RBCC

Full text data of SMIM1

SMIM1 [Confidence: high (a blood group or CD marker)]
Small integral membrane protein 1 (Vel blood group antigen)

BGMUT 33
1492 33 SMIM1 SMIM1 64-80del. Vel/SMIM1 64-80del. 64-80del S22fs coding sequence, emphasis on exons 3 and 4 in gDNA; also coding sequence in mRNA Vel- rare 23563606; 23563608; 23505126 KC751412; KC152643; KC152644 Storry J.R. et al.; Cvejic A. et al.; Baillif BA et al. SMIM1 is not apparent in Velneg individuals Blumenfeld OO. 2013-05-21 03:40:44.630 NA

UniProt B2RUZ4
ID SMIM1_HUMAN Reviewed; 78 AA.
AC B2RUZ4;
DT 16-DEC-2008, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUL-2008, sequence version 1.
DT 22-JAN-2014, entry version 36.
DE RecName: Full=Small integral membrane protein 1;
DE AltName: Full=Vel blood group antigen;
GN Name=SMIM1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PROTEIN SEQUENCE OF 1-10 AND 43-52, IDENTIFICATION BY MASS
RP SPECTROMETRY, POLYMORPHISM, SUBUNIT, AND DISULFIDE BOND.
RX PubMed=23505126; DOI=10.1002/emmm.201302466;
RA Ballif B.A., Helias V., Peyrard T., Menanteau C., Saison C.,
RA Lucien N., Bourgouin S., Le Gall M., Cartron J.P., Arnaud L.;
RT "Disruption of SMIM1 causes the Vel- blood type.";
RL EMBO Mol. Med. 5:751-761(2013).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22 AND SER-27, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [5]
RP POLYMORPHISM, SUBUNIT, DISULFIDE BOND, TISSUE SPECIFICITY, AND
RP TOPOLOGY.
RX PubMed=23563606; DOI=10.1038/ng.2600;
RA Storry J.R., Joud M., Christophersen M.K., Thuresson B., Akerstrom B.,
RA Sojka B.N., Nilsson B., Olsson M.L.;
RT "Homozygosity for a null allele of SMIM1 defines the Vel-negative
RT blood group phenotype.";
RL Nat. Genet. 45:537-541(2013).
RN [6]
RP POLYMORPHISM, VARIANTS LYS-51 AND ARG-51, AND CHARACTERIZATION OF
RP VARIANTS LYS-51 AND ARG-51.
RX PubMed=23563608; DOI=10.1038/ng.2603;
RA Cvejic A., Haer-Wigman L., Stephens J.C., Kostadima M.,
RA Smethurst P.A., Frontini M., van den Akker E., Bertone P.,
RA Bielczyk-Maczynska E., Farrow S., Fehrmann R.S., Gray A., de Haas M.,
RA Haver V.G., Jordan G., Karjalainen J., Kerstens H.H., Kiddle G.,
RA Lloyd-Jones H., Needs M., Poole J., Soussan A.A., Rendon A.,
RA Rieneck K., Sambrook J.G., Schepers H., Sillje H.H., Sipos B.,
RA Swinkels D., Tamuri A.U., Verweij N., Watkins N.A., Westra H.J.,
RA Stemple D., Franke L., Soranzo N., Stunnenberg H.G., Goldman N.,
RA van der Harst P., van der Schoot C.E., Ouwehand W.H., Albers C.A.;
RT "SMIM1 underlies the Vel blood group and influences red blood cell
RT traits.";
RL Nat. Genet. 45:542-545(2013).
CC -!- FUNCTION: Regulator of red blood cells formation (By similarity).
CC -!- SUBUNIT: Homooligomer; disulfide-linked.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass membrane protein
CC (Potential).
CC -!- TISSUE SPECIFICITY: Highly expressed in the bone marrow and
CC expressed at lower levels in non-hematopoietic tissues. Highly
CC expressed in erythroleukemia cell lines. Up-regulated in CD34+
CC hematopoietic progenitors cultured toward red blood cells.
CC -!- POLYMORPHISM: SMIM1 is responsible for the Vel blood group system
CC (VEL) [MIM:615264]. The Vel antigen is present on red blood cells
CC from all people except rare Vel-negative individuals who can form
CC antibodies to Vel in response to transfusion or pregnancy. These
CC antibodies may cause severe hemolytic reactions in blood
CC recipients. In most cases, Vel-negative individuals are homozygous
CC for a 17 nucleotide frameshift deletion in exon 3. In some cases,
CC Vel-negative are heterozygous for the 17 nucleotide frameshift
CC deletion and a missense variant at position 51.
CC -!- SIMILARITY: Belongs to the SMIM1 family.
CC -----------------------------------------------------------------------
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DR EMBL; AL365330; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC146945; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC146957; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; NP_001157196.1; NM_001163724.1.
DR UniGene; Hs.22047; -.
DR ProteinModelPortal; B2RUZ4; -.
DR PhosphoSite; B2RUZ4; -.
DR PRIDE; B2RUZ4; -.
DR Ensembl; ENST00000444870; ENSP00000457386; ENSG00000235169.
DR GeneID; 388588; -.
DR KEGG; hsa:388588; -.
DR UCSC; uc001akw.4; human.
DR CTD; 388588; -.
DR GeneCards; GC01P003691; -.
DR HGNC; HGNC:44204; SMIM1.
DR MIM; 615242; gene.
DR MIM; 615264; phenotype.
DR neXtProt; NX_B2RUZ4; -.
DR HOVERGEN; HBG108688; -.
DR OMA; YYVHKCK; -.
DR OrthoDB; EOG75F4GT; -.
DR NextBio; 102198; -.
DR PRO; PR:B2RUZ4; -.
DR ArrayExpress; B2RUZ4; -.
DR Bgee; B2RUZ4; -.
DR Genevestigator; B2RUZ4; -.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW Blood group antigen; Complete proteome; Direct protein sequencing;
KW Disulfide bond; Membrane; Phosphoprotein; Polymorphism;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1 78 Small integral membrane protein 1.
FT /FTId=PRO_0000356182.
FT TOPO_DOM 1 46 Extracellular (Potential).
FT TRANSMEM 47 67 Helical; (Potential).
FT TOPO_DOM 68 78 Cytoplasmic (Potential).
FT MOD_RES 22 22 Phosphoserine.
FT MOD_RES 27 27 Phosphoserine.
FT VARIANT 51 51 M -> K (polymorphism found in Vel-
FT negative population; heterozygous with
FT the 17 nucleotide frameshift deletion).
FT /FTId=VAR_069360.
FT VARIANT 51 51 M -> R (polymorphism found in Vel-
FT negative population; heterozygous with
FT the 17 nucleotide frameshift deletion).
FT /FTId=VAR_069361.
SQ SEQUENCE 78 AA; 8749 MW; 72B2879DC4986A82 CRC64;
MQPQESHVHY SRWEDGSRDG VSLGAVSSTE EASRCRRISQ RLCTGKLGIA MKVLGGVALF
WIIFILGYLT GYYVHKCK
//

