HNRNPA2B1

Chr 7AD

heterogeneous nuclear ribonucleoprotein A2/B1

Also known as: HNRNPA2, HNRNPB1, HNRPA2, HNRPA2B1, HNRPB1, IBMPFD2, OPDM2, OPMD2

This protein binds RNA and packages nascent pre-mRNAs into ribonucleoprotein particles, regulates mRNA splicing and transport, and processes microRNAs by recognizing methylated adenosine marks. Mutations cause autosomal dominant inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia, and oculopharyngeal muscular dystrophy. The pathogenic mechanism involves loss of function of this highly constrained protein.

Summary from RefSeq, OMIM, UniProt, Mechanism

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Primary Disease Associations & Inheritance

?Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2MIM #615422

Oculopharyngeal muscular dystrophy 2MIM #620460

Active trials

Pubs (1 yr)

P/LP submissions

—

P/LP missense

0.22

LOEUF· LoF intol.

LOF

Mechanism· predicted

Clinical Summary— HNRNPA2B1

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Gene-Disease Validity (ClinGen)

inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 · ADModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint

0.22LOEUF

pLI 0.997

Z-score 4.13

OE 0.05 (0.01–0.22)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint

3.00Z-score

OE missense 0.39 (0.32–0.47)

75 obs / 192.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios

LoF OE0.05 (0.01–0.22)

0≤0.351.4

Missense OE0.39 (0.32–0.47)

0≤0.61.4

Synonymous OE1.86

0≤1.21.6

LoF obs/exp: 1 / 21.8Missense obs/exp: 75 / 192.1Syn Z: -5.37

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongHNRNPA2B1-related early-onset oculopharyngeal muscular dystrophyOTHERAD

0.4289th %ile

GOF

0.3293th %ile

LOF

0.78top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.22

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.