GYPA

Summary

GYPA (glycophorin A (MNS blood group), HGNC:4702) is a protein-coding gene on chromosome 4q31.21, encoding Glycophorin-A (P02724). Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane.

Glycophorins A (GYPA) and B (GYPB) are major sialoglycoproteins of the human erythrocyte membrane which bear the antigenic determinants for the MN and Ss blood groups. In addition to the M or N and S or s antigens that commonly occur in all populations, about 40 related variant phenotypes have been identified. These variants include all the variants of the Miltenberger complex and several isoforms of Sta, as well as Dantu, Sat, He, Mg, and deletion variants Ena, S-s-U- and Mk. Most of the variants are the result of gene recombinations between GYPA and GYPB.

Source: NCBI Gene 2993 — RefSeq curated summary.

At a glance

• Gene–disease (curated): blood group, mn (Limited, GenCC)
• GWAS associations: 40
• Clinical variants (ClinVar): 24 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_002099

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4702
Approved symbol	GYPA
Name	glycophorin A (MNS blood group)
Location	4q31.21
Locus type	gene with protein product
Status	Approved
Aliases	GPA, MN, CD235a, PAS-2
Ensembl gene	ENSG00000170180
Ensembl biotype	protein_coding
OMIM	617922
Entrez	2993

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 14 protein_coding, 3 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000324022, ENST00000360771, ENST00000503627, ENST00000504786, ENST00000508337, ENST00000509346, ENST00000510771, ENST00000512064, ENST00000512789, ENST00000514603, ENST00000535709, ENST00000616983, ENST00000641688, ENST00000642295, ENST00000642713, ENST00000642738, ENST00000643148, ENST00000643254, ENST00000644398, ENST00000646447

RefSeq mRNA: 3 — MANE Select: NM_002099 NM_001308187, NM_001308190, NM_002099

CCDS: CCDS34069, CCDS77965, CCDS82959

Canonical transcript exons

ENST00000641688 — 7 exons

Exon	Start	End
ENSE00003585014	144118714	144118752
ENSE00003602840	144119686	144119781
ENSE00003627791	144116854	144116939
ENSE00003648852	144114689	144114767
ENSE00003718011	144120490	144120588
ENSE00003720025	144109303	144111410
ENSE00003831035	144140599	144140718

Expression profiles

Bgee: expression breadth ubiquitous, 158 present calls, max score 94.02.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1027 / max 54.5477, expressed in 27 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54208	0.0368	9
203361	0.0282	13
203362	0.0219	7
203360	0.0157	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	94.02	gold quality
bone marrow	UBERON:0002371	91.64	gold quality
bone marrow cell	CL:0002092	91.04	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.41	silver quality
adrenal tissue	UBERON:0018303	78.04	gold quality
monocyte	CL:0000576	74.44	gold quality
mononuclear cell	CL:0000842	74.21	gold quality
leukocyte	CL:0000738	71.91	gold quality
blood	UBERON:0000178	66.22	gold quality
calcaneal tendon	UBERON:0003701	63.35	gold quality
ganglionic eminence	UBERON:0004023	62.60	gold quality
frontal pole	UBERON:0002795	61.82	gold quality
middle frontal gyrus	UBERON:0002702	59.63	gold quality
paraflocculus	UBERON:0005351	59.38	gold quality
pancreatic ductal cell	CL:0002079	58.99	silver quality
apex of heart	UBERON:0002098	58.13	gold quality
spleen	UBERON:0002106	57.28	gold quality
embryo	UBERON:0000922	56.72	gold quality
corpus callosum	UBERON:0002336	56.14	gold quality
adult mammalian kidney	UBERON:0000082	55.38	gold quality
endometrium epithelium	UBERON:0004811	55.01	gold quality
ventricular zone	UBERON:0003053	54.67	silver quality
tendon	UBERON:0000043	54.58	gold quality
cerebellar vermis	UBERON:0004720	54.28	gold quality
kidney	UBERON:0002113	53.39	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	52.21	gold quality
vermiform appendix	UBERON:0001154	52.19	gold quality
thymus	UBERON:0002370	51.93	gold quality
caecum	UBERON:0001153	51.35	gold quality
epithelial cell of pancreas	CL:0000083	51.02	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-MTAB-7407	yes	1618.19
E-HCAD-24	yes	1376.98
E-MTAB-10042	yes	1133.11
E-MTAB-9388	yes	649.01
E-ANND-5	yes	644.59
E-MTAB-8205	yes	377.98
E-HCAD-4	yes	140.97
E-CURD-112	yes	75.88
E-MTAB-9221	yes	12.51
E-HCAD-9	yes	11.39
E-MTAB-9067	yes	8.84
E-HCAD-10	yes	7.84
E-ANND-3	yes	5.12
E-CURD-98	no	3833.49
E-MTAB-9467	no	1.23

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EBP, GATA1, LMO2, SP1, TAL1, TCF3, YY1

miRNA regulators (miRDB)

86 targeting GYPA, 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-6867-5P	100.00	82.21	3464
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909

Literature-anchored findings (GeneRIF, showing 40)

• Natural selection of polymorphisms/variants on the erythrocyte surface (PMID:11861881)
• Somatic cell mutations found at the gene locus in erythrocytes of radiation workers at a nuclear facility (PMID:12492375)
• Distinct regions of human glycophorin A enhance human red cell anion exchanger transport function and surface trafficking (PMID:12813056)
• band 3 in the red cell can take up two different structures: one with high anion transport activity when glycophorin A is present and one with lower anion transport activity when glycophorin A is absent (PMID:14604989)
• Porcine Kupffer cells bind xenogeneic human RBC by recognition of a carbohydrate epitope on glycophorin A. (PMID:16003235)
• This study demonstrates the systematic classification of ten alleles (five M and five N alleles) of the MN blood group system to major or minor variations of the standard alleles. (PMID:16205834)
• glycophorin A somatic mutation frequency levels in newborns are not related to maternal lifestyle factors or drug metabolizing enzyme genotypes (PMID:16424825)
• GYPA & GYPB genotypes carrying MNSs antigens were analyzed in Thai patients with cerebral malaria & mild malaria; no statistical difference was found; it is concluded that MNSs antigens do not reveal the difference in susceptibility to cerebral malaria (PMID:17372674)
• single mutations in glycophorin A can result in the observed fourth power relationship with age of oncet in polycythemia rubra vera (PMID:17452518)
• GPA-NN mutagens contributed to the pathogenesis of chronic benzene poisoning. (PMID:17456399)
• GPA depletion does not alter band 3’s native conformation at the DIDS binding site. It modulates a conformational equilibrium between 2 states of the binary complex formed by the competitive inhibitor DIDS, reversibly bound to properly folded band 3. (PMID:19071041)
• AE1 and GPA form a complex in the endoplasmic reticulum of human K562 cells. (PMID:19438409)
• Heterozygous missense mutation E758K in the human AE1/SLC4A1/band 3 gene in two unrelated patients with well-compensated hereditary spherostomatocytic anemia induces glycophorin A-independent, endogenous cation transport. (PMID:19907019)
• Energy transfer between differently labelled glycophorin A transmembrane helices decreased with increasing Sodium Dodecyl Sulfate mole fractions albeit without modifying the helicity of the peptides. (PMID:20074546)
• The Sta gene found in this family has A246 & C252, C302, and G307. The putative crossing-over point is between nucleotides 252 to 302 in Intron 3. (PMID:20233359)
• ABH blood group antigens in N-glycan of human glycophorin A. (PMID:20434428)
• Data indicate that changes of the glycophorin A dimerization propensities in different lipid bilayers suggest that the lipid bilayer thickness severely influences the monomer-dimer equilibrium of the transmembrane domain. (PMID:20603102)
• Beta-branched residues adjacent to GG4 motifs promote the efficient association of glycophorin A transmembrane helices. (PMID:21072853)
• the GG genotype of the rs 1489759 HHIP single-nucleotide polymorphism (SNP) and the CC genotype of the rs 2202507 GYPA SNP confers a ‘‘protective’’ effect on COPD (OR 0.59, p50.006 for HHIP and OR50.65, p50.006 for GYPA) and lung cancer. (PMID:21119205)
• Data suggest that glycophorin A (Gpa) increases expression and activity of Cl-/HCO3- exchanger Ae1, that G719D mutation renders Ae1 mutant constructs GPA-unresponsive, and suggests a role for Ae1 amino acids 22-28 in GPA responsiveness. (PMID:21455273)
• The expression of glycophorin A and osteoprotegerin is locally increased in carotid atherosclerotic lesions of symptomatic compared to asymptomatic patients. (PMID:23722820)
• These data demonstrate the importance of PfEBA175 regions other than the DBL domains in the interaction with GYPA and merit their inclusion in an EBA175-based vaccine. (PMID:24043627)
• MNSs blood group glycophorin variants in Taiwan: a genotype-serotype correlation study of ‘Mi(a)’ and St(a) with report of two new alleles for St(a). (PMID:24858913)
• PfEBA-175 engages multiple glycans of GpA encoded by exon 3 and that the presentation of glycans is likely required for high-avidity binding. (PMID:25205096)
• The authors demonstrate that the initial vacuolar membrane around internalized Babesia divergens is formed from protein and lipid components of the red blood cells plasma membrane, including band 3, glycophorin A and spectrin. (PMID:25628009)
• CD235a could be the most sensitive predictor similar to CD4. (PMID:25716234)
• GPA-deficient band 3 null erythrocytes are resistant to malaria infection. (PMID:25778531)
• Glycophorin-A-rich microparticles are released from evolving growing thrombi into the distal perfusing blood, and can be measured in peripheral blood. CD235a(+) cMPs may constitute a novel systemic biomarker of ongoing thrombosis. (PMID:26239059)
• While weak interactions between glycophorin and band 3 undoubtedly exist, glycophorin A and band 3 must have separate interactions in the membrane that control their lateral mobility. (PMID:27580023)
• The authors show that Plasmodium falciparum EBA-175 mediates substantial changes in the deformability of erythrocytes by binding to glycophorin A and activating a phosphorylation cascade that includes erythrocyte cytoskeletal proteins resulting in changes in the viscoelastic properties of the host cell. (PMID:28226242)
• a complex structural rearrangement involving the loss of GYPB and gain of two GYPB-A hybrid genes reduces the risk of severe malaria by 40% and has recently increased in frequency in parts of Kenya (PMID:28522690)
• Cell viability and surface expression of transferrin receptor (CD71) and glycophorin A (GPA) were analyzed before and after re-culture by flow cytometry. These studies show differential sensitivities of these surface proteins on K562 cells to proteases, and suggest molecular mechanisms of transmembrane protein transport and cycling. (PMID:28980921)
• These results are consistent with malaria acting as a selective pressure on GYPA, but also suggest that another selective force has resulted in a similar pattern of variation in Europeans. Accordingly, GYPA has perhaps a more complex evolutionary history, wherein on a global scale, spatially varying selective pressures have governed its natural history. (PMID:29362874)
• Characterization of GYP*Mur and novel GYP*Bun-like hybrids in Thai blood donors reveals a qualitatively altered s antigen. (PMID:32201961)
• A new antigen SUMI carried on glycophorin A encoded by the GYPA*M with c.91A>C (p.Thr31Pro) belongs to the MNS blood group system. (PMID:32358867)
• 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)
• Diagnostic value of glycophorin-A in comparison with P57 immunohistochemical staining method in differentiating complete and partial molar pregnancies. (PMID:34146830)
• Characterization of alternatively spliced transcript variants of glycophorin A and glycophorin B genes in Chinese blood donors. (PMID:35138639)
• Fatal haemolytic transfusion reaction due to anti-En[a] and identification of a novel GYPA c.295delG variant in a Thai family. (PMID:36102166)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gypa	ENSMUSG00000051839

