UniProtKB/Swiss-Prot O60494: Variant p.Ile2984Val

Cubilin
Gene: CUBN
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Variant information Variant position:

2984 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LB/B The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Isoleucine (I) to Valine (V) at position 2984 (I2984V, p.Ile2984Val). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Similar physico-chemical property. Both residues are medium size and hydrophobic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

3 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Variant description:

Not found in West Africans; occurs with variants F-2153 and G-3002 only in individuals of European ancestry. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs1801239 [ dbSNP | Ensembl ]

Sequence information Variant position:

2984 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

3623 The length of the canonical sequence.
Location on the sequence:

SFHLEARSAVTGSCVNDGVH I IRGYSVMSTPFATVCGDEMP The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         SFHLEARSAVTG--SCVNDGVHIIRGYSVMSTPFATVCGDEMP--

                              SFHLEARSAITG--SCANDGVHIIRGSNLSSTPFATVCGNE

Mouse                         SFHLEDRSAVSG--TCDYDGLHIIKGHNLSSTPLVTICGSE

Rat                           SFHLEDRSAITG--TCDHDGLHIIKGRNLSSTPLVTICGSE

Pig                           SFHLEARSTVSG--SCDSDGVHIIRGHSLSSTPLVTLCGDE

Caenorhabditis elegans        DFDLATMRTSFGRAPCEDDYLQII--DTGTDRVLHTFCASE

Drosophila                    NFDLEQGPIS----VCLYDNLTVTTKDKGKDPQQTTLCGVK

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

Type	Positions	Description
Chain	36 – 3623	Cubilin
Domain	2920 – 3035	CUB 22
Disulfide bond	2977 – 2999

Literature citations
Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1.
Aminoff M.; Carter J.E.; Chadwick R.B.; Johnson C.; Graesbeck R.; Abdelaal M.A.; Broch H.; Jenner L.B.; Verroust P.J.; Moestrup S.K.; de la Chapelle A.; Krahe R.;
Nat. Genet. 21:309-313(1999)
Cited for: INVOLVEMENT IN IGS1; VARIANT IGS1 LEU-1297; VARIANTS ILE-124; SER-253; THR-389; HIS-1032; TYR-1545; SER-1559; ILE-1769; PHE-2153; ARG-2575; ARG-2691; ILE-2879; VAL-2984; GLY-3002; ILE-3422 AND LYS-3552; Human C-terminal CUBN variants associate with chronic proteinuria and normal renal function.
Bedin M.; Boyer O.; Servais A.; Li Y.; Villoing-Gaude L.; Tete M.J.; Cambier A.; Hogan J.; Baudouin V.; Krid S.; Bensman A.; Lammens F.; Louillet F.; Ranchin B.; Vigneau C.; Bouteau I.; Isnard-Bagnis C.; Mache C.J.; Schaefer T.; Pape L.; Goedel M.; Huber T.B.; Benz M.; Klaus G.; Hansen M.; Latta K.; Gribouval O.; Moriniere V.; Tournant C.; Grohmann M.; Kuhn E.; Wagner T.; Bole-Feysot C.; Jabot-Hanin F.; Nitschke P.; Ahluwalia T.S.; Koettgen A.; Andersen C.B.F.; Bergmann C.; Antignac C.; Simons M.;
J. Clin. Invest. 130:335-344(2020)
Cited for: INVOLVEMENT IN PROCHOB; VARIANTS PROCHOB MET-55; 1158-TRP--SER-3623 DEL; HIS-1303; 1487-ARG--SER-3623 DEL; 1810-ARG--SER-3623 DEL; TYR-1854; VAL-1928; TYR-1947; 2030-ARG--SER-3623 DEL; ARG-2261; TRP-2599; LEU-2822; 2831-CYS--SER-3623 DEL; 2833-TRP--SER-3623 DEL; 2903-GLN--SER-3623 DEL; SER-3018; ARG-3027; ARG-3308; 3317-GLN--SER-3623 DEL; CYS-3366; TYR-3492; ASP-3520; HIS-3609 AND 3618-ARG--SER-3623 DEL; VARIANTS VAL-1690; ASP-2157; VAL-2914 AND VAL-2984; CUBN is a gene locus for albuminuria.
Boger C.A.; Chen M.H.; Tin A.; Olden M.; Kottgen A.; de Boer I.H.; Fuchsberger C.; O'Seaghdha C.M.; Pattaro C.; Teumer A.; Liu C.T.; Glazer N.L.; Li M.; O'Connell J.R.; Tanaka T.; Peralta C.A.; Kutalik Z.; Luan J.; Zhao J.H.; Hwang S.J.; Akylbekova E.; Kramer H.; van der Harst P.; Smith A.V.; Lohman K.; de Andrade M.; Hayward C.; Kollerits B.; Tonjes A.; Aspelund T.; Ingelsson E.; Eiriksdottir G.; Launer L.J.; Harris T.B.; Shuldiner A.R.; Mitchell B.D.; Arking D.E.; Franceschini N.; Boerwinkle E.; Egan J.; Hernandez D.; Reilly M.; Townsend R.R.; Lumley T.; Siscovick D.S.; Psaty B.M.; Kestenbaum B.; Haritunians T.; Bergmann S.; Vollenweider P.; Waeber G.; Mooser V.; Waterworth D.; Johnson A.D.; Florez J.C.; Meigs J.B.; Lu X.; Turner S.T.; Atkinson E.J.; Leak T.S.; Aasarod K.; Skorpen F.; Syvanen A.C.; Illig T.; Baumert J.; Koenig W.; Kramer B.K.; Devuyst O.; Mychaleckyj J.C.; Minelli C.; Bakker S.J.; Kedenko L.; Paulweber B.; Coassin S.; Endlich K.; Kroemer H.K.; Biffar R.; Stracke S.; Volzke H.; Stumvoll M.; Magi R.; Campbell H.; Vitart V.; Hastie N.D.; Gudnason V.; Kardia S.L.; Liu Y.; Polasek O.; Curhan G.; Kronenberg F.; Prokopenko I.; Rudan I.; Arnlov J.; Hallan S.; Navis G.; Parsa A.; Ferrucci L.; Coresh J.; Shlipak M.G.; Bull S.B.; Paterson N.J.; Wichmann H.E.; Wareham N.J.; Loos R.J.; Rotter J.I.; Pramstaller P.P.; Cupples L.A.; Beckmann J.S.; Yang Q.; Heid I.M.; Rettig R.; Dreisbach A.W.; Bochud M.; Fox C.S.; Kao W.H.;
J. Am. Soc. Nephrol. 22:555-570(2011)
Cited for: VARIANT VAL-2984; Linkage disequilibrium analysis reveals an albuminuria risk haplotype containing three missense mutations in the cubilin gene with striking differences among European and African ancestry populations.
Tzur S.; Wasser W.G.; Rosset S.; Skorecki K.;
BMC Nephrol. 13:142-142(2012)
Cited for: VARIANTS PHE-2153; VAL-2984 AND GLY-3002;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.