HNRNPC

protein-coding

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

Gene summary

This gene belongs to the subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene can act as a tetramer and is involved in the assembly of 40S hnRNP particles. Multiple transcript variants encoding at least two different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

HNRPC

MANE transcript

NM_004500.4

Inheritance

ClinVar variants

P:2U:49B:2

Top phenotype

Intellectual developmental disorder, autosomal dominant 74

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr14:21,209,136-21,269,494

External References & Databases

Ensembl (ENSG00000092199)

Transcript & Mutation Effects

hg38 • Region Span ~60.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder, autosomal dominant 74STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0958203

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Intellectual developmental disorder, autosomal dominant 74AD

Manifestation: Craniofacial; Neurologic

Intervention: General

Rationale: 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

Refs: 37541189

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HNRNPC variants in ClinVar

4 Conditions Cataloged

Inborn genetic diseasesTotal: 20

not providedTotal: 18

Intellectual developmental disorder, autosomal dominant 74Total: 4

HNRNPC-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004500.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar			1
missense	1 clinvar		36 clinvar	2 clinvar		39
nonsense						0
start loss						0
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)			11 clinvar			11
Total	2	0	49	2	0	53

Highest pathogenic variant AF is 0.000006574449

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 258 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004500.4	RefSeq	NP_004491.2	7	MANE Select
ENST00000553300.6	Ensembl	ENSP00000450544.1	7	MANE Select
NM_001077442.2	RefSeq	NP_001070910.1	7	Standard
NM_001077443.2	RefSeq	NP_001070911.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Spliceosome - Homo sapiens (human)
mRNA Processing
SUMOylation of RNA binding proteins
Post-translational protein modification
SUMO E3 ligases SUMOylate target proteins

Biological Process

mRNA splicing, via spliceosome
osteoblast differentiation
RNA splicing
RNA metabolic process
negative regulation of telomere maintenance via telomerase

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

Cellular Component

nuclear chromatin
extracellular region
nucleus
nucleoplasm
spliceosomal complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000320084
Coding exons: 7
Length: 60359
Individuals with no LoFs: 125231
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125248
p: 0.0000679

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.89	70	179	0.391	0.0000103	2007
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00058	0.00058	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000044	0.000044	rare
South Asian	0	0.0	absent
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.281

Intolerance Scores

LoFtool: 0.379
RVIS EVS: -0.08
RVIS percentile EVS: 47.79

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.995

Gene Damage Prediction

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