Paralogs (2): GYPE (ENSG00000197465), GYPB (ENSG00000250361)

Protein

Protein identifiers

Glycophorin-A — P02724 (reviewed: P02724)

Alternative names: MN sialoglycoprotein, PAS-2, Sialoglycoprotein alpha

All UniProt accessions (10): P02724, A0A087WU29, A0A2R8Y7F9, D6RJD8, E7EQF3, E9PD10, E9PH25, K9JI14, K9JIK7, Q13030

UniProt curated annotations — full annotation on UniProt →

Function. Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane. Glycophorin A is the major intrinsic membrane protein of the erythrocyte. The N-terminal glycosylated segment, which lies outside the erythrocyte membrane, has MN blood group receptors. Appears to be important for the function of SLC4A1 and is required for high activity of SLC4A1. May be involved in translocation of SLC4A1 to the plasma membrane. (Microbial infection) Appears to be a receptor for Hepatitis A virus (HAV). (Microbial infection) Receptor for P.falciparum erythrocyte-binding antigen 175 (EBA-175); binding of EBA-175 is dependent on sialic acid residues of the O-linked glycans.

Subunit / interactions. Homodimer. Component of the ankyrin-1 complex in the erythrocyte, composed of ANK1, RHCE, RHAG, SLC4A1, EPB42, GYPA, GYPB and AQP1. Interacts with SLC4A1; a GYPA monomer is bound at each end of the SLC4A1 dimer forming a heterotetramer. (Microbial infection) Interacts with Streptococcus gordonii hsa protein. (Microbial infection) Interacts (in a sialic acid-independent manner) with P.falciparum MSP1 subunit p83.

Subcellular location. Cell membrane.

Post-translational modifications. The major O-linked glycan are NeuAc-alpha-(2-3)-Gal-beta-(1-3)-[NeuAc-alpha-(2-6)]-GalNAcOH (about 78 %) and NeuAc-alpha-(2-3)-Gal-beta-(1-3)-GalNAcOH (17 %). Minor O-glycans (5 %) include NeuAc-alpha-(2-3)-Gal-beta-(1-3)-[NeuAc-alpha-(2-6)]-GalNAcOH NeuAc-alpha-(2-8)-NeuAc-alpha-(2-3)-Gal-beta-(1-3)-GalNAcOH. About 1% of all O-linked glycans carry blood group A, B and H determinants. They derive from a type-2 precursor core structure, Gal-beta-(1,3)-GlcNAc-beta-1-R, and the antigens are synthesized by addition of fucose (H antigen-specific) and then N-acetylgalactosamine (A antigen-specific) or galactose (B antigen-specific). Specifically O-linked-glycans are NeuAc-alpha-(2-3)-Gal-beta-(1-3)-GalNAcOH-(6-1)-GlcNAc-beta-(4-1)-[Fuc-alpha-(1-2)]-Gal-beta-(3-1)-GalNAc-alpha (about 1%, B antigen-specific) and NeuAc-alpha-(2-3)-Gal-beta-(1-3)-GalNAcOH-(6-1)-GlcNAc-beta-(4-1)-[Fuc-alpha-(1-2)]-Gal-beta (1 %, O antigen-, A antigen- and B antigen-specific).

Polymorphism. Along with GYPB, GYPA is responsible for the MNS blood group system [MIM:111300]. The molecular basis of the GPA M/N bloodgroup antigen is a variation at positions 20 and 24. Ser-20 and Gly-24 correspond to M; ‘Leu-20’ and ‘Glu-24’ correspond to N (shown). GYPA polymorphisms are involved in resistance to malaria [MIM:611162].

Miscellaneous. Involved in several unequal homologous recombinations or gene conversion events, predominantly with GYPB and more rarely with GYPE. The resulting fusion proteins are observed in different phenotypes and encode low incidence bloodgroup antigens.

