HSCB

Summary

HSCB (HscB mitochondrial iron-sulfur cluster cochaperone, HGNC:28913) is a protein-coding gene on chromosome 22q12.1, encoding Iron-sulfur cluster co-chaperone protein HscB (Q8IWL3). Acts as a co-chaperone in iron-sulfur cluster assembly in mitochondria. It is a selective cancer dependency (DepMap: 62.2% of cell lines).

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.

Source: NCBI Gene 150274 — RefSeq curated summary.

At a glance

• Gene–disease (curated): anemia, sideroblastic, 5 (Moderate, GenCC)
• GWAS associations: 13
• Clinical variants (ClinVar): 55 total — 4 pathogenic
• Phenotypes (HPO): 8
• Cancer dependency (DepMap): dependent in 62.2% of screened cell lines
• MANE Select transcript: NM_172002

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28913
Approved symbol	HSCB
Name	HscB mitochondrial iron-sulfur cluster cochaperone
Location	22q12.1
Locus type	gene with protein product
Status	Approved
Aliases	HSC20, DNAJC20, Jac1
Ensembl gene	ENSG00000100209
Ensembl biotype	protein_coding
OMIM	608142
Entrez	150274

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000216027, ENST00000398941, ENST00000420442, ENST00000450178, ENST00000483861, ENST00000485599, ENST00000495977, ENST00000910454, ENST00000910455, ENST00000913000, ENST00000913001

RefSeq mRNA: 5 — MANE Select: NM_172002 NM_001318314, NM_001318315, NM_001318316, NM_001363856, NM_172002

CCDS: CCDS13845, CCDS82704, CCDS87014

Canonical transcript exons

ENST00000216027 — 6 exons

Exon	Start	End
ENSE00001048167	28742039	28742331
ENSE00003546666	28744615	28744704
ENSE00003582449	28745864	28746008
ENSE00003587713	28743882	28743978
ENSE00003631598	28751241	28751288
ENSE00003645654	28757078	28757510

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 92.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.2015 / max 150.0727, expressed in 1811 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191568	17.7023	1807
191569	1.5454	989
191567	0.9538	633

Top tissues by expression

254 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	92.36	gold quality
buccal mucosa cell	CL:0002336	90.63	gold quality
right lobe of liver	UBERON:0001114	88.99	gold quality
right adrenal gland	UBERON:0001233	88.80	gold quality
right adrenal gland cortex	UBERON:0035827	88.76	gold quality
left adrenal gland	UBERON:0001234	88.57	gold quality
left adrenal gland cortex	UBERON:0035825	88.46	gold quality
body of pancreas	UBERON:0001150	88.07	gold quality
endocervix	UBERON:0000458	87.99	gold quality
adrenal cortex	UBERON:0001235	87.95	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.83	gold quality
granulocyte	CL:0000094	87.71	gold quality
monocyte	CL:0000576	87.65	gold quality
saliva-secreting gland	UBERON:0001044	87.65	gold quality
epithelial cell of pancreas	CL:0000083	87.60	silver quality
left ovary	UBERON:0002119	87.48	gold quality
leukocyte	CL:0000738	87.42	gold quality
adrenal gland	UBERON:0002369	87.36	gold quality
pancreas	UBERON:0001264	87.14	gold quality
islet of Langerhans	UBERON:0000006	87.06	gold quality
minor salivary gland	UBERON:0001830	86.91	gold quality
liver	UBERON:0002107	86.85	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.50	gold quality
right ovary	UBERON:0002118	86.45	gold quality
ovary	UBERON:0000992	86.23	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.21	gold quality
adenohypophysis	UBERON:0002196	85.87	gold quality
body of stomach	UBERON:0001161	85.81	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	85.72	gold quality
corpus epididymis	UBERON:0004359	85.56	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.18
E-GEOD-100618	no	71.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting HSCB, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-520E-5P	99.27	68.90	1513
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-552-3P	96.68	64.12	1026

