RHCE

Summary

RHCE (Rh blood group CcEe antigens, HGNC:10008) is a protein-coding gene on chromosome 1p36.11, encoding Blood group Rh(CE) polypeptide (P18577). Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane.

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.

Source: NCBI Gene 6006 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Rh deficiency syndrome (Strong, GenCC)
• GWAS associations: 23
• Clinical variants (ClinVar): 75 total — 4 pathogenic
• Phenotypes (HPO): 21
• MANE Select transcript: NM_020485

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10008
Approved symbol	RHCE
Name	Rh blood group CcEe antigens
Location	1p36.11
Locus type	gene with protein product
Status	Approved
Aliases	CD240CE, SLC42A4
Ensembl gene	ENSG00000188672
Ensembl biotype	protein_coding
OMIM	111700
Entrez	6006

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000294413, ENST00000340849, ENST00000346452, ENST00000349320, ENST00000349438, ENST00000413854, ENST00000495048, ENST00000527187, ENST00000527747, ENST00000533771

RefSeq mRNA: 5 — MANE Select: NM_020485 NM_001330430, NM_020485, NM_138616, NM_138617, NM_138618

CCDS: CCDS30634, CCDS30635, CCDS30636, CCDS30637, CCDS81283

Canonical transcript exons

ENST00000294413 — 10 exons

Exon	Start	End
ENSE00001834005	25420639	25420825
ENSE00003391888	25362249	25362553
ENSE00003495089	25391994	25392141
ENSE00003508223	25388976	25389113
ENSE00003609847	25385711	25385844
ENSE00003610030	25390749	25390915
ENSE00003625843	25402596	25402746
ENSE00003669530	25408683	25408869
ENSE00003720027	25375349	25375428
ENSE00003747907	25370467	25370540

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 96.03.

FANTOM5 (CAGE): breadth broad, TPM avg 1.3469 / max 62.5457, expressed in 567 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11092	1.3050	563
11091	0.0420	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
trabecular bone tissue	UBERON:0002483	96.03	gold quality
bone marrow	UBERON:0002371	89.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.70	gold quality
bone marrow cell	CL:0002092	84.17	gold quality
endothelial cell	CL:0000115	83.50	gold quality
amniotic fluid	UBERON:0000173	74.58	silver quality
buccal mucosa cell	CL:0002336	74.31	gold quality
islet of Langerhans	UBERON:0000006	71.99	gold quality
blood	UBERON:0000178	69.87	gold quality
stromal cell of endometrium	CL:0002255	69.55	gold quality
mucosa of stomach	UBERON:0001199	67.67	gold quality
endometrium epithelium	UBERON:0004811	67.35	gold quality
pituitary gland	UBERON:0000007	67.24	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	66.99	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	66.97	gold quality
pancreatic ductal cell	CL:0002079	66.58	silver quality
esophagus squamous epithelium	UBERON:0006920	66.35	gold quality
adenohypophysis	UBERON:0002196	66.13	gold quality
secondary oocyte	CL:0000655	65.90	silver quality
nucleus accumbens	UBERON:0001882	65.87	gold quality
minor salivary gland	UBERON:0001830	65.84	gold quality
monocyte	CL:0000576	65.83	gold quality
mononuclear cell	CL:0000842	65.68	gold quality
leukocyte	CL:0000738	65.11	gold quality
tibia	UBERON:0000979	65.07	gold quality
gastrocnemius	UBERON:0001388	64.83	gold quality
spinal cord	UBERON:0002240	64.58	gold quality
putamen	UBERON:0001874	64.21	gold quality
epithelium of esophagus	UBERON:0001976	64.13	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	34.58
E-HCAD-9	yes	9.05
E-MTAB-9388	yes	8.19
E-MTAB-9067	yes	6.96
E-ANND-3	yes	5.77
E-HCAD-10	no	1.93

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting RHCE, 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-4775	99.98	75.00	6394
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-889-3P	99.40	69.76	2103
HSA-MIR-302A-5P	99.39	68.21	1913
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-6511B-5P	97.98	65.64	823
HSA-MIR-6811-5P	97.98	64.96	848
HSA-MIR-301A-5P	96.88	68.07	931
HSA-MIR-301B-5P	96.88	67.75	946

Literature-anchored findings (GeneRIF, showing 40)

