HNRNPH1

Chr 5AD

heterogeneous nuclear ribonucleoprotein H1

Also known as: HNRPH, HNRPH1, NEDCDS, hnRNPH

NCBI Gene: 3187 ENSG00000169045 UniProt: P31943 OMIM: 601035

HNRNPH1 encodes a heterogeneous nuclear ribonucleoprotein that binds RNA and regulates pre-mRNA alternative splicing, serving as a component of hnRNP complexes that process pre-mRNAs before they become functional cytoplasmic mRNAs. Mutations cause autosomal dominant neurodevelopmental disorder with craniofacial dysmorphism and skeletal defects. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.11), indicating intolerance to reduced gene dosage.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of a subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins that complex with heterogeneous nuclear RNA. 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 may shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has three repeats of quasi-RRM domains that bind to RNA and is very similar to the family member HNRPF. This gene may be associated with hereditary lymphedema type I. Alternatively spliced transcript variants have been described [provided by RefSeq, Mar 2012]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with craniofacial dysmorphism and skeletal defectsMIM #620083

Clinical highlights

Gene-disease validity (ClinGen)

syndromic intellectual disability · 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)

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P/LP submissions

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P/LP missense

0.11

LOEUF· LoF intol.

LOF

Mechanism· G2P