MIM 615242
*RECORD*
*FIELD* NO
615242
*FIELD* TI
*615242 SMALL INTEGRAL MEMBRANE PROTEIN 1; SMIM1
*FIELD* TX

CLONING

Using microarrays for SNP profiling of 20 individuals with the
read moreVel-negative blood group phenotype, followed by transcriptional network
modeling, Storry et al. (2013) identified SMIM1 as a candidate for the
gene underlying Vel antigen expression. By 5-prime and 3-prime RACE of
Vel-positive blood mRNA, they cloned SMIM1. The deduced 78-amino acid
protein has a calculated molecular mass of about 8.7 kD. SMIM1 was
predicted to be a type I transmembrane protein with an approximately
50-amino acid extracellular domain containing several potential sites
for O-glycosylation. The transmembrane domain contains a potential GxxxG
helix-helix dimerization motif. Analysis of human microarray profiles
revealed highest SMIM1 expression in CD34 (142230)-positive erythroid
cultures and in bone marrow, followed by salivary gland and testis. Much
lower expression was detected in several other tissues, including brain.
Western blot analysis of Vel-positive blood and glycophorin A (GPA;
111300)-positive bone marrow detected SMIM1 as a monomer with an
apparent molecular mass of 9 to 10 kD and as reduction-resistant
homodimers of about 20 kD, consistent with the presence of the
transmembrane dimerization motif. Orthologs of SMIM1 were detected in 45
other species from primates to sea squirt. Flow cytometry detected cell
surface expression of SMIM1 in transfected K562 erythroleukemia cells.

GENE STRUCTURE

Storry et al. (2013) determined that the SMIM1 gene contains 4 exons.
Exons 1 and 2 are noncoding, and intron 2 contains a GATA motif
conserved in primates and rodents, but not in dog, bovine, or elephant.

MAPPING

By genomic sequence analysis, Storry et al. (2013) mapped the SMIM1 gene
to chromosome 1p36.

GENE FUNCTION

Ballif et al. (2013) identified SMIM1 as the Vel antigen on red blood
cells. A purified anti-Vel antibody detected a band of about 32 kD in
red blood cell membranes extracted from Vel-positive individuals.
Electrophoresis studies showed that the Vel antigen migrated at about 18
kD under reducing conditions, suggesting that it forms a molecular
homodimer via disulfide bonds. Mass spectrometry, peptide sequencing,
and BLAST analysis suggested that the SMIM1 encodes the Vel antigen.

MOLECULAR GENETICS

- Vel Blood Group System

By SNP mapping followed by candidate gene sequencing of 20 individuals
with the Vel-negative blood group phenotype (615264), Storry et al.
(2013) identified a homozygous 17-bp deletion in the SMIM1 gene
(615242.0001) in all individuals. The findings were confirmed in 15
additional Vel-negative individuals, predominantly of European descent.
Direct genotyping identified 30 heterozygous deletion carriers among 520
Swedish blood donors. The deletion was not found in the 1000 Genomes
Project data, but was found in the National Heart, Lung, and Blood
Institute (NHLBI) Exome Sequencing Project (ESP) database: in 57 of
5,763 European Americans and 6 of 3,198 in African Americans, yielding
heterozygote frequencies of about 1 in 50 and 1 in 267, respectively.

By exome sequencing of 5 individuals negative for the Vel antigen,
Cvejic et al. (2013) found that 4 were homozygous and 1 was heterozygous
for a 17-bp frameshift deletion in the SMIM1 gene. Combined with a
follow-up study of additional Vel-negative individuals, a total of 63 of
69 Vel-negative individuals were found to be homozygous for the
deletion. Five individuals classified as Vel-negative were heterozygous
for the deletion and 1 was heterozygous for a missense mutation (M51R)
only. Heterozygosity for the null allele in these individuals was most
likely explained by misclassification of extremely weak Vel expression
as Vel-negative. In addition, 19 of 20 individuals with weak Vel
expression were heterozygous for the deletion. One individual with weak
expression was heterozygous for a missense mutation (M51K). The 2
missense mutations may lead to inability of the SMIM1 protein to
incorporate in the membrane, or may modify the epitope, leading to
decreased binding of the antibody. Functional studies were not performed
on the M51R or M51K variants. Expression of the Vel antigen on
SMIM1-transfected HEK293T cells confirmed that SMIM1 is the gene
underlying the Vel blood group. All 24 Vel-negative individuals or those
with weak Vel expression who were heterozygous for the deletion were
homozygous for the major A allele of SNP dbSNP rs1175550, which is
present in intron 2 of the STIM1 gene and is associated with decreased
SMIM1 transcript levels. The findings suggested that this SNP
contributes to variable expression of the Vel antigen.