• identification as a mammalian ammonium transporter (PMID:11861637)
• RHCE represents the ancestral RH position, while RHD is the duplicated gene (PMID:11902138)
• Molecular analysis of Hor+, Mol+ variants revealed a hybrid gene structure RHCe-D(5)-Ce, in which exon 5 of RHCE (RHCe allele) was replaced by exon 5 of RHD (the so-called RHCeVA allele). (PMID:12084172)
• strong selection might be working to maintain the RHCE/RHD antigen variation in the two-locus system (PMID:12857961)
• disruption of f (Rh6) by Arg229 deletion suggests that external loop 4 is a major structural element contributing to the expression of RHCE cis interacting antigenic products. (PMID:14996197)
• The single-point mutation T500A in exon 4 of the RHCE gene is a molecular basis of the rare Rhesus antigen Ew. (PMID:14996199)
• A high incidence of Trp16Cys in RHCE ce was seen in sickle cell disease. Many of these patients were heterozygous for VS antigen. cDNA analysis showed that the 2 mutations were on different alleles, weakening expression of the e antigen on RBCs. (PMID:15023184)
• Review. The genetic, structural, and immunologic features of RHCE are reviewed. (PMID:15373666)
• RhCE may not function directly in ammonia transport and may be evolving a new function in the RBC membrane. (PMID:16563829)
• Review. 3-D models of the subunit and oligomeric architecture are proposed, using hydrophobic cluster analysis. (PMID:16584906)
• Although the F223V substitution is regarded as the initial event in the evolution of the weak D Type 4 cluster, the current DFV allele probably evolved independently, as evident from different RHCE haplotypes (PMID:17900276)
• It is possible to examine fetal c allele of RHCE gene in the plasma of pregnant women with anti-c by means of a noninvasive method. (PMID:18382999)
• The nucleotide 340C>T change in RHCE exon 3 (predicted to encode 114Trp) of the RHCE*ce(S)(340) allele is associated with a JAL+ phenotype and the altered expression of the c, V and VS antigens. (PMID:19076333)
• Homology modeling of the JAL+ RhCE protein suggests that the Arg–>Trp change eliminates a critical loop-stabilizing H-bond between the side chain of Arg114 and the e-specific amino acid Ala226. (PMID:19170983)
• the previously described RhCeMA and ce(s)(340) alleles encode the JAL antigen. (PMID:19207167)
• RHcE(M167K) known as E variant I was the most frequent allele, found in 70 of 122 analyzed blood donors in the northwest of Germany. Among 13 referred samples, C typing problems predominated. (PMID:19453979)
• Single-amino-acid substitutions were the molecular basis for variant RhCE antigen expression in most samples of German blood donors and patients . (PMID:19453980)
• The low prevalence Rh antigen, Be(a), is associated with a single nucleotide change in exon 5 of RHCE*ce; that of 662C>G. and This changes proline-221 of Rhce to arginine, which may impose a steric and/or charge-related effect on the protein. (PMID:19951310)
• JAL and JAHK antigens are expressed by Ce and ce and varients of RhCE protein (PMID:20233350)
• Study identifies a novel allele, RHCE*ce 48C, 733G, 941C, 1006T which is predicted to encode 16Cys, 245Val, 314Ala, and 336CyS and was shown to encode c, V/VS, and an altered expression of e and hrB antigens. (PMID:20576012)
• RHCE*ceAR encodes a partial c (RH4) antigen. (PMID:20932075)
• Allele-specific oligonucleotide polymerase chain reaction for the determination of Rh C/c and Rh E/e antigens in thalassaemic patients. (PMID:21251469)
• A novel allele of RHCE, RHCE*cE 907delC, silences c and E and in the homozygous state resulting in a D- - phenotype and production of anti-Rh17. (PMID:21517889)
• The rare RHCE*ceBI allele appears to be in cis either with RHD*DOL1 or with RHD*DOL2 in people of African descent. (PMID:22690701)
• Low-prevalence Rh antigen STEM (RH49) is encoded by two different RHCE*ce818T alleles that are often in cis to RHD*DOL. (PMID:22738288)
• RHD*DIVa and RHCE*ceTI almost always, but not invariably, travel together. This haplotype is found in people of African ancestry and the red blood cells can demonstrate aberrant reactivity with anti-C. RHCE*ceTI encodes partial c and e antigens. (PMID:22804620)
• A novel RHCE*cE allele, RHCE*cE734C, was found in two probands whose red blood cells had weakened c expression and typed E- with conventional anti-E reagents. (PMID:22958092)
• In addition to hybrid alleles and nucleotide deletion, intronic mutations may be associated with the nonexpression of RhCE antigens. (PMID:23252593)
• Two novel RHCE*ce 48C,733G,1006T alleles have been identified: RHD*186T and RHD*DIIIa150C. (PMID:23286557)
• A QMPSF-based method is reliable to individually quantify the exons of both RH genes, including hybrid D-CE genes in compound heterozygous samples. (PMID:23550903)
• RHD*weak partial 4.0 is associated with an altered RHCE*ce(48C, 105T, 733G, 744C, 1025T) allele in the Tunisian population. (PMID:23742316)
• RHCE*ceMO was present in one in 50 African-American persons with an allele frequency of 0.01, is often linked to RHD*DAU0, and is potentially of clinical significance for transfusion. (PMID:23772606)
• Frequencies of aberrant RHD and RHCE alleles were similar, irrespective of location and ethnicity. (PMID:24033223)
• These data showed the presence of the (C)ce(s) haplotype at a low frequency (0.625%) compared to that among Africans in whom it is common. Nevertheless, the presence of RHD-CE-D(s) in Tunisians, even at a lower frequency (PMID:24333089)
• Rh antibodies in SCD patients with RH variants can be clinically significant and, therefore, matching patients based on RH variants should be considered. (PMID:24960646)
• Through molecular genotyping we also identified polymorphisms in RhCE, Kell, Duffy, Colton, Lutheran and Scianna loci in donors and patients. (PMID:25582271)
• One allele was found to be the known allele RHCE*Ol.20.01(RHCE*ce733G) and the second was novel: RHCE*Ol.06.02(RHCE*ce254G,733G). (PMID:25695437)
• An uneven distribution of RH variant alleles between Dogon and Fulani, in Mali. A high incidence of predicted partial-C phenotype encoded by RHCE*Ce-D(4)-ce was found in Fulani. (PMID:25857637)
• RHCE*cE94G encodes variable expression of c (RH4). (PMID:26286238)
• Six new RHCE alleles were identified, namely, RHCE*cE84A, RHCE*ce202G, RHCE*ce307T, RHCE*Ce377G, RHCE*ce697G,712G,733G,744C, and RHCE*Ce733G in individuals of diverse racial origin. (PMID:26435076)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rhd	ENSDARG00000002194
mus_musculus	Rhd	ENSMUSG00000028825
rattus_norvegicus	Rhd	ENSRNOG00000017130
drosophila_melanogaster	Rh50	FBGN0028699
caenorhabditis_elegans		WBGENE00004358
caenorhabditis_elegans		WBGENE00004359

