HUS1

HUS1 checkpoint clamp component, the group of Checkpoint clamp complex

Basic information

Region (hg38): 7:47961882-47979615

Links

ENSG00000136273

∙ NCBI:3364 ∙ OMIM:603760 ∙ HGNC:5309 ∙ Uniprot:O60921 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HUS1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HUS1 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						0
missense			15 clinvar			15
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	15	0	0

Variants in HUS1

This is a list of pathogenic ClinVar variants found in the HUS1 region.

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

Position	Phenotype	Significance	ClinVar
7-47965392-G-T	not specified	Uncertain significance (Nov 29, 2023)	3107639
7-47967842-C-A	not specified	Uncertain significance (Dec 01, 2022)	2331262
7-47967887-T-C	not specified	Uncertain significance (Jan 10, 2023)	2455290
7-47969279-T-C	not specified	Uncertain significance (Dec 28, 2023)	3107638
7-47969283-C-A	not specified	Uncertain significance (May 31, 2023)	2553681
7-47976816-G-A	not specified	Uncertain significance (Apr 16, 2024)	3285083
7-47978425-C-T	not specified	Uncertain significance (Jun 07, 2024)	3285084
7-47978520-G-A	not specified	Uncertain significance (Sep 01, 2021)	2346664
7-47978543-A-C	not specified	Uncertain significance (Jun 26, 2023)	2602455
7-47978568-A-G	not specified	Uncertain significance (Sep 12, 2023)	2622739
7-47978742-G-A	not specified	Uncertain significance (Aug 10, 2021)	2213590
7-47978746-G-T	not specified	Uncertain significance (Dec 08, 2023)	3107637
7-47978772-G-A	not specified	Uncertain significance (Aug 16, 2021)	2341226
7-47978775-G-C	not specified	Uncertain significance (Sep 16, 2021)	2250805
7-47978799-C-T	not specified	Uncertain significance (Jul 20, 2022)	2302880
7-47979469-T-C		Benign (Mar 29, 2018)	771411
7-47979482-A-C	not specified	Uncertain significance (Jan 05, 2022)	2270322
7-47979492-C-A	not specified	Uncertain significance (May 03, 2023)	2569114

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HUS1	protein_coding	protein_coding	ENST00000258774	8	283851

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000301	0.803	125713	0	35	125748	0.000139

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.415	163	149	1.10	0.00000722	1870
Missense in Polyphen		35	39.806	0.87927		527
Synonymous	0.640	49	55.0	0.890	0.00000300	496
Loss of Function	1.24	9	14.0	0.644	6.72e-7	175

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000581	0.0000581
Ashkenazi Jewish	0.000496	0.000496
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000205	0.000202
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

Function: FUNCTION: Component of the 9-1-1 cell-cycle checkpoint response complex that plays a major role in DNA repair. The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex. Acts then as a sliding clamp platform on DNA for several proteins involved in long-patch base excision repair (LP-BER). The 9-1-1 complex stimulates DNA polymerase beta (POLB) activity by increasing its affinity for the 3'-OH end of the primer-template and stabilizes POLB to those sites where LP-BER proceeds; endonuclease FEN1 cleavage activity on substrates with double, nick, or gap flaps of distinct sequences and lengths; and DNA ligase I (LIG1) on long-patch base excision repair substrates. The 9-1-1 complex is necessary for the recruitment of RHNO1 to sites of double-stranded breaks (DSB) occurring during the S phase. {ECO:0000269|PubMed:21659603}.;
Pathway: Cellular senescence - Homo sapiens (human);ATR Signaling;HDR through Single Strand Annealing (SSA);HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA);DNA Repair;Gene expression (Transcription);DNA Double-Strand Break Repair;role of brca1 brca2 and atr in cancer susceptibility;Generic Transcription Pathway;Homology Directed Repair;RNA Polymerase II Transcription;G2/M DNA damage checkpoint;Activation of ATR in response to replication stress;G2/M Checkpoints;Cell Cycle Checkpoints;Fanconi anemia pathway;Regulation of TP53 Activity through Phosphorylation;Regulation of TP53 Activity;Transcriptional Regulation by TP53;Cell Cycle;Regulation of Telomerase;Processing of DNA double-strand break ends;ATR signaling pathway;Presynaptic phase of homologous DNA pairing and strand exchange;Homologous DNA Pairing and Strand Exchange;HDR through Homologous Recombination (HRR) (Consensus)

Recessive Scores

pRec: 0.0828

Intolerance Scores

loftool: 0.811
rvis_EVS: 0.46
rvis_percentile_EVS: 78.46

Haploinsufficiency Scores

pHI
hipred: Y
hipred_score: 0.576
ghis: 0.473

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.812

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Hus1
Phenotype: growth/size/body region phenotype; cellular 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); hematopoietic 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); embryo 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); limbs/digits/tail phenotype;

Gene ontology

Biological process: DNA damage checkpoint;telomere maintenance;double-strand break repair via homologous recombination;regulation of protein phosphorylation;DNA repair;nucleotide-excision repair;protein phosphorylation;cellular response to DNA damage stimulus;negative regulation of DNA replication;response to UV;embryo development ending in birth or egg hatching;intra-S DNA damage checkpoint;mitotic DNA replication checkpoint;meiotic DNA integrity checkpoint;cellular response to ionizing radiation
Cellular component: nucleus;nucleoplasm;nucleolus;cytosol;checkpoint clamp complex;site of double-strand break
Molecular function: protein binding