STEAP3

STEAP3 metalloreductase, the group of STEAP family

Basic information

Region (hg38): 2:119223830-119265652

Links

ENSG00000115107 ∙ NCBI:55240 ∙ OMIM:609671 ∙ HGNC:24592 ∙ Uniprot:Q658P3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• severe congenital hypochromic anemia with ringed sideroblasts (Moderate), mode of inheritance: AD
• severe congenital hypochromic anemia with ringed sideroblasts (Limited), mode of inheritance: AD
• severe congenital hypochromic anemia with ringed sideroblasts (Supportive), mode of inheritance: Unknown
• severe congenital hypochromic anemia with ringed sideroblasts (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypochromic microcytic anemia with iron overload 2	AD	Endocrine; Hematologic	Individuals have been described with transfusion-dependent anemia; The condition may involve primary endocrine anomalies, and surveillance for involvement (eg, adrenal failure or thyroid insufficiency) may benefit medical management	Endocrine; Hematologic	22031863

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the STEAP3 gene.

• not provided (47 variants)
• Inborn genetic diseases (28 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the STEAP3 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				7	7	14
missense			33	12	4	49
nonsense				1		1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					2	2
non coding				2	1	3
Total	0	0	33	22	12

Variants in STEAP3

This is a list of pathogenic ClinVar variants found in the STEAP3 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-119231022-C-A		not specified	Uncertain significance (Jan 06, 2023)
2-119245509-A-G			Likely benign (May 03, 2023)
2-119245512-G-T		not specified	Uncertain significance (Feb 05, 2024)
2-119245547-C-T			Likely benign (Oct 01, 2023)
2-119245571-C-T		STEAP3-related disorder	Likely benign (Aug 07, 2023)
2-119245572-G-A			Likely benign (Sep 01, 2022)
2-119245595-C-T			Likely benign (Nov 12, 2023)
2-119245617-C-T		not specified	Uncertain significance (Dec 13, 2022)
2-119245618-G-A		not specified	Uncertain significance (Jul 20, 2022)
2-119245670-C-A		not specified	Uncertain significance (Jan 19, 2022)
2-119245683-C-T		not specified	Uncertain significance (Oct 27, 2022)
2-119245711-C-A		not specified	Uncertain significance (Jul 06, 2021)
2-119245720-C-T		not specified	Uncertain significance (Sep 29, 2022)
2-119245726-A-G		not specified	Uncertain significance (Dec 05, 2023)
2-119245747-C-T		not specified	Uncertain significance (Jun 07, 2023)
2-119245748-G-A			Benign (Feb 16, 2023)
2-119245796-C-A		Severe congenital hypochromic anemia with ringed sideroblasts	Pathogenic (Dec 15, 2011)
2-119245817-G-A		STEAP3-related disorder	Likely benign (Jan 13, 2020)
2-119245845-C-G		not specified	Uncertain significance (Sep 29, 2022)
2-119245873-G-A		not specified	Uncertain significance (Nov 12, 2021)
2-119245887-G-A		not specified	Uncertain significance (May 23, 2023)
2-119245902-C-A		not specified	Uncertain significance (Dec 06, 2022)
2-119245936-A-G		not specified	Uncertain significance (Jan 23, 2023)
2-119245988-G-C			Uncertain significance (Jan 25, 2024)
2-119247675-G-A		STEAP3-related disorder	Benign/Likely benign (Sep 05, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
STEAP3	protein_coding	protein_coding	ENST00000393110	5	41845

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.32e-9	0.229	125609	1	138	125748	0.000553

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.224	330	319	1.04	0.0000219	3176
Missense in Polyphen		147	135.66	1.0836		1350
Synonymous	-0.162	154	151	1.02	0.0000111	1081
Loss of Function	0.524	14	16.3	0.860	6.99e-7	180

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000583	0.000579
Ashkenazi Jewish	0.00	0.00
East Asian	0.00376	0.00376
Finnish	0.000572	0.000508
European (Non-Finnish)	0.000256	0.000255
Middle Eastern	0.00376	0.00376
South Asian	0.000491	0.000490
Other	0.000656	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Endosomal ferrireductase required for efficient transferrin-dependent iron uptake in erythroid cells. Participates in erythroid iron homeostasis by reducing Fe(3+) to Fe(2+). Can also reduce of Cu(2+) to Cu(1+), suggesting that it participates in copper homeostasis. Uses NADP(+) as acceptor. May play a role downstream of p53/TP53 to interface apoptosis and cell cycle progression. Indirectly involved in exosome secretion by facilitating the secretion of proteins such as TCTP. {ECO:0000269|PubMed:15319436, ECO:0000269|PubMed:16651434}.
• Disease: DISEASE: Anemia, hypochromic microcytic, with iron overload 2 (AHMIO2) [MIM:615234]: A hematologic disease characterized by abnormal hemoglobin content in the erythrocytes which are reduced in size, severe anemia, erythropoietic hyperplasia of bone marrow, massive hepatic iron deposition, and hepatosplenomegaly. {ECO:0000269|PubMed:22031863}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: p53 signaling pathway - Homo sapiens (human);Ferroptosis - Homo sapiens (human);Iron metabolism in placenta;Copper homeostasis;TP53 Regulates Transcription of Cell Death Genes;Gene expression (Transcription);Transferrin endocytosis and recycling;Generic Transcription Pathway;TP53 Regulates Transcription of Cell Death Genes;RNA Polymerase II Transcription;Transport of small molecules;TP53 Regulates Transcription of Genes Involved in Cytochrome C Release;Transcriptional Regulation by TP53;Direct p53 effectors;Iron uptake and transport (Consensus)

Intolerance Scores

• loftool: 0.151
• rvis_EVS: -0.1
• rvis_percentile_EVS: 45.65

Haploinsufficiency Scores

• pHI: 0.210
• hipred: N
• hipred_score: 0.486
• ghis: 0.425

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.788

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Steap3
• Phenotype: homeostasis/metabolism 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; liver/biliary system phenotype; immune system phenotype

Gene ontology

• Biological process: apoptotic process;cell cycle;protein secretion;copper ion import;transferrin transport;regulation of apoptotic process;iron ion homeostasis;oxidation-reduction process;iron ion import across cell outer membrane
• Cellular component: cytoplasm;endosome;multivesicular body;plasma membrane;endosome membrane;integral component of membrane
• Molecular function: protein binding;cupric reductase activity;oxidoreductase activity, oxidizing metal ions, NAD or NADP as acceptor;metal ion binding;ferric-chelate reductase (NADPH) activity