Paralogs (4): RHAG (ENSG00000112077), RHBG (ENSG00000132677), RHCG (ENSG00000140519), RHD (ENSG00000187010)

Protein

Protein identifiers

Blood group Rh(CE) polypeptide — P18577 (reviewed: P18577)

Alternative names: Rh polypeptide 1, Rh30A, RhIXB, Rhesus C/E antigens

All UniProt accessions (8): E7EQ47, E7EU00, E9PKB3, F6XSS0, P18577, H0YCJ8, Q5VSJ7, Q5VSJ8

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. Mediates the primary membrane attachment site for ANK1 when associated with RHAG. May participate in the ammonium and carbon dioxide transport through the heterotrimer form.

Subunit / interactions. Heterotrimer; a RHCE monomer interacts with a RHAG homodimer. Component of the ankyrin-1 complex in the erythrocyte, composed of ANK1, RHCE, RHAG, SLC4A1, EPB42, GYPA, GYPB and AQP1. Interacts (via the N- and C-terminal) with ANK1 (via ANk 1-5 repeats); mediates the primary membrane attachment site for ANK1.

Subcellular location. Membrane.

Tissue specificity. Restricted to tissues or cell lines expressing erythroid characters. Isoform 4g and isoform RhPI-Alpha are expressed in immature erythroblasts but not in mature erythroblasts.

Disease relevance. Rh-null, amorph type (RHNA) [MIM:617970] An autosomal recessive condition characterized by red blood cells that lack all Rh antigens, have increased osmotic fragility, diminished lifespan, and show changes in morphology resulting in stomatocytosis. Rh-null individuals have mild to moderate hemolytic anemia. They are at risk of having adverse reactions in response to transfusion or pregnancy, because they may produce antibodies against several of the Rh antigens. The disease is caused by variants affecting the gene represented in this entry.