Similarity. Belongs to the glycophorin A family.

Isoforms (3)

UniProt ID	Names	Canonical?
P02724-1	1	yes
P02724-2	2
P02724-3	3

RefSeq proteins (3): NP_001295116, NP_001295119, NP_002090* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001195	Glycophorin	Family
IPR018938	Glycophorin_CS	Conserved_site
IPR049535	GYPA_B	Family

Pfam: PF01102

UniProt features (58 total): glycosylation site 17, sequence variant 17, mutagenesis site 8, sequence conflict 3, modified residue 3, topological domain 2, splice variant 2, signal peptide 1, chain 1, transmembrane region 1, region of interest 1, strand 1, helix 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
5EH6	X-RAY DIFFRACTION	1.92
7UZ3	ELECTRON MICROSCOPY	2.35
7V0K	ELECTRON MICROSCOPY	2.4
8CS9	ELECTRON MICROSCOPY	2.74
7V07	ELECTRON MICROSCOPY	2.8
5EH4	X-RAY DIFFRACTION	2.81
8CTE	ELECTRON MICROSCOPY	2.9
8CRR	ELECTRON MICROSCOPY	3
8CRT	ELECTRON MICROSCOPY	3
8CRQ	ELECTRON MICROSCOPY	3.2
7V19	ELECTRON MICROSCOPY	3.3
8CT3	ELECTRON MICROSCOPY	3.3
8CSL	ELECTRON MICROSCOPY	25
1AFO	SOLUTION NMR
2KPE	SOLUTION NMR
2KPF	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P02724-F1	59.40	0.04

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 (3): 133, 138, 148

Glycosylation sites (17): 22, 23, 29, 30, 31, 32, 36, 38, 41, 44, 45, 52, 56, 63, 66, 69, 21

Mutagenesis-validated functional residues (8):

Position	Phenotype
87	diminishes dimerization.
88	diminishes dimerization.
90	diminishes dimerization.
91	diminishes dimerization.
94	diminishes dimerization.
95	diminishes dimerization.
98	diminishes dimerization.
102	abolishes dimerization.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-202733	Cell surface interactions at the vascular wall

MSigDB gene sets: 109 (showing top): IVANOVA_HEMATOPOIESIS_MATURE_CELL, ADDYA_ERYTHROID_DIFFERENTIATION_BY_HEMIN, MORF_RAD51L3, GNF2_ANK1, RAMALHO_STEMNESS_DN, GOBP_BIOLOGICAL_PROCESS_INVOLVED_IN_INTERACTION_WITH_HOST, GNF2_SPTA1, GOBP_VIRAL_LIFE_CYCLE, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, WELCH_GATA1_TARGETS, MORF_THPO, GNF2_PCAF, REACTOME_CELL_SURFACE_INTERACTIONS_AT_THE_VASCULAR_WALL, GNF2_MAP2K3, SHEN_SMARCA2_TARGETS_DN

GO Biological Process (2): biological_process (GO:0008150), symbiont entry into host cell (GO:0046718)

GO Molecular Function (4): virus receptor activity (GO:0001618), identical protein binding (GO:0042802), molecular_function (GO:0003674), protein binding (GO:0005515)

GO Cellular Component (6): nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), ankyrin-1 complex (GO:0170014), cellular_component (GO:0005575)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
viral life cycle	1
symbiont entry into host	1
symbiont entry into host cell	1
exogenous protein binding	1
protein binding	1
binding	1
nuclear lumen	1
cytoplasm	1
membrane	1
cell periphery	1
membrane protein complex	1

Protein interactions and networks

STRING

1240 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GYPA	SLC4A1	P02730	941
GYPA	CD47	Q08722	940
GYPA	GYPC	P04921	936
GYPA	GYPB	P06028	899
GYPA	ATAD1	Q8NBU5	884
GYPA	RHAG	Q02094	846
GYPA	SCARB2	Q14108	838
GYPA	CD36	P16671	837
GYPA	SCARB1	Q8WTV0	828
GYPA	CD19	P15391	822
GYPA	IL3RA	P26951	819
GYPA	FCGR3B	O75015	803
GYPA	FCGR3A	P08637	803
GYPA	ANK1	P16157	801
GYPA	CD34	P28906	793

