721, P16739, P16742, P16744, P16795, P16843, P16845, P17590, P24935, P32515, P35770, P42287, P68326, P68329, P69338, P69339, Q03345, Q28913, Q28914, Q63064

Diamond homologs: P02724, P02726, P02727, P06028, P14220, P14221, P15421, Q28913, Q28914, Q28915

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

705 predictions. Top by Δscore:

Variant	Effect	Δscore
4:143879609:T:C	donor_gain	1.0000
4:143879615:T:A	donor_gain	1.0000
4:143880409:A:AC	donor_gain	0.9900
4:143880410:C:CC	donor_gain	0.9900
4:143880507:TTC:T	acceptor_gain	0.9900
4:143880508:TC:T	acceptor_gain	0.9900
4:143880508:TCCTG:T	acceptor_loss	0.9900
4:143880509:CC:C	acceptor_gain	0.9900
4:143880509:CCTG:C	acceptor_loss	0.9900
4:143880510:C:CC	acceptor_gain	0.9900
4:143880510:CTGT:C	acceptor_loss	0.9900
4:143880511:T:A	acceptor_loss	0.9900
4:143905468:TA:T	donor_loss	0.9900
4:143905470:CCTGA:C	donor_gain	0.9900
4:143876854:CC:C	acceptor_gain	0.9800
4:143876855:CC:C	acceptor_gain	0.9800
4:143879608:A:AC	donor_gain	0.9800
4:143880402:AAAAC:A	donor_loss	0.9800
4:143880403:AAACA:A	donor_loss	0.9800
4:143880404:AACAA:A	donor_loss	0.9800
4:143880405:ACAAA:A	donor_loss	0.9800
4:143880406:CAAA:C	donor_loss	0.9800
4:143880407:AAAC:A	donor_loss	0.9800
4:143880408:AAC:A	donor_loss	0.9800
4:143880409:A:AG	donor_loss	0.9800
4:143905469:A:AC	donor_gain	0.9800
4:143905470:C:CC	donor_gain	0.9800
4:143876853:TCCC:T	acceptor_loss	0.9700
4:143876855:CCTA:C	acceptor_loss	0.9700
4:143876856:C:G	acceptor_loss	0.9700

AlphaMissense

487 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:143876790:C:G	G68R	0.871
4:143876790:C:T	G68R	0.871
4:143905487:A:C	F7L	0.827
4:143905487:A:T	F7L	0.827
4:143905489:A:G	F7L	0.827
4:143876789:C:T	G68E	0.732
4:143880433:A:C	S38R	0.678
4:143880433:A:T	S38R	0.678
4:143880435:T:G	S38R	0.678
4:143905485:A:T	V8E	0.660
4:143880484:A:C	S21R	0.630
4:143880484:A:T	S21R	0.630
4:143880486:T:G	S21R	0.630
4:143880497:A:T	I17K	0.606
4:143905494:A:G	I5T	0.600
4:143876801:A:T	L64H	0.577
4:143905496:T:A	K4N	0.568
4:143905496:T:G	K4N	0.568
4:143905479:A:C	L10R	0.565

dbSNP variants (sampled 300 via entrez): RS1000045332 (4:143873151 C>T), RS1000259137 (4:143903072 C>G), RS1000349496 (4:143897751 C>T), RS1000396586 (4:143892572 G>A,C), RS10004191 (4:143891414 C>G,T), RS1000479049 (4:143904544 G>C,T), RS1000826263 (4:143897557 T>C), RS1001024754 (4:143879497 C>G), RS10010554 (4:143893363 C>A,T), RS1001107544 (4:143898951 G>A), RS1001244732 (4:143895134 T>C), RS1001354726 (4:143880960 G>C), RS1001432268 (4:143889728 G>A,C), RS1001495676 (4:143885628 C>A), RS1001554185 (4:143881177 C>G,T)

Disease associations

OMIM: gene MIM:138590 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003145_1	Severe malaria	4.000000e-11
GCST003145_3	Severe malaria	1.000000e-10
GCST008359_9	Response to cognitive-behavioural therapy in anxiety disorder	7.000000e-06
GCST010725_4	Malaria	4.000000e-10
GCST010725_84	Malaria	7.000000e-11
GCST010725_89	Malaria	7.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007820	cognitive behavioural therapy

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	decreases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	increases expression	1
cupric chloride	affects expression	1
Formaldehyde	decreases expression	1
Progesterone	increases expression	1
Tamoxifen	decreases expression	1
Toluene	decreases methylation, increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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