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UniProtKB/Swiss-Prot P39905: Variant p.Arg93Trp

Glial cell line-derived neurotrophic factor
Gene: GDNF
Variant information

Variant position:  93
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Unclassified
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 Arginine (R) to Tryptophan (W) at position 93 (R93W, p.Arg93Trp).
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 basic (R) to large size and aromatic (W)
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:  Congenital central hypoventilation syndrome (CCHS) [MIM:209880]: Rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia. {ECO:0000269|PubMed:9497256}. 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:  Hirschsprung disease 3 (HSCR3) [MIM:613711]: A disorder of neural crest development characterized by absence of enteric ganglia along a variable length of the intestine. It is the most common cause of congenital intestinal obstruction. Early symptoms range from complete acute neonatal obstruction, characterized by vomiting, abdominal distention and failure to pass stool, to chronic constipation in the older child. {ECO:0000269|PubMed:10917288, ECO:0000269|PubMed:8896568, ECO:0000269|PubMed:8896569, ECO:0000269|PubMed:8968758}. Note=Disease susceptibility is associated with variations 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:  Pheochromocytoma (PCC) [MIM:171300]: A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. {ECO:0000269|PubMed:9215674}. Note=The gene represented in this entry may act as a disease modifier.
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 HSCR3, CCHS and PCC; unknown pathological significance.
Any additional useful information about the variant.

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



Sequence information

Variant position:  93
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  211
The length of the canonical sequence.

Location on the sequence:   KRLKRSPDKQMAVLPRRERN  R QAAAANPENSRGKGRRGQRG
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                         KRLKRSPDKQMAVLPRRERNRQAAAANPENSRGKGRRGQR--------------G

Mouse                         KRLKRSPDKQAAALPRRERNRQAAAASPENSRGKGRRGQR-

Rat                           KRLKRSPDKQAAALPRRERNRQAAAASPENSRGKGRRGQR-

Xenopus laevis                KRLKRSSNKQPPS--RRDRGRQSLAANTQISSKKTVKDRK-

Zebrafish                     GRLRRSSDVEPQM--KRDRVRQKAAANTEKSGGRGRGERKR

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 78 – 211 Glial cell line-derived neurotrophic factor


Literature citations

Genetic predisposition to phaeochromocytoma: analysis of candidate genes GDNF, RET and VHL.
Woodward E.R.; Eng C.; McMahon R.; Voutilainen R.; Affara N.A.; Ponder B.A.; Maher E.R.;
Hum. Mol. Genet. 6:1051-1056(1997)
Cited for: POSSIBLE INVOLVEMENT IN PCC; VARIANT PCC TRP-93;

Germline mutations in glial cell line-derived neurotrophic factor (GDNF) and RET in a Hirschsprung disease patient.
Angrist M.; Bolk S.; Halushka M.; Lapchak P.A.; Chakravarti A.;
Nat. Genet. 14:341-344(1996)
Cited for: VARIANT HSCR3 TRP-93;

Mutations of the RET-GDNF signaling pathway in Ondine's curse.
Amiel J.; Salomon R.; Attie T.; Pelet A.; Trang H.; Mokhtari M.; Gaultier C.; Munnich A.; Lyonnet S.;
Am. J. Hum. Genet. 62:715-717(1998)
Cited for: VARIANT CCHS TRP-93;

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.