CCNH

cyclin H, the group of Cyclins|CDK activating kinase complex

Basic information

Region (hg38): 5:87318416-87413029

Links

ENSG00000134480 ∙ NCBI:902 ∙ OMIM:601953 ∙ HGNC:1594 ∙ Uniprot:P51946 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• Capillary malformation-arteriovenous malformation syndrome (80 variants)
• not provided (38 variants)
• Capillary malformation-arteriovenous malformation 1 (18 variants)
• RASA1-related disorder (5 variants)
• Cardiovascular phenotype (5 variants)
• not specified (4 variants)
• Basal cell carcinoma, susceptibility to, 1;Capillary malformation-arteriovenous malformation 1 (3 variants)
• Vascular malformation (2 variants)
• Capillary infantile hemangioma (1 variants)
• Hereditary hemorrhagic telangiectasia (1 variants)
• Inborn genetic diseases (1 variants)
• Capillary malformation-arteriovenous malformation 1;Basal cell carcinoma, susceptibility to, 1 (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CCNH 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		1
missense			15		3	18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region	1			1		2
non coding	122	43	345	392	36	938
Total	122	43	360	393	39

Highest pathogenic variant AF is 0.00000660

Variants in CCNH

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

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

Position	Type	Phenotype	Significance	ClinVar
5-87331265-C-G			Likely benign (Oct 12, 2021)
5-87331278-T-A			Likely benign (Dec 21, 2018)
5-87331321-G-A			Likely benign (Jun 19, 2018)
5-87331329-T-G		Capillary malformation-arteriovenous malformation syndrome	Likely benign (Oct 13, 2023)
5-87331329-TTC-T		Capillary malformation-arteriovenous malformation syndrome	Likely benign (Sep 15, 2022)
5-87331344-C-G		Capillary malformation-arteriovenous malformation syndrome	Likely benign (Dec 08, 2022)
5-87331346-A-C		Capillary malformation-arteriovenous malformation syndrome	Likely pathogenic (Mar 19, 2022)
5-87331351-G-A		Angioosteohypertrophic syndrome	Pathogenic (Jun 06, 2021)
5-87331357-C-A		Capillary malformation-arteriovenous malformation syndrome	Uncertain significance (Nov 01, 2022)
5-87331357-C-T		Cardiovascular phenotype • Capillary malformation-arteriovenous malformation syndrome	Likely benign (Jan 16, 2024)
5-87331366-T-C		Capillary malformation-arteriovenous malformation syndrome • Cardiovascular phenotype	Likely benign (Mar 19, 2023)
5-87331374-C-T		Capillary malformation-arteriovenous malformation syndrome • Capillary malformation-arteriovenous malformation 1	Uncertain significance (Jan 02, 2024)
5-87331375-G-A		Capillary malformation-arteriovenous malformation 1 • Capillary malformation-arteriovenous malformation syndrome	Conflicting classifications of pathogenicity (Aug 09, 2023)
5-87331384-A-AG		RASA1-related disorder	Pathogenic (Dec 01, 2023)
5-87331385-G-A		Capillary malformation-arteriovenous malformation syndrome	Uncertain significance (Mar 14, 2023)
5-87331384-A-AGAAC		Capillary malformation-arteriovenous malformation syndrome	Pathogenic (Jun 07, 2019)
5-87331389-G-A		Capillary malformation-arteriovenous malformation 1	Uncertain significance (-)
5-87331389-GC-G		Capillary malformation-arteriovenous malformation syndrome	Pathogenic (Mar 29, 2023)
5-87331395-G-A		Capillary malformation-arteriovenous malformation syndrome • Cardiovascular phenotype	Uncertain significance (Jan 22, 2024)
5-87331395-G-C		Capillary malformation-arteriovenous malformation syndrome	Uncertain significance (Jun 29, 2023)
5-87331405-G-A		Cardiovascular phenotype	Likely benign (Sep 30, 2020)
5-87331407-A-T		Capillary malformation-arteriovenous malformation syndrome	Uncertain significance (Mar 17, 2023)
5-87331408-G-A		Capillary malformation-arteriovenous malformation syndrome • Cardiovascular phenotype	Likely benign (Oct 26, 2023)
5-87331410-C-T		Capillary malformation-arteriovenous malformation syndrome	Uncertain significance (May 14, 2019)
5-87331414-C-G		Capillary malformation-arteriovenous malformation syndrome	Likely benign (Dec 17, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CCNH	protein_coding	protein_coding	ENST00000256897	9	21526

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000813	0.985	125679	0	65	125744	0.000258

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.102	168	172	0.978	0.00000869	2123
Missense in Polyphen		36	37.336	0.96423		468
Synonymous	-0.427	68	63.7	1.07	0.00000344	582
Loss of Function	2.16	8	17.8	0.448	9.30e-7	236

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00152	0.00151
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000275	0.000264
Middle Eastern	0.000109	0.000109
South Asian	0.000208	0.000196
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulates CDK7, the catalytic subunit of the CDK- activating kinase (CAK) enzymatic complex. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Involved in cell cycle control and in RNA transcription by RNA polymerase II. Its expression and activity are constant throughout the cell cycle. {ECO:0000269|PubMed:10024882, ECO:0000269|PubMed:7533895}.
• Pathway: Nucleotide excision repair - Homo sapiens (human);Cell cycle - Homo sapiens (human);Basal transcription factors - Homo sapiens (human);Cell Cycle;Eukaryotic Transcription Initiation;G1 to S cell cycle control;DNA Repair;Disease;RNA Pol II CTD phosphorylation and interaction with CE during HIV infection;NoRC negatively regulates rRNA expression;Negative epigenetic regulation of rRNA expression;Formation of the HIV-1 Early Elongation Complex;Epigenetic regulation of gene expression;Gene expression (Transcription);sonic hedgehog receptor ptc1 regulates cell cycle;Formation of HIV-1 elongation complex containing HIV-1 Tat;Tat-mediated elongation of the HIV-1 transcript;HIV Transcription Elongation;il-2 receptor beta chain in t cell activation;cyclins and cell cycle regulation;Formation of HIV elongation complex in the absence of HIV Tat;Generic Transcription Pathway;Transcription of the HIV genome;Late Phase of HIV Life Cycle;HIV Life Cycle;HIV Infection;RNA Polymerase II HIV Promoter Escape;RNA Polymerase II Pre-transcription Events;RNA Polymerase II Transcription Initiation;RNA Polymerase II Transcription Initiation And Promoter Clearance;RNA Pol II CTD phosphorylation and interaction with CE;Formation of RNA Pol II elongation complex ;RNA Polymerase I Promoter Clearance;HIV Transcription Initiation;RNA Polymerase II Transcription;Metabolism of RNA;Infectious disease;RNA Polymerase I Transcription Termination;RNA Polymerase I Transcription;Cyclin D associated events in G1;G1 Phase;RNA Polymerase II Transcription Elongation;Cyclin E associated events during G1/S transition ;RNA Polymerase I Transcription Initiation;RNA Polymerase I Promoter Escape;Mitotic G1-G1/S phases;Cyclin A:Cdk2-associated events at S phase entry;RNA Polymerase II Promoter Escape;RNA Polymerase I Chain Elongation;AndrogenReceptor;S Phase;RNA Polymerase II Transcription Pre-Initiation And Promoter Opening;Cyclin A/B1/B2 associated events during G2/M transition;IL-7 signaling;TP53 Regulates Transcription of DNA Repair Genes;G2/M Transition;Mitotic G2-G2/M phases;JAK STAT pathway and regulation;G1/S Transition;EPO signaling;Transcriptional Regulation by TP53;mRNA Capping;Formation of the Early Elongation Complex;RUNX1 regulates transcription of genes involved in differentiation of HSCs;Cell Cycle;Formation of Incision Complex in GG-NER;VEGF;Global Genome Nucleotide Excision Repair (GG-NER);Cell Cycle, Mitotic;Formation of TC-NER Pre-Incision Complex;Transcriptional regulation by RUNX1;Retinoic acid receptors-mediated signaling;Dual incision in TC-NER;Gap-filling DNA repair synthesis and ligation in TC-NER;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair (Consensus)

Recessive Scores

• pRec: 0.133

Intolerance Scores

• loftool: 0.848
• rvis_EVS: 0.11
• rvis_percentile_EVS: 61.73

Haploinsufficiency Scores

• pHI: 0.680
• hipred: Y
• hipred_score: 0.669
• ghis: 0.491

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ccnh

Gene ontology

• Biological process: regulation of cyclin-dependent protein serine/threonine kinase activity;transcription-coupled nucleotide-excision repair;nucleotide-excision repair, preincision complex assembly;regulation of transcription by RNA polymerase II;transcription initiation from RNA polymerase I promoter;termination of RNA polymerase I transcription;transcription by RNA polymerase II;transcription initiation from RNA polymerase II promoter;transcription elongation from RNA polymerase II promoter;7-methylguanosine mRNA capping;protein phosphorylation;cell cycle;positive regulation of transcription by RNA polymerase II;protein stabilization
• Cellular component: nucleus;nucleoplasm;transcription factor TFIIH holo complex;cyclin-dependent protein kinase activating kinase holoenzyme complex;transcription factor TFIIK complex
• Molecular function: protein binding;DNA-dependent ATPase activity;RNA polymerase II CTD heptapeptide repeat kinase activity;cyclin-dependent protein serine/threonine kinase regulator activity