UniProtKB/SwissProt variant VAR

Variant information

Variant position:

602

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 602 (R602H, p.Arg602His).

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 NPDB and NPDA; expresses protein level comparable to wild-type SMPD1 expressing cells; retains about 10% residual enzyme activity; loss of location to lysosome.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs370129081 [ dbSNP | Ensembl ]

Sequence information

Variant position:

602

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:

631

The length of the canonical sequence.

Location on the sequence:

PSEPCGTPCRLATLCAQLSA R ADSPALCRHLMPDGSLPEAQ

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                         PSEPCGTPCRLATLCAQLSARADSPALCRHLMPDGSLPEAQ

Mouse                         PSEPCGTPCRLATLCAQLSARADSPALCRHLMPNGSLPDAN

Bovine                        PSEPCGTPCRLATLCAQLSARSDSPALCRHLVPDASLPDVQ

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	47 – 631	Sphingomyelin phosphodiesterase
Disulfide bond	596 – 609
Beta strand	602 – 604

Literature citations

The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations.
Simonaro C.M.; Desnick R.J.; McGovern M.M.; Wasserstein M.P.; Schuchman E.H.;
Am. J. Hum. Genet. 71:1413-1419(2002)
Cited for: VARIANTS NPDB VAL-51; TRP-94; PRO-139; ARG-159; PRO-198; CYS-202; MET-227; CYS-230; ASP-234; SER-247; ARG-250; HIS-291; ALA-325; ARG-332; ASP-359; HIS-378; LEU-378; PRO-381; VAL-415; TYR-423; ARG-433; PRO-434; CYS-437; VAL-454; ASP-458; TRP-476; LEU-477; LEU-482; ASN-490; SER-496; CYS-498; GLN-516; VAL-517; ARG-535; PRO-551; ASN-578; HIS-602 AND PRO-602; VARIANT VAL-487;

Functional in vitro characterization of 14 SMPD1 mutations identified in Italian patients affected by Niemann Pick type B disease.
Dardis A.; Zampieri S.; Filocamo M.; Burlina A.; Bembi B.; Pittis M.G.;
Hum. Mutat. 26:164-164(2005)
Cited for: VARIANTS NPDB ALA-132 AND TYR-565; CHARACTERIZATION OF VARIANTS NPDB PRO-105; ALA-132; PRO-227; CYS-246; THR-283; TYR-565; HIS-602 AND PRO-602;

A novel mechanism of lysosomal acid sphingomyelinase maturation: requirement for carboxyl-terminal proteolytic processing.
Jenkins R.W.; Idkowiak-Baldys J.; Simbari F.; Canals D.; Roddy P.; Riner C.D.; Clarke C.J.; Hannun Y.A.;
J. Biol. Chem. 286:3777-3788(2011)
Cited for: CATALYTIC ACTIVITY; FUNCTION; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS NPDB HIS-602; PRO-602 AND ARG-610 DEL;

Spectrum of SMPD1 mutations in Asian-Indian patients with acid sphingomyelinase (ASM)-deficient Niemann-Pick disease.
Ranganath P.; Matta D.; Bhavani G.S.; Wangnekar S.; Jain J.M.; Verma I.C.; Kabra M.; Puri R.D.; Danda S.; Gupta N.; Girisha K.M.; Sankar V.H.; Patil S.J.; Ramadevi A.R.; Bhat M.; Gowrishankar K.; Mandal K.; Aggarwal S.; Tamhankar P.M.; Tilak P.; Phadke S.R.; Dalal A.;
Am. J. Med. Genet. A 170:2719-2730(2016)
Cited for: VARIANTS ALA-36; PHE-510 AND GLY-605; VARIANTS NPDA ARG-216; CYS-230; SER-255; ARG-319; PRO-324; ARG-343; ARG-363; HIS-391; ARG-393; SER-426; ILE-494; HIS-498; ARG-535 AND HIS-602; VARIANTS NPDB PRO-105; PHE-282; ASP-320; CYS-369; SER-465; LEU-520 AND LYS-549;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P17405: Variant p.Arg602His