CTR9

Chr 11

CTR9 component of Paf1/RNA polymerase II complex

Also known as: SH2BP1, TSBP, p150, p150TSP

NCBI Gene: 9646ENSG00000198730UniProt: Q6PD62

The protein encoded by this gene is a component of the PAF1 complex, which associates with RNA polymerase II and functions in transcriptional regulation and elongation. This complex also plays a role in the modification of histones. [provided by RefSeq, Oct 2016]

569
ClinVar variants
25
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— CTR9
🧬
Gene-Disease Validity (ClinGen)
CTR9-related neurodevelopmental disorder · ADModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
25 Pathogenic / Likely Pathogenic· 287 VUS of 569 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.14LOEUF
pLI 1.000
Z-score 7.18
OE 0.06 (0.03–0.14)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
4.30Z-score
OE missense 0.52 (0.48–0.57)
337 obs / 644.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.06 (0.03–0.14)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.52 (0.48–0.57)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.04
0≤1.21.6
LoF obs/exp: 4 / 67.8Missense obs/exp: 337 / 644.2Syn Z: -0.45

ClinVar Variant Classifications

569 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic14
VUS287
Likely Benign207
Benign43
Conflicting7
11
Pathogenic
14
Likely Pathogenic
287
VUS
207
Likely Benign
43
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
10
0
11
Likely Pathogenic
0
14
0
0
14
VUS
8
250
26
3
287
Likely Benign
0
7
97
103
207
Benign
0
3
34
6
43
Conflicting
—7
Total9274167112569

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CTR9 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

CTR9-related neurodevelopmental disorder

moderate
ADDominant NegativeAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variant

CTR9-related Wilms tumour

moderate
ADLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Cancer
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
📖
GeneReview available — CTR9
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Inherited blood cancer predisposition through altered transcription elongation.
Zhao J et al.·Cell
2024
Large-scale discovery of novel neurodevelopmental disorder-related genes through a unified analysis of single-nucleotide and copy number variants.
Hamanaka K et al.·Genome Med
2022
Novel CTR9 germline pathogenic splice site variant in siblings with Wilms tumor from Tanzania.
Iman A et al.·Eur J Med Genet
2024
Heterozygous variants in CTR9, which encodes a major component of the PAF1 complex, are associated with a neurodevelopmental disorder.
Meuwissen M et al.·Genet Med
2022
Recent advances in Wilms' tumor predisposition.
Maciaszek JL et al.·Hum Mol Genet
2020Review
Drosophila CG2469 Encodes a Homolog of Human CTR9 and Is Essential for Development.
Chaturvedi D et al.·G3 (Bethesda)
2016
Distinct pathways for genetic and epigenetic predisposition in familial and bilateral Wilms tumor.
Wegert J et al.·Genome Med
2025
Identification of a novel CTR9 germline mutation in a family with Wilms tumor.
Martins AG et al.·Eur J Med Genet
2018Case report
Risk prediction of pulmonary tuberculosis using genetic and conventional risk factors in adult Korean population.
Hong EP et al.·PLoS One
2017
Genomic Insights into Idiopathic Granulomatous Mastitis through Whole-Exome Sequencing: A Case Report of Eight Patients.
Ong SS et al.·Int J Mol Sci
2024Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools