RHCE

protein-coding

Rh blood group CcEe antigens, the group of Blood group antigens|CD molecules

Gene summary

The Rh blood group system is the second most clinically significant of the blood groups, second only to ABO. It is also the most polymorphic of the blood groups, with variations due to deletions, gene conversions, and missense mutations. The Rh blood group includes this gene which encodes both the RhC and RhE antigens on a single polypeptide and a second gene which encodes the RhD protein. The classification of Rh-positive and Rh-negative individuals is determined by the presence or absence of the highly immunogenic RhD protein on the surface of erythrocytes. A mutation in this gene results in amorph-type Rh-null disease. Alternative splicing of this gene results in multiple transcript variants encoding several different isoforms. [provided by RefSeq, Aug 2016]

Previous symbols:

MANE transcript

NM_020485.8

Inheritance

AR, BG

ClinVar variants

P:4U:46B:18

Top phenotype

Rhesus blood group

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr1:25,362,249-25,430,192

External References & Databases

Ensembl (ENSG00000188672)

Transcript & Mutation Effects

hg38 • Region Span ~67.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Rh deficiency syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0019107

Submitter: PanelApp Australia

Rh deficiency syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019107

Submitter: Orphanet

Clinical Genomic Database (CGD)

Rhesus blood groupBG

Manifestation: Hematologic

Intervention: Hematologic

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

Refs: 1824267; 8220426; 9657769

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RHCE variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 53

not providedTotal: 9

RH-NULL, AMORPH TYPETotal: 4

altered RhC expressionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020485.8. 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			1 clinvar	6 clinvar		7
missense			44 clinvar	10 clinvar	2 clinvar	56
nonsense						0
start loss						0
frameshift	3 clinvar					3
splice donor/acceptor (+/-2bp)	1 clinvar		1 clinvar			2
Total	4	0	46	16	2	68

Highest pathogenic variant AF is 0.0000020525367

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020485.8	RefSeq	NP_065231.4	10	MANE Select
ENST00000294413.13	Ensembl	ENSP00000294413.6	10	MANE Select
NM_001330430.4	RefSeq	NP_001317359.1	8	Standard
NM_138616.5	RefSeq	NP_619522.3	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

ammonium transmembrane transport

Molecular Function

ammonium transmembrane transporter activity

Cellular Component

integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000294413
Coding exons: 10
Length: 67944
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 15
Defined: 125748
p: 0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.403	211	228	0.925	0.0000131	2667
Missense (PolyPhen)		39	60.826	0.64117		835
Synonymous	0.149	95	96.9	0.981	0.00000631	876
Loss of Function	2.31	8	18.8	0.426	9.75e-7	208

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0	0.0	absent
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be part of an oligomeric complex which is likely to have a transport or channel function in the erythrocyte membrane.;

Recessive Scores

pRec: 0.119

Intolerance Scores

LoFtool: 0.624
RVIS EVS: 1.69
RVIS percentile EVS: 96.38

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.00564

Gene Damage Prediction

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