CTR9

CTR9 homolog, Paf1/RNA polymerase II complex component, the group of Paf1/RNA polymerase II complex |Tetratricopeptide repeat domain containing

Basic information

Region (hg38): 11:10751018-10801625

Previous symbols: [ "SH2BP1" ]

Links

ENSG00000198730 ∙ NCBI:9646 ∙ OMIM:609366 ∙ HGNC:16850 ∙ Uniprot:Q6PD62 ∙ 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 CTR9 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CTR9 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			2	133	12	147
missense		11	215	8	3	237
nonsense			5			5
start loss						0
frameshift			3			3
inframe indel			2			2
splice donor/acceptor (+/-2bp)			3	1		4
splice region			27	26	1	54
non coding			2	80	33	115
Total	0	11	232	222	48

Variants in CTR9

This is a list of pathogenic ClinVar variants found in the CTR9 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-10751418-G-T			Likely benign (Jan 19, 2024)
11-10751425-T-C			Uncertain significance (Apr 10, 2023)
11-10751430-C-T			Likely benign (Jan 11, 2024)
11-10751435-T-G		CTR9-related disorder	Uncertain significance (Apr 29, 2024)
11-10751442-C-G			Likely benign (Sep 07, 2022)
11-10751455-G-A		CTR9-related neurodevelopmental disorder	Likely pathogenic (Apr 01, 2021)
11-10751456-A-G		Inborn genetic diseases	Likely pathogenic (Feb 23, 2024)
11-10751457-G-A			Uncertain significance (Jun 19, 2022)
11-10751462-G-T			Uncertain significance (May 10, 2021)
11-10751463-T-C			Uncertain significance (Jul 18, 2023)
11-10751463-T-G			Uncertain significance (Apr 16, 2021)
11-10751466-C-A			Likely benign (Nov 02, 2023)
11-10751469-G-T			Likely benign (Jan 08, 2024)
11-10751502-G-A			Benign (Jan 10, 2019)
11-10752445-C-T			Benign (Apr 09, 2019)
11-10752577-G-A			Likely benign (Feb 28, 2019)
11-10752658-CT-C			Benign (Apr 06, 2021)
11-10752665-A-AT		CTR9-related disorder	Likely benign (Aug 13, 2021)
11-10752676-T-C		CTR9-related neurodevelopmental disorder	Conflicting classifications of pathogenicity (Mar 22, 2024)
11-10752682-T-A		Inborn genetic diseases	Likely pathogenic (Feb 15, 2024)
11-10752700-C-G		CTR9-related neurodevelopmental disorder • Inborn genetic diseases	Pathogenic/Likely pathogenic (Feb 15, 2024)
11-10752700-C-T			Uncertain significance (Apr 29, 2023)
11-10752701-G-A		CTR9-related disorder	Likely benign (Feb 23, 2023)
11-10752702-G-C		CTR9-related neurodevelopmental disorder	Likely pathogenic (Apr 01, 2021)
11-10752709-A-G		Inborn genetic diseases	Uncertain significance (Jan 24, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CTR9	protein_coding	protein_coding	ENST00000361367	25	28757

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.25e-8	125729	0	16	125745	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.30	337	644	0.523	0.0000351	7736
Missense in Polyphen		51	180.83	0.28203		2066
Synonymous	-0.452	241	232	1.04	0.0000128	2112
Loss of Function	7.18	4	67.8	0.0590	0.00000361	844

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000364	0.000358
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000442	0.0000440
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non- phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both indepentently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Required for mono- and trimethylation on histone H3 'Lys-4' (H3K4me3) and dimethylation on histone H3 'Lys-79' (H3K4me3). Required for Hox gene transcription. Required for the trimethylation of histone H3 'Lys- 4' (H3K4me3) on genes involved in stem cell pluripotency; this function is synergistic with CXXC1 indicative for an involvement of the SET1 complex. Involved in transcriptional regulation of IL6-responsive genes and in JAK-STAT pathway; may regulate DNA- association of STAT3 (By similarity). {ECO:0000250, ECO:0000269|PubMed:16024656, ECO:0000269|PubMed:16307923, ECO:0000269|PubMed:19345177, ECO:0000269|PubMed:19952111, ECO:0000269|PubMed:20178742, ECO:0000269|PubMed:20541477, ECO:0000269|PubMed:21329879}.
• Pathway: Endoderm Differentiation;Gene expression (Transcription);RNA Polymerase II Pre-transcription Events;Post-translational protein modification;Formation of RNA Pol II elongation complex ;Metabolism of proteins;RNA Polymerase II Transcription;RNA Polymerase II Transcription Elongation;Protein ubiquitination;E3 ubiquitin ligases ubiquitinate target proteins (Consensus)

Recessive Scores

• pRec: 0.110

Intolerance Scores

• rvis_EVS: -1.11
• rvis_percentile_EVS: 6.83

Haploinsufficiency Scores

• pHI: 0.402
• hipred: Y
• hipred_score: 0.825
• ghis: 0.660

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.980

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ctr9
• Phenotype: growth/size/body region phenotype; immune system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype

Zebrafish Information Network

• Gene name: ctr9
• Affected structure: cardiac muscle cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;endodermal cell fate commitment;inner cell mass cell differentiation;trophectodermal cell differentiation;blastocyst growth;blastocyst hatching;transcription by RNA polymerase II;transcription elongation from RNA polymerase II promoter;JAK-STAT cascade;histone monoubiquitination;Wnt signaling pathway;protein ubiquitination;stem cell population maintenance;positive regulation of transcription elongation from RNA polymerase II promoter;histone H2B ubiquitination;negative regulation of myeloid cell differentiation;positive regulation of transcription by RNA polymerase II;regulation of histone H3-K4 methylation;positive regulation of histone H3-K4 methylation;interleukin-6-mediated signaling pathway;cellular response to lipopolysaccharide;histone H3-K4 trimethylation;negative regulation of mRNA polyadenylation;regulation of genetic imprinting;positive regulation of histone H3-K79 methylation;positive regulation of histone H2B ubiquitination
• Cellular component: nucleoplasm;Cdc73/Paf1 complex;nuclear speck;transcriptionally active chromatin
• Molecular function: RNA polymerase II complex binding;protein binding;SH2 domain binding