HSCB

protein-coding

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

Gene summary

This gene encodes a DnaJ-type co-chaperone and member of the heat shock cognate B (HscB) family of proteins. The encoded protein plays a role in the synthesis of iron-sulfur clusters, protein cofactors that are involved in the redox reactions of mitochondrial electron transport and other processes. Cells in which this gene is knocked down exhibit reduced activity of iron-sulfur cluster-dependent enzymes including succinate dehydrogenase and aconitase. The encoded protein may stimulate the ATPase activity of the mitochondrial stress-70 protein. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

MANE transcript

NM_172002.5

Inheritance

ClinVar variants

P:1U:41B:1

Top phenotype

Anemia, sideroblastic, 5

gnomAD constraint

pLI —, LoF o/e 0.46

Max pathogenic AF

—

Genomic locus

chr22:28,742,039-28,757,515

External References & Databases

Ensembl (ENSG00000100209)

Transcript & Mutation Effects

hg38 • Region Span ~15.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

anemia, sideroblastic, 5LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0030436

Submitter: Labcorp Genetics (formerly Invitae)

anemia, sideroblastic, 5MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0030436

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Anemia, sideroblastic, 5AR

Manifestation: Hematologic

Intervention: Hematologic

Rationale: The condition may involve severe anemia, and treatment with transfusions has been reported

Refs: 32634119

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HSCB variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 37

Anemia, sideroblastic, 5Total: 4

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_172002.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar			1
missense			39 clinvar	1 clinvar		40
nonsense						0
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	0	41	1	0	43

Highest pathogenic variant AF is 0.00001301062

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 39 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_172002.5	RefSeq	NP_741999.3	6	MANE Select
ENST00000216027.8	Ensembl	ENSP00000216027.3	6	MANE Select
NM_001318314.2	RefSeq	NP_001305243.1	4	Standard
NM_001318315.2	RefSeq	NP_001305244.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of proteins
Mitochondrial iron-sulfur cluster biogenesis
Metabolism
Mitochondrial protein import

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

Molecular Function

ATPase activator activity
molecular_function
protein binding
identical protein binding
metal ion binding

Cellular Component

nucleus
cytoplasm
mitochondrion
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000216027
Coding exons: 6
Length: 15485
Individuals with no LoFs: 125722
Homozygous LoFs: 0
Heterozygous LoFs: 26
Defined: 125748
p: 0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.192	122	128	0.952	0.00000611	1554
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000064	0.000062	rare
Latino/Admixed American	0.000087	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00038	0.00038	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000063	0.000062	rare
South Asian	0.00023	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Acts as a co-chaperone in iron-sulfur cluster assembly in mitochondria. {ECO:0000269|PubMed:20668094}.;

Recessive Scores

pRec: 0.123

Intolerance Scores

LoFtool: 0.774
RVIS EVS: 0.22
RVIS percentile EVS: 67.92

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.231

Gene Damage Prediction

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