Ballif et al. (2013) also found that all 4 Vel-negative individuals
studied carried the same homozygous 17-bp deletion in exon 3 of the
SMIM1 gene. Subsequent screening identified the homozygous 17-bp
deletion in 68 of 70 Vel-negative individuals. Two individuals carried
the 17-bp deletion in the heterozygous state, and 1 was confirmed to
have weak Vel-positivity. The other was an elderly individual who may
have no longer expressed even weak antigen. In addition, 7 of 9
individuals with weak Vel-positivity were found to be heterozygous for
the deletion. Exogenous expression of SMIM1 in erythroleukemia cells
resulted in Vel expression at the cell surface, confirming that SMIM1
encodes the Vel antigen.

- Other Associations

Cvejic et al. (2013) found that the major A allele of SNP dbSNP
rs1175550 in the SMIM1 gene, which is associated with lower expression
of SMIM1, was associated with decreased mean hemoglobin concentration in
red blood cells (p = 8.6 x 10(-15)) and nominally associated with
correlated parameters, such as mean red blood cell volume and count.
These findings suggested a possible biologic role for SMIM1.

ANIMAL MODEL

Cvejic et al. (2013) found that morpholino-mediated knockdown of Smim1
caused a mild reduction in the total number of mature primitive
erythrocytes in zebrafish.

*FIELD* AV
.0001
VEL BLOOD GROUP SYSTEM, VEL-NULL PHENOTYPE
SMIM1, 17-BP DEL, NT64

In 20 individuals with the Vel-negative blood group phenotype (615264),
mostly of Swedish origin, Storry et al. (2013) identified a homozygous
17-bp deletion (64_80del17) in exon 3 of the SMIM1 gene, resulting in a
frameshift at residue ser22 and premature termination 5-prime to the
encoded transmembrane domain. The mutation was found by SNP mapping
followed by candidate gene sequencing. The findings were confirmed in 15
additional Vel-negative individuals, mostly of European origin.
Haplotype analysis indicated a founder effect. Genotype screening
estimated that about 1 in 17 Swedish blood donors is a heterozygous
deletion carrier and 1 in 1,200 is a homozygous deletion knockout. Blood
from a Vel-negative individual showed no capped and polyadenylated SMIM1
mRNA, suggesting that it is subject to nonsense-mediated mRNA decay and
consistent with a null allele. The phenotype is significant in that
antibodies to Vel are associated with severe hemolytic transfusion
reactions.

Cvejic et al. (2013) and Ballif et al. (2013) independently and
simultaneously identified the homozygous 17-bp deletion in the SMIM1
gene as the genetic basis for the Vel-negative blood group.
Heterozygosity for the deletion was associated with weak Vel expression,
consistent with a dosage effect. A common origin for the deletion was
apparent.

*FIELD* RF
1. Ballif, B. A.; Helias, V.; Peyrard, T.; Menanteau, C.; Saison,
C.; Lucien, N.; Bourgouin, S.; Le Gall, M.; Cartron, J.-P.; Arnaud,
L.: Disruption of SMIM1 causes the Vel- blood type. EMBO Molec.
Med. 5: 751-761, 2013.

2. Cvejic, A.; Haer-Wigman, L.; Stephens, J. C.; Kostadima, M.; Smethurst,
P. A.; Frontini, M.; van den Akker, E.; Bertone, P.; Bielczyk-Maczynska,
E.; Farrow, S.; Fehrmann, R. S. N.; Gray, A.; and 30 others: SMIM1
underlies the Vel blood group and influences red blood cell traits. Nature
Genet. 45: 542-545, 2013.

3. Storry, J. R.; Joud, M.; Christophersen, M. K.; Thuresson, B.;
Akerstrom, B.; Sojka, B. N.; Nilsson, B.; Olsson, M. L.: Homozygosity
for a null allele of SMIM1 defines the Vel-negative blood group phenotype. Nature
Genet. 45: 537-541, 2013.

