UniProtKB/Swiss-Prot P21817: Variant p.Arg4861His

Ryanodine receptor 1
Gene: RYR1
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Variant information Variant position:

4861 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LP/P [Disclaimer] 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 Arginine (R) to Histidine (H) at position 4861 (R4861H, p.Arg4861His). 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:

Change from large size and basic (R) to medium size and polar (H) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

0 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:

In CMYP1A and MHS1; release of calcium from intracellular stores in the absence of any pharmacological activator of RYR. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs63749869 [ dbSNP | Ensembl ]

Sequence information Variant position:

4861 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

5038 The length of the canonical sequence.
Location on the sequence:

TVGLLAVVVYLYTVVAFNFF R KFYNKSEDEDEPDMKCDDMM 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                         TVGLLAVVVYLYTVVAFNFFRKFYNKSEDEDEPDMKCDDMM

Mouse                         TVGLLAVVVYLYTVVAFNFFRKFYNKSEDEDEPDMKCDDMM

Rat                           TVGLLAVVVYLYTVVAFNFFRKFYNKSEDEDEPDMKCDDMM

Pig                           TVGLLAVVVYLYTVVAFNFFRKFYNKSEDEDEPDMKCDDMM

Rabbit                        TVGLLAVVVYLYTVVAFNFFRKFYNKSEDEDEPDMKCDDMM

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 – 5038	Ryanodine receptor 1
Topological domain	4858 – 4880	Lumenal
Modified residue	4864 – 4864	Phosphotyrosine
Modified residue	4867 – 4867	Phosphoserine

Literature citations
Familial and sporadic forms of central core disease are associated with mutations in the C-terminal domain of the skeletal muscle ryanodine receptor.
Monnier N.; Romero N.B.; Lerale J.; Landrieu P.; Nivoche Y.; Fardeau M.; Lunardi J.;
Hum. Mol. Genet. 10:2581-2592(2001)
Cited for: VARIANTS CMYP1A MET-2168; 4214-ARG--PHE-4216 DEL; 4647-LEU-SER-4648 DEL; PRO-4793; CYS-4796; CYS-4825; PHE-4860 DEL; HIS-4861; TRP-4893; THR-4898; GLU-4899 AND GLY-4914; Identification of four novel mutations in the C-terminal membrane spanning domain of the ryanodine receptor 1: association with central core disease and alteration of calcium homeostasis.
Tilgen N.; Zorzato F.; Halliger-Keller B.; Muntoni F.; Sewry C.; Palmucci L.M.; Schneider C.; Hauser E.; Lehmann-Horn F.; Mueller C.R.; Treves S.;
Hum. Mol. Genet. 10:2879-2887(2001)
Cited for: VARIANTS CMYP1A HIS-4861; ARG-4891; THR-4898; ARG-4899 AND VAL-4906; CHARACTERIZATION OF VARIANTS CMYP1A MET-2168; HIS-4861; TRP-4893; THR-4898 AND ARG-4899; FUNCTION; TRANSPORTER ACTIVITY; Central core disease: clinical, pathological, and genetic features.
Quinlivan R.M.; Muller C.R.; Davis M.; Laing N.G.; Evans G.A.; Dwyer J.; Dove J.; Roberts A.P.; Sewry C.A.;
Arch. Dis. Child. 88:1051-1055(2003)
Cited for: VARIANTS CMYP1A HIS-4861; CYS-4864; TRP-4893 AND THR-4940; Principal mutation hotspot for central core disease and related myopathies in the C-terminal transmembrane region of the RYR1 gene.
Davis M.R.; Haan E.; Jungbluth H.; Sewry C.; North K.; Muntoni F.; Kuntzer T.; Lamont P.; Bankier A.; Tomlinson P.; Sanchez A.; Walsh P.; Nagarajan L.; Oley C.; Colley A.; Gedeon A.; Quinlivan R.; Dixon J.; James D.; Mueller C.R.; Laing N.G.;
Neuromuscul. Disord. 13:151-157(2003)
Cited for: VARIANT CORE/ROD DISEASE ILE-4637; VARIANTS CMYP1A ASP-4638; PRO-4651; CYS-4861; HIS-4861; GLN-4893; THR-4898; GLY-4914; THR-4914; 4927-VAL-ILE-4928 DEL AND THR-4940; RYR1 mutations in UK central core disease patients: more than just the C-terminal transmembrane region of the RYR1 gene.
Shepherd S.; Ellis F.; Halsall J.; Hopkins P.; Robinson R.;
J. Med. Genet. 41:E33-E33(2004)
Cited for: VARIANTS CMYP1A GLY-160; ASP-4638; PHE-4814; HIS-4861 AND MET-4938; VARIANTS MHS1 CYS-614; MET-2346; GLY-2348; TRP-2452; HIS-2458; PRO-4824 AND GLU-4939; Central core disease due to recessive mutations in RYR1 gene: is it more common than described?
Kossugue P.M.; Paim J.F.; Navarro M.M.; Silva H.C.; Pavanello R.C.M.; Gurgel-Giannetti J.; Zatz M.; Vainzof M.;
Muscle Nerve 35:670-674(2007)
Cited for: VARIANTS CMYP1A CYS-4861; HIS-4861; VAL-4897 AND THR-4914; VARIANTS CMYP1B GLN-4558; VAL-4846 AND ILE-4849; Ryanodine receptor type 1 gene variants in the malignant hyperthermia-susceptible population of the United States.
Brandom B.W.; Bina S.; Wong C.A.; Wallace T.; Visoiu M.; Isackson P.J.; Vladutiu G.D.; Sambuughin N.; Muldoon S.M.;
Anesth. Analg. 116:1078-1086(2013)
Cited for: VARIANTS MHS1 ALA-40; CYS-163; ARG-248; ARG-341; PRO-487; ALA-518; CYS-614; HIS-1043; HIS-2163; MET-2206; HIS-2248; HIS-2351; MET-2354; LEU-2358; GLN-2383; ARG-2434; HIS-2454; ARG-3711; VAL-4178; ARG-4230; GLU-4837; HIS-4861 AND GLY-4906; VARIANTS CMYP1A TRP-975; MET-2168 AND GLY-3238; VARIANTS MET-974; LEU-1109; ARG-1393; LEU-1787; CYS-2060 AND VAL-2321; Novel RYR1 missense mutations in six Chinese patients with central core disease.
Gu M.; Zhang S.; Hu J.; Yuan Y.; Wang Z.; Da Y.; Wu S.;
Neurosci. Lett. 566:32-35(2014)
Cited for: VARIANTS CMYP1A HIS-4861; ALA-4897 AND THR-4898;

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.