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UniProtKB/Swiss-Prot P08686: Variant p.His62Leu

Steroid 21-hydroxylase
Gene: CYP21A2
Variant information

Variant position:  62
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 Histidine (H) to Leucine (L) at position 62 (H62L, p.His62Leu).
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 polar (H) to medium size and hydrophobic (L)
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:  Adrenal hyperplasia 3 (AH3) [MIM:201910]: A form of congenital adrenal hyperplasia, a common recessive disease due to defective synthesis of cortisol. Congenital adrenal hyperplasia is characterized by androgen excess leading to ambiguous genitalia in affected females, rapid somatic growth during childhood in both sexes with premature closure of the epiphyses and short adult stature. Four clinical types: 'salt wasting' (SW, the most severe type), 'simple virilizing' (SV, less severely affected patients), with normal aldosterone biosynthesis, 'non-classic form' or late-onset (NC or LOAH) and 'cryptic' (asymptomatic). {ECO:0000269|PubMed:10051010, ECO:0000269|PubMed:10094562, ECO:0000269|PubMed:10198222, ECO:0000269|PubMed:10364682, ECO:0000269|PubMed:10391209, ECO:0000269|PubMed:10408778, ECO:0000269|PubMed:10408786, ECO:0000269|PubMed:10443693, ECO:0000269|PubMed:10496074, ECO:0000269|PubMed:10720040, ECO:0000269|PubMed:11232002, ECO:0000269|PubMed:11598371, ECO:0000269|PubMed:11600539, ECO:0000269|PubMed:11746135, ECO:0000269|PubMed:12213891, ECO:0000269|PubMed:12222711, ECO:0000269|PubMed:12788866, ECO:0000269|PubMed:12887291, ECO:0000269|PubMed:12915679, ECO:0000269|PubMed:1406699, ECO:0000269|PubMed:1406709, ECO:0000269|PubMed:14676460, ECO:0000269|PubMed:14715874, ECO:0000269|PubMed:1496017, ECO:0000269|PubMed:15110320, ECO:0000269|PubMed:15126570, ECO:0000269|PubMed:16046588, ECO:0000269|PubMed:1644925, ECO:0000269|PubMed:16984992, ECO:0000269|PubMed:18319307, ECO:0000269|PubMed:18381579, ECO:0000269|PubMed:18445671, ECO:0000269|PubMed:1864962, ECO:0000269|PubMed:1937474, ECO:0000269|PubMed:20080860, ECO:0000269|PubMed:2072928, ECO:0000269|PubMed:21169732, ECO:0000269|PubMed:22014889, ECO:0000269|PubMed:2303461, ECO:0000269|PubMed:27721825, ECO:0000269|PubMed:3038528, ECO:0000269|PubMed:3257825, ECO:0000269|PubMed:3260007, ECO:0000269|PubMed:3267225, ECO:0000269|PubMed:3497399, ECO:0000269|PubMed:3871526, ECO:0000269|PubMed:7749410, ECO:0000269|PubMed:8478006, ECO:0000269|PubMed:8485582, ECO:0000269|PubMed:8989258, ECO:0000269|PubMed:9067760, ECO:0000269|PubMed:9187661, ECO:0000269|PubMed:9497336, ECO:0000269|PubMed:9580109}. 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 AH3; non-classic form; simple virilizing form when associated with a second mild mutation such as S-453 or L-30; activity is significantly reduced in association with S-453.
Any additional useful information about the variant.

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



Sequence information

Variant position:  62
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  494
The length of the canonical sequence.

Location on the sequence:   PDLPIYLLGLTQKFGPIYRL  H LGLQDVVVLNSKRTIEEAMV
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                         PDLPIYLLGLTQKFGPIYRLHLGLQDVVVLNSKRTIEEAMV

                              PDLPLHLLGLTQKLGPIYRLRLGLQDVVVLNSKRTIEEAMV

Mouse                         PNLPIYLLGLTQKLGPIYRIRLGMQDVVVLNSNRTIEEALI

Rat                           PNLPVYLFGLAQKLGPIYRIRLGLQDVVVLNSNKTIEEALI

Pig                           PNLPIYLLGLTQRLGPIYRLRLGLQDVVVLNSKRTIEEALV

Bovine                        PNLPIHLLSLTQKLGPVYRLRLGLQEVVVLNSKRTIEEAMI

Cat                           PDLPIYLLGLTQKLGPVYRLRLGLQDVVVLNSKRTIEEALI

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 – 494 Steroid 21-hydroxylase
Beta strand 57 – 63


Literature citations

Follow-up of 68 children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency: relevance of genotype for management.
Pinto G.; Tardy V.; Trivin C.; Thalassinos C.; Lortat-Jacob S.; Nihoul-Fekete C.; Morel Y.; Brauner R.;
J. Clin. Endocrinol. Metab. 88:2624-2633(2003)
Cited for: VARIANTS AH3 LEU-30; LEU-62; ASN-172; LEU-281; PRO-341; TRP-356; SER-453 AND PRO-483;

p.H62L, a rare mutation of the CYP21 gene identified in two forms of 21-hydroxylase deficiency.
Menassa R.; Tardy V.; Despert F.; Bouvattier-Morel C.; Brossier J.P.; Cartigny M.; Morel Y.;
J. Clin. Endocrinol. Metab. 93:1901-1908(2008)
Cited for: VARIANTS AH3 LEU-30; LEU-62; ASN-172; TRP-356 AND SER-453; CHARACTERIZATION OF VARIANTS AH3 LEU-62 AND SER-453;

Inhibition of CYP21A2 enzyme activity caused by novel missense mutations identified in Brazilian and Scandinavian patients.
Soardi F.C.; Barbaro M.; Lau I.F.; Lemos-Marini S.H.; Baptista M.T.; Guerra-Junior G.; Wedell A.; Lajic S.; de Mello M.P.;
J. Clin. Endocrinol. Metab. 93:2416-2420(2008)
Cited for: VARIANTS AH3 ARG-56; LEU-62; ARG-107; PRO-142; ASN-172; TRP-356; CYS-408 AND SER-453; CHARACTERIZATION OF VARIANTS AH3 ARG-56; LEU-62; ARG-107; PRO-142; CYS-408 AND SER-453;

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.