HNRNPC

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

Basic information

Region (hg38): 14:21209136-21269494

Previous symbols: [ "HNRPC" ]

Links

ENSG00000092199

∙ NCBI:3183 ∙ OMIM:164020 ∙ HGNC:5035 ∙ Uniprot:P07910 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 74	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	Craniofacial; Neurologic	37541189

ClinVar

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

Inborn_genetic_diseases (17 variants)
not_provided (11 variants)
Intellectual_developmental_disorder,_autosomal_dominant_74 (3 variants)
HNRNPC-related_condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HNRNPC gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004500.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous						0
missense	1 clinvar		23 clinvar	1 clinvar		25
nonsense						0
start loss						0
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)						0
Total	2	0	24	1	0

Highest pathogenic variant AF is 0.00000657445

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HNRNPC	protein_coding	protein_coding	ENST00000320084	7	60359

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.978	0.0223	125231	0	17	125248	0.0000679

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.89	70	179	0.391	0.0000103	2007
Missense in Polyphen		5	34.403	0.14534		491
Synonymous	-1.06	74	63.3	1.17	0.00000350	572
Loss of Function	3.48	1	16.1	0.0622	9.62e-7	185

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000579	0.000577
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000441	0.0000441
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000493	0.000492

dbNSFP

Source: dbNSFP

Function: FUNCTION: Binds pre-mRNA and nucleates the assembly of 40S hnRNP particles (PubMed:8264621). Interacts with poly-U tracts in the 3'-UTR or 5'-UTR of mRNA and modulates the stability and the level of translation of bound mRNA molecules (PubMed:12509468, PubMed:16010978, PubMed:7567451, PubMed:8264621). Single HNRNPC tetramers bind 230-240 nucleotides. Trimers of HNRNPC tetramers bind 700 nucleotides (PubMed:8264621). May play a role in the early steps of spliceosome assembly and pre-mRNA splicing. N6- methyladenosine (m6A) has been shown to alter the local structure in mRNAs and long non-coding RNAs (lncRNAs) via a mechanism named 'm(6)A-switch', facilitating binding of HNRNPC, leading to regulation of mRNA splicing (PubMed:25719671). {ECO:0000269|PubMed:12509468, ECO:0000269|PubMed:16010978, ECO:0000269|PubMed:25719671, ECO:0000269|PubMed:7567451, ECO:0000269|PubMed:8264621}.;
Pathway: Spliceosome - Homo sapiens (human);mRNA Processing;SUMOylation of RNA binding proteins;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;Metabolism of RNA;mRNA Splicing - Major Pathway;SUMOylation;Regulation of Telomerase;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

pRec: 0.281

Intolerance Scores

loftool: 0.379
rvis_EVS: -0.08
rvis_percentile_EVS: 47.79

Haploinsufficiency Scores

pHI: 0.162
hipred: N
hipred_score: 0.380
ghis: 0.523

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: N
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.995

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Hnrnpc
Phenotype: embryo phenotype; 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);

Gene ontology

Biological process: mRNA splicing, via spliceosome;osteoblast differentiation;RNA splicing;RNA metabolic process;negative regulation of telomere maintenance via telomerase;ATP-dependent chromatin remodeling;3'-UTR-mediated mRNA stabilization
Cellular component: nuclear chromatin;extracellular region;nucleus;nucleoplasm;spliceosomal complex;telomerase holoenzyme complex;cytosol;actin cytoskeleton;membrane;protein-containing complex;extracellular exosome;catalytic step 2 spliceosome
Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;RNA binding;mRNA 3'-UTR binding;protein binding;poly(U) RNA binding;nucleosomal DNA binding;identical protein binding;telomerase RNA binding;N6-methyladenosine-containing RNA binding