HNRNPA2B1

heterogeneous nuclear ribonucleoprotein A2/B1, the group of RNA binding motif containing|Heterogeneous nuclear ribonucleoproteins

Basic information

Region (hg38): 7:26171150-26201529

Previous symbols: [ "HNRPA2B1" ]

Links

ENSG00000122566 ∙ NCBI:3181 ∙ OMIM:600124 ∙ HGNC:5033 ∙ Uniprot:P22626 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• amyotrophic lateral sclerosis (Moderate), mode of inheritance: AD
• inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 (Strong), mode of inheritance: AD
• inclusion body myopathy with Paget disease of bone and frontotemporal dementia (Supportive), mode of inheritance: AD
• inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 (Limited), mode of inheritance: AD
• amyotrophic lateral sclerosis (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2; Oculopharyngeal muscular dystrophy 2	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal; Neurologic	23455423; 35484142

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HNRNPA2B1 gene.

• Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 (218 variants)
• not provided (54 variants)
• Inborn genetic diseases (12 variants)
• not specified (5 variants)
• HNRNPA2B1-related condition (2 variants)
• Keratoconus (1 variants)
• Frontotemporal dementia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HNRNPA2B1 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			1	65	5	71
missense		2	30	1		33
nonsense						0
start loss						0
frameshift			4			4
inframe indel			7			7
splice donor/acceptor (+/-2bp)						0
splice region			11	10	4	25
non coding			14	101	20	135
Total	0	2	56	167	25

Variants in HNRNPA2B1

This is a list of pathogenic ClinVar variants found in the HNRNPA2B1 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-26177970-G-A		not specified	Uncertain significance (Apr 10, 2023)
7-26177976-G-T		not specified	Uncertain significance (Oct 25, 2022)
7-26178021-G-C		not specified	Uncertain significance (Sep 01, 2021)
7-26178073-C-T		not specified	Uncertain significance (Nov 09, 2023)
7-26183702-G-C		not specified	Uncertain significance (Dec 21, 2022)
7-26183723-C-T		not specified	Uncertain significance (Mar 29, 2022)
7-26183735-T-C		not specified	Uncertain significance (Oct 18, 2021)
7-26183746-T-C		not specified	Likely benign (Dec 15, 2023)
7-26183761-T-C		not specified	Uncertain significance (Sep 26, 2023)
7-26184594-C-G		not specified	Uncertain significance (Apr 19, 2023)
7-26184630-A-G		Keratoconus	Likely benign (Nov 01, 2022)
7-26184767-C-T		not specified	Uncertain significance (Jan 04, 2024)
7-26184801-T-C		not specified	Uncertain significance (Aug 12, 2021)
7-26184819-A-C		not specified	Uncertain significance (Sep 17, 2021)
7-26184827-A-C		not specified	Uncertain significance (Dec 17, 2023)
7-26184842-T-C		not specified	Uncertain significance (Jan 24, 2024)
7-26184880-A-C		not specified	Uncertain significance (Dec 08, 2023)
7-26184891-C-G		not specified	Uncertain significance (Dec 17, 2023)
7-26184918-A-C		not specified	Uncertain significance (Dec 19, 2023)
7-26185029-A-T		not specified	Uncertain significance (Jun 21, 2022)
7-26185041-G-T		not specified	Uncertain significance (Dec 13, 2023)
7-26185047-G-A		not specified	Uncertain significance (Nov 06, 2023)
7-26185068-C-A		not specified	Uncertain significance (Sep 07, 2022)
7-26185112-C-T		not specified	Uncertain significance (Nov 08, 2022)
7-26185116-G-A		not specified	Uncertain significance (May 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HNRNPA2B1	protein_coding	protein_coding	ENST00000354667	11	11603

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00268	125567	0	2	125569	0.00000796

