UniProtKB/Swiss-Prot Q8IU99: Variant p.Leu86Pro

Calcium homeostasis modulator protein 1
Gene: CALHM1
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Variant information Variant position:

86 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 Leucine (L) to Proline (P) at position 86 (L86P, p.Leu86Pro). 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
Polymorphism:

Leu-86 causes a dysregulation of Ca(2+) homeostasis and amyloid precursor protein (APP) metabolism and has been suggested to be a risk factor for the development of Alzheimer disease (PubMed:18585350, PubMed:20061624, PubMed:20164592). However, this association with Alzheimer disease could not be confirmed in a number of studies performed in different populations (PubMed:19472444, PubMed:19070563, PubMed:19191331, PubMed:19191332, PubMed:19545933, PubMed:19655363, PubMed:21378601). According to a meta-analysis study, Leu-86 is likely not a genetic determinant of Alzheimer disease but may modulate age of onset by interacting with the effect of the APOE*4 allele of the APOE gene (PubMed:20847397). Additional information on the polymorphism described.
Other resources:

Links to websites of interest for the variant.

Variant rs2986017 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

LLGLVMNNNVSMLAEEWKRP L GRRAKDPAVLRYMFCSMAQR 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                         LLGLVMNNNVSMLAEEWKRPLGRRAKDPAVLRYMFCSMAQR

Mouse                         LLGLVMNNNISMLAEEWKRPAGRRAKDPAVLRYMFCSMAQR

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	1 – 346	Calcium homeostasis modulator protein 1
Topological domain	72 – 108	Cytoplasmic
Site	74 – 74	Not glycosylated
Mutagenesis	72 – 72	N -> G. Significant inhibition on the control of cytosolic Ca(2+) levels. Does not affect ion channel activity.
Mutagenesis	74 – 74	N -> A. Has no effect on glycosylation.

Literature citations
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
The MGC Project Team;
Genome Res. 14:2121-2127(2004)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]; VARIANT PRO-86; A polymorphism in CALHM1 influences Ca2+ homeostasis, Abeta levels, and Alzheimer's disease risk.
Dreses-Werringloer U.; Lambert J.-C.; Vingtdeux V.; Zhao H.; Vais H.; Siebert A.; Jain A.; Koppel J.; Rovelet-Lecrux A.; Hannequin D.; Pasquier F.; Galimberti D.; Scarpini E.; Mann D.; Lendon C.; Campion D.; Amouyel P.; Davies P.; Foskett J.K.; Campagne F.; Marambaud P.;
Cell 133:1149-1161(2008)
Cited for: FUNCTION; SUBUNIT; SUBCELLULAR LOCATION; TISSUE SPECIFICITY; GLYCOSYLATION AT ASN-140; VARIANT PRO-86; POLYMORPHISM; MUTAGENESIS OF ASN-72; ASN-74 AND ASN-140; CALHM1 polymorphism is not associated with late-onset Alzheimer disease.
Beecham G.W.; Schnetz-Boutaud N.; Haines J.L.; Pericak-Vance M.A.;
Ann. Hum. Genet. 73:379-381(2009)
Cited for: VARIANT PRO-86; No association between CALHM1 and Alzheimer's disease risk.
Bertram L.; Schjeide B.M.; Hooli B.; Mullin K.; Hiltunen M.; Soininen H.; Ingelsson M.; Lannfelt L.; Blacker D.; Tanzi R.E.;
Cell 135:993-994(2008)
Cited for: VARIANT PRO-86; No association between CALHM1 variation and risk of Alzheimer disease.
Minster R.L.; Demirci F.Y.; DeKosky S.T.; Kamboh M.I.;
Hum. Mutat. 30:E566-E569(2009)
Cited for: VARIANT PRO-86; No association between CALHM1 and risk for Alzheimer dementia in a Belgian population.
Sleegers K.; Brouwers N.; Bettens K.; Engelborghs S.; van Miegroet H.; De Deyn P.P.; Van Broeckhoven C.;
Hum. Mutat. 30:E570-E574(2009)
Cited for: VARIANT PRO-86; CALHM1 variant is not associated with Alzheimer's disease among Asians.
Tan E.K.; Ho P.; Cheng S.Y.; Yih Y.; Li H.H.; Fook-Chong S.; Lee W.L.; Zhao Y.;
Neurobiol. Aging 32:546.E11-546.E12(2011)
Cited for: VARIANT PRO-86; The P86L common allele of CALHM1 does not influence risk for Alzheimer disease in Japanese cohorts.
Inoue K.; Tanaka N.; Yamashita F.; Sawano Y.; Asada T.; Goto Y.;
Am. J. Med. Genet. B Neuropsychiatr. Genet. 153:532-535(2010)
Cited for: VARIANT PRO-86; CALHM1 P86L polymorphism is a risk factor for Alzheimer's disease in the Chinese population.
Cui P.J.; Zheng L.; Cao L.; Wang Y.; Deng Y.L.; Wang G.; Xu W.; Tang H.D.; Ma J.F.; Zhang T.; Ding J.Q.; Cheng Q.; Chen S.D.;
J. Alzheimers Dis. 19:31-35(2010)
Cited for: VARIANT PRO-86; CALHM1 P86L polymorphism is associated with late-onset Alzheimer's disease in a recessive model.
Boada M.; Antunez C.; Lopez-Arrieta J.; Galan J.J.; Moron F.J.; Hernandez I.; Marin J.; Martinez-Lage P.; Alegret M.; Carrasco J.M.; Moreno C.; Real L.M.; Gonzalez-Perez A.; Tarraga L.; Ruiz A.;
J. Alzheimers Dis. 20:247-251(2010)
Cited for: VARIANT PRO-86; The CALHM1 P86L polymorphism is a genetic modifier of age at onset in Alzheimer's disease: a meta-analysis study.
Lambert J.C.; Sleegers K.; Gonzalez-Perez A.; Ingelsson M.; Beecham G.W.; Hiltunen M.; Combarros O.; Bullido M.J.; Brouwers N.; Bettens K.; Berr C.; Pasquier F.; Richard F.; Dekosky S.T.; Hannequin D.; Haines J.L.; Tognoni G.; Fievet N.; Dartigues J.F.; Tzourio C.; Engelborghs S.; Arosio B.; Coto E.; De Deyn P.; Del Zompo M.; Mateo I.; Boada M.; Antunez C.; Lopez-Arrieta J.; Epelbaum J.; Schjeide B.M.; Frank-Garcia A.; Giedraitis V.; Helisalmi S.; Porcellini E.; Pilotto A.; Forti P.; Ferri R.; Delepine M.; Zelenika D.; Lathrop M.; Scarpini E.; Siciliano G.; Solfrizzi V.; Sorbi S.; Spalletta G.; Ravaglia G.; Valdivieso F.; Vepsalainen S.; Alvarez V.; Bosco P.; Mancuso M.; Panza F.; Nacmias B.; Bossu P.; Hanon O.; Piccardi P.; Annoni G.; Mann D.; Marambaud P.; Seripa D.; Galimberti D.; Tanzi R.E.; Bertram L.; Lendon C.; Lannfelt L.; Licastro F.; Campion D.; Pericak-Vance M.A.; Soininen H.; Van Broeckhoven C.; Alperovitch A.; Ruiz A.; Kamboh M.I.; Amouyel P.;
J. Alzheimers Dis. 22:247-255(2010)
Cited for: VARIANT PRO-86; No association between CALHM1 polymorphism and Alzheimer's disease risk in a Hungarian population.
Feher A.; Juhasz A.; Rimanoczy A.; Pakaski M.; Kalman J.; Janka Z.;
Psychiatr. Genet. 21:249-252(2011)
Cited for: VARIANT PRO-86;

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.