UniProtKB/Swiss-Prot Q5TA45: Variant p.His414Tyr

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

414 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 Histidine (H) to Tyrosine (Y) at position 414 (H414Y, p.His414Tyr). 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 medium size and polar (H) to large size and aromatic (Y) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

2 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; may affect function; the orthologous mutation in Ints11-null Drosophila is unable to rescue larvae lethality. Any additional useful information about the variant.

Sequence information Variant position:

414 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:

DAKGIMQLVGQAEPESVLLV H GEAKKMEFLKQKIEQELRVN 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                         DAKGIMQLVGQAEPESVLLVHGEAKKMEFLKQKIEQELRVN

Mouse                         DAKGIMQLVGQAEPESVLLVHGEAKKMEFLRQKIEQEFRVS

Rat                           DAKGIMQLVGQAEPESVLLVHGEAKKMEFLRQKIEQEFRVS

Bovine                        DAKGIMQLVGQAEPENVLLVHGEAKKMEFLKQKIEQEFRVN

Chicken                       DAKGIMQLIRQAEPRNVLLVHGEAKKMEFLKQKIEQEFHVN

Zebrafish                     DAKGIMQLIRMAEPRNMLLVHGEAKKMEFLKDKIEQEFSIS

Drosophila                    DAKGIMQLIQNCEPKNVMLVHGEAGKMKFLRSKIKDEFNLE

Slime mold                    DAKGILQLIKMSNPRNVILVHGEKEKMGFLSQKIIKEMGVN

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
Binding site	414 – 414
Beta strand	408 – 415

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.