HNRNPK

heterogeneous nuclear ribonucleoprotein K, the group of Heterogeneous nuclear ribonucleoproteins|MicroRNA protein coding host genes

Basic information

Region (hg38): 9:83968083-83980631

Previous symbols: [ "HNRPK" ]

Links

ENSG00000165119 ∙ NCBI:3190 ∙ OMIM:600712 ∙ HGNC:5044 ∙ Uniprot:P61978 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Au-Kline syndrome (Strong), mode of inheritance: AD
• Au-Kline syndrome (Moderate), mode of inheritance: AD
• Au-Kline syndrome (Strong), mode of inheritance: AD
• Au-Kline syndrome (Strong), mode of inheritance: AD
• Au-Kline syndrome (Supportive), mode of inheritance: AD
• neurodevelopmental disorder-craniofacial dysmorphism-cardiac defect-hip dysplasia syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Au-Kline syndrome	AD	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Musculoskeletal; Neurologic	26173930

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HNRNPK gene.

• Au-Kline syndrome (19 variants)
• not provided (12 variants)
• Inborn genetic diseases (2 variants)
• Intellectual disability (1 variants)
• HNRNPK-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HNRNPK gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	30	4	35
missense	3	15	49	5		72
nonsense	4	4				8
start loss						0
frameshift	15	1				16
inframe indel		3	2	1		6
splice donor/acceptor (+/-2bp)	7	9	2			18
splice region	1	2	9	13	1	26
non coding	1	1	1	21	37	61
Total	30	33	55	57	41

Variants in HNRNPK

This is a list of pathogenic ClinVar variants found in the HNRNPK region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-83969358-A-G			Uncertain significance (Jul 10, 2019)
9-83969432-T-C			Uncertain significance (Jun 10, 2022)
9-83969444-TAAAAG-T			Likely benign (Feb 14, 2023)
9-83969444-T-TAA			Likely benign (Dec 06, 2023)
9-83969454-GA-G			Benign (Jan 20, 2024)
9-83969454-G-GA			Benign (Sep 04, 2023)
9-83969456-A-G			Likely benign (Oct 24, 2022)
9-83969988-A-G			Benign (May 12, 2021)
9-83969995-G-GT			Benign (May 15, 2021)
9-83970155-A-C		Au-Kline syndrome	Conflicting classifications of pathogenicity (Mar 12, 2024)
9-83970161-C-T		Au-Kline syndrome	Pathogenic (Jul 20, 2023)
9-83970164-G-C		Au-Kline syndrome	Uncertain significance (Mar 12, 2021)
9-83970197-G-A			Likely benign (Dec 18, 2023)
9-83970226-G-T			Likely benign (Aug 10, 2023)
9-83970228-TC-T		Intellectual disability	Pathogenic (Oct 16, 2020)
9-83970233-G-A			Likely benign (Dec 19, 2023)
9-83970241-C-T		Au-Kline syndrome	Likely pathogenic (-)
9-83970250-C-A			Likely pathogenic (Oct 23, 2020)
9-83970263-C-T			Likely benign (Jan 12, 2024)
9-83970272-C-T			Likely benign (Aug 09, 2022)
9-83970273-G-T			Pathogenic (Jul 07, 2016)
9-83970282-CG-C			Pathogenic (Apr 17, 2023)
9-83970283-G-A		Au-Kline syndrome	Pathogenic (May 04, 2022)
9-83970287-T-C			Likely benign (Jun 03, 2023)
9-83970298-G-A		Au-Kline syndrome	Uncertain significance (Feb 22, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HNRNPK	protein_coding	protein_coding	ENST00000376263	15	12572

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000171	125435	0	1	125436	0.00000399

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.99	93	281	0.330	0.0000162	3016
Missense in Polyphen		16	72.446	0.22086		945
Synonymous	-1.22	106	91.1	1.16	0.00000521	906
Loss of Function	5.15	0	30.9	0.00	0.00000163	344

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000882	0.00000882
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single- stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction (By similarity). As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest. {ECO:0000250, ECO:0000269|PubMed:16360036, ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:22825850}.
• Disease: DISEASE: Au-Kline syndrome (AUKS) [MIM:616580]: A disorder characterized by intellectual disability, facial dysmorphism, cardiac defects, and connective tissue and skeletal abnormalities. Dysmorphic features include long palpebral fissures, ptosis, a broad prominent nasal bridge, hypoplastic alae nasi, an open downturned mouth, ears with underdeveloped and thick helices, high palate, and a unique tongue with a prominent median crease. Hypotonia, hyporeflexia, and high pain tolerance are additional features. {ECO:0000269|PubMed:26173930}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: MicroRNAs in cancer - Homo sapiens (human);Viral carcinogenesis - Homo sapiens (human);Spliceosome - Homo sapiens (human);Herpes simplex infection - Homo sapiens (human);mRNA Processing;SUMOylation of RNA binding proteins;Post-translational protein modification;SUMO E3 ligases SUMOylate target proteins;Metabolism of proteins;Metabolism of RNA;mRNA Splicing - Major Pathway;BCR;SUMOylation;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

• pRec: 0.673

Intolerance Scores

• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.28

Haploinsufficiency Scores

• pHI: 0.886
• hipred: Y
• hipred_score: 0.756
• ghis: 0.705

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.787

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Hnrnpk

Gene ontology

• Biological process: mRNA splicing, via spliceosome;RNA processing;signal transduction;regulation of low-density lipoprotein particle clearance;viral process;RNA metabolic process;negative regulation of apoptotic process;positive regulation of low-density lipoprotein particle receptor biosynthetic process;positive regulation of transcription by RNA polymerase II;negative regulation of mRNA splicing, via spliceosome;positive regulation of receptor-mediated endocytosis;regulation of lipid transport by positive regulation of transcription from RNA polymerase II promoter;regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
• Cellular component: nuclear chromatin;podosome;nucleus;nucleoplasm;cytoplasm;focal adhesion;cytoplasmic stress granule;membrane;cell projection;extracellular exosome;catalytic step 2 spliceosome
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription activator activity, RNA polymerase II-specific;single-stranded DNA binding;RNA binding;protein binding;protein domain specific binding;identical protein binding;cadherin binding