HR

HR lysine demethylase and nuclear receptor corepressor

Basic information

Region (hg38): 8:22114419-22133384

Previous symbols: [ "ALUNC" ]

Links

ENSG00000168453NCBI:55806OMIM:602302HGNC:5172Uniprot:O43593AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • atrichia with papular lesions (Definitive), mode of inheritance: AR
  • alopecia universalis congenita (Supportive), mode of inheritance: AR
  • Marie Unna hereditary hypotrichosis (Supportive), mode of inheritance: AD
  • atrichia with papular lesions (Supportive), mode of inheritance: AR
  • atrichia with papular lesions (Strong), mode of inheritance: AR
  • hypotrichosis 4 (Strong), mode of inheritance: AD
  • atrichia with papular lesions (Strong), mode of inheritance: AR
  • alopecia universalis congenita (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Atrichia with papular lesions; Alopecia universalis congenitaARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingDermatologic13150805; 13763141; 5570254; 9758627; 10205263; 10827399; 11410842; 12271294; 11982770; 12880440; 17869066; 10417283; 11069461; 10854110; 10777357; 15149494; 17680008; 21272494; 21919222; 22584530

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HR gene.

  • Inborn_genetic_diseases (197 variants)
  • not_provided (159 variants)
  • Alopecia_universalis_congenita (119 variants)
  • Atrichia_with_papular_lesions (119 variants)
  • HR-related_disorder (17 variants)
  • Hypotrichosis_4 (1 variants)
  • Intellectual_disability,_autosomal_dominant_14 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HR gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005144.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
13
clinvar
38
clinvar
15
clinvar
66
missense
3
clinvar
233
clinvar
27
clinvar
13
clinvar
276
nonsense
5
clinvar
1
clinvar
6
start loss
0
frameshift
5
clinvar
4
clinvar
9
splice donor/acceptor (+/-2bp)
2
clinvar
1
clinvar
3
Total 15 6 246 65 28

Highest pathogenic variant AF is 0.0000211391

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
HRprotein_codingprotein_codingENST00000381418 1818970
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
7.44e-101.001256930551257480.000219
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.6746527020.9280.00004487481
Missense in Polyphen164204.320.802662364
Synonymous-0.4093143051.030.00002012538
Loss of Function3.802555.60.4500.00000301556

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0004010.000392
Ashkenazi Jewish0.0001090.0000992
East Asian0.0002780.000272
Finnish0.0003730.000370
European (Non-Finnish)0.0002280.000220
Middle Eastern0.0002780.000272
South Asian0.0001400.000131
Other0.0004920.000489

dbNSFP

Source: dbNSFP

Function
FUNCTION: Histone demethylase that specifically demethylates both mono- and dimethylated 'Lys-9' of histone H3. May act as a transcription regulator controlling hair biology (via targeting of collagens), neural activity, and cell cycle. {ECO:0000269|PubMed:24334705}.;
Disease
DISEASE: Alopecia universalis congenita (ALUNC) [MIM:203655]: A rare disorder characterized by loss of hair from the entire body. No hair are present in hair follicles on skin biopsy. {ECO:0000269|PubMed:12406339, ECO:0000269|PubMed:24334705, ECO:0000269|PubMed:9445480, ECO:0000269|PubMed:9736769}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Atrichia with papular lesions (APL) [MIM:209500]: An autosomal recessive disease characterized by papillary lesions over most of the body and almost complete absence of hair. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hypotrichosis 4 (HYPT4) [MIM:146550]: An autosomal dominant condition characterized by reduced amount of hair, alopecia, little or no eyebrows, eyelashes or body hair, and coarse, wiry, twisted hair in early childhood. {ECO:0000269|PubMed:19122663, ECO:0000269|PubMed:24961381}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.124

Intolerance Scores

loftool
0.695
rvis_EVS
1.24
rvis_percentile_EVS
93.31

Haploinsufficiency Scores

pHI
0.201
hipred
Y
hipred_score
0.644
ghis
0.499

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
S
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.708

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Hr
Phenotype
integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; vision/eye phenotype; craniofacial phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); neoplasm; pigmentation phenotype; embryo phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype;

Gene ontology

Biological process
regulation of transcription, DNA-templated;histone H3-K9 demethylation;negative regulation of transcription, DNA-templated;oxidation-reduction process
Cellular component
chromatin;nucleus;nucleoplasm;nuclear body
Molecular function
transcription regulatory region sequence-specific DNA binding;DNA binding;DNA-binding transcription factor activity;transcription corepressor activity;oxidoreductase activity;chromatin DNA binding;histone demethylase activity (H3-K9 specific);metal ion binding