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 62.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 9)

• structural analysis of human J-type co-chaperone HscB reveals a tetracysteine metal-binding domain (PMID:18713742)
• A cysteine-rich N-terminal domain, which clearly distinguishes hHSC20 from the specialized DnaJ type III proteins of fungi and most bacteria, was found to be important for the integrity and function of the human co-chaperone. (PMID:20668094)
• NFS1 binds preferentially to the D-state of ISCU while mtHSP70 binds preferentially to the D-state of ISCU and HSC20 binds preferentially to the S-state of ISCU. (PMID:23940031)
• The delivery of assembled Fe-S clusters to recipient proteins is a crucial step in the biogenesis of Fe-S proteins; review focuses on recent insights into the molecular mechanism of amino acid motif recognition and discrimination by the co-chaperone HSC20 and finds co-chaperone HSC20 binds to LYR motifs present in Fe-S recipient proteins or their binding partners. [Review] (PMID:27714045)
• the crucial role of HSC20 in the assembly of the mitochondrial respiratory chain, is reported. (PMID:28380382)
• Nfu is shown to bind to both chaperone proteins with binding affinities similar to those observed for IscU binding to the homologous HSPA9 and Hsc20, while Nfu can also stimulate the ATPase activity of HSPA9 (PMID:29211945)
• Cytosolic HSC20 is indispensable for cytoplasmic Fe-S assembly and delivery, which is initiated de novo in the cytosol. (PMID:29309586)
• Structural characterization of the human DjC20/HscB cochaperone in solution. (PMID:37871810)
• PI3K/HSCB axis facilitates FOG1 nuclear translocation to promote erythropoiesis and megakaryopoiesis. (PMID:38757931)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	hscb	ENSDARG00000075416
mus_musculus	Hscb	ENSMUSG00000043510
rattus_norvegicus	Hscb	ENSRNOG00000037508
drosophila_melanogaster	Hsc20	FBGN0263606
caenorhabditis_elegans		WBGENE00001033

Protein

Protein identifiers

Iron-sulfur cluster co-chaperone protein HscB — Q8IWL3 (reviewed: Q8IWL3)

Alternative names: DnaJ homolog subfamily C member 20

All UniProt accessions (4): Q8IWL3, A0A384NYJ4, B0QYH2, F8WBY7

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a co-chaperone in iron-sulfur cluster assembly in mitochondria. Required for incorporation of iron-sulfur clusters into SDHB, the iron-sulfur protein subunit of succinate dehydrogenase that is involved in complex II of the mitochondrial electron transport chain. Recruited to SDHB by interaction with SDHAF1 which first binds SDHB and then recruits the iron-sulfur transfer complex formed by HSC20, HSPA9 and ISCU through direct binding to HSC20. Plays an essential role in hematopoiesis. Acts as a co-chaperone in iron-sulfur cluster assembly in the cytoplasm. Also mediates complex formation between components of the cytosolic iron-sulfur biogenesis pathway and the CIA targeting complex composed of CIAO1, DIPK1B/FAM69B and MMS19 by binding directly to the scaffold protein ISCU and to CIAO1. This facilitates iron-sulfur cluster insertion into a number of cytoplasmic and nuclear proteins including POLD1, ELP3, DPYD and PPAT.

Subunit / interactions. Interacts with ISCU and HSPA9 to form an iron-sulfur transfer complex. Interacts with SDHAF1 (via the first LYR motif); the interaction recruits the iron-sulfur transfer complex composed of HSC20, HSPA9 and ISCU and mediates the incorporation of iron-sulfur clusters into SDHB which also interacts with HSC20. Interacts with the cytoplasmic form of ISCU and with CIA complex member CIAO1 (via LYR motif). Homodimer. Interacts with ISCU (cytoplasmic form); this interaction stabilizes the (Fe-S) clusters on ISCU. Interacts with the CIA complex member CIAO1 (via LYR motif).

Subcellular location. Cytoplasm Mitochondrion.

Tissue specificity. Expressed in lung, brain, stomach, spleen, ovary, testis, liver, muscle and heart.

Disease relevance. Anemia, sideroblastic, 5 (SIDBA5) [MIM:619523] A form of sideroblastic anemia, a bone marrow disorder defined by the presence of pathologic iron deposits in erythroblast mitochondria. Sideroblastic anemia is characterized by anemia of varying severity, hypochromic peripheral erythrocytes, systemic iron overload secondary to chronic ineffective erythropoiesis, and the presence of bone marrow ringed sideroblasts. Sideroblasts are characterized by iron-loaded mitochondria clustered around the nucleus. SIDBA5 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Pathway. Cofactor biosynthesis; iron-sulfur cluster biosynthesis.

Similarity. Belongs to the HscB family.

RefSeq proteins (5): NP_001305243, NP_001305244, NP_001305245, NP_001350785, NP_741999* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004640	HscB	Family
IPR009073	HscB_oligo_C	Domain
IPR036386	HscB_C_sf	Homologous_superfamily
IPR036869	J_dom_sf	Homologous_superfamily
IPR040682	HscB_4_cys	Domain

Pfam: PF07743, PF18256

UniProt features (27 total): helix 8, mutagenesis site 5, binding site 4, chain 2, strand 2, turn 2, sequence variant 2, sequence conflict 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3BVO	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IWL3-F1	83.63	0.70

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 41; 44; 58; 61

Mutagenesis-validated functional residues (5):

Position	Phenotype
44	abolishes self-interaction and interaction with hspa9 and the cia complex but does not alter subcellular localization; w
58	abolishes self-interaction and interaction with hspa9 and the cia complex but does not alter subcellular localization; w
61	abolishes self-interaction and interaction with hspa9 and the cia complex but does not alter subcellular localization; w
102–104	does not interact with hspa9. does not inhibit interaction with iscu.
41	abolishes self-interaction and interaction with hspa9 and the cia complex but does not alter subcellular localization; w

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1268020	Mitochondrial protein import
R-HSA-1362409	Mitochondrial iron-sulfur cluster biogenesis
R-HSA-6799198	Complex I biogenesis
R-HSA-9865881	Complex III assembly

MSigDB gene sets: 150 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, RRAGTTGT_UNKNOWN, GOBP_EMBRYONIC_HEMOPOIESIS, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_ERYTHROCYTE_HOMEOSTASIS, GGGTGGRR_PAX4_03, AACWWCAANK_UNKNOWN, TGCTGAY_UNKNOWN, IRF1_Q6, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, WONG_MITOCHONDRIA_GENE_MODULE, GOBP_EMBRYO_DEVELOPMENT, GOBP_EMBRYONIC_ORGAN_DEVELOPMENT, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN

GO Biological Process (5): iron-sulfur cluster assembly (GO:0016226), [2Fe-2S] cluster assembly (GO:0044571), protein complex oligomerization (GO:0051259), primitive hemopoiesis (GO:0060215), primitive erythrocyte differentiation (GO:0060319)

GO Molecular Function (6): ATPase activator activity (GO:0001671), identical protein binding (GO:0042802), metal ion binding (GO:0046872), protein-folding chaperone binding (GO:0051087), molecular_function (GO:0003674), protein binding (GO:0005515)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Respiratory electron transport	2
Protein localization	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein binding	2
cytoplasm	2
metallo-sulfur cluster assembly	1
iron-sulfur cluster assembly	1
protein-containing complex assembly	1
embryonic hemopoiesis	1
erythrocyte differentiation	1
primitive hemopoiesis	1
ATP-dependent activity	1
molecular function activator activity	1
cation binding	1
binding	1
nuclear lumen	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2228 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSCB	UQCR10	Q9UDW1	957
HSCB	HSPA9	P30036	908
HSCB	ISCU	Q9H1K1	900
HSCB	NFU1	Q9UMS0	826
HSCB	GLRX5	Q86SX6	825
HSCB	OSBP2	Q969R2	810
HSCB	NFS1	Q9Y697	781
HSCB	LYRM4	Q9HD34	768
HSCB	SDHAF1	A6NFY7	755
HSCB	PMP2	P02689	752
HSCB	LYRM7	Q5U5X0	744
HSCB	CTNNB1	P35222	722
HSCB	HSPA4	P34932	700
HSCB	FXN	Q16595	696
HSCB	ISCA2	Q86U28	669
HSCB	ISCA1	Q9BUE6	669

IntAct

114 interactions, top by confidence:

A	B	Type	Score
HSCB	SDHB	psi-mi:“MI:0407”(direct interaction)	0.820
SDHB	SDHA	psi-mi:“MI:0914”(association)	0.820
HSCB	SDHB	psi-mi:“MI:0915”(physical association)	0.820
HSCB	SDHB	psi-mi:“MI:0914”(association)	0.820
SDHAF1	SDHB	psi-mi:“MI:0914”(association)	0.790
SDHB	SDHAF1	psi-mi:“MI:0914”(association)	0.790
SDHAF1	HSCB	psi-mi:“MI:0407”(direct interaction)	0.750
HSCB	SDHAF1	psi-mi:“MI:0914”(association)	0.750
HSCB	HSPA9	psi-mi:“MI:0914”(association)	0.740
HSCB	HSPA9	psi-mi:“MI:0915”(physical association)	0.740
HSCB	LYRM7	psi-mi:“MI:0915”(physical association)	0.700
AGTRAP	HSCB	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (898): HSCB (Two-hybrid), ISCU (Reconstituted Complex), HSCB (Affinity Capture-Western), HSCB (Affinity Capture-MS), HSCB (Negative Genetic), HSCB (Negative Genetic), LIAS (Negative Genetic), PITRM1 (Positive Genetic), PMPCB (Positive Genetic), TTC4 (Positive Genetic), HSCB (Synthetic Lethality), HSCB (Affinity Capture-MS), FDX1 (Affinity Capture-MS), FDXR (Affinity Capture-MS), SDHAF1 (Affinity Capture-MS)

ESM2 similar proteins: A1A4J8, A5PK26, O35231, O88396, P19686, P19687, P36407, P48760, P97576, Q07617, Q0P5N5, Q15027, Q1JQC5, Q1L5Z9, Q32KL4, Q3SZC1, Q3UY23, Q4G069, Q4R380, Q502I6, Q5R435, Q5R8E4, Q5RA81, Q5U2X2, Q60443, Q6DKK2, Q6PBQ2, Q7SXA9, Q80VP5, Q80Y81, Q80ZX8, Q8BMS4, Q8BUI3, Q8C9A2, Q8CGS5, Q8CI66, Q8IWL3, Q8K2H4, Q8K3A0, Q8NFF5

Diamond homologs: A0KXI7, A1AE64, A1JKQ5, A1RJ55, A1SUI7, A3D574, A4SP10, A4TMV1, A4VNX9, A4WDA8, A4XY40, A4Y7D4, A5F3G7, A6V0V1, A6WNY2, A7FFX4, A7ZPX0, A8A333, A8AD55, A8EXS4, A8GHY0, A8GMI9, A8GR50, A8GVT0, A9L3Q7, A9MHJ7, A9N1X8, A9R815, B0BWJ8, B0KPH9, B1IWD4, B1JRZ1, B1KNI6, B1LNI2, B1XB02, B2K9R4, B2TXV2, B4EZU5, B4T0R9, B4TDB3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
HSCB	“up-regulates activity”	“iron-sulfur cluster”	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 69 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Respiratory electron transport	7	11.7×	3e-04
Aerobic respiration and respiratory electron transport	7	10.9×	3e-04
Organelle biogenesis and maintenance	6	7.0×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

