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UniProtKB/Swiss-Prot Q2LD37: Variant p.Pro3050His

Transmembrane protein KIAA1109
Gene: KIAA1109
Variant information

Variant position:  3050
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
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 Proline (P) to Histidine (H) at position 3050 (P3050H, p.Pro3050His).
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 hydrophobic (P) to medium size and polar (H)
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

Involvement in disease:  Alkuraya-Kucinskas syndrome (ALKKUCS) [MIM:617822]: An autosomal recessive syndrome characterized by brain atrophy and arthrogryposis. Patients present with cerebral parenchymal underdevelopment, lissencephaly, severe to mild ventriculomegaly, and cerebellar hypoplasia with brainstem dysgenesis. Most affected individuals die in utero or soon after birth. The few patients who survive have variable intellectual disability and may have seizures. Facial dysmorphism, cardiac and ophthalmologic anomalies, such as microphthalmia and cataract, are additional features. {ECO:0000269|PubMed:25558065, ECO:0000269|PubMed:29290337}. 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 ALKKUCS; unknown pathological significance.
Any additional useful information about the variant.



Sequence information

Variant position:  3050
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  5005
The length of the canonical sequence.

Location on the sequence:   TSKVSATDMSTIPPSASLNL  P PVTMSGKYIMEEHDSYSDQV
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                         TSKVSATDMSTIPPSASLNLPPVTMSGKYIMEEHDSYSDQV

Mouse                         TSKVSATDMSTIPPSASLNLPPVTMSGKYIMEEHDSYSDQV

Zebrafish                     QSKVSPVDVSAMPPTASLTLPPVTMSGQYIIQEHEGHSDTA

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.

TypePositionsDescription
Chain 1 – 5005 Transmembrane protein KIAA1109
Alternative sequence 985 – 5005 Missing. In isoform 5.
Alternative sequence 2875 – 5005 Missing. In isoform 2.


Literature citations

KIAA1109 Variants Are Associated with a Severe Disorder of Brain Development and Arthrogryposis.
Gueneau L.; Fish R.J.; Shamseldin H.E.; Voisin N.; Tran Mau-Them F.; Preiksaitiene E.; Monroe G.R.; Lai A.; Putoux A.; Allias F.; Ambusaidi Q.; Ambrozaityte L.; Cimbalistiene L.; Delafontaine J.; Guex N.; Hashem M.; Kurdi W.; Jamuar S.S.; Ying L.J.; Bonnard C.; Pippucci T.; Pradervand S.; Roechert B.; van Hasselt P.M.; Wiederkehr M.; Wright C.F.; Xenarios I.; van Haaften G.; Shaw-Smith C.; Schindewolf E.M.; Neerman-Arbez M.; Sanlaville D.; Lesca G.; Guibaud L.; Reversade B.; Chelly J.; Kucinskas V.; Alkuraya F.S.; Reymond A.;
Am. J. Hum. Genet. 102:116-132(2018)
Cited for: INVOLVEMENT IN ALKKUCS; VARIANTS ALKKUCS 519-TYR--HIS-5005 DEL; CYS-968; CYS-1329; ILE-1573; MET-1867; GLN-1958; HIS-3050; ARG-3385 AND 4023-GLU--HIS-5005 DEL;

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.