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UniProtKB/Swiss-Prot Q9P2K1: Variant p.Gln1096His

Coiled-coil and C2 domain-containing protein 2A
Gene: CC2D2A
Chromosomal location: 4p15.33
Variant information

Variant position:  1096
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Glutamine (Q) to Histidine (H) at position 1096 (Q1096H, p.Gln1096His).
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:  Similar physico-chemical property. Both residues are medium size and polar.
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:  Joubert syndrome 9 (JBTS9) [MIM:612285]: A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. {ECO:0000269|PubMed:18387594, ECO:0000269|PubMed:18950740, ECO:0000269|PubMed:19777577, ECO:0000269|PubMed:22241855, ECO:0000269|PubMed:22425360, ECO:0000269|PubMed:23012439, ECO:0000269|PubMed:26477546}. 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 JBTS9.
Any additional useful information about the variant.



Sequence information

Variant position:  1096
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1620
The length of the canonical sequence.

Location on the sequence:   KHAASPSTYSPTHNADYPLG  Q VLVRPFVEVSFQRTVCHTTT
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                         KHAASPSTYSPTHNADYPLGQVLVRPFVEVSFQRTVCHTTT

Mouse                         KQTASPSTHSPLHNADYPLGQVLVRPFVEVSFQRTICHTTT

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 – 1620 Coiled-coil and C2 domain-containing protein 2A
Domain 1062 – 1174 C2
Alternative sequence 112 – 1620 Missing. In isoform 4.
Alternative sequence 123 – 1620 Missing. In isoform 3.


Literature citations

CC2D2A is mutated in Joubert syndrome and interacts with the ciliopathy-associated basal body protein CEP290.
Gorden N.T.; Arts H.H.; Parisi M.A.; Coene K.L.M.; Letteboer S.J.F.; van Beersum S.E.C.; Mans D.A.; Hikida A.; Eckert M.; Knutzen D.; Alswaid A.F.; Oezyurek H.; Dibooglu S.; Otto E.A.; Liu Y.; Davis E.E.; Hutter C.M.; Bammler T.K.; Farin F.M.; Dorschner M.; Topcu M.; Zackai E.H.; Rosenthal P.; Owens K.N.; Katsanis N.; Vincent J.B.; Hildebrandt F.; Rubel E.W.; Raible D.W.; Knoers N.V.A.M.; Chance P.F.; Roepman R.; Moens C.B.; Glass I.A.; Doherty D.;
Am. J. Hum. Genet. 83:559-571(2008)
Cited for: VARIANTS JBTS9 HIS-1096; SER-1122; CYS-1528 AND PRO-1551; TISSUE SPECIFICITY; SUBCELLULAR LOCATION; INTERACTION WITH CEP290;

Genotype-phenotype correlation in CC2D2A-related Joubert syndrome reveals an association with ventriculomegaly and seizures.
Bachmann-Gagescu R.; Ishak G.E.; Dempsey J.C.; Adkins J.; O'Day D.; Phelps I.G.; Gunay-Aygun M.; Kline A.D.; Szczaluba K.; Martorell L.; Alswaid A.; Alrasheed S.; Pai S.; Izatt L.; Ronan A.; Parisi M.A.; Mefford H.; Glass I.; Doherty D.;
J. Med. Genet. 49:126-137(2012)
Cited for: VARIANTS JBTS9 ARG-117; GLU-507; PRO-559; ALA-1045; HIS-1096; MET-1116; SER-1122; ALA-1151; CYS-1284; HIS-1284; GLN-1330; ALA-1430; CYS-1528 AND VAL-1556; VARIANTS ILE-660; ILE-684 AND VAL-701;

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.