PCBP2

Chr 12

poly(rC) binding protein 2

Also known as: HNRNPE2, HNRPE2, hnRNP-E2

NCBI Gene: 5094 ENSG00000197111 UniProt: Q15366

The protein encoded by this gene appears to be multifunctional. Along with PCBP-1 and hnRNPK, it is one of the major cellular poly(rC)-binding proteins. The encoded protein contains three K-homologous (KH) domains which may be involved in RNA binding. Together with PCBP-1, this protein also functions as a translational coactivator of poliovirus RNA via a sequence-specific interaction with stem-loop IV of the IRES, promoting poliovirus RNA replication by binding to its 5'-terminal cloverleaf structure. It has also been implicated in translational control of the 15-lipoxygenase mRNA, human papillomavirus type 16 L2 mRNA, and hepatitis A virus RNA. The encoded protein is also suggested to play a part in formation of a sequence-specific alpha-globin mRNP complex which is associated with alpha-globin mRNA stability. This multiexon structural mRNA is thought to be retrotransposed to generate PCBP-1, an intronless gene with functions similar to that of PCBP2. This gene and PCBP-1 have paralogous genes (PCBP3 and PCBP4) which are thought to have arisen as a result of duplication events of entire genes. This gene also has two processed pseudogenes (PCBP2P1 and PCBP2P2). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2018]

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (2)

gnomad: Error: gnomAD API error: 400

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in PCBP2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 520

249 rare PASS variants

Rare truncating (LoF)

1 in 15,000

16 rare PASS variants

Rare synonymous (reference)

1 in 140

234 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PCBP2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 470	1 in 15,000
South Asian	~43k	1 in 370	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 510	≈ 1 in 30,000
European (Finnish)	~27k	1 in 1,000	none seen
Admixed American	~22k	1 in 1,000	≈ 1 in 22,000
African / African American	~21k	1 in 570	≈ 1 in 21,000
East Asian	~20k	1 in 950	none seen
Ashkenazi Jewish	~13k	1 in 1,900	none seen
Middle Eastern	~2,884	≈ 1 in 2,500	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 12 of 14 coding exons well covered in gnomAD exomes; exons 5, 12 marginal. Genomes: all 14.? see exons ↓