UniProtKB/SwissProt variant VAR

Variant information

Variant position:

5048

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

Type of variant:

Disease [Disclaimer]

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Arginine (R) to Histidine (H) at position 5048 (R5048H, p.Arg5048His).

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

Involvement in disease:

Kabuki syndrome 1 (KABUK1) [MIM:147920]: A congenital mental retardation syndrome with additional features, including postnatal dwarfism, a peculiar facies characterized by long palpebral fissures with eversion of the lateral third of the lower eyelids, a broad and depressed nasal tip, large prominent earlobes, a cleft or high-arched palate, scoliosis, short fifth finger, persistence of fingerpads, radiographic abnormalities of the vertebrae, hands, and hip joints, and recurrent otitis media in infancy. {ECO:0000269|PubMed:20711175, ECO:0000269|PubMed:21280141, ECO:0000269|PubMed:21607748, ECO:0000269|PubMed:21658225, ECO:0000269|PubMed:21671394, ECO:0000269|PubMed:22126750, ECO:0000269|PubMed:23320472, ECO:0000269|PubMed:23913813, ECO:0000269|PubMed:24739679}. Note=The disease is caused by mutations affecting the gene represented in this entry.

The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:

In KABUK1.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs886041404 [ dbSNP | Ensembl ]

Sequence information

Variant position:

5048

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

Protein sequence length:

5537

The length of the canonical sequence.

Location on the sequence:

DMRRCCFCHEEGDGATDGPA R LLNLDLDLWVHLNCALWSTE

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                         DMRRCCFCHEEGDGATDGPARLLNLDLDLWVHLNCALWSTE

Mouse                         DNRRCCFCHEEGDGATDGPARLLNLDLDLWVHLNCALWSTE

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 – 5537	Histone-lysine N-methyltransferase 2D
Zinc finger	5029 – 5069	C2HC pre-PHD-type 2

Literature citations

MLL2 and KDM6A mutations in patients with Kabuki syndrome.
Miyake N.; Koshimizu E.; Okamoto N.; Mizuno S.; Ogata T.; Nagai T.; Kosho T.; Ohashi H.; Kato M.; Sasaki G.; Mabe H.; Watanabe Y.; Yoshino M.; Matsuishi T.; Takanashi J.; Shotelersuk V.; Tekin M.; Ochi N.; Kubota M.; Ito N.; Ihara K.; Hara T.; Tonoki H.; Ohta T.; Saito K.; Matsuo M.; Urano M.; Enokizono T.; Sato A.; Tanaka H.; Ogawa A.; Fujita T.; Hiraki Y.; Kitanaka S.; Matsubara Y.; Makita T.; Taguri M.; Nakashima M.; Tsurusaki Y.; Saitsu H.; Yoshiura K.; Matsumoto N.; Niikawa N.;
Am. J. Med. Genet. A 161A:2234-2243(2013)
Cited for: VARIANTS KABUK1 ARG-1376; CYS-1423; GLY-1445; PHE-1526; CYS-5030; GLY-5040; CYS-5048; HIS-5048; GLN-5154; HIS-5179; ARG-5189 AND GLN-5351;

MLL2 mutation detection in 86 patients with Kabuki syndrome: a genotype-phenotype study.
Makrythanasis P.; van Bon B.W.; Steehouwer M.; Rodriguez-Santiago B.; Simpson M.; Dias P.; Anderlid B.M.; Arts P.; Bhat M.; Augello B.; Biamino E.; Bongers E.M.; Del Campo M.; Cordeiro I.; Cueto-Gonzalez A.M.; Cusco I.; Deshpande C.; Frysira E.; Izatt L.; Flores R.; Galan E.; Gener B.; Gilissen C.; Granneman S.M.; Hoyer J.; Yntema H.G.; Kets C.M.; Koolen D.A.; Marcelis C.L.; Medeira A.; Micale L.; Mohammed S.; de Munnik S.A.; Nordgren A.; Psoni S.; Reardon W.; Revencu N.; Roscioli T.; Ruiterkamp-Versteeg M.; Santos H.G.; Schoumans J.; Schuurs-Hoeijmakers J.H.; Silengo M.C.; Toledo L.; Vendrell T.; van der Burgt I.; van Lier B.; Zweier C.; Reymond A.; Trembath R.C.; Perez-Jurado L.; Dupont J.; de Vries B.B.; Brunner H.G.; Veltman J.A.; Merla G.; Antonarakis S.E.; Hoischen A.;
Clin. Genet. 84:539-545(2013)
Cited for: VARIANTS KABUK1 HIS-170; LEU-170; GLN-647; ARG-1380; ARG-1471; ARG-3876; SER-3897; CYS-5030; CYS-5048; HIS-5048; CYS-5214; TRP-5432 AND PHE-5498; VARIANTS LEU-2557; LEU-2652 AND PRO-4010;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O14686: Variant p.Arg5048His