GYPC

Summary

GYPC (glycophorin C (Gerbich blood group), HGNC:4704) is a protein-coding gene on chromosome 2q14.3, encoding Glycophorin-C (P04921). This protein is a minor sialoglycoprotein in human erythrocyte membranes.

Glycophorin C (GYPC) is an integral membrane glycoprotein. It is a minor species carried by human erythrocytes, but plays an important role in regulating the mechanical stability of red cells. A number of glycophorin C mutations have been described. The Gerbich and Yus phenotypes are due to deletion of exon 3 and 2, respectively. The Webb and Duch antigens, also known as glycophorin D, result from single point mutations of the glycophorin C gene. The glycophorin C protein has very little homology with glycophorins A and B. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 2995 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary elliptocytosis (Supportive, GenCC)
• GWAS associations: 17
• Clinical variants (ClinVar): 85 total — 1 pathogenic
• Phenotypes (HPO): 23
• MANE Select transcript: NM_002101

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4704
Approved symbol	GYPC
Name	glycophorin C (Gerbich blood group)
Location	2q14.3
Locus type	gene with protein product
Status	Approved
Aliases	GPC, GYPD, Ge, CD236, CD236R, GPD
Ensembl gene	ENSG00000136732
Ensembl biotype	protein_coding
OMIM	110750
Entrez	2995

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000259254, ENST00000356887, ENST00000409836, ENST00000459787, ENST00000484700, ENST00000971946

RefSeq mRNA: 3 — MANE Select: NM_002101 NM_001256584, NM_002101, NM_016815

CCDS: CCDS2136, CCDS46402, CCDS58724

Canonical transcript exons

ENST00000259254 — 4 exons

Exon	Start	End
ENSE00001832190	126656158	126656312
ENSE00001888435	126695946	126696667
ENSE00003601745	126690255	126690311
ENSE00003666760	126693864	126693947

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 99.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 145.9996 / max 10108.7807, expressed in 1443 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22386	115.1596	1436
22385	17.3528	1311
22384	3.8276	1014
22387	3.2369	1049
22388	2.4732	884
22380	0.9771	562
22381	0.8975	467
22383	0.8904	586
22379	0.5969	352
22389	0.4919	297

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	99.02	gold quality
trabecular bone tissue	UBERON:0002483	98.99	gold quality
bone marrow	UBERON:0002371	98.70	gold quality
diaphragm	UBERON:0001103	98.55	gold quality
apex of heart	UBERON:0002098	98.28	gold quality
omental fat pad	UBERON:0010414	98.28	gold quality
peritoneum	UBERON:0002358	98.26	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.14	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.12	gold quality
bone marrow cell	CL:0002092	98.03	gold quality
heart left ventricle	UBERON:0002084	97.78	gold quality
cardiac ventricle	UBERON:0002082	97.75	gold quality
triceps brachii	UBERON:0001509	97.74	gold quality
stromal cell of endometrium	CL:0002255	97.67	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.67	gold quality
lower esophagus	UBERON:0013473	97.63	gold quality
ascending aorta	UBERON:0001496	97.62	gold quality
thoracic aorta	UBERON:0001515	97.61	gold quality
descending thoracic aorta	UBERON:0002345	97.49	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.46	gold quality
adipose tissue	UBERON:0001013	97.45	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.39	gold quality
connective tissue	UBERON:0002384	97.33	gold quality
aorta	UBERON:0000947	97.30	gold quality
right coronary artery	UBERON:0001625	97.30	gold quality
upper lobe of left lung	UBERON:0008952	97.27	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.24	gold quality
upper lobe of lung	UBERON:0008948	97.16	gold quality
left ovary	UBERON:0002119	97.15	gold quality
popliteal artery	UBERON:0002250	97.13	gold quality

Single-cell (SCXA)

Detected in 26 experiment(s), a significant marker in 20.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	2083.94
E-MTAB-6308	yes	1477.05
E-MTAB-11121	yes	940.81
E-GEOD-137537	yes	782.10
E-HCAD-1	yes	511.80
E-GEOD-125970	yes	162.68
E-HCAD-4	yes	99.37
E-MTAB-8142	yes	86.60
E-CURD-112	yes	69.36
E-MTAB-6701	yes	49.64
E-MTAB-10042	yes	43.37
E-HCAD-10	yes	30.54
E-CURD-122	yes	22.31
E-MTAB-9221	yes	21.82
E-MTAB-8410	yes	12.28

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting GYPC, 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-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-4757-5P	99.12	64.51	981
HSA-MIR-3160-3P	99.07	64.78	955
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-558	97.50	67.16	977
HSA-MIR-4486	96.96	60.61	931
HSA-MIR-12128	96.67	66.98	1471

Literature-anchored findings (GeneRIF, showing 14)

• Recombinant Ge2, Ge3 & Ge4 antigens were cloned, expressed and purified. Yus and Ge mutants behaved in SDS-PAGE similarly to normal GPC forms with diffuse glycosylation. (PMID:12058555)
• Data show that the receptor for Plasmodium falciparum erythrocyte-binding antigen 140 (EBA140) is glycophorin C (GYPC) and that this interaction mediates a principal P. falciparum invasion pathway into human erythrocytes. (PMID:12469115)
• Glycophorin C is identified as the receptor for PfEBP-2, the erythrocyte binding ligand of Plasmodium falciparum, and the binding domain on GPC is determined to be amino acid residues 14 through 22 within exon 2. (PMID:12576308)
• Neither mutation was associated with altered susceptibility to asymptomatic Plasmodium falciparum or P. vivax infection. Contribution of these erythrocyte polymorphisms to susceptibility to clinical malaria morbidity requires further study. (PMID:14695625)
• A high GYPC gene expression is associated with an unfavorable outcome, in contrast, a high TRIP3 gene expression is associated with a favorable outcome in childhood ALL. (PMID:19149918)
• The molecular evolution of GYPC among the Hominoidea (Greater and Lesser Apes) and the pattern of polymorphism at the locus in a global human sample, were examined. (PMID:19679754)
• The Gerbich blood group system (PMID:20932076)
• Glycophorin C delta (exon3) is not associated with protection against severe anaemia in Papua New Guinea. (PMID:21061946)
• Precise definition of the binding site for the EBA-140 ligand on glycophorin C may be important with respect to human erythrocyte invasion inhibition strategies based on a receptor. (PMID:24379273)
• Rosetting assays using CD236R knockdown normocytes derived from hematopoietic stem cells further supports the role of glycophorin C as a receptor in P vivax rosette formation. (PMID:24652986)
• Plasmodium falciparum STEVOR functions as an erythrocyte-binding protein that recognizes Glycophorin C (GPC) on the red blood cell (RBC) surface and that its binding correlates with the level of GPC on the RBC surface. (PMID:25011110)
• The authors set out to understand the similarities and differences among the GYPC deletion alleles Yus and Gerbich by positional PCR sequence analysis to identify the breakpoints. They developed a set of diagnostic PCRs that can be used to classify both Yus and Gerbich phenotypic variants on the basis of their nucleotide deletion. The Yus phenotype was defined by 4 different breakpoints and the Ger (PMID:28272739)
• Lu/BCAM-mediated binding to laminin-alpha5 is restricted by interacting, in cis, with glycophorin-C-derived sialic acid residues. (PMID:29344581)
• Novel variant in glycophorin c gene protects against ribavirin-induced anemia during chronic hepatitis C treatment. (PMID:34562771)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gypc	ENSDARG00000041546
mus_musculus	Gypc	ENSMUSG00000090523
rattus_norvegicus	Gypc	ENSRNOG00000029939

Protein

Protein identifiers

Glycophorin-C — P04921 (reviewed: P04921)

Alternative names: Glycoconnectin, Glycophorin-D, Glycoprotein beta, PAS-2’, Sialoglycoprotein D

All UniProt accessions (1): P04921

UniProt curated annotations — full annotation on UniProt →

Function. This protein is a minor sialoglycoprotein in human erythrocyte membranes. The blood group Gerbich antigens and receptors for Plasmodium falciparum merozoites are most likely located within the extracellular domain. Glycophorin-C plays an important role in regulating the stability of red cells.

Subcellular location. Cell membrane.

Tissue specificity. Glycophorin-C is expressed in erythrocytes. Glycophorin-D and IsoGPC are ubiquitously expressed.

Post-translational modifications. O-glycosylated with core 1 or possibly core 8 glycans.

Polymorphism. GYPC is responsible for the Gerbich blood group system (Ge) [MIM:616089]. Ge negative individuals carry a deletion of GYPC exon 3. Deletion of exon 3 in GYPC results in resistance to Plasmodium falciparum invasion and protection against severe malaria [MIM:611162].

Similarity. Belongs to the glycophorin-C family.

Isoforms (3)

UniProt ID	Names	Canonical?
P04921-1	Glycophorin-C	yes
P04921-2	Glycophorin-D
P04921-3	3, IsoGPC

RefSeq proteins (3): NP_001243513, NP_002092, NP_058131 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001195	Glycophorin	Family
IPR003585	Neurexin-like	Domain
IPR042192	Glycophorin-C	Family

UniProt features (32 total): glycosylation site 15, sequence variant 4, topological domain 2, modified residue 2, splice variant 2, region of interest 2, compositionally biased region 2, chain 1, transmembrane region 1, site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2EJY	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04921-F1	66.30	0.15

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): 8 (not glycosylated; in variant webb antigen)

Post-translational modifications (2): 122, 104

Glycosylation sites (15): 3, 4, 6, 8, 9, 10, 15, 24, 26, 27, 28, 31, 32, 33, 42

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 301 (showing top): RNGTGGGC_UNKNOWN, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GRUETZMANN_PANCREATIC_CANCER_DN, GNF2_PRDX2, GOBP_RESPONSE_TO_FLUID_SHEAR_STRESS, MODULE_64, PARK_TRETINOIN_RESPONSE_AND_RARA_PLZF_FUSION, GNF2_ANK1, FOSTER_TOLERANT_MACROPHAGE_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GNF2_SPTA1, ONDER_CDH1_TARGETS_2_UP, AACTTT_UNKNOWN, ACEVEDO_LIVER_CANCER_UP

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), membrane (GO:0016020), cortical cytoskeleton (GO:0030863)

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
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1
cytoskeleton	1
cell cortex	1

Protein interactions and networks

STRING

932 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GYPC	EPB41	P11171	996
GYPC	GYPB	P06028	958
GYPC	GYPA	P02724	936
GYPC	ADD2	P35612	902
GYPC	GYPE	P15421	895
GYPC	ADD1	P35611	894
GYPC	ADD3	Q9UEY8	886
GYPC	PILRA	Q9UKJ1	878
GYPC	DMTN	Q08495	874
GYPC	ACKR1	Q16570	856
GYPC	CD44	P16070	849
GYPC	GCNT2	Q8N0V5	843
GYPC	TLR2	O60603	801
GYPC	TNFRSF14	Q92956	759
GYPC	ERVW-1	Q9UQF0	738

IntAct

149 interactions, top by confidence:

A	B	Type	Score
MPP1	GYPC	psi-mi:“MI:0407”(direct interaction)	0.680
GYPC	MPP1	psi-mi:“MI:0407”(direct interaction)	0.680
MPP1	GYPC	psi-mi:“MI:0915”(physical association)	0.680
GPR42	GYPC	psi-mi:“MI:0915”(physical association)	0.560
GYPC	RHBDD1	psi-mi:“MI:0915”(physical association)	0.560
GYPC	AQP6	psi-mi:“MI:0915”(physical association)	0.560
ABHD16A	GYPC	psi-mi:“MI:0915”(physical association)	0.560
GYPC	SLC10A6	psi-mi:“MI:0915”(physical association)	0.560
GYPC	SHISAL1	psi-mi:“MI:0915”(physical association)	0.560
GYPC	PLPPR2	psi-mi:“MI:0915”(physical association)	0.560
GYPC	TMEM88	psi-mi:“MI:0915”(physical association)	0.560
TSPAN15	GYPC	psi-mi:“MI:0915”(physical association)	0.560
GYPC	TMEM14B	psi-mi:“MI:0915”(physical association)	0.560
GYPC	GRIP2	psi-mi:“MI:0407”(direct interaction)	0.440
GYPC	MPP7	psi-mi:“MI:0407”(direct interaction)	0.440
GYPC	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
GYPC	PARD3	psi-mi:“MI:0407”(direct interaction)	0.440
HTRA1	GYPC	psi-mi:“MI:0407”(direct interaction)	0.440
GYPC	PALS2	psi-mi:“MI:0407”(direct interaction)	0.440
GRIP2	GYPC	psi-mi:“MI:0407”(direct interaction)	0.440
GYPC	MPDZ	psi-mi:“MI:0407”(direct interaction)	0.440
GYPC	HTRA3	psi-mi:“MI:0407”(direct interaction)	0.440
GYPC	GORASP2	psi-mi:“MI:0407”(direct interaction)	0.440
RADIL	GYPC	psi-mi:“MI:0407”(direct interaction)	0.440
GYPC	MAGI3	psi-mi:“MI:0407”(direct interaction)	0.440
GYPC	PARD3B	psi-mi:“MI:0407”(direct interaction)	0.440
GYPC	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440
GYPC	DVL3	psi-mi:“MI:0407”(direct interaction)	0.440
GYPC	GORASP1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (17): GYPC (Proximity Label-MS), GYPC (Proximity Label-MS), GYPC (Proximity Label-MS), GYPC (Two-hybrid), GYPC (Two-hybrid), GYPC (Two-hybrid), GYPC (Two-hybrid), TMEM14B (Two-hybrid), KIAA1644 (Two-hybrid), RHBDD1 (Two-hybrid), SLC10A6 (Two-hybrid), TMEM88 (Two-hybrid), ABHD16A (Two-hybrid), GYPC (Reconstituted Complex), GYPC (Synthetic Lethality)

ESM2 similar proteins: A0JPB5, A2A699, A5PLA0, A6QPA0, A8MVW0, B0BN44, B4DS77, D3ZZP4, O35451, P04921, P28906, Q06186, Q08DP3, Q08EA8, Q13113, Q1LVN1, Q28270, Q5F3A4, Q5FVQ7, Q5HZE8, Q5R5B8, Q60846, Q640B5, Q64314, Q7TNI2, Q810F0, Q86VZ4, Q8C4Q9, Q8CB67, Q8IUW5, Q8K064, Q8K201, Q8K2J7, Q8NC54, Q8NEA5, Q8R138, Q8TBP5, Q8WWG9, Q96L08, Q99941

Diamond homologs: P04921, Q0V8T0, Q0V8T3, Q0V8T6, Q1WIM2, Q1WIM3, Q28F36, Q5RD64, Q6AYP5, Q6DJ83, Q6XFR6, Q78HU7, Q7ZXX1, Q8BLQ9, Q8N126, Q8N3J6, Q8R5M8, Q99N28, Q99P47, Q9BY67, Q9C0A0, Q9CPW0, Q9UHC6, A2RUV9, B3EWZ3, O14786, O15537, O54991, O60462, O88783, P12263, P21956, P25304, P28824, P31696, P70490, P78357, P79385, P79795, P97333

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GYPC	“form complex”	“4.1 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 91 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
Ras activation upon Ca2+ influx through NMDA receptor	5	49.2×	2e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	46.9×	2e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	46.9×	2e-06
Long-term potentiation	5	41.0×	3e-06
Assembly and cell surface presentation of NMDA receptors	9	39.4×	9e-11
Neurexins and neuroligins	11	37.3×	8e-13
Protein-protein interactions at synapses	6	27.5×	2e-06
RHOA GTPase cycle	5	6.4×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	66.8×	7e-14
protein localization to synapse	6	52.8×	2e-07
receptor clustering	7	50.2×	2e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	6	34.2×	2e-06
cell-cell adhesion	9	10.5×	1e-05
protein-containing complex assembly	8	10.5×	5e-05
protein localization to plasma membrane	7	8.8×	6e-04
regulation of small GTPase mediated signal transduction	5	8.3×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	55
Likely benign	9
Benign	9