IntAct

111 interactions, top by confidence:

A	B	Type	Score
KEAP1	GYPA	psi-mi:“MI:0915”(physical association)	0.780
GYPA	KEAP1	psi-mi:“MI:0915”(physical association)	0.780
SGTA	GYPA	psi-mi:“MI:0915”(physical association)	0.720
CREB3	GYPA	psi-mi:“MI:0915”(physical association)	0.670
GYPA	GYPA	psi-mi:“MI:0915”(physical association)	0.670
GYPA	CREB3	psi-mi:“MI:0915”(physical association)	0.670
GYPA	EVA1A	psi-mi:“MI:0915”(physical association)	0.670
GYPA	SLC4A1	psi-mi:“MI:0403”(colocalization)	0.660
GYPA	SLC4A1	psi-mi:“MI:0915”(physical association)	0.660
SLC4A1	GYPA	psi-mi:“MI:0403”(colocalization)	0.660
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
GYPA	GOLGA7	psi-mi:“MI:0914”(association)	0.640
GYPA	EBP	psi-mi:“MI:0915”(physical association)	0.560
GYPA	IL10RA	psi-mi:“MI:0915”(physical association)	0.560
TMBIM6	GYPA	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (186): SGTA (Two-hybrid), KEAP1 (Two-hybrid), GYPA (Two-hybrid), CREB3 (Two-hybrid), KEAP1 (Two-hybrid), SGTA (Two-hybrid), ATR (Affinity Capture-MS), CLDND1 (Affinity Capture-MS), TMEM192 (Affinity Capture-MS), GOLGA7 (Affinity Capture-MS), FAM115C (Affinity Capture-MS), EEF1A2 (Affinity Capture-MS), SLC22A18 (Affinity Capture-MS), STAT2 (Affinity Capture-MS), DNM3 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GSN8, A0A1B0GSZ0, A0A1B0GWG4, A0JNM1, A2A2V5, A2APA5, A7E1Z1, A7MB05, A9CBA0, B0S728, F5HGU6, O39519, O44535, O88472, P02724, P02727, P0CAX8, P14221, P16742, P18345, P69338, P69339, Q02223, Q0VFL4, Q149F5, Q28913, Q2KIK3, Q2LCV6, Q2TAV2, Q498C7, Q5JX69, Q5R7R7, Q60664, Q68D42, Q68FB2, Q69569, Q6AYF7, Q7M750, Q80WK2, Q86SP6

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

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GYPA	“form complex”	“Ankyrin complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	18
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
17714	NM_002099.8(GYPA):c.232G>A (p.Gly78Arg)	Pathogenic

SpliceAI

854 predictions. Top by Δscore:

Variant	Effect	Δscore
4:144116848:TCTCA:T	donor_loss	1.0000
4:144116849:CTCA:C	donor_loss	1.0000
4:144116850:TCACC:T	donor_loss	1.0000
4:144116851:CA:C	donor_loss	1.0000
4:144116852:A:AT	donor_loss	1.0000
4:144116853:CCTT:C	donor_loss	1.0000
4:144116935:TATCT:T	acceptor_gain	1.0000
4:144116938:CT:C	acceptor_gain	1.0000
4:144116940:C:CC	acceptor_gain	1.0000
4:144119679:AACAT:A	donor_loss	1.0000
4:144119680:ACAT:A	donor_loss	1.0000
4:144119681:CAT:C	donor_loss	1.0000
4:144119682:ATA:A	donor_loss	1.0000
4:144119683:TA:T	donor_loss	1.0000
4:144119684:A:AC	donor_gain	1.0000
4:144119685:C:CC	donor_gain	1.0000
4:144119685:C:CT	donor_loss	1.0000
4:144111420:T:C	acceptor_gain	0.9900
4:144111420:T:TC	acceptor_gain	0.9900
4:144111422:A:C	acceptor_gain	0.9900
4:144114768:C:CC	acceptor_gain	0.9900
4:144116936:ATCTC:A	acceptor_loss	0.9900
4:144116937:TCT:T	acceptor_gain	0.9900
4:144116937:TCTC:T	acceptor_loss	0.9900
4:144116938:CTC:C	acceptor_gain	0.9900
4:144116939:TCT:T	acceptor_gain	0.9900
4:144116940:C:G	acceptor_gain	0.9900
4:144116940:CTAC:C	acceptor_loss	0.9900
4:144116941:T:A	acceptor_loss	0.9900
4:144119782:C:CC	acceptor_gain	0.9900

