HSCB

HscB mitochondrial iron-sulfur cluster cochaperone, the group of DNAJ (HSP40) heat shock proteins

Basic information

Region (hg38): 22:28742039-28757515

Links

ENSG00000100209 ∙ NCBI:150274 ∙ OMIM:608142 ∙ HGNC:28913 ∙ Uniprot:Q8IWL3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• anemia, sideroblastic, 5 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Anemia, sideroblastic, 5	AR	Hematologic	The condition may involve severe anemia, and treatment with transfusions has been reported	Hematologic	32634119

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HSCB 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			16	1		17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	16	2	0

Variants in HSCB

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

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

Position	Type	Phenotype	Significance	ClinVar
22-28742059-C-T			Likely benign (May 28, 2019)
22-28742108-A-G			Likely benign (May 28, 2019)
22-28742109-G-C		not specified	Uncertain significance (Apr 06, 2023)
22-28742163-G-A		not specified	Uncertain significance (Sep 16, 2021)
22-28742216-T-C		not specified	Uncertain significance (Jun 18, 2024)
22-28742219-T-G		Anemia, sideroblastic, 5	Uncertain significance (May 20, 2023)
22-28742240-G-T		Anemia, sideroblastic, 5	Uncertain significance (Sep 22, 2024)
22-28742283-C-T		not specified	Uncertain significance (Jul 14, 2022)
22-28742289-A-G		not specified	Uncertain significance (Aug 22, 2023)
22-28743887-G-A		not specified	Uncertain significance (Jan 26, 2023)
22-28743903-T-TA		Anemia, sideroblastic, 5	Pathogenic (Sep 17, 2021)
22-28743941-G-A		not specified • Anemia, sideroblastic, 5	Uncertain significance (Sep 22, 2024)
22-28743967-C-G		not specified	Uncertain significance (Jun 21, 2023)
22-28744670-C-A		not specified	Uncertain significance (Dec 21, 2023)
22-28745957-G-A		not specified	Uncertain significance (Jan 03, 2024)
22-28745999-A-G		not specified	Uncertain significance (Feb 15, 2023)
22-28751276-G-A		not specified	Uncertain significance (Apr 29, 2024)
22-28757111-A-G		not specified	Uncertain significance (Dec 12, 2023)
22-28757115-G-T		not specified	Uncertain significance (Feb 23, 2023)
22-28757117-G-C		not specified	Uncertain significance (Jan 03, 2024)
22-28757138-A-G		not specified	Uncertain significance (Aug 12, 2021)
22-28757143-A-G		not specified	Uncertain significance (May 05, 2023)
22-28757145-C-G		not specified	Uncertain significance (Apr 09, 2024)
22-28757164-C-T		not specified	Uncertain significance (May 31, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HSCB	protein_coding	protein_coding	ENST00000216027	6	15485

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00352	0.957	125722	0	26	125748	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.192	122	128	0.952	0.00000611	1554
Missense in Polyphen		23	28.469	0.80791		381
Synonymous	-0.369	52	48.7	1.07	0.00000233	423
Loss of Function	1.80	6	13.0	0.461	5.61e-7	146

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000151	0.000149
Ashkenazi Jewish	0.00	0.00
East Asian	0.000384	0.000381
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.0000635	0.0000615
Middle Eastern	0.000384	0.000381
South Asian	0.000231	0.000229
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a co-chaperone in iron-sulfur cluster assembly in mitochondria. {ECO:0000269|PubMed:20668094}.
• Pathway: Metabolism of proteins;Mitochondrial iron-sulfur cluster biogenesis;Metabolism;Mitochondrial protein import (Consensus)

Recessive Scores

• pRec: 0.123

Intolerance Scores

• loftool: 0.774
• rvis_EVS: 0.22
• rvis_percentile_EVS: 67.92

Haploinsufficiency Scores

• pHI: 0.102
• hipred: N
• hipred_score: 0.146
• ghis: 0.526

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.231

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hscb

Gene ontology

• Biological process: iron-sulfur cluster assembly;positive regulation of ATPase activity;[2Fe-2S] cluster assembly;protein complex oligomerization;protein maturation by iron-sulfur cluster transfer
• Cellular component: nucleus;cytoplasm;mitochondrion;cytosol
• Molecular function: ATPase activator activity;molecular_function;protein binding;identical protein binding;metal ion binding;chaperone binding