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UniProtKB/Swiss-Prot Q16678: Variant p.Glu387Lys

Cytochrome P450 1B1
Gene: CYP1B1
Variant information

Variant position:  387
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 Glutamate (E) to Lysine (K) at position 387 (E387K, p.Glu387Lys).
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 (E) to large size and basic (K)
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:  Glaucoma 3, primary congenital, A (GLC3A) [MIM:231300]: An autosomal recessive form of primary congenital glaucoma (PCG). PCG is characterized by marked increase of intraocular pressure at birth or early childhood, large ocular globes (buphthalmos) and corneal edema. It results from developmental defects of the trabecular meshwork and anterior chamber angle of the eye that prevent adequate drainage of aqueous humor. {ECO:0000269|PubMed:10227395, ECO:0000269|PubMed:10655546, ECO:0000269|PubMed:11184479, ECO:0000269|PubMed:11527932, ECO:0000269|PubMed:11774072, ECO:0000269|PubMed:11980847, ECO:0000269|PubMed:12036985, ECO:0000269|PubMed:12525557, ECO:0000269|PubMed:14635112, ECO:0000269|PubMed:14640114, ECO:0000269|PubMed:15255109, ECO:0000269|PubMed:15342693, ECO:0000269|PubMed:15475877, ECO:0000269|PubMed:16490498, ECO:0000269|PubMed:16688110, ECO:0000269|PubMed:16735994, ECO:0000269|PubMed:16862072, ECO:0000269|PubMed:18470941, ECO:0000269|PubMed:9463332, ECO:0000269|PubMed:9497261}. Note=The disease is caused by mutations affecting distinct genetic loci, including 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 GLC3A; allele CYP1B1*20.
Any additional useful information about the variant.

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



Sequence information

Variant position:  387
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  543
The length of the canonical sequence.

Location on the sequence:   DRLPCMGDQPNLPYVLAFLY  E AMRFSSFVPVTIPHATTANT
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                         DRLPCMGDQPNLPYVLAFLYEAMRFSSFVPVTIPHATTANT

Mouse                         DRLPCMSDQPNLPYVMAFLYESMRFSSFLPVTIPHATTANT

Rat                           DRLPCMSDQPNLPYVMAFLYESMRFTSFLPVTLPHATTANT

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 – 543 Cytochrome P450 1B1
Site 395 – 395 Major determinant of CYP1B1 17beta-estradiol hydroxylation regiospecificity
Mutagenesis 395 – 395 V -> L. Invertes the 4OH E2:2OH E2 hydroxylation preference from 5.1 to 0.45.
Helix 379 – 392


Literature citations

Sequence analysis and homology modeling suggest that primary congenital glaucoma on 2p21 results from mutations disrupting either the hinge region or the conserved core structures of cytochrome P4501B1.
Stoilov I.; Akarsu A.N.; Alozie I.; Child A.; Barsoum-Homsy M.; Turacli M.E.; Or M.; Lewis R.A.; Ozdemir N.; Brice G.; Aktan S.G.; Chevrette L.; Coca-Prados M.; Sarfarazi M.;
Am. J. Hum. Genet. 62:573-584(1998)
Cited for: VARIANT GLC3A TRP-365; VARIANTS CYS-57; GLU-61; TRP-365; LEU-379; LYS-387; HIS-390; VAL-432; LEU-437 AND TRP-469;

Identification of a single ancestral CYP1B1 mutation in Slovak Gypsies (Roms) affected with primary congenital glaucoma.
Plasilova M.; Stoilov I.; Sarfarazi M.; Kadasi L.; Ferakova E.; Ferak V.;
J. Med. Genet. 36:290-294(1999)
Cited for: VARIANT GLC3A LYS-387;

Molecular genetics of primary congenital glaucoma in Brazil.
Stoilov I.R.; Costa V.P.; Vasconcellos J.P.C.; Melo M.B.; Betinjane A.J.; Carani J.C.E.; Oltrogge E.V.; Sarfarazi M.;
Invest. Ophthalmol. Vis. Sci. 43:1820-1827(2002)
Cited for: VARIANTS GLC3A HIS-368; LYS-387; LEU-437 AND GLY-443; VARIANTS GLY-48; SER-119; VAL-432 AND SER-453;

Novel cytochrome P450 1B1 (CYP1B1) mutations in patients with primary congenital glaucoma in France.
Colomb E.; Kaplan J.; Garchon H.-J.;
Hum. Mutat. 22:496-496(2003)
Cited for: VARIANTS GLC3A LYS-229; ARG-232; LYS-387; SER-390; SER-399 AND TYR-423; VARIANTS GLY-48; SER-119; VAL-432 AND SER-453;

CYP1B1 mutations in French patients with early-onset primary open-angle glaucoma.
Melki R.; Colomb E.; Lefort N.; Brezin A.P.; Garchon H.-J.;
J. Med. Genet. 41:647-651(2004)
Cited for: VARIANTS GLC3A ASN-81; LYS-229; ARG-232; SER-269--PHE-271 DEL; LYS-387; HIS-390; TYR-423 AND GLY-443; VARIANTS GLY-48; SER-119; VAL-432 AND SER-453;

Primary congenital glaucoma and Rieger's anomaly: extended haplotypes reveal founder effects for eight distinct CYP1B1 mutations.
Chavarria-Soley G.; Michels-Rautenstrauss K.; Pasutto F.; Flikier D.; Flikier P.; Cirak S.; Bejjani B.; Winters D.L.; Lewis R.A.; Mardin C.; Reis A.; Rautenstrauss B.;
Mol. Vis. 12:523-531(2006)
Cited for: VARIANTS GLC3A GLU-61; ASN-81; LYS-229; LEU-343 DEL; HIS-368; LYS-387 AND TRP-469;

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.