55 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	37
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1272075	NM_172002.5(HSCB):c.259dup (p.Thr87fs)	Pathogenic
1272076	NC_000022.11:g.28741962G>A	Pathogenic
2425696	NC_000022.10:g.(?29130452)(29160933_?)del	Pathogenic
832675	NC_000022.10:g.(?29083875)(30090801_?)del	Pathogenic

SpliceAI

854 predictions. Top by Δscore:

Variant	Effect	Δscore
22:28744705:G:GG	donor_gain	1.0000
22:28745861:TAGCT:T	acceptor_loss	1.0000
22:28745862:A:AG	acceptor_gain	1.0000
22:28745862:A:G	acceptor_loss	1.0000
22:28745863:G:GA	acceptor_gain	1.0000
22:28745863:GCT:G	acceptor_gain	1.0000
22:28745863:GCTA:G	acceptor_gain	1.0000
22:28745863:GCTAA:G	acceptor_gain	1.0000
22:28746016:A:G	donor_gain	1.0000
22:28751239:A:AG	acceptor_gain	1.0000
22:28751240:G:GG	acceptor_gain	1.0000
22:28742328:ACTGG:A	donor_loss	0.9900
22:28742329:CTGGT:C	donor_loss	0.9900
22:28742330:TGGTA:T	donor_loss	0.9900
22:28742332:GTACG:G	donor_loss	0.9900
22:28742333:T:G	donor_loss	0.9900
22:28742398:G:T	donor_gain	0.9900
22:28742402:G:GT	donor_gain	0.9900
22:28742419:G:GT	donor_gain	0.9900
22:28743877:TCCA:T	acceptor_loss	0.9900
22:28743878:CCA:C	acceptor_loss	0.9900
22:28743879:CA:C	acceptor_loss	0.9900
22:28743880:A:AG	acceptor_gain	0.9900
22:28743880:AG:A	acceptor_loss	0.9900
22:28743881:G:GA	acceptor_loss	0.9900
22:28743881:G:GG	acceptor_gain	0.9900
22:28743881:GCA:G	acceptor_gain	0.9900
22:28743881:GCAAC:G	acceptor_gain	0.9900
22:28744613:A:AG	acceptor_gain	0.9900
22:28744614:G:GG	acceptor_gain	0.9900

AlphaMissense

1563 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:28742315:T:C	F74L	0.970
22:28742317:C:A	F74L	0.970
22:28742317:C:G	F74L	0.970
22:28743892:T:C	F83L	0.969
22:28743894:C:A	F83L	0.969
22:28743894:C:G	F83L	0.969
22:28743949:C:G	H102D	0.963
22:28743951:C:A	H102Q	0.949
22:28743951:C:G	H102Q	0.949
22:28743961:T:C	F106L	0.949
22:28743963:C:A	F106L	0.949
22:28743963:C:G	F106L	0.949
22:28744692:A:C	R137S	0.942
22:28744692:A:T	R137S	0.942
22:28744703:T:C	L141P	0.935
22:28744660:G:C	A127P	0.934
22:28743947:T:A	V101D	0.930
22:28744691:G:T	R137I	0.930
22:28744693:G:A	G138R	0.929
22:28744693:G:C	G138R	0.929
22:28744642:T:C	S121P	0.920
22:28744694:G:A	G138E	0.920
22:28745921:T:C	F161L	0.920
22:28745923:C:A	F161L	0.920
22:28745923:C:G	F161L	0.920
22:28744661:C:A	A127D	0.918
22:28744673:T:A	L131H	0.917
22:28743939:G:C	Q98H	0.911
22:28743939:G:T	Q98H	0.911
22:28745865:T:C	L142P	0.911

dbSNP variants (sampled 300 via entrez): RS1000056953 (22:28747439 T>C), RS1000182655 (22:28757744 G>A), RS1000230246 (22:28746925 G>A,T), RS1000335618 (22:28751702 T>A,C), RS1000337552 (22:28752171 C>G,T), RS1000370177 (22:28751874 G>A), RS1000444313 (22:28746644 A>G), RS1000509360 (22:28755403 C>T), RS1000618263 (22:28757353 C>T), RS1000649813 (22:28755168 T>C), RS1000674038 (22:28750832 G>A), RS1000699418 (22:28749987 T>C,G), RS1000702260 (22:28750605 G>A), RS1000714297 (22:28756621 A>G), RS1000721006 (22:28750279 C>A,T)

