HNRNPK

Chr 9AD

heterogeneous nuclear ribonucleoprotein K

Also known as: AUKS, CSBP, HNRPK, TUNP

NCBI Gene: 3190 ENSG00000165119 UniProt: P61978 OMIM: 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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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 is located in the nucleoplasm and has three repeats of KH domains that binds to RNAs. It is distinct among other hnRNP proteins in its binding preference; it binds tenaciously to poly(C). This protein is also thought to have a role during cell cycle progession. Several alternatively spliced transcript variants have been described for this gene, however, not all of them are fully characterized. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Au-Kline syndromeMIM #616580

Clinical highlights

Gene-disease validity (ClinGen)

neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

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P/LP missense

0.10

LOEUF· LoF intol.

LOF

Mechanism· G2P

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GeneReview available — HNRNPK