NM_000342.3(SLC4A1):c.2279G>A (p.Arg760Gln) AND Hereditary spherocytosis type 4

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 1, 2005
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000019358.32

Allele description [Variation Report for NM_000342.3(SLC4A1):c.2279G>A (p.Arg760Gln)]

NM_000342.3(SLC4A1):c.2279G>A (p.Arg760Gln)

Gene:

SLC4A1:solute carrier family 4 member 1 (Diego blood group) [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.31

Genomic location:

Preferred name:

NM_000342.3(SLC4A1):c.2279G>A (p.Arg760Gln)

HGVS:

NC_000017.11:g.44253150C>T
NG_007498.1:g.19985G>A
NM_000342.4:c.2279G>AMANE SELECT
NP_000333.1:p.Arg760Gln
LRG_803t1:c.2279G>A
LRG_803:g.19985G>A
LRG_803p1:p.Arg760Gln
NC_000017.10:g.42330518C>T
P02730:p.Arg760Gln

Protein change:

R760Q; ARG760GLN

Links:

UniProtKB: P02730#VAR_013806; OMIM: 109270.0028; dbSNP: rs121912755

NCBI 1000 Genomes Browser:

rs121912755

Molecular consequence:

NM_000342.4:c.2279G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary spherocytosis type 4
Synonyms:: Spherocytosis type 4; SLC4A1-Related Spherocytosis
Identifiers:: MONDO: MONDO:0012981; MedGen: C2675212; Orphanet: 822; OMIM: 612653

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000039648	OMIM	no assertion criteria provided	Pathogenic (Nov 1, 2005)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 7530501, 16227998 Gore, D. M., Chetty, M. C., Coles, S. C., Gover, P. M., Stewart G. W. Hereditary spherocytosis with a low temperature Na/K leak and thrombosis. (Abstract) Brit. J. Haemat. 117 Suppl 1: 9-10, 2002.

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000039648

OMIM

no assertion criteria provided

Pathogenic
(Nov 1, 2005)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

Gore, D. M., Chetty, M. C., Coles, S. C., Gover, P. M., Stewart G. W. Hereditary spherocytosis with a low temperature Na/K leak and thrombosis. (Abstract) Brit. J. Haemat. 117 Suppl 1: 9-10, 2002.

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Mutations of conserved arginines in the membrane domain of erythroid band 3 lead to a decrease in membrane-associated band 3 and to the phenotype of hereditary spherocytosis.

Jarolim P, Rubin HL, Brabec V, Chrobak L, Zolotarev AS, Alper SL, Brugnara C, Wichterle H, Palek J.

Blood. 1995 Feb 1;85(3):634-40.

PubMed [citation]

PMID:: 7530501

Monovalent cation leaks in human red cells caused by single amino-acid substitutions in the transport domain of the band 3 chloride-bicarbonate exchanger, AE1.

Bruce LJ, Robinson HC, Guizouarn H, Borgese F, Harrison P, King MJ, Goede JS, Coles SE, Gore DM, Lutz HU, Ficarella R, Layton DM, Iolascon A, Ellory JC, Stewart GW.

Nat Genet. 2005 Nov;37(11):1258-63. Epub 2005 Oct 9.

PubMed [citation]

PMID:: 16227998

Details of each submission

From OMIM, SCV000039648.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

Jarolim et al. (1995) identified an arg760-to-gln (R760Q) substitution in the band 3 gene, designated band 3 Prague II, in 2 patients with hereditary spherocytosis (SPH4; 612653).

In 2 families with SPH4 that were previously reported by Gore et al. (2002), Bruce et al. (2005) identified heterozygosity for a 2279G-A transition in exon 17 of the SLC4A1 gene, resulting in the R760Q substitution at a highly conserved residue. Expression of R760Q in Xenopus laevis oocytes induced abnormal sodium and potassium fluxes, and induced chloride transport was low, suggesting that the substitution converts the protein from an anion exchanger into an unregulated cation channel.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jan 13, 2025

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