GYPC

protein-coding

glycophorin C (Gerbich blood group), the group of Blood group antigens|CD molecules

Gene summary

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. [provided by RefSeq, Feb 2012]

MANE transcript

NM_002101.5

Inheritance

AD, BG

ClinVar variants

P:1U:52B:10

Top phenotype

Blood group, Gerbich; Blood group, Webb; Blood group, Duch

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr2:126,656,133-126,696,667

External References & Databases

Ensembl (ENSG00000136732)

Transcript & Mutation Effects

hg38 • Region Span ~40.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hereditary elliptocytosisSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0017319

Submitter: Orphanet

Clinical Genomic Database (CGD)

Blood group, Gerbich; Blood group, Webb; Blood group, DuchBG

Manifestation: Hematologic

Intervention: Hematologic

Rationale: Variants associated with a blood group may be important in specific situations (eg, related to transfusion)

Refs: 5011657; 7095818; 3539763; 1991173; 1719701; 1413665; 8157284; 11719395; 12469115

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GYPC variants in ClinVar

6 Conditions Cataloged

not providedTotal: 40

not specifiedTotal: 27

GYPC-related disorderTotal: 4

Blood group, Gerbich systemTotal: 3

Glycophorin c, gerbich variantTotal: 1

Malaria, resistance toTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002101.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				2 clinvar		2
missense			47 clinvar	8 clinvar		55
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)	1 clinvar		4 clinvar			5
Total	1	0	52	10	0	63

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002101.5	RefSeq	NP_002092.1	4	MANE Select
ENST00000259254.9	Ensembl	ENSP00000259254.4	4	MANE Select
NM_001256584.2	RefSeq	NP_001243513.1	3	Standard
NM_016815.4	RefSeq	NP_058131.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Malaria - Homo sapiens (human)
Cell surface interactions at the vascular wall
Hemostasis

Biological Process

leukocyte migration

Molecular Function

protein binding

Cellular Component

plasma membrane
integral component of plasma membrane
membrane
extrinsic component of plasma membrane
cortical cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000259254
Coding exons: 4
Length: 40738
Individuals with no LoFs: 125728
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 125734
p: 0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.30	107	75.2	1.42	0.00000430	829
Missense (PolyPhen)		26	20.196	1.2874		253
Synonymous	-1.34	38	28.8	1.32	0.00000180	252
Loss of Function	1.29	2	5.18	0.386	2.24e-7	58

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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.;

Intolerance Scores

LoFtool: 0.821
RVIS EVS: 0.64
RVIS percentile EVS: 83.78

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.491

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium