HR

HR lysine demethylase and nuclear receptor corepressor

Basic information

Region (hg38): 8:22114419-22133384

Previous symbols: [ "ALUNC" ]

Links

ENSG00000168453 ∙ NCBI:55806 ∙ OMIM:602302 ∙ HGNC:5172 ∙ Uniprot:O43593 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypotrichosis 4 (Definitive), mode of inheritance: AR
• 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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Atrichia with papular lesions; Alopecia universalis congenita	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dermatologic	13150805; 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.

• not provided (7 variants)
• Alopecia universalis congenita (3 variants)
• Atrichia with papular lesions (2 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			15	21	15	51
missense	2		135	15	18	170
nonsense	3	1				4
start loss						0
frameshift	4	1	1			6
inframe indel						0
splice donor/acceptor (+/-2bp)	1	1				2
splice region			5	3	3	11
non coding	1	2	41	9	31	84
Total	11	5	192	45	64

Highest pathogenic variant AF is 0.0000345

Variants in HR

This is a list of pathogenic ClinVar variants found in the HR region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-22114430-A-G		Atrichia with papular lesions • Alopecia universalis congenita	Uncertain significance (Jan 13, 2018)
8-22114438-C-G		Alopecia universalis congenita • Atrichia with papular lesions	Uncertain significance (Jan 13, 2018)
8-22114447-A-G		Atrichia with papular lesions • Alopecia universalis congenita	Uncertain significance (Jan 13, 2018)
8-22114448-T-TA		Atrichia with papular lesions • Alopecia universalis	Benign (Jun 14, 2016)
8-22114550-G-A		Alopecia universalis congenita • Atrichia with papular lesions	Uncertain significance (Jan 13, 2018)
8-22114555-G-A		Alopecia universalis congenita • Atrichia with papular lesions	Uncertain significance (Jan 13, 2018)
8-22114575-G-A		Atrichia with papular lesions • Alopecia universalis congenita	Uncertain significance (Jan 13, 2018)
8-22114646-G-A		Alopecia universalis congenita • Atrichia with papular lesions	Uncertain significance (Jan 13, 2018)
8-22114680-G-T		Atrichia with papular lesions • Alopecia universalis congenita	Uncertain significance (Jan 12, 2018)
8-22114769-A-G		Atrichia with papular lesions • Alopecia universalis congenita	Benign (Jan 13, 2018)
8-22114796-G-A		Alopecia universalis congenita • Atrichia with papular lesions	Uncertain significance (Jan 12, 2018)
8-22114806-C-T		Alopecia universalis congenita • Atrichia with papular lesions	Likely benign (Jan 12, 2018)
8-22114815-G-A		Atrichia with papular lesions • Alopecia universalis congenita	Uncertain significance (Jan 13, 2018)
8-22114880-C-G		Alopecia universalis congenita • Atrichia with papular lesions	Benign (Jan 12, 2018)
8-22114880-C-T		Atrichia with papular lesions • Alopecia universalis congenita	Uncertain significance (Jan 13, 2018)
8-22114944-C-A		Alopecia universalis congenita • Atrichia with papular lesions	Benign (Jan 13, 2018)
8-22114949-C-G		Alopecia universalis congenita • Atrichia with papular lesions	Uncertain significance (Jan 13, 2018)
8-22114954-G-C		Alopecia universalis congenita • Atrichia with papular lesions	Uncertain significance (Jan 13, 2018)
8-22114966-C-T		Alopecia universalis congenita • Atrichia with papular lesions	Uncertain significance (Jan 12, 2018)
8-22115083-C-G		Alopecia universalis congenita • Atrichia with papular lesions	Uncertain significance (Jan 13, 2018)
8-22115101-A-C		Alopecia universalis congenita • Atrichia with papular lesions	Benign (Jan 13, 2018)
8-22115103-G-A		Atrichia with papular lesions • Alopecia universalis congenita	Uncertain significance (Jan 12, 2018)
8-22115121-G-A		Alopecia universalis congenita • Atrichia with papular lesions	Uncertain significance (Jan 12, 2018)
8-22115280-G-A		Atrichia with papular lesions • Alopecia universalis congenita	Uncertain significance (Jan 13, 2018)
8-22115397-C-T		Alopecia universalis congenita • Atrichia with papular lesions	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HR	protein_coding	protein_coding	ENST00000381418	18	18970

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.44e-10	1.00	125693	0	55	125748	0.000219

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.674	652	702	0.928	0.0000448	7481
Missense in Polyphen		164	204.32	0.80266		2364
Synonymous	-0.409	314	305	1.03	0.0000201	2538
Loss of Function	3.80	25	55.6	0.450	0.00000301	556

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000401	0.000392
Ashkenazi Jewish	0.000109	0.0000992
East Asian	0.000278	0.000272
Finnish	0.000373	0.000370
European (Non-Finnish)	0.000228	0.000220
Middle Eastern	0.000278	0.000272
South Asian	0.000140	0.000131
Other	0.000492	0.000489

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

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