*FIELD* CN
Cassandra L. Kniffin - updated: 6/3/2013

*FIELD* CD
Patricia A. Hartz: 5/21/2013

*FIELD* ED
carol: 08/28/2013
carol: 6/4/2013
ckniffin: 6/3/2013
mgross: 5/21/2013

MIM 615264
*RECORD*
*FIELD* NO
615264
*FIELD* TI
#615264 BLOOD GROUP, VEL SYSTEM; VEL
VEL-NULL PHENOTYPE, INCLUDED
*FIELD* TX
A number sign (#) is used with this entry because the Vel blood group
read moresystem is determined by the SMIM1 gene (615242), which encodes the Vel
antigen, on chromosome 1p36.

DESCRIPTION

The Vel blood group system is defined by the presence of the Vel antigen
on red blood cells. Vel is a high frequency antigen that shows variable
strength, ranging from strong to weak. The rare Vel-negative blood type
is inherited as an autosomal recessive trait and is typically unveiled
when Vel-negative individuals develop anti-Vel antibodies after
transfusion or pregnancy; Vel alloantibodies are never 'naturally
occurring.' Individuals with anti-Vel antibodies may develop severe
acute hemolytic transfusion reactions when transfused with Vel-positive
blood. Individuals negative for the Vel antigen are rare and are
required for the safe transfusion of patients with antibodies to Vel
(summary by Daniels, 2002; Storry et al., 2013; Cvejic et al., 2013;
Ballif et al., 2013).

CLINICAL FEATURES

Sussman and Miller (1952) first described the Vel-negative blood group
phenotype in a 66-year-old woman who developed a severe acute
intravascular hemolytic episode after a blood transfusion due to
antibodies against a newly defined antigen named 'Vel.' She had a
history of 3 pregnancies and colon cancer requiring transfusions.

Levine et al. (1961) reported a family in which 7 individuals spanning 3
generations were negative for the Vel red blood cell antigen. The
proband was a woman who had been pregnant 6 times and received blood
transfusions at least twice. She developed a severe transfusion reaction
and was found to carry the Vel antibody in her serum, whereas her red
cells lacked the Vel antigen. The other Vel-negative family members did
not have serum anti-Vel antibodies.

Subsequent reports of hemolytic reactions after transfusion of
Vel-positive RBCs to Vel-negative individuals with antibody to Vel, as
well as hemolytic disease of the newborns of Vel-negative mothers,
established Vel as a clinically important blood group antigen (summary
by Storry et al., 2013).

MAPPING

By SNP analysis of 20 Vel-negative individuals primarily of Swedish
origin, including 5 individuals from 2 families, Storry et al. (2013)
identified a 97-kb haplotype block on chromosome 1p36 that segregated
with the phenotype. A homozygous founder mutation was postulated.

MOLECULAR GENETICS

By SNP mapping followed by candidate gene sequencing of 20 Vel-negative
individuals, Storry et al. (2013) identified a homozygous 17-bp deletion
in the SMIM1 gene (615242.0001) in all individuals. The findings were
confirmed in 15 additional Vel-negative individuals, predominantly of
European descent. Direct genotyping identified 30 heterozygous deletion
carriers among 520 Swedish blood donors. The deletion was not found in
the 1000 Genomes Project data, but was found in the National Heart,
Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP)
database: 57 of 5,763 European Americans and 6 of 3,198 in African
Americans, yielding heterozygote frequencies of about 1 in 50 and 1 in
267, respectively.

By exome sequencing of 5 individuals negative for the Vel antigen,
Cvejic et al. (2013) found that 4 were homozygous and 1 was heterozygous
for a 17-bp frameshift deletion in the SMIM1 gene. Combined with a
follow-up study of additional Vel-negative individuals, a total of 63 of
69 Vel-negative individuals were found to be homozygous for the
deletion. Five individuals classified as Vel-negative were heterozygous
for the deletion and 1 was heterozygous for a missense mutation (M51R)
only. Heterozygosity for the null allele in these individuals is most
likely explained by misclassification of extremely weak Vel expression
as Vel-negative. In addition, 19 of 20 individuals with weak Vel
expression were heterozygous for the deletion. One individual with weak
expression was heterozygous for a missense mutation (M51K). The 2
missense mutations may lead to inability of the SMIM1 protein to
incorporate in the membrane, or may modify the epitope, leading to
decreased binding of the antibody. Functional studies were not performed
on the M51R or M51K variants. Expression of the Vel antigen on
SMIM1-transfected HEK293T cells confirmed that SMIM1 is the gene
underlying the Vel blood group. All 24 Vel-negative individuals or those
with weak Vel expression who were heterozygous for the deletion were
homozygous for the major A allele of SNP dbSNP rs1175550, which is
present in intron 2 of the STIM1 gene and is associated with decreased
SMIM1 transcript levels. The findings suggested that this SNP
contributes to variable expression of the Vel antigen.

Ballif et al. (2013) simultaneously identified the homozygous 17-bp
deletion in the SMIM1 gene as the genetic basis for the Vel-negative
blood group. Heterozygosity for the deletion was associated with weak
Vel expression, consistent with a dosage effect. A common origin for the
deletion was apparent.

POPULATION GENETICS

Population studies estimate the prevalence of Vel-negative individuals
at 1 in 4,000 in Europe, with a slightly higher prevalence in northern
Scandinavia (1 in 1,700) (summary by Storry et al., 2013).

*FIELD* RF
1. Ballif, B. A.; Helias, V.; Peyrard, T.; Menanteau, C.; Saison,
C.; Lucien, N.; Bourgouin, S.; Le Gall, M.; Cartron, J.-P.; Arnaud,
L.: Disruption of SMIM1 causes the Vel-blood type. EMBO Molec. Med. 5:
751-761, 2013.

2. Cvejic, A.; Haer-Wigman, L.; Stephens, J. C.; Kostadima, M.; Smethurst,
P. A.; Frontini, M.; van den Akker, E.; Bertone, P.; Bielczyk-Maczynska,
E.; Farrow, S.; Fehrmann, R. S. N.; Gray, A.; and 30 others: SMIM1
underlies the Vel blood group and influences red blood cell traits. Nature
Genet. 45: 542-545, 2013.

3. Daniels, G.: Human Blood Groups. Oxford: Blackwell (2nd ed.),
2002. Pp. 505-513.

4. Levine, P.; White, J. A.; Stroup, M.: Seven Ve(a) (Vel) negative
members in three generations of a family. Transfusion 1: 111-115,
1961.

5. Storry, J. R.; Joud, M.; Christophersen, M. K.; Thuresson, B.;
Akerstrom, B.; Sojka, B. N.; Nilsson, B.; Olsson, M. L.: Homozygosity
for a null allele of SMIM1 defines the Vel-negative blood group phenotype. Nature
Genet. 45: 537-541, 2013.

6. Sussman, L. N.; Miller, E. B.: Un nouveau facteur sanguin 'Vel'. Rev.
Hemat 7: 368-371, 1952.

*FIELD* CS
INHERITANCE:
Autosomal recessive

HEMATOLOGY:
Acute hemolytic transfusion reaction when transfused with Vel-positive
blood

MISCELLANEOUS:
Clinical manifestations only occur if Vel-negative individuals have
anti-Vel antibodies and are transfused with Vel-positive blood;
Antibodies can develop after pregnancy or transfusion

MOLECULAR BASIS:
Caused by mutation in the small integral membrane protein 1 gene (SMIM1,
615242.0001)

*FIELD* CD
Cassandra L. Kniffin: 6/20/2013

*FIELD* ED
joanna: 08/01/2013
ckniffin: 7/9/2013

*FIELD* CD
Cassandra L. Kniffin: 5/30/2013

*FIELD* ED
carol: 08/01/2013
ckniffin: 7/9/2013
carol: 6/5/2013
carol: 6/4/2013
ckniffin: 6/3/2013

RBCC Red Blood Cell Collection

Full text data of SMIM1