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UniProtKB/Swiss-Prot Q9Y2M0: Variant p.Asp960Asn

Fanconi-associated nuclease 1
Gene: FAN1
Chromosomal location: 15q13.2-q13.3
Variant information

Variant position:  960
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 Aspartate (D) to Asparagine (N) at position 960 (D960N, p.Asp960Asn).
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 acidic (D) to medium size and polar (N)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  1
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:  Interstitial nephritis, karyomegalic (KMIN) [MIM:614817]: A rare kidney disease characterized by chronic tubulointerstitial nephritis associated with massively enlarged tubular epithelial cell nuclei. The clinical picture is associated with recurrent upper respiratory tract infections in addition to chronic kidney disease beginning in the third decade of life. {ECO:0000269|PubMed:22772369}. 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 KMIN.
Any additional useful information about the variant.

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



Sequence information

Variant position:  960
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1017
The length of the canonical sequence.

Location on the sequence:   LSGVCRHLAADFRHCRGGLP  D LVVWNSQSRHFKLVEVKGPN
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                         LSGVCRHLAADFRHCRGGLPDLVVW-------------NSQSRHFKLVEVKGPN

Mouse                         LSGVCRRLAADFRHCRGGLPDLVVW-------------NSQ

Zebrafish                     LSGVFLRMAKDYRHCRGGLPDLVVW-------------STS

Caenorhabditis elegans        LILILRRLAENYRNSRSGFPDLTLW-------------NPE

Slime mold                    IAFISRLLTEDFKSFSHGMPDLLLWKLNNNNDDDIDDKNNN

Fission yeast                 LAQIFLALTQDYKNSSSGIPDLCLW-------------NPS

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 – 1017 Fanconi-associated nuclease 1
Domain 895 – 1007 VRR-NUC
Metal binding 960 – 960 Magnesium or manganese 1
Metal binding 960 – 960 Magnesium or manganese 2
Metal binding 975 – 975 Magnesium or manganese 1
Metal binding 976 – 976 Magnesium or manganese 1; via carbonyl oxygen
Alternative sequence 534 – 1017 Missing. In isoform 2.
Mutagenesis 952 – 952 R -> A. Strongly reduced affinity for sites that have a 5'-terminal phosphate anchor at a flap of 1 nucleotide; when associated with A-706.
Mutagenesis 960 – 960 D -> A. Loss of nuclease activity. Loss of nuclease activity; when associated with A-864; A-975 and A-977.
Mutagenesis 975 – 975 E -> A. Loss of nuclease activity; when associated with A-864; A-960 and A-977.
Mutagenesis 977 – 977 K -> A. Loss of nuclease activity; when associated with A-864; A-960 and A-975.
Beta strand 960 – 964


Literature citations

FAN1 mutations cause karyomegalic interstitial nephritis, linking chronic kidney failure to defective DNA damage repair.
Zhou W.; Otto E.A.; Cluckey A.; Airik R.; Hurd T.W.; Chaki M.; Diaz K.; Lach F.P.; Bennett G.R.; Gee H.Y.; Ghosh A.K.; Natarajan S.; Thongthip S.; Veturi U.; Allen S.J.; Janssen S.; Ramaswami G.; Dixon J.; Burkhalter F.; Spoendlin M.; Moch H.; Mihatsch M.J.; Verine J.; Reade R.; Soliman H.; Godin M.; Kiss D.; Monga G.; Mazzucco G.; Amann K.; Artunc F.; Newland R.C.; Wiech T.; Zschiedrich S.; Huber T.B.; Friedl A.; Slaats G.G.; Joles J.A.; Goldschmeding R.; Washburn J.; Giles R.H.; Levy S.; Smogorzewska A.; Hildebrandt F.;
Nat. Genet. 44:910-915(2012)
Cited for: VARIANTS KMIN ARG-871; PRO-929; ASP-937 AND ASN-960;

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.