HNRNPK

Chr 9AD

heterogeneous nuclear ribonucleoprotein K

Also known as: AUKS, CSBP, HNRPK, TUNP

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 SummaryHNRNPK
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Gene-Disease Validity (ClinGen)
neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — HNRNPK
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.10LOEUF
pLI 1.000
Z-score 5.15
OE 0.00 (0.000.10)
Highly constrained

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

Missense Constraint
3.99Z-score
OE missense 0.33 (0.280.39)
93 obs / 281.5 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.000.10)
00.351.4
Missense OE0.33 (0.280.39)
00.61.4
Synonymous OE1.16
01.21.6
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 · 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

0 submitted variants 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
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