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.00	75	192	0.390	0.00000925	2284
Missense in Polyphen		8	28.353	0.28216		383
Synonymous	-5.37	118	63.6	1.86	0.00000330	651
Loss of Function	4.13	1	21.8	0.0459	0.00000100	291

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.00000882	0.00000880
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Heterogeneous nuclear ribonucleoprotein (hnRNP) that associates with nascent pre-mRNAs, packaging them into hnRNP particles. The hnRNP particle arrangement on nascent hnRNA is non- random and sequence-dependent and serves to condense and stabilize the transcripts and minimize tangling and knotting. Packaging plays a role in various processes such as transcription, pre-mRNA processing, RNA nuclear export, subcellular location, mRNA translation and stability of mature mRNAs (PubMed:19099192). Forms hnRNP particles with at least 20 other different hnRNP and heterogeneous nuclear RNA in the nucleus. Involved in transport of specific mRNAs to the cytoplasm in oligodendrocytes and neurons: acts by specifically recognizing and binding the A2RE (21 nucleotide hnRNP A2 response element) or the A2RE11 (derivative 11 nucleotide oligonucleotide) sequence motifs present on some mRNAs, and promotes their transport to the cytoplasm (PubMed:10567417). Specifically binds single-stranded telomeric DNA sequences, protecting telomeric DNA repeat against endonuclease digestion (By similarity). Also binds other RNA molecules, such as primary miRNA (pri-miRNAs): acts as a nuclear 'reader' of the N6-methyladenosine (m6A) mark by specifically recognizing and binding a subset of nuclear m6A-containing pri-miRNAs. Binding to m6A-containing pri- miRNAs promotes pri-miRNA processing by enhancing binding of DGCR8 to pri-miRNA transcripts (PubMed:26321680). Involved in miRNA sorting into exosomes following sumoylation, possibly by binding (m6A)-containing pre-miRNAs (PubMed:24356509). Acts as a regulator of efficiency of mRNA splicing, possibly by binding to m6A- containing pre-mRNAs (PubMed:26321680). {ECO:0000250|UniProtKB:A7VJC2, ECO:0000269|PubMed:10567417, ECO:0000269|PubMed:24356509, ECO:0000269|PubMed:26321680, ECO:0000303|PubMed:19099192}.
• Disease: DISEASE: Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 (IBMPFD2) [MIM:615422]: An autosomal dominant disease characterized by disabling muscle weakness clinically resembling to limb girdle muscular dystrophy, osteolytic bone lesions consistent with Paget disease, and premature frontotemporal dementia. Clinical features show incomplete penetrance. {ECO:0000269|PubMed:23455423}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation;mRNA Processing;Metabolism of RNA;mRNA Splicing - Major Pathway;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

• pRec: 0.230

Intolerance Scores

• loftool: 0.121
• rvis_EVS: -0.23
• rvis_percentile_EVS: 36.86

Haploinsufficiency Scores

• pHI: 0.795
• hipred: Y
• hipred_score: 0.793
• ghis: 0.692

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: N
• gene_indispensability_score: 0.333

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hnrnpa2b1

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;mRNA splicing, via spliceosome;mRNA processing;mRNA export from nucleus;RNA metabolic process;primary miRNA processing;interleukin-12-mediated signaling pathway;G-quadruplex DNA unwinding;negative regulation of mRNA splicing, via spliceosome;RNA transport;positive regulation of telomere maintenance via telomere lengthening;positive regulation of telomerase RNA reverse transcriptase activity;miRNA transport
• Cellular component: chromosome, telomeric region;nucleus;nucleoplasm;spliceosomal complex;cytoplasm;Cajal body;membrane;nuclear matrix;extracellular exosome;catalytic step 2 spliceosome;ribonucleoprotein complex
• Molecular function: RNA binding;mRNA binding;mRNA 3'-UTR binding;protein binding;miRNA binding;single-stranded telomeric DNA binding;pre-mRNA intronic binding;G-rich strand telomeric DNA binding;N6-methyladenosine-containing RNA binding