HELLS

helicase, lymphoid specific, the group of DNA helicases

Basic information

Region (hg38): 10:94545329-94613905

Links

ENSG00000119969

∙ NCBI:3070 ∙ OMIM:603946 ∙ HGNC:4861 ∙ Uniprot:Q9NRZ9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

immunodeficiency-centromeric instability-facial anomalies syndrome 4 (Strong), mode of inheritance: AR
immunodeficiency-centromeric instability-facial anomalies syndrome (Supportive), mode of inheritance: AR
immunodeficiency-centromeric instability-facial anomalies syndrome 4 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency-centromeric instability-facial anomalies syndrome 4	AR	Allergy/Immunology/Infectious	Individuals have been described with recurrent childhood infections, and awareness may allow prompt and aggressive treatment of infections	Allergy/Immunology/Infectious; Craniofacial; Neurologic	26216346

ClinVar

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

not_provided (357 variants)
Inborn_genetic_diseases (58 variants)
Immunodeficiency-centromeric_instability-facial_anomalies_syndrome_4 (18 variants)
HELLS-related_disorder (9 variants)
not_specified (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HELLS gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018063.5. 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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				98 clinvar	5 clinvar	103
missense	1 clinvar		141 clinvar	6 clinvar		148
nonsense	8 clinvar					8
start loss			1	1		2
frameshift	4 clinvar	1 clinvar				5
splice donor/acceptor (+/-2bp)	1 clinvar	3 clinvar			1 clinvar	5
Total	14	4	142	105	6

Highest pathogenic variant AF is 0.00000977374

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HELLS	protein_coding	protein_coding	ENST00000348459	22	68116

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000206	125711	0	9	125720	0.0000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.99	258	433	0.595	0.0000218	5549
Missense in Polyphen		30	135.33	0.22168		1756
Synonymous	-0.145	145	143	1.02	0.00000684	1481
Loss of Function	6.01	7	55.1	0.127	0.00000336	644

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.000200	0.000198
East Asian	0.00	0.00
Finnish	0.0000947	0.0000924
European (Non-Finnish)	0.0000277	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.0000709	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Plays an essential role in normal development and survival. Involved in regulation of the expansion or survival of lymphoid cells. Required for de novo or maintenance DNA methylation. May control silencing of the imprinted CDKN1C gene through DNA methylation. May play a role in formation and organization of heterochromatin, implying a functional role in the regulation of transcription and mitosis (By similarity). {ECO:0000250|UniProtKB:Q60848}.;
Disease: DISEASE: Immunodeficiency-centromeric instability-facial anomalies syndrome 4 (ICF4) [MIM:616911]: A rare disorder characterized by a variable immunodeficiency resulting in recurrent infections, facial anomalies, and branching of chromosomes 1, 9, and 16. Other variable symptoms include growth retardation, failure to thrive, and psychomotor retardation. Laboratory studies show limited hypomethylation of DNA in a small fraction of the genome in some, but not all, patients. {ECO:0000269|PubMed:26216346}. Note=The disease may be caused by mutations affecting the gene represented in this entry.;
Pathway: Apoptosis;Apoptosis-related network due to altered Notch3 in ovarian cancer;Apoptotic Signaling Pathway;Validated transcriptional targets of deltaNp63 isoforms (Consensus)

Recessive Scores

pRec: 0.323

Intolerance Scores

loftool: 0.223
rvis_EVS: 0.02
rvis_percentile_EVS: 55.61

Haploinsufficiency Scores

pHI: 0.638
hipred: Y
hipred_score: 0.756
ghis: 0.651

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: S
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.914

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Hells
Phenotype: limbs/digits/tail phenotype; skeleton phenotype; renal/urinary system phenotype; immune system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; pigmentation 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); 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; growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan);

Zebrafish Information Network

Gene name: hells
Affected structure: head
Phenotype tag: abnormal
Phenotype quality: aplastic/hypoplastic

Gene ontology

Biological process: methylation-dependent chromatin silencing;cell cycle;multicellular organism development;maintenance of DNA methylation;pericentric heterochromatin assembly;lymphocyte proliferation;cell division
Cellular component: chromosome, centromeric region;nucleus;pericentric heterochromatin
Molecular function: helicase activity;protein binding;ATP binding