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UniProtKB/Swiss-Prot O43511: Variant p.Phe335Leu

Pendrin
Gene: SLC26A4
Variant information

Variant position:  335
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 Phenylalanine (F) to Leucine (L) at position 335 (F335L, p.Phe335Leu).
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 large size and aromatic (F) to medium size and hydrophobic (L)
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:  Deafness, autosomal recessive, 4 (DFNB4) [MIM:600791]: 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. DFNB4 is associated with an enlarged vestibular aqueduct. {ECO:0000269|PubMed:10190331, ECO:0000269|PubMed:10700480, ECO:0000269|PubMed:11748854, ECO:0000269|PubMed:12676893, ECO:0000269|PubMed:14508505, ECO:0000269|PubMed:14679580, ECO:0000269|PubMed:19204907, ECO:0000269|PubMed:20108392, ECO:0000269|PubMed:20597900, ECO:0000269|PubMed:24051746, ECO:0000269|PubMed:28281779, ECO:0000269|PubMed:9500541}. 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:  Pendred syndrome (PDS) [MIM:274600]: An autosomal recessive disorder characterized by congenital sensorineural hearing loss in association with thyroid goiter. The disorder may account for up to 10% of the cases of hereditary deafness. The deafness is most often associated with a Mondini cochlear defect. Deafness occurs early, starting at birth or during the first years of life. It is bilateral, sometimes asymmetrical, fluctuant and often progressive. Thyroid perturbations, such as thyroid goiter and/or hypothyroidism appear most commonly during adolescence, but they can be congenital or appear later. {ECO:0000269|PubMed:10602116, ECO:0000269|PubMed:10718825, ECO:0000269|PubMed:10878664, ECO:0000269|PubMed:11317356, ECO:0000269|PubMed:11375792, ECO:0000269|PubMed:11748854, ECO:0000269|PubMed:11919333, ECO:0000269|PubMed:11932316, ECO:0000269|PubMed:12788906, ECO:0000269|PubMed:12974744, ECO:0000269|PubMed:14679580, ECO:0000269|PubMed:15355436, ECO:0000269|PubMed:15531480, ECO:0000269|PubMed:15689455, ECO:0000269|PubMed:19204907, ECO:0000269|PubMed:9398842, ECO:0000269|PubMed:9618166, ECO:0000269|PubMed:9618167}. 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 PDS and DFNB4.
Any additional useful information about the variant.

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



Sequence information

Variant position:  335
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  780
The length of the canonical sequence.

Location on the sequence:   YGANLEKNYNAGIVKSIPRG  F LPPELPPVSLFSEMLAASFS
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                         YGANLEKNYNAGIVKSIPRGFLPPELPPVSLFSEMLAASFS

Mouse                         YGANLEKNYNAGIVKSIPSGFLPPVLPSVGLFSDMLAASFS

Rat                           YGANLEANYNAGIVKSIPSGFLPPVLPSVGLFSDMLAASFS

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 – 780 Pendrin
Topological domain 317 – 344 Extracellular
Alternative sequence 1 – 431 Missing. In isoform 2.


Literature citations

Pendred syndrome, DFNB4, and PDS/SLC26A4 identification of eight novel mutations and possible genotype-phenotype correlations.
Campbell C.; Cucci R.A.; Prasad S.; Green G.E.; Edeal J.B.; Galer C.E.; Karniski L.P.; Sheffield V.C.; Smith R.J.H.;
Hum. Mutat. 17:403-411(2001)
Cited for: VARIANTS PDS GLN-29; CYS-105; ASP-106; PHE-138; VAL-209; PRO-236; LEU-335; PRO-416; ASP-480; HIS-530; ALA-653 AND GLU-672; VARIANT SER-597;

Pendred syndrome and DFNB4-mutation screening of SLC26A4 by denaturing high-performance liquid chromatography and the identification of eleven novel mutations.
Prasad S.; Koelln K.A.; Cucci R.A.; Trembath R.C.; Van Camp G.; Smith R.J.H.;
Am. J. Med. Genet. A 124:1-9(2004)
Cited for: VARIANTS PDS/DFNB4 GLY-24; GLN-29; CYS-78; VAL-104; CYS-105; ASP-106; PHE-138; ALA-139; VAL-209; PRO-236; HIS-271; LEU-335; GLY-384; HIS-409; MET-410; PRO-416; ARG-421; ALA-429 DEL; TRP-445; ASP-480; HIS-530; CYS-556; TYR-565; ALA-653; GLU-672; SER-683 AND ARG-723; VARIANTS TYR-324 AND SER-597;

Hypo-functional SLC26A4 variants associated with nonsyndromic hearing loss and enlargement of the vestibular aqueduct: genotype-phenotype correlation or coincidental polymorphisms?
Choi B.Y.; Stewart A.K.; Madeo A.C.; Pryor S.P.; Lenhard S.; Kittles R.; Eisenman D.; Kim H.J.; Niparko J.; Thomsen J.; Arnos K.S.; Nance W.E.; King K.A.; Zalewski C.K.; Brewer C.C.; Shawker T.; Reynolds J.C.; Butman J.A.; Karniski L.P.; Alper S.L.; Griffith A.J.;
Hum. Mutat. 30:599-608(2009)
Cited for: VARIANTS PDS PHE-138; VAL-209; PRO-236; GLY-384; MET-402; PRO-416; TRP-445; ARG-514; HIS-530; TYR-565 AND THR-775; VARIANTS DFNB4 LEU-335; MET-402; SER-530 AND THR-775; VARIANTS SER-597; GLY-609 AND CYS-776;

Use of SLC26A4 mutation testing for unilateral enlargement of the vestibular aqueduct.
Chattaraj P.; Reimold F.R.; Muskett J.A.; Shmukler B.E.; Chien W.W.; Madeo A.C.; Pryor S.P.; Zalewski C.K.; Butman J.A.; Brewer C.C.; Kenna M.A.; Alper S.L.; Griffith A.J.;
JAMA Otolaryngol. Head Neck Surg. 139:907-913(2013)
Cited for: VARIANTS DFNB4 THR-185 AND LEU-335; VARIANTS LEU-335; GLY-384; TRP-445; SER-597; CYS-775 AND CYS-776; CHARACTERIZATION OF VARIANT DFNB4 THR-185;

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.