Disease associations

OMIM: gene MIM:608142 | disease phenotypes: MIM:619523, MIM:114480

GenCC curated gene-disease

Disease	Classification	Inheritance
anemia, sideroblastic, 5	Moderate	Autosomal recessive

Mondo (2): anemia, sideroblastic, 5 (MONDO:0030436), hereditary breast carcinoma (MONDO:0016419)

Orphanet (1): Hereditary breast cancer (Orphanet:227535)

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001903	Anemia
HP:0003621	Juvenile onset
HP:0004828	Refractory anemia with ringed sideroblasts
HP:0004840	Hypochromic microcytic anemia
HP:0031851	Reduced hematocrit

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST000777_4	Esophageal cancer and gastric cancer	1.000000e-08
GCST002553_2	Pancreatic cancer	1.000000e-08
GCST003985_20	Breast size	7.000000e-07
GCST004621_177	Red cell distribution width	8.000000e-18
GCST007095_109	Systolic blood pressure	3.000000e-07
GCST007095_110	Systolic blood pressure	3.000000e-07
GCST007098_11	Diastolic blood pressure	1.000000e-06
GCST007098_12	Diastolic blood pressure	4.000000e-06
GCST007099_176	Systolic blood pressure	3.000000e-08
GCST90000032_17	Myeloproliferative neoplasms	1.000000e-07
GCST90002395_617	Mean platelet volume	3.000000e-09
GCST90020025_1779	Waist-to-hip ratio adjusted for BMI	2.000000e-10
GCST90020027_398	Waist-hip index	1.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0004251	myeloproliferative disorder
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C562840	Breast Cancer, Familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment	3
Valproic Acid	decreases methylation, increases expression	2
aristolochic acid I	increases expression	1
potassium perchlorate	increases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
ICG 001	decreases expression	1
jinfukang	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	increases expression	1
Cisplatin	increases expression	1
Formaldehyde	increases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Sodium Dodecyl Sulfate	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Triiodothyronine	decreases expression	1
Tunicamycin	increases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1
Thapsigargin	increases expression	1

Clinical trials (associated diseases)

10 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00040222	Not specified	COMPLETED	Clinical, Genetic, Behavioral, Laboratory and Epidemiologic Characterization of Individuals and Families at High Risk of Breast/Ovarian Cancer
NCT02557776	Not specified	COMPLETED	Written Genetic Counseling and Mutation Analysis of BRCA1 and BRCA2 to Patients With Breast Cancer
NCT03495544	Not specified	UNKNOWN	Study Estimating Association Between Germline Mutations and PD-L1 Expression in Breast Cancer
NCT03959267	Not specified	COMPLETED	Testing a Culturally Adapted Telephone Genetic Counseling Intervention
NCT04058418	Not specified	COMPLETED	Specialist Recommendation on FBC (Familial Breast Cancer) Chemoprevention Prescribing
NCT04125914	Not specified	ACTIVE_NOT_RECRUITING	Weight Management and Health Behavior Intervention in Lowering Cancer Risk for BRCA Positive and Lynch Syndrome Families
NCT04169542	Not specified	RECRUITING	Impact of COVID-19 Pandemic on Out-of-Pocket Costs, Lost Wages, and Unemployment in Patients With Breast Cancer Undergoing Breast Surgery
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT07292246	Not specified	RECRUITING	A Prospective CohorT Study of HandX - Assisted ENdoscopic MAstectomy: Feasibility and Safety (ATHENA I Study)
NCT07307664	Not specified	RECRUITING	Increasing Germline Genetic Testing for Patients With Cancer