Polymorphism. RhCE and RhD are responsible for the RH blood group system. The molecular basis of the E=Rh3/e=Rh5 blood group antigens is a single variation in position 226; Pro-226 corresponds to Rh3 and Ala-226 to Rh5. Variant p.Trp16Cys is associated with altered expression of E antigen. The molecular basis of the C=Rh2/c=Rh4 blood group antigens are variations in position 16, 60, 68 and 103; p.Cys16Trp, p.Ile60Leu, p.Ser68Asn and p.Ser103Pro are found in antigen Rh4.

Similarity. Belongs to the ammonium transporter (TC 2.A.49) family. Rh subfamily.

Isoforms (14)

UniProt ID	Names	Canonical?
P18577-1	RHI	yes
P18577-2	RHIV, 1e
P18577-3	RHVI, 7c
P18577-4	RHVIII
P18577-5	1c
P18577-6	1d
P18577-7	1h
P18577-8	2e
P18577-9	4g, RhPI-Beta
P18577-10	7a
P18577-11	8a
P18577-12	8e
P18577-13	8h
P18577-14	RhPI-Alpha

RefSeq proteins (5): NP_001317359, NP_065231, NP_619522, NP_619523, NP_619524 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002229	RhesusRHD	Family
IPR024041	NH4_transpt_AmtB-like_dom	Domain
IPR029020	Ammonium/urea_transptr	Homologous_superfamily

Pfam: PF00909

UniProt features (104 total): sequence variant 24, sequence conflict 21, helix 19, splice variant 17, transmembrane region 11, strand 5, turn 5, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
7UZQ	ELECTRON MICROSCOPY	2.17
7V0K	ELECTRON MICROSCOPY	2.4
8CSX	ELECTRON MICROSCOPY	2.4
7V0S	ELECTRON MICROSCOPY	2.5
8CS9	ELECTRON MICROSCOPY	2.74
8CTE	ELECTRON MICROSCOPY	2.9
8CRT	ELECTRON MICROSCOPY	3
8CSL	ELECTRON MICROSCOPY	25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P18577-F1	83.75	0.46

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9037628	Rhesus blood group biosynthesis

MSigDB gene sets: 151 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, E2F_Q4, GNF2_ANK1, E2F_Q3, GATA3_01, GNF2_SPTA1, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, GNF2_PCAF, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_TRANSMEMBRANE_TRANSPORT, GATA_Q6, GNF2_MAP2K3, REACTOME_METABOLISM_OF_CARBOHYDRATES_AND_CARBOHYDRATE_DERIVATIVES, E2F_Q3_01

GO Biological Process (2): ammonium transmembrane transport (GO:0072488), ammonium homeostasis (GO:0097272)

GO Molecular Function (1): ammonium channel activity (GO:0008519)

GO Cellular Component (3): plasma membrane (GO:0005886), ankyrin-1 complex (GO:0170014), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Blood group systems biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transmembrane transport	1
nitrogen compound transport	1
inorganic ion homeostasis	1
channel activity	1
ammonium transmembrane transport	1
membrane	1
cell periphery	1
membrane protein complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

470 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RHCE	GYPB	P06028	955
RHCE	TMEM50A	O95807	948
RHCE	CD47	Q08722	932
RHCE	RHAG	Q02094	899
RHCE	DHCR24	Q15392	869
RHCE	PPP1R3A	Q16821	849
RHCE	H3BT10	H3BT10	832
RHCE	GYPA	P02724	722
RHCE	KEL	P23276	722
RHCE	PGD	P52209	712
RHCE	BSG	P35613	694
RHCE	RBL2	Q08999	688
RHCE	FUCA1	P04066	675
RHCE	GYPC	P04921	633
RHCE	GATA1	P15976	561

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: O88298, P18577, P58873, Q02094, Q02161, Q0IIV2, Q18PF6, Q19KI0, Q20CR3, Q28426, Q28427, Q28446, Q28481, Q28812, Q28813, Q28814, Q28849, Q2T9S6, Q3BBX8, Q3BCQ4, Q3BCQ5, Q3BCQ7, Q4VUI0, Q4VUZ1, Q5NVA3, Q5U4V1, Q68FT6, Q69D47, Q6DCG4, Q6WRY0, Q7T070, Q7TNK7, Q7TNN9, Q8BUX5, Q8CBB2, Q8CF94, Q8JI14, Q8WMW0, Q8WMW2, Q8WNQ5

Diamond homologs: O88298, P18577, Q02094, Q02161, Q0IIV2, Q18PF5, Q18PF6, Q19KH7, Q19KI0, Q20CR3, Q28426, Q28427, Q28446, Q28481, Q28812, Q28813, Q28814, Q28849, Q2T9S6, Q3BBX7, Q3BBX8, Q3BCQ4, Q3BCQ5, Q3BCQ7, Q4VUI0, Q4VUZ1, Q5NVA3, Q5U4V1, Q68FT6, Q69D47, Q69D48, Q6DCG4, Q6WRY0, Q6XL41, Q7T070, Q7T3R4, Q7TNK7, Q7TNN9, Q8BUX5, Q8CF94

SIGNOR signaling

1 interactions.

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

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	39
Likely benign	13
Benign	6

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
17710	NM_020485.8(RHCE):c.966_968delinsC (p.His323fs)	Pathogenic
523640	NM_020485.8(RHCE):c.634+1G>T	Pathogenic
523641	NM_020485.8(RHCE):c.963del (p.Ile322fs)	Pathogenic
523642	NM_020485.8(RHCE):c.1044_1050dup (p.Thr351fs)	Pathogenic

SpliceAI

1630 predictions. Top by Δscore:

Variant	Effect	Δscore
1:25385709:A:AC	donor_gain	1.0000
1:25385710:C:CC	donor_gain	1.0000
1:25385719:G:A	donor_gain	1.0000
1:25385724:T:A	donor_gain	1.0000
1:25391989:CTTAC:C	donor_loss	1.0000
1:25391991:T:TG	donor_loss	1.0000
1:25391992:A:C	donor_loss	1.0000
1:25391992:AC:A	donor_gain	1.0000
1:25391993:CC:C	donor_gain	1.0000
1:25362554:C:CC	acceptor_gain	0.9900
1:25375344:CTGA:C	donor_loss	0.9900
1:25375345:TGA:T	donor_loss	0.9900
1:25375346:GAC:G	donor_loss	0.9900
1:25375347:A:G	donor_loss	0.9900
1:25385710:CATG:C	donor_gain	0.9900
1:25388970:TCTTA:T	donor_loss	0.9900
1:25388971:CTT:C	donor_loss	0.9900
1:25388972:TTAC:T	donor_loss	0.9900
1:25388973:T:TG	donor_loss	0.9900
1:25388975:C:CG	donor_loss	0.9900
1:25388975:CCGG:C	donor_gain	0.9900
1:25389109:TAAGT:T	acceptor_gain	0.9900
1:25389115:T:G	acceptor_loss	0.9900
1:25391992:A:AC	donor_gain	0.9900
1:25391993:C:CC	donor_gain	0.9900
1:25391993:CCCAG:C	donor_gain	0.9900
1:25392138:CTGT:C	acceptor_gain	0.9900
1:25392139:TGT:T	acceptor_gain	0.9900
1:25392142:C:CC	acceptor_gain	0.9900
1:25402594:A:AC	donor_gain	0.9900

AlphaMissense

2709 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:25392091:A:C	F179L	0.952
1:25392091:A:T	F179L	0.952
1:25392093:A:G	F179L	0.952
1:25390806:A:C	S248R	0.950
1:25390806:A:T	S248R	0.950
1:25390808:T:G	S248R	0.950
1:25408793:G:C	S75R	0.931
1:25408793:G:T	S75R	0.931
1:25408795:T:G	S75R	0.931
1:25408750:A:G	W90R	0.930
1:25408750:A:T	W90R	0.930
1:25392103:G:C	F175L	0.918
1:25392103:G:T	F175L	0.918
1:25392105:A:G	F175L	0.918
1:25408781:G:C	F79L	0.910
1:25408781:G:T	F79L	0.910
1:25408783:A:G	F79L	0.910
1:25362551:A:C	F410L	0.907
1:25362551:A:T	F410L	0.907
1:25362553:A:G	F410L	0.907
1:25375360:C:T	G381D	0.891
1:25370473:G:C	F407L	0.885
1:25370473:G:T	F407L	0.885
1:25370475:A:G	F407L	0.885
1:25390893:G:C	F219L	0.875
1:25390893:G:T	F219L	0.875
1:25390895:A:G	F219L	0.875
1:25390901:A:G	W217R	0.873
1:25390901:A:T	W217R	0.873
1:25370472:A:G	W408R	0.872

dbSNP variants (sampled 300 via entrez): RS1000013500 (1:25374589 C>T), RS1000062340 (1:25418024 T>G), RS1000081734 (1:25424239 T>G), RS1000133718 (1:25419279 T>C), RS1000155467 (1:25398857 T>C), RS1000208464 (1:25398531 C>G), RS1000331096 (1:25387139 T>C), RS1000477126 (1:25392486 C>T), RS1000503738 (1:25396806 C>G), RS1000531383 (1:25381441 C>T), RS1000597905 (1:25396574 G>A), RS1000663601 (1:25420087 T>G), RS1000721360 (1:25391655 A>G), RS1000807554 (1:25406266 T>C,G), RS1000856056 (1:25413165 A>G,T)