AlphaMissense

954 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:144116898:C:G	G105R	0.971
4:144116898:C:T	G105R	0.971
4:144116897:C:T	G105E	0.969
4:144116906:C:T	G102D	0.963
4:144116918:C:T	G98E	0.959
4:144118724:G:C	F87L	0.957
4:144118724:G:T	F87L	0.957
4:144118726:A:G	F87L	0.957
4:144116919:C:G	G98R	0.952
4:144116919:C:T	G98R	0.952
4:144116907:C:G	G102R	0.951
4:144116909:G:T	A101D	0.950
4:144116912:A:C	M100R	0.949
4:144116910:C:G	A101P	0.939
4:144116912:A:T	M100K	0.938
4:144118725:A:C	F87C	0.924
4:144118725:A:G	F87S	0.919
4:144116924:A:T	I96N	0.917
4:144116888:A:G	L108P	0.911
4:144116900:A:T	I104N	0.892
4:144116927:A:T	I95N	0.882
4:144114711:A:C	S138R	0.880
4:144114711:A:T	S138R	0.880
4:144114713:T:G	S138R	0.880
4:144116927:A:C	I95S	0.878
4:144116891:A:T	I107N	0.863
4:144116888:A:T	L108H	0.860
4:144116888:A:C	L108R	0.857
4:144116915:A:T	V99E	0.857
4:144116861:A:G	L117P	0.855

dbSNP variants (sampled 300 via entrez): RS1000010510 (4:144110195 T>A), RS1000083724 (4:144110519 T>C), RS1000235860 (4:144141721 G>C), RS1000286599 (4:144141938 T>C), RS1000327378 (4:144112740 A>G,T), RS1000352895 (4:144136887 G>A), RS1000356233 (4:144116675 G>A), RS1000379602 (4:144113050 G>A), RS1000808571 (4:144136607 GA>G,GAA), RS1000828941 (4:144132651 C>A,G), RS1000987927 (4:144128032 A>G,T), RS1001153982 (4:144133729 A>G,T), RS1001157921 (4:144121276 GA>G,GAA), RS10012458 (4:144119263 C>A,G,T), RS1001394933 (4:144129454 A>G)

Disease associations

OMIM: gene MIM:617922 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
blood group, mn	Limited	Autosomal dominant

Mondo (1): (MONDO:0020616)

Orphanet (0):

HPO phenotypes

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

GWAS associations

40 associations (top):

