RHD

protein-coding

Rh blood group D antigen, the group of CD molecules|Blood group antigens

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 the RhD protein, and a second gene that encodes both the RhC and RhE antigens on a single polypeptide. The two genes, and a third unrelated gene, are found in a cluster on chromosome 1. 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. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

MANE transcript

NM_016124.6

Inheritance

AR, BG

ClinVar variants

U:52B:14

Top phenotype

Rhesus blood group

gnomAD constraint

pLI —, LoF o/e 0.56

Max pathogenic AF

—

Genomic locus

chr1:25,272,393-25,330,445

External References & Databases

Ensembl (ENSG00000187010)

Transcript & Mutation Effects

hg38 • Region Span ~58.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

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: 8808597; 9845715; 986418; 10504121; 21277262

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RHD variants in ClinVar

11 Conditions Cataloged

not specifiedTotal: 28

not providedTotal: 13

weakened D expression by serologyTotal: 3

RhD category D-VIITotal: 1

serologic weak D phenotypeTotal: 1

Rhd, weak d, type ITotal: 1

Weakened expression of D antigenTotal: 1

Blood group antigen abnormalityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016124.6. 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	4 clinvar	2 clinvar	8
missense			49 clinvar	7 clinvar	1 clinvar	57
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	52	11	3	66

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016124.6	RefSeq	NP_057208.3	10	MANE Select
ENST00000328664.9	Ensembl	ENSP00000331871.4	10	MANE Select
NM_001127691.3	RefSeq	NP_001121163.1	7	Standard
NM_001282867.1	RefSeq	NP_001269796.1	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: ENST00000328664
Coding exons: 10
Length: 58053
Individuals with no LoFs: 112308
Homozygous LoFs: 140
Heterozygous LoFs: 514
Defined: 112962
p: 0.00290

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.326	226	213	1.06	0.0000125	2666
Missense (PolyPhen)		71	69.28	1.0248		994
Synonymous	-0.489	97	91.1	1.07	0.00000620	857
Loss of Function	1.72	10	17.8	0.561	9.56e-7	208

Population LoF Frequency

Population	CAF	p-value	Status
African	0.044	0.036	notable
Latino/Admixed American	0.0023	0.0019	notable
Ashkenazi Jewish	0.00087	0.00076	rare
East Asian	0.00038	0.00033	rare
Finnish	0.00010	0.000052	rare
European (Non-Finnish)	0.00016	0.00012	rare
South Asian	0.00042	0.00031	rare
Other	0.0011	0.00091	notable

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.;

Intolerance Scores

LoFtool: 0.938
RVIS EVS: 3.31
RVIS percentile EVS: 99.42

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.00250

Gene Damage Prediction

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