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UniProtKB/Swiss-Prot Q9HC10: Variant p.Leu1011Pro

Otoferlin
Gene: OTOF
Chromosomal location: 2p23.1
Variant information

Variant position:  1011
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 Leucine (L) to Proline (P) at position 1011 (L1011P, p.Leu1011Pro).
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 hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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:  Deafness, autosomal recessive, 9 (DFNB9) [MIM:601071]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:10192385, ECO:0000269|PubMed:12127154, ECO:0000269|PubMed:16097006, ECO:0000269|PubMed:16283880, ECO:0000269|PubMed:16371502, ECO:0000269|PubMed:26437881}. 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.

Involvement in disease:  Auditory neuropathy, autosomal recessive, 1 (AUNB1) [MIM:601071]: A form of sensorineural hearing loss with absent or severely abnormal auditory brainstem response, in the presence of normal cochlear outer hair cell function and normal otoacoustic emissions. Auditory neuropathies result from a lesion in the area including the inner hair cells, connections between the inner hair cells and the cochlear branch of the auditory nerve, the auditory nerve itself and auditory pathways of the brainstem. In some cases AUNB1 phenotype can be temperature sensitive. {ECO:0000269|PubMed:16371502, ECO:0000269|PubMed:18381613}. 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 AUNB1 and DFNB9.
Any additional useful information about the variant.

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



Sequence information

Variant position:  1011
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1997
The length of the canonical sequence.

Location on the sequence:   NQSQCTEVLNETLCPTWDQM  L VFDNLELYGEAHELRDDPPI
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                         NQSQCTEVLNETLCPTWDQMLVFDNLELYGEAHELRDDPPI

Mouse                         NQSQCTEVLNETLCPTWDQMLVFDNLELYGEAHELRDDPPI

Rat                           NQSQCTEVLNETLCPTWDQMLVFDNLELYGEAHELRDDPPI

Zebrafish                     THSQVTEVLSETLCPTWDQLLVFDNVELYGEAGELRDDPPI

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 – 1997 Otoferlin
Topological domain 1 – 1963 Cytoplasmic
Domain 947 – 1052 C2 3


Literature citations

A novel missense mutation in a C2 domain of OTOF results in autosomal recessive auditory neuropathy.
Tekin M.; Akcayoz D.; Incesulu A.;
Am. J. Med. Genet. A 138:6-10(2005)
Cited for: VARIANT DFNB9 PRO-1011;

OTOF mutations revealed by genetic analysis of hearing loss families including a potential temperature sensitive auditory neuropathy allele.
Varga R.; Avenarius M.R.; Kelley P.M.; Keats B.J.; Berlin C.I.; Hood L.J.; Morlet T.G.; Brashears S.M.; Starr A.; Cohn E.S.; Smith R.J.H.; Kimberling W.J.;
J. Med. Genet. 43:576-581(2006)
Cited for: VARIANTS DFNB9 GLN-490; HIS-794 AND ALA-1825; VARIANTS AUNB1 THR-515; PRO-1011; GLN-1939 AND ARG-1987; VARIANTS VAL-53; CYS-82; MET-575; SER-773; TRP-822; PRO-1083; GLN-1157; GLU-1322; MET-1625; SER-1646 AND ASP-1888;

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.