Disease associations

OMIM: gene MIM:111700 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Rh deficiency syndrome	Strong	Autosomal recessive

Mondo (2): megacolon (MONDO:0001273), Rh deficiency syndrome (MONDO:0019107)

Orphanet (0):

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000952	Jaundice
HP:0001433	Hepatosplenomegaly
HP:0001511	Intrauterine growth retardation
HP:0001562	Oligohydramnios
HP:0001649	Tachycardia
HP:0001878	Hemolytic anemia
HP:0001923	Reticulocytosis
HP:0001972	Macrocytic anemia
HP:0002789	Tachypnea
HP:0002904	Hyperbilirubinemia
HP:0004444	Spherocytosis
HP:0004446	Stomatocytosis
HP:0005268	Miscarriage
HP:0005502	Increased red cell osmotic fragility
HP:0011273	Anisocytosis
HP:0012418	Hypoxemia
HP:0020181	Reduced haptoglobin level
HP:0025435	Increased circulating lactate dehydrogenase concentration
HP:0032231	Hypochromia
HP:0032366	Positive direct antiglobulin test

GWAS associations

23 associations (top):

Study	Trait	p-value
GCST004603_160	Platelet count	6.000000e-32
GCST004605_53	Mean corpuscular hemoglobin concentration	3.000000e-11
GCST004616_105	Platelet distribution width	4.000000e-13
GCST004619_141	Reticulocyte fraction of red cells	2.000000e-12
GCST004621_6	Red cell distribution width	6.000000e-34
GCST004622_101	Reticulocyte count	1.000000e-13
GCST006804_93	Red cell distribution width	3.000000e-24
GCST006979_868	Heel bone mineral density	7.000000e-10
GCST007442_4	Low density lipoprotein cholesterol levels	1.000000e-08
GCST90002385_605	High light scatter reticulocyte count	9.000000e-18
GCST90002385_606	High light scatter reticulocyte count	5.000000e-15
GCST90002386_311	High light scatter reticulocyte percentage of red cells	3.000000e-14
GCST90002390_591	Mean corpuscular hemoglobin	4.000000e-25
GCST90002396_119	Mean reticulocyte volume	5.000000e-11
GCST90002397_618	Mean spheric corpuscular volume	2.000000e-14
GCST90002397_619	Mean spheric corpuscular volume	4.000000e-23
GCST90002400_17	Plateletcrit	2.000000e-11
GCST90002402_533	Platelet count	9.000000e-17
GCST90002404_457	Red cell distribution width	3.000000e-102
GCST90002405_596	Reticulocyte count	6.000000e-36
GCST90002405_598	Reticulocyte count	9.000000e-15
GCST90002406_134	Reticulocyte fraction of red cells	3.000000e-33
GCST90002406_136	Reticulocyte fraction of red cells	2.000000e-14

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007984	platelet component distribution width
EFO:0007986	reticulocyte count
EFO:0009188	Red cell distribution width
EFO:0009270	heel bone mineral density
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0007985	platelet crit

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008531	Megacolon	C06.405.469.158.701
C562717	Rh Deficiency Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation	2
Cadmium Chloride	decreases expression, increases abundance	2
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
sodium arsenite	increases expression	1
CGP 52608	increases reaction, affects binding	1
licochalcone B	increases expression	1
jinfukang	decreases expression	1
Ethanol	decreases expression	1
Cadmium	decreases expression, increases abundance	1
Lead	decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Dronabinol	decreases expression	1
Triclosan	increases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C0XG	BEL-A RHCE KO	Transformed cell line	Sex unspecified

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04340856	Not specified	COMPLETED	Retrospective, Uncontrolled Cohort Study on the Therapy of Chronic Megalon
NCT07470892	Not specified	NOT_YET_RECRUITING	Preoperative Fish Oil PN and Prognosis After Constipation Surgery