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1339988	GRCh37/hg19 2q14.3-22.2(chr2:122699106-143799629)x1	Pathogenic

SpliceAI

633 predictions. Top by Δscore:

Variant	Effect	Δscore
2:126656311:CGGTG:C	donor_loss	1.0000
2:126656313:G:GG	donor_gain	1.0000
2:126656313:GTGA:G	donor_loss	1.0000
2:126690309:CAGGT:C	donor_loss	1.0000
2:126690312:GT:G	donor_loss	1.0000
2:126690313:T:A	donor_loss	1.0000
2:126693855:T:TA	acceptor_gain	1.0000
2:126693862:A:AG	acceptor_gain	1.0000
2:126693862:A:C	acceptor_loss	1.0000
2:126693863:G:GA	acceptor_gain	1.0000
2:126693863:GA:G	acceptor_gain	1.0000
2:126693863:GAGC:G	acceptor_gain	1.0000
2:126693863:GAGCC:G	acceptor_gain	1.0000
2:126693944:GCAG:G	donor_gain	1.0000
2:126693948:G:GG	donor_gain	1.0000
2:126693948:GTGA:G	donor_loss	1.0000
2:126695940:CTGCA:C	acceptor_loss	1.0000
2:126695941:TGCAG:T	acceptor_loss	1.0000
2:126695942:GCAG:G	acceptor_loss	1.0000
2:126695943:CAG:C	acceptor_loss	1.0000
2:126695945:GGT:G	acceptor_gain	1.0000
2:126695945:GGTGT:G	acceptor_gain	1.0000
2:126656308:CCTCG:C	donor_gain	0.9900
2:126656309:CTCG:C	donor_gain	0.9900
2:126656310:TCG:T	donor_gain	0.9900
2:126656311:CG:C	donor_gain	0.9900
2:126656312:GG:G	donor_gain	0.9900
2:126656314:T:A	donor_loss	0.9900
2:126690253:A:AG	acceptor_gain	0.9900
2:126690254:G:GG	acceptor_gain	0.9900

AlphaMissense

842 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:126696138:T:A	I128N	0.990
2:126696131:T:C	Y126H	0.989
2:126696046:G:C	K97N	0.988
2:126696046:G:T	K97N	0.988
2:126696033:C:T	T93I	0.987
2:126696132:A:G	Y126C	0.986
2:126696056:T:C	F101L	0.985
2:126696058:T:A	F101L	0.985
2:126696058:T:G	F101L	0.985
2:126696134:T:C	F127L	0.984
2:126696136:T:A	F127L	0.984
2:126696136:T:G	F127L	0.984
2:126696138:T:C	I128T	0.983
2:126696138:T:G	I128S	0.981
2:126696127:G:C	K124N	0.980
2:126696127:G:T	K124N	0.980
2:126696132:A:C	Y126S	0.980
2:126696131:T:G	Y126D	0.974
2:126696026:T:C	Y91H	0.973
2:126696040:G:C	E95D	0.973
2:126696040:G:T	E95D	0.973
2:126696129:A:T	E125V	0.972
2:126696135:T:C	F127S	0.972
2:126693947:G:C	G64R	0.967
2:126696047:G:C	G98R	0.965
2:126696026:T:G	Y91D	0.963
2:126696039:A:T	E95V	0.961
2:126696020:G:C	G89R	0.960
2:126695946:G:A	G64D	0.958
2:126696131:T:A	Y126N	0.957

dbSNP variants (sampled 300 via entrez): RS1000002500 (2:126669780 C>T), RS1000079687 (2:126656015 C>A,G,T), RS1000136462 (2:126669480 T>A,C), RS1000191954 (2:126684722 T>G), RS1000260229 (2:126655500 A>G), RS1000304579 (2:126683361 A>G), RS1000341798 (2:126691978 C>A), RS1000447122 (2:126687764 C>T), RS1000458237 (2:126696229 A>T), RS1000537888 (2:126663971 T>A,C), RS1000579845 (2:126695380 G>A,C), RS1000624372 (2:126678489 A>T), RS1000639167 (2:126673612 G>A,T), RS1000799229 (2:126691389 T>C), RS1000833669 (2:126659285 C>A,T)

Disease associations

OMIM: gene MIM:110750 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary elliptocytosis	Supportive	Autosomal dominant

Mondo (1): hereditary elliptocytosis (MONDO:0017319)

Orphanet (0):

HPO phenotypes

23 total (23 of 23 shown, HPO-id order):

HPO	Term
HP:0000952	Jaundice
HP:0001081	Cholelithiasis
HP:0001744	Splenomegaly
HP:0001789	Hydrops fetalis
HP:0001877	Abnormal erythrocyte morphology
HP:0001878	Hemolytic anemia
HP:0001923	Reticulocytosis
HP:0001945	Fever
HP:0002007	Frontal bossing
HP:0002027	Abdominal pain
HP:0002904	Hyperbilirubinemia
HP:0003265	Neonatal hyperbilirubinemia
HP:0003546	Exercise intolerance
HP:0004445	Elliptocytosis
HP:0004446	Stomatocytosis
HP:0004447	Poikilocytosis
HP:0004804	Congenital hemolytic anemia
HP:0005502	Increased red cell osmotic fragility
HP:0006579	Prolonged neonatal jaundice
HP:0008897	Postnatal growth retardation
HP:0012378	Fatigue
HP:0025143	Chills
HP:0200042	Skin ulcer

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST001428_15	Intelligence	1.000000e-06
GCST002379_1	Pyoderma gangrenosum in inflammatory bowel disease	6.000000e-06
GCST003225_21	Pelvic organ prolapse (moderate/severe)	2.000000e-06
GCST003225_7	Pelvic organ prolapse (moderate/severe)	5.000000e-06
GCST005023_44	Initial pursuit acceleration	2.000000e-06
GCST006061_173	Atrial fibrillation	7.000000e-06
GCST006414_68	Atrial fibrillation	6.000000e-11
GCST006630_47	Diastolic blood pressure	3.000000e-13
GCST008044_10	Systolic blood pressure	1.000000e-08
GCST008044_12	Systolic blood pressure	6.000000e-07
GCST008529_23	Tea consumption	2.000000e-06
GCST009391_377	Metabolite levels	9.000000e-06
GCST010083_48	Hemoglobin levels	3.000000e-08
GCST90002385_447	High light scatter reticulocyte count	4.000000e-12
GCST90002386_261	High light scatter reticulocyte percentage of red cells	2.000000e-09
GCST90002405_136	Reticulocyte count	1.000000e-15
GCST90002406_56	Reticulocyte fraction of red cells	2.000000e-12

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0006835	pyoderma gangrenosum
EFO:0008434	initial pursuit acceleration
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0010091	tea consumption measurement
EFO:0010436	triacylglycerol 56:9 measurement
EFO:0004509	hemoglobin measurement
EFO:0007986	reticulocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004612	Elliptocytosis, Hereditary	C15.378.050.141.150.365; C16.320.070.365

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	5
trichostatin A	affects cotreatment, increases expression	3
(+)-JQ1 compound	decreases expression, affects cotreatment	3
Tobacco Smoke Pollution	decreases expression	3
Cyclosporine	decreases expression, increases expression	3
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Particulate Matter	increases abundance, increases expression, affects cotreatment, decreases expression	2
bisphenol F	increases expression	1
ginger extract	decreases expression, decreases reaction, increases abundance	1
bisphenol A	decreases expression, decreases reaction, increases abundance	1
1,6-hexamethylene diisocyanate	increases methylation	1
sodium arsenite	decreases expression, increases abundance	1
manganese chloride	decreases expression, increases abundance	1
potassium chromate(VI)	decreases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
clothianidin	increases expression	1
mirdametinib	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Rosiglitazone	increases expression	1
Decitabine	decreases expression	1
Sunitinib	increases expression	1
Vorinostat	affects cotreatment, increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00723567	Not specified	COMPLETED	A Novel Mutation of the Spectrin Gene
NCT01923376	Not specified	WITHDRAWN	Hepatic Encephalopathy: Lactulose or Polyethylene Glycol (H.E.L.P.)