HNRNPA1

heterogeneous nuclear ribonucleoprotein A1, the group of Heterogeneous nuclear ribonucleoproteins|RNA binding motif containing|Spliceosomal A complex

Basic information

Region (hg38): 12:54280192-54287088

Previous symbols: [ "HNRPA1" ]

Links

ENSG00000135486 ∙ NCBI:3178 ∙ OMIM:164017 ∙ HGNC:5031 ∙ Uniprot:P09651 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3 (Strong), mode of inheritance: AD
• amyotrophic lateral sclerosis type 20 (Strong), mode of inheritance: AD
• amyotrophic lateral sclerosis (Supportive), mode of inheritance: AD
• inclusion body myopathy with Paget disease of bone and frontotemporal dementia (Supportive), mode of inheritance: AD
• amyotrophic lateral sclerosis type 20 (Strong), mode of inheritance: AD
• inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Amyotrophic lateral sclerosis 20; Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3; Myopathy, distal, 3	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	20116073; 23455423; 34722876

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HNRNPA1 gene.

• not provided (41 variants)
• Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3 (4 variants)
• HNRNPA1-related condition (2 variants)
• Amyotrophic lateral sclerosis type 20 (2 variants)
• Inborn genetic diseases (2 variants)
• Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3;Amyotrophic lateral sclerosis type 20 (1 variants)
• Chronic progressive multiple sclerosis (1 variants)
• not specified (1 variants)
• HNRNPA1-related multisystem proteinopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HNRNPA1 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				8	1	9
missense		3	21	1		25
nonsense			1			1
start loss						0
frameshift			3			3
inframe indel			1		1	2
splice donor/acceptor (+/-2bp)				1		1
splice region					1	1
non coding				1	5	6
Total	0	3	26	11	7

Variants in HNRNPA1

This is a list of pathogenic ClinVar variants found in the HNRNPA1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-54280451-A-G			Benign (Jun 19, 2021)
12-54280818-C-T			Uncertain significance (May 13, 2022)
12-54280829-T-C			Benign (Dec 31, 2019)
12-54281329-G-A			Benign (May 12, 2021)
12-54281394-A-G			Likely benign (Sep 28, 2017)
12-54281460-G-A			Likely benign (Dec 20, 2018)
12-54281496-C-CT			Uncertain significance (Oct 01, 2019)
12-54281778-A-G		not specified	Benign (-)
12-54281875-T-C		HNRNPA1-related disorder	Likely benign (Aug 16, 2021)
12-54281897-GTGGA-G		Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3	Uncertain significance (Jan 03, 2022)
12-54281950-G-A		HNRNPA1-related disorder	Likely benign (Sep 01, 2023)
12-54281951-T-G		HNRNPA1-related disorder	Likely benign (Jun 25, 2019)
12-54282245-A-G		HNRNPA1-related disorder	Likely benign (Aug 18, 2020)
12-54282257-C-T		HNRNPA1-related disorder	Likely benign (Dec 16, 2022)
12-54282272-C-T		HNRNPA1-related disorder	Likely benign (Feb 26, 2019)
12-54282296-T-C			Likely benign (Jul 07, 2018)
12-54282381-G-GT		Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3;Amyotrophic lateral sclerosis type 20	Likely benign (Aug 24, 2021)
12-54282410-T-G			Likely benign (Jun 01, 2020)
12-54282415-A-T			Uncertain significance (Apr 01, 2019)
12-54282449-A-G			Benign/Likely benign (Apr 01, 2024)
12-54282491-G-C			Uncertain significance (Feb 01, 2024)
12-54282586-T-C			Likely benign (May 18, 2018)
12-54282619-C-T			Likely benign (Dec 31, 2019)
12-54282620-G-A			Likely benign (Dec 31, 2019)
12-54282628-T-C		HNRNPA1-related disorder	Likely benign (Aug 19, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HNRNPA1	protein_coding	protein_coding	ENST00000340913	10	6896

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000888	124728	0	1	124729	0.00000401

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.82	94	209	0.450	0.0000102	2439
Missense in Polyphen		6	42.627	0.14076		619
Synonymous	-1.19	87	74.0	1.18	0.00000373	700
Loss of Function	4.18	0	20.3	0.00	0.00000105	248

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000258	0.0000646
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and may modulate splice site selection (PubMed:17371836). May bind to specific miRNA hairpins (PubMed:28431233). {ECO:0000269|PubMed:17371836, ECO:0000269|PubMed:28431233}.
• Disease: DISEASE: Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3 (IBMPFD3) [MIM:615424]: 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.; DISEASE: Amyotrophic lateral sclerosis 20 (ALS20) [MIM:615426]: A neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5- 10% of the cases. {ECO:0000269|PubMed:23455423, ECO:0000269|PubMed:27694260}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Spliceosome - Homo sapiens (human);mRNA Processing;FGFR2 alternative splicing;Signaling by FGFR2;Signal Transduction;Signaling by FGFR;Metabolism of RNA;mRNA Splicing - Major Pathway;EGFR1;Coregulation of Androgen receptor activity;IL6;Signaling by Receptor Tyrosine Kinases;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Intolerance Scores

• loftool: 0.220
• rvis_EVS: -0.19
• rvis_percentile_EVS: 39.68

Haploinsufficiency Scores

• pHI: 0.806
• hipred: Y
• hipred_score: 0.712
• ghis: 0.655

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.997

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Hnrnpa1
• Phenotype: growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); digestive/alimentary phenotype; renal/urinary system phenotype

Gene ontology

• Biological process: regulation of alternative mRNA splicing, via spliceosome;mRNA splicing, via spliceosome;RNA export from nucleus;fibroblast growth factor receptor signaling pathway;viral process;RNA metabolic process;negative regulation of telomere maintenance via telomerase;positive regulation of telomere maintenance via telomerase;cellular response to glucose starvation;mRNA transport;nuclear export;import into nucleus;cellular response to sodium arsenite
• Cellular component: nucleus;nucleoplasm;spliceosomal complex;cytoplasm;membrane;extracellular exosome;catalytic step 2 spliceosome;ribonucleoprotein complex
• Molecular function: single-stranded DNA binding;RNA binding;single-stranded RNA binding;mRNA binding;protein binding;protein domain specific binding;miRNA binding;pre-mRNA binding;telomeric repeat-containing RNA binding;G-rich strand telomeric DNA binding