HNRNPK

Chr 9AD

heterogeneous nuclear ribonucleoprotein K

Also known as: AUKS, CSBP, HNRPK, TUNP

NCBI Gene: 3190ENSG00000165119UniProt: P61978OMIM: 600712

The protein functions as an RNA-binding protein that complexes with heterogeneous nuclear RNA in the nucleus, influencing pre-mRNA processing and mRNA metabolism, with a distinct binding preference for poly(C) sequences. Loss-of-function mutations cause Au-Kline syndrome, inherited in an autosomal dominant pattern. The gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the disease mechanism.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.101 OMIM phenotype
Clinical Summary— HNRNPK
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Gene-Disease Validity (ClinGen)
neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
109 unique Pathogenic / Likely Pathogenic· 107 VUS of 386 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — HNRNPK
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.10LOEUF
pLI 1.000
Z-score 5.15
OE 0.00 (0.00–0.10)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
3.99Z-score
OE missense 0.33 (0.28–0.39)
93 obs / 281.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.10)
0≤0.351.4
Missense OE0.33 (0.28–0.39)
0≤0.61.4
Synonymous OE1.16
0≤1.21.6
LoF obs/exp: 0 / 30.9Missense obs/exp: 93 / 281.5Syn Z: -1.22
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveHNRNPK-related Au-Kline syndromeLOFAD
DN
0.2598th %ile
GOF
0.2597th %ile
LOF
0.86top 5%

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

LOFprediction above median · 1 literature citation · 43% of P/LP variants are LoF · LOEUF 0.10

Literature Evidence

LOFClinical spectrum of Kabuki-like syndrome caused by HNRNPK haploinsufficiency.PMID:28374925

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

386 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic57
Likely Pathogenic52
VUS107
Likely Benign92
Benign48
Conflicting11
57
Pathogenic
52
Likely Pathogenic
107
VUS
92
Likely Benign
48
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
27
2
28
0
57
Likely Pathogenic
20
24
8
0
52
VUS
3
87
15
2
107
Likely Benign
0
5
47
40
92
Benign
0
1
44
3
48
Conflicting
—11
Total5011914245367

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

View in ClinVar →

Protein Context — Lollipop Plot

HNRNPK · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
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
Long noncoding RNA uc.263/264 cluster facilitates colorectal cancer progression by interacting with hnRNPK and activating The Wnt signaling pathway.
Zhang Y et al.·Biochem Pharmacol
2026
Azoospermia phenotype and scRNA-seq reveal hnRNPK as a factor essential for male germ cell development in mice.
Gao H et al.·Nucleic Acids Res
2026Open Access
DDX1 crotonylation mediates ACOX1 alternative splicing through HNRNPK to increase peroxisomal oxidative damage.
Liu J et al.·Free Radic Biol Med
2026
Prenatal diagnosis of a de novo pathogenic HNRNPK variant in a Chinese fetus with abnormal ultrasound soft markers: a case report.
Zhu Y et al.·Front Genet
2025Open AccessCase report
CircSMEK1 Suppresses HCC via the hnRNPK-IGF2-AKT Axis: A Diagnostic Biomarker and Therapeutic Target.
Guo P et al.·Adv Sci (Weinh)
2025Open Access
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