Study	Trait	p-value
GCST002306_21	Bipolar disorder (body mass index interaction)	5.000000e-06
GCST002587_8	Blood pressure (smoking interaction)	7.000000e-07
GCST002795_2	Chronic obstructive pulmonary disease	9.000000e-08
GCST003145_1	Severe malaria	4.000000e-11
GCST003145_3	Severe malaria	1.000000e-10
GCST004602_30	Mean corpuscular volume	1.000000e-12
GCST004603_223	Platelet count	4.000000e-09
GCST004607_227	Plateletcrit	2.000000e-12
GCST004625_10	Monocyte count	1.000000e-12
GCST004630_144	Mean corpuscular hemoglobin	6.000000e-13
GCST005956_60	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST005962_45	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	2.000000e-06
GCST005996_45	Red blood cell count	1.000000e-08
GCST006445_7	Femoral neck bone mineral density	6.000000e-06
GCST007094_23	Diastolic blood pressure	7.000000e-11
GCST007095_115	Systolic blood pressure	5.000000e-06
GCST007098_16	Diastolic blood pressure	1.000000e-06
GCST007099_105	Systolic blood pressure	3.000000e-09
GCST007692_17	Chronic obstructive pulmonary disease	6.000000e-26
GCST008359_9	Response to cognitive-behavioural therapy in anxiety disorder	7.000000e-06
GCST008664_3	Lung function (low FEV1 vs high FEV1)	2.000000e-13
GCST008839_107	Height	1.000000e-13
GCST010725_4	Malaria	4.000000e-10
GCST010725_84	Malaria	7.000000e-11
GCST010725_89	Malaria	7.000000e-11
GCST010988_82	Adult body size	2.000000e-10
GCST011163_1	Diabetic neuropathy in type 2 diabetes	3.000000e-11
GCST012227_1296	Hip circumference adjusted for BMI	8.000000e-09
GCST012227_1297	Hip circumference adjusted for BMI	2.000000e-08
GCST012227_1298	Hip circumference adjusted for BMI	2.000000e-08

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0006335	systolic blood pressure
EFO:0006526	pack-years measurement
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0005091	monocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004305	erythrocyte count
EFO:0007785	femoral neck bone mineral density
EFO:0006336	diastolic blood pressure
EFO:0007820	cognitive behavioural therapy
EFO:0004314	forced expiratory volume
EFO:0008039	BMI-adjusted hip circumference
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5806 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetradecanoylphorbol Acetate	decreases expression, decreases reaction, increases expression, increases reaction	2
diphenyleneiodonium	decreases reaction, decreases expression	1
6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid	decreases expression, decreases reaction	1
hydroxyhydroquinone	decreases expression	1
cobaltous chloride	decreases expression	1
hydroquinone	decreases expression	1
lysophosphatidic acid	affects cotreatment, increases expression, increases reaction	1
artenimol	affects expression	1
acetovanillone	decreases expression, decreases reaction	1
apigetrin	increases expression	1
midostaurin	decreases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, decreases expression	1
tellimagrandin I	increases expression, decreases expression, decreases reaction	1
CGP 52608	affects binding, increases reaction	1
alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide	decreases expression, decreases reaction	1
chebulinic acid	increases expression, decreases reaction	1
U 0126	decreases expression, decreases reaction	1
2-palmitoylglycerol	increases expression	1
pyrazolanthrone	decreases reaction, decreases expression	1
3-(4-(4-((1-(2-chlorophenyl)ethoxy)carbonyl amino)-3-methyl-5-isoxazolyl) benzylsulfanyl) propanoic acid	affects cotreatment, decreases reaction, increases expression	1
teriflunomide	decreases reaction, increases expression	1
10-(4’-(N-diethylamino)butyl)-2-chlorophenoxazine	decreases expression, decreases reaction	1
Resveratrol	increases expression	1
Arsenic Trioxide	decreases expression	1
Acetylcysteine	decreases expression, decreases reaction	1
Arsenic	increases mutagenesis	1
Cytidine	increases expression, decreases reaction	1
Guanosine Triphosphate	increases expression	1
Quercetin	decreases expression, decreases reaction	1
Uridine	decreases reaction, increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL961629	Binding	Binding affinity to transmembrane alpha-helix of glycophorin A by surface plasmon resonance method	Interaction of ladder-shaped polyethers with transmembrane alpha-helix of glycophorin A as evidenced by saturation transfer difference NMR and surface plasmon resonance. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0XC	BEL-A GPA KO	Transformed cell line	Sex unspecified
CVCL_ZF32	PBDEP-4-dGYPA	Transformed cell line	Sex unspecified

Clinical trials (associated diseases)

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