STEAP2

protein-coding

STEAP2 metalloreductase, the group of STEAP family

Gene summary

This gene is a member of the STEAP family and encodes a multi-pass membrane protein that localizes to the Golgi complex, the plasma membrane, and the vesicular tubular structures in the cytosol. A highly similar protein in mouse has both ferrireductase and cupric reductase activity, and stimulates the cellular uptake of both iron and copper in vitro. Increased transcriptional expression of the human gene is associated with prostate cancer progression. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

Previous symbols:

PCANAP1

MANE transcript

NM_001244944.2

Inheritance

—

ClinVar variants

U:62B:6

Top phenotype

STEAP2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr7:90,167,590-90,238,137

External References & Databases

Ensembl (ENSG00000157214)

Transcript & Mutation Effects

hg38 • Region Span ~70.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to STEAP2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 58

STEAP2-related disorderTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001244944.2. 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			2 clinvar	3 clinvar		5
missense			59 clinvar	2 clinvar	1 clinvar	62
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	62	5	1	68

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 66 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001244944.2	RefSeq	NP_001231873.1	4	MANE Select
ENST00000394621.7	Ensembl	ENSP00000378119.2	4	MANE Select
NM_001040665.2	RefSeq	NP_001035755.1	4	Standard
NM_001040666.2	RefSeq	NP_001035756.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mineral absorption - Homo sapiens (human)
Copper homeostasis
Transferrin endocytosis and recycling
Transport of small molecules
Iron uptake and transport

Biological Process

Golgi to plasma membrane transport
endocytosis
response to hormone
copper ion import
regulated exocytosis

Molecular Function

transporter activity
cupric reductase activity
metal ion binding
ferric-chelate reductase (NADPH) activity

Cellular Component

endosome
early endosome
cytosol
plasma membrane
endosome membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000287908
Coding exons: 4
Length: 70548
Individuals with no LoFs: 125607
Homozygous LoFs: 0
Heterozygous LoFs: 134
Defined: 125741
p: 0.000533

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.753	223	257	0.868	0.0000123	3187
Missense (PolyPhen)		51	66.153	0.77094		839
Synonymous	2.22	64	91.0	0.703	0.00000436	963
Loss of Function	1.68	14	22.6	0.619	0.00000149	246

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00035	0.00035	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00022	0.00022	rare
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00082	0.00082	rare
South Asian	0.00039	0.00039	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Metalloreductase that has the ability to reduce both Fe(3+) to Fe(2+) and Cu(2+) to Cu(1+). Uses NAD(+) as acceptor (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.345
RVIS EVS: 0.51
RVIS percentile EVS: 80.1

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.140

Gene Damage Prediction

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