HCLS1

hematopoietic cell-specific Lyn substrate 1

Basic information

Region (hg38): 3:121631399-121660927

Links

ENSG00000180353 ∙ NCBI:3059 ∙ OMIM:601306 ∙ HGNC:4844 ∙ Uniprot:P14317 ∙ 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 HCLS1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HCLS1 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				1		1
missense			34	4		38
nonsense						0
start loss						0
frameshift						0
inframe indel					1	1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	34	5	1

Variants in HCLS1

This is a list of pathogenic ClinVar variants found in the HCLS1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-121631902-G-A		not specified	Uncertain significance (Jan 30, 2024)
3-121631920-C-G		not specified	Uncertain significance (Nov 14, 2023)
3-121631920-C-T		not specified	Uncertain significance (Apr 28, 2022)
3-121631940-G-C		not specified	Uncertain significance (May 30, 2023)
3-121631950-C-T		not specified	Uncertain significance (Feb 28, 2024)
3-121632113-C-A		not specified	Uncertain significance (Mar 04, 2024)
3-121632142-G-A		not specified	Uncertain significance (May 07, 2024)
3-121632169-G-A		not specified	Uncertain significance (Aug 17, 2022)
3-121632338-G-C		not specified	Uncertain significance (Sep 25, 2023)
3-121632368-C-T		not specified	Uncertain significance (Dec 12, 2023)
3-121632468-G-GGGCTCAGGCTCA			Benign (Jan 12, 2024)
3-121632508-T-G		not specified	Uncertain significance (Jan 05, 2022)
3-121632518-G-A		not specified	Likely benign (Jan 30, 2024)
3-121632520-C-A		not specified	Uncertain significance (Mar 27, 2023)
3-121633078-T-A		not specified	Uncertain significance (Feb 11, 2022)
3-121633087-T-G		not specified	Uncertain significance (Jan 10, 2022)
3-121633098-G-A		not specified	Uncertain significance (Dec 14, 2023)
3-121633119-G-C		not specified	Uncertain significance (Apr 20, 2024)
3-121633158-A-G		not specified	Likely benign (Mar 12, 2024)
3-121633158-A-T		not specified	Uncertain significance (Jan 24, 2023)
3-121634239-G-A		not specified	Uncertain significance (Jul 06, 2021)
3-121634307-C-A		not specified	Uncertain significance (Sep 22, 2022)
3-121634307-C-T		not specified	Uncertain significance (Aug 17, 2022)
3-121634314-G-C		not specified	Uncertain significance (Dec 13, 2023)
3-121634325-G-A		not specified	Uncertain significance (Sep 26, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HCLS1	protein_coding	protein_coding	ENST00000314583	13	29529

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000132	0.998	125699	0	49	125748	0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.0535	283	280	1.01	0.0000159	3157
Missense in Polyphen		27	31.234	0.86444		288
Synonymous	0.467	103	109	0.943	0.00000695	928
Loss of Function	2.72	15	31.5	0.476	0.00000180	346

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000357	0.000355
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000546	0.0000544
Finnish	0.0000477	0.0000462
European (Non-Finnish)	0.000284	0.000281
Middle Eastern	0.0000546	0.0000544
South Asian	0.000163	0.000163
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Substrate of the antigen receptor-coupled tyrosine kinase. Plays a role in antigen receptor signaling for both clonal expansion and deletion in lymphoid cells. May also be involved in the regulation of gene expression.
• Pathway: Tight junction - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Shigellosis - Homo sapiens (human);Pathogenic Escherichia coli infection - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathogenic Escherichia coli infection;B Cell Receptor Signaling Pathway;TYROBP Causal Network;BCR;IL5;Fc-epsilon receptor I signaling in mast cells (Consensus)

Recessive Scores

• pRec: 0.133

Intolerance Scores

• loftool: 0.790
• rvis_EVS: 0.54
• rvis_percentile_EVS: 81.07

Haploinsufficiency Scores

• pHI: 0.517
• hipred: Y
• hipred_score: 0.706
• ghis: 0.500

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.901

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hcls1
• Phenotype: hematopoietic system phenotype; immune system phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;regulation of transcription, DNA-templated;positive regulation of cell population proliferation;response to hormone;positive regulation of phosphatidylinositol 3-kinase signaling;actin filament polymerization;erythrocyte differentiation;regulation of actin filament polymerization;positive regulation of granulocyte differentiation;positive regulation of peptidyl-serine phosphorylation;intracellular signal transduction;positive regulation of protein import into nucleus;positive regulation of tyrosine phosphorylation of STAT protein;positive regulation of macrophage differentiation;positive regulation of transcription by RNA polymerase II;positive regulation of peptidyl-tyrosine phosphorylation;positive regulation of DNA-binding transcription factor activity;positive regulation of protein kinase B signaling;cellular response to cytokine stimulus;negative regulation of leukocyte apoptotic process;positive regulation of actin cytoskeleton reorganization
• Cellular component: nucleus;transcription factor complex;cytoplasm;mitochondrion;cytosol;plasma membrane
• Molecular function: RNA polymerase II transcription factor binding;actin binding;protein binding;SH3 domain binding;protein kinase binding;protein-containing complex binding