HNRNPA2B1

Chr 7AD

heterogeneous nuclear ribonucleoprotein A2/B1

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

NCBI Gene: 3181ENSG00000122566UniProt: P22626OMIM: 600124

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.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.222 OMIM phenotypes
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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ClinVar Variants
37 unique Pathogenic / Likely Pathogenic· 110 VUS of 472 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — HNRNPA2B1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

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
DN
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.

ClinVar Variant Classifications

472 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic6
VUS110
Likely Benign266
Benign28
Conflicting3
31
Pathogenic
6
Likely Pathogenic
110
VUS
266
Likely Benign
28
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
27
0
31
Likely Pathogenic
0
2
4
0
6
VUS
8
69
31
2
110
Likely Benign
0
3
159
104
266
Benign
0
0
25
3
28
Conflicting
—3
Total1175246109444

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HNRNPA2B1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Interleukin enhancer binding factor 3 exacerbates cardiac inflammation and injury following myocardial infarction by inhibiting Lys48-linked ubiquitination on HNRNPA2B1 in macrophages.
Zhang X et al.·Cell Mol Immunol
2026
Exosomal hnRNPA2B1 suppresses irinotecan-induced ferroptosis in pancreatic cancer.
Zhou XL et al.·Hepatobiliary Pancreat Dis Int
2026
LncRNA 4930544M13Rik-201 regulates CACNA2D1 expression via interacting with hnRNPA2B1 to promote neuropathic pain following nerve injury.
Fang Z et al.·Brain Res Bull
2026
Ligand-specific conformational dynamics and interaction landscapes of hnRNPA2B1 reveal a structural basis for its functional regulation.
Zhou Z et al.·Curr Res Struct Biol
2026Open AccessFunctional
Mechanistic studies on HNRNPA2B1 suggest binding but not selective recognition of m6A.
Park R et al.·RNA Biol
2026Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients