UniProtKB/Swiss-Prot Q5TA45: Variant p.Arg217Trp

Integrator complex subunit 11
Gene: INTS11
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Variant information Variant position:

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

US 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 Tryptophan (W) at position 217 (R217W, p.Arg217Trp). 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 large size and aromatic (W) 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:

In NEDMLOB; uncertain significance. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs370089867 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

PNLLITESTYATTIRDSKRC R ERDFLKKVHETVERGGKVLI 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                         PNLLITESTYATTIRDSKRCRERDFLKKVHETVERGGKVLI

Mouse                         PNLLITESTYATTIRDSKRCRERDFLKKVHETVERGGKVLI

Rat                           PNLLITESTYATTIRDSKRCRERDFLKKVHETVERGGKVLI

Bovine                        PSLLITESTYATTIRDSKRCRERDFLKKVHETVERGGKVLI

Chicken                       PDLLITESTYATTIRDSKRCRERDFLKKVHETVERGGKVLI

Zebrafish                     PDILISESTYATTIRDSKRCRERDFLKKVHETVERGGKVLI

Drosophila                    PDLLISESTYATTIRDSKRCRERDFLKKVHECVAKGGKVLI

Slime mold                    PDVLITETTYATTIRDSKRGRERDFLKRIHECVEKGGKVLI

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 – 600	Integrator complex subunit 11
Active site	203 – 203
Mutagenesis	203 – 203	E -> Q. Abolished RNA endonuclease activity. Abolishes the ability of the Integrator complex to process U1 and U2 snRNA genes. Does not affect interaction with INTS9.
Mutagenesis	210 – 210	I -> E. Decreased nuclear localization of BRAT1.
Helix	215 – 230

Literature citations
Bi-allelic variants in INTS11 are associated with a complex neurological disorder.
Tepe B.; Macke E.L.; Niceta M.; Weisz Hubshman M.; Kanca O.; Schultz-Rogers L.; Zarate Y.A.; Schaefer G.B.; Granadillo De Luque J.L.; Wegner D.J.; Cogne B.; Gilbert-Dussardier B.; Le Guillou X.; Wagner E.J.; Pais L.S.; Neil J.E.; Mochida G.H.; Walsh C.A.; Magal N.; Drasinover V.; Shohat M.; Schwab T.; Schmitz C.; Clark K.; Fine A.; Lanpher B.; Gavrilova R.; Blanc P.; Burglen L.; Afenjar A.; Steel D.; Kurian M.A.; Prabhakar P.; Goesswein S.; Di Donato N.; Bertini E.S.; Wangler M.F.; Yamamoto S.; Tartaglia M.; Klee E.W.; Bellen H.J.;
Am. J. Hum. Genet. 110:774-789(2023)
Cited for: VARIANTS NEDMLOB SER-12; LEU-17; SER-39; SER-55; PHE-138; TRP-217; GLY-218; GLN-219; GLU-396; SER-407; TYR-414; MET-515; GLU-551 AND CYS-578; INVOLVEMENT IN NEDMLOB; CHARACTERIZATION OF VARIANTS NEDMLOB LEU-17; SER-55; PHE-138; GLU-396; TYR-414 AND MET-515;

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.