HNRNPC

Chr 14AD

heterogeneous nuclear ribonucleoprotein C

Also known as: HNRNP, HNRPC, MRD74, SNRPC

NCBI Gene: 3183ENSG00000092199UniProt: P07910

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]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 74MIM #620688
AD
1
Active trials
36
Pathogenic / LP
85
ClinVar variants
78
Pubs (1 yr)
2.9
Missense Z
0.29
LOEUF· LoF intolerant
Clinical Summary— HNRNPC
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
36 Pathogenic / Likely Pathogenic· 48 VUS of 85 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

pubtator: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.29LOEUF
pLI 0.978
Z-score 3.48
OE 0.06 (0.02–0.29)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.89Z-score
OE missense 0.39 (0.32–0.48)
70 obs / 179.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.06 (0.02–0.29)
0≤0.351.4
Missense OE0.39 (0.32–0.48)
0≤0.61.4
Synonymous OE1.17
0≤1.21.6
LoF obs/exp: 1 / 16.1Missense obs/exp: 70 / 179.0Syn Z: -1.06
LOF
DN
0.2798th %ile
GOF
0.2895th %ile
LOF
0.85top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.29

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

85 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic4
VUS48
Likely Benign1
32
Pathogenic
4
Likely Pathogenic
48
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
30
0
32
Likely Pathogenic
0
0
4
0
4
VUS
1
25
22
0
48
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total22756085

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

View in ClinVar →

HNRNPC · protein map & ClinVar variants

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

Clinical Literature
Landmark / reviewRecent case evidence
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
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