HR T1022A - GET-Evidence

Curation:
Currentness:

HR T1022A

(HR Thr1022Ala)


Short summary

Probably benign. One study implicated it in causing alopecia universalis, but a later report noted the variant has an allele frequency inconsistent with the rarity of that disease.

Variant evidence
Computational

This gene is implicated in this disease.

Functional -
Case/Control 2

Allele frequency of this in HapMap and as observed by Cicho et al. is evidence that this variant alone is not causal.

See Cichon S et al. 1998 (9736769).

Familial
 
Clinical importance
Severity
Treatability
Penetrance -
 

Impact

Low clinical importance, Uncertain benign

(The "low clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

recessive

Summary of published research, and additional commentary

 

Total cases/controls case+ case– control+ control– p-value odds ratio
Alopecia Universalis
0 0 14 1212 - -

 

Allele frequency

  • C @ chr8:21976710: 9.7% (1043/10758) in EVS
  • C @ chr8:22032654: 7.9% (10/126) in GET-Evidence
  • Frequency shown in summary reports: 9.7% (1043/10758)

Publications
 

Ahmad W, Faiyaz ul Haque M, Brancolini V, Tsou HC, ul Haque S, Lam H, Aita VM, Owen J, deBlaquiere M, Frank J, Cserhalmi-Friedman PB, Leask A, McGrath JA, Peacocke M, Ahmad M, Ott J, Christiano AM. Alopecia universalis associated with a mutation in the human hairless gene. Science. 1998 Jan 30;279(5351):720-4. PubMed PMID: 9445480.

This variant is implicated as causing alopecia universalis in a large consanguineous Pakistani kindred with a LOD = 6.19.

Cases/controls case+ case– control+ control– p-value odds ratio
Alopecia Universalis
- - 14 1212 - -

 

Cichon S, Anker M, Vogt IR, Rohleder H, Pützstück M, Hillmer A, Farooq SA, Al-Dhafri KS, Ahmad M, Haque S, Rietschel M, Propping P, Kruse R, Nöthen MM. Cloning, genomic organization, alternative transcripts and mutational analysis of the gene responsible for autosomal recessive universal congenital alopecia. Hum Mol Genet. 1998 Oct;7(11):1671-9. Erratum in: Hum Mol Genet 1998 Nov;7(12):1987-8. PubMed PMID: 9736769.

This group implicates the same gene but, in a note added in the proof, added that they genotyped 606 German controls and found this variant heterozygous in 14. This would predict an incidence of the disease in 1 out of 40,000, but alopecia universalis is an extremely rare disorder.

Genomes
 

hu04FD18 - CGI sample GS00253-DNA_F01_200_37
het C @ chr8:21976710

 

 

GS18501 - var-GS18501-1100-36-ASM
het C @ chr8:22032655

 

GS18505 - var-GS18505-1100-36-ASM
het C @ chr8:22032655

 

GS18508 - var-GS18508-1100-36-ASM
het C @ chr8:22032655

 

GS19017 - var-GS19017-1100-36-ASM
hom C @ chr8:22032655

 

GS19025 - var-GS19025-1100-36-ASM
het C @ chr8:22032655

 

GS19129 - var-GS19129-1100-36-ASM
het C @ chr8:22032655

 

GS19701 - var-GS19701-1100-36-ASM
het C @ chr8:22032655

 

Other external references
 

    dbSNP
  • rs7014851
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PolyPhen-2
  • Score: 0 (benign)
    Web search results (27 hits -- see all)
  • Community Academic Profiles - Faculty & Researchers ...
    HR is a VDR corepressor, and it has been hypothesized that VDR.HR suppress gene expression during specific ... R620Q, T1022A) due to non-synonymous polymorphisms in the HR gene. ...
    med.stanford.edu/profiles/gcrc/...&pubid=241592&fid=4315
  • Interactions of the vitamin D receptor with the corepressor ...
    HR is a VDR corepressor, and it has been hypothesized that VDR.HR suppress gene expression during specific ... R620Q, T1022A) due to non-synonymous polymorphisms in the HR gene. ...
    www.ncbi.nlm.nih.gov/pubmed/17609203
  • NURSA | Hairless is a nuclear receptor corepressor essential ...
    HR is a corepressor for multiple nuclear receptors. HR interacts with ... Mutation of the Hr gene results in congenital hair loss in both mice and men. ...
    www.nursa.org/article.cfm?doi=10.1621/nrs.07010
  • John Libbey Eurotext : Éditions médicales et scientifiques ...
    John Libbey Eurotext éditeur spécialisé dans le domaine médical et scientifique ... of evidence for HR mutations implicated in APL. As additional HR mutation-induced cases ...
    john-libbey-eurotext.fr/e-docs/.../vers_alt/VersionPDF.pdf
  • Supplementary Table xls.1
    Administrator B**a***=***£***h*J*\I08*X*@*ì*"*******1* É*ÿ**Arial1* É*ÿ**Arial1 ... G871V rs7014851*HR NM_005144 NP_005135*T1022A*hairless homolog (mouse) ...
    icr.ac.uk/research/research_sections/.../2843.xls
  • BLUE TEXT Recommended Grade RED TEXT OEM Approved Grade
    CASIO HR-5. Alpha 700-2.4. CASIO HR-10. Alpha 700-2.4. CASIO IT-3000 ... T1022A-19.5 (Discontinued) BLUE TEXT. Recommended Grade. RED TEXT. OEM Approved Grade ...
    appletonideas.com/Appleton/en_US/01/pdf/...
  • Alopecia Universalis Associated with a Mutation in the Human ...
    T1022A. The mutation created a new. cleavage site for the restriction ... whereas the hr/hr mouse displays a more. pleiotropic defect because of ...
    web.ccsu.edu/technology/mulrooney/.../ahmad alopecia.pdf
  • Type I- 95%
    ... SWISS-PROT ID Variant site Phosphorylation site SWISS-PROT variant ID Removed ... GALC P54803 Y551S 551 VAR_003403 Src (0.816) GLD, belgian patient PLK4 O00444 ...
    www.nih.go.kr/phosphovariant/html/family_whole/TypeI-_95.txt

Other in silico analyses
 

  • NBLOSUM100 score = 1
  • GET-Evidence autoscore = 2

Edit history
 

Gene search

"GENE" or "GENE A123C":

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