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UniProtKB/Swiss-Prot Q8NCM8: Variant p.Ala2304Thr

Cytoplasmic dynein 2 heavy chain 1
Gene: DYNC2H1
Chromosomal location: 11q21-q22.1
Variant information

Variant position:  2304
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 Alanine (A) to Threonine (T) at position 2304 (A2304T, p.Ala2304Thr).
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 small size and hydrophobic (A) to medium size and polar (T)
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:  Short-rib thoracic dysplasia 3 with or without polydactyly (SRTD3) [MIM:613091]: A form of short-rib thoracic dysplasia, a group of autosomal recessive ciliopathies that are characterized by a constricted thoracic cage, short ribs, shortened tubular bones, and a 'trident' appearance of the acetabular roof. Polydactyly is variably present. Non-skeletal involvement can include cleft lip/palate as well as anomalies of major organs such as the brain, eye, heart, kidneys, liver, pancreas, intestines, and genitalia. Some forms of the disease are lethal in the neonatal period due to respiratory insufficiency secondary to a severely restricted thoracic cage, whereas others are compatible with life. Disease spectrum encompasses Ellis-van Creveld syndrome, asphyxiating thoracic dystrophy (Jeune syndrome), Mainzer-Saldino syndrome, and short rib-polydactyly syndrome. {ECO:0000269|PubMed:19361615, ECO:0000269|PubMed:19442771, ECO:0000269|PubMed:22499340, ECO:0000269|PubMed:23456818}. Note=The disease is caused by mutations affecting the gene represented in this entry. In some cases DYNC2H1 mutations result in disease phenotype in the presence of mutations in NEK1 indicating digenic inheritance (digenic short rib-polydactyly syndrome 3/6 with polydactyly) (PubMed:21211617). {ECO:0000269|PubMed:21211617}.
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 SRTD3.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  2304
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  4307
The length of the canonical sequence.

Location on the sequence:   KQPFILVGPEGCGKGMLLRY  A FSQLRSTQIATVHCSAQTTS
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                         KQPFILVGPEGCGKGMLLRYAFSQLRSTQIATVHCSAQTTS

Mouse                         KQPFILVGPEGCGKGMLLRYAFSQLRSTEIATIHCSAQTTS

Rat                           KQPFILVGPEGCGKGMLLRYAFSQLRSTEIATIHCSAQTTS

Caenorhabditis elegans        RESFLITGTTGCGKQQLLKHCFQNDPESQLASLYCSAQSSS

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 – 4307 Cytoplasmic dynein 2 heavy chain 1
Region 2251 – 2505 AAA 3
Alternative sequence 736 – 4122 Missing. In isoform 3.
Helix 2297 – 2307


Literature citations

Exome sequencing identifies DYNC2H1 mutations as a common cause of asphyxiating thoracic dystrophy (Jeune syndrome) without major polydactyly, renal or retinal involvement.
Schmidts M.; Arts H.H.; Bongers E.M.; Yap Z.; Oud M.M.; Antony D.; Duijkers L.; Emes R.D.; Stalker J.; Yntema J.B.; Plagnol V.; Hoischen A.; Gilissen C.; Forsythe E.; Lausch E.; Veltman J.A.; Roeleveld N.; Superti-Furga A.; Kutkowska-Kazmierczak A.; Kamsteeg E.J.; Elcioglu N.; van Maarle M.C.; Graul-Neumann L.M.; Devriendt K.; Smithson S.F.; Wellesley D.; Verbeek N.E.; Hennekam R.C.; Kayserili H.; Scambler P.J.; Beales P.L.; Knoers N.V.; Roepman R.; Mitchison H.M.;
J. Med. Genet. 50:309-323(2013)
Cited for: VARIANTS SRTD3 CYS-330; PRO-871; ILE-1228; THR-1240; VAL-1379; ASP-1442; LYS-1991; VAL-2227; THR-2304; SER-2362; GLN-2481; TRP-2532; MET-2555; CYS-2573; THR-2640; MET-2819; GLY-3015; LEU-3381; CYS-3806; GLY-3847 AND ARG-4232;

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.