CTR9

Chr 11

CTR9 component of Paf1/RNA polymerase II complex

Also known as: SH2BP1, TSBP, p150, p150TSP

CTR9 encodes a component of the PAF1 complex that regulates RNA polymerase II transcription and histone modifications, particularly affecting Hox gene expression and stem cell development. Mutations cause autosomal dominant developmental disorders with features including intellectual disability, growth deficiency, and multiple congenital anomalies. This gene is highly constrained against loss-of-function variants (pLI >0.99), indicating that heterozygous mutations are likely pathogenic.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 0.14
Clinical SummaryCTR9
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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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.14LOEUF
pLI 1.000
Z-score 7.18
OE 0.06 (0.030.14)
Highly constrained

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

Missense Constraint
4.30Z-score
OE missense 0.52 (0.480.57)
337 obs / 644.2 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.06 (0.030.14)
00.351.4
Missense OE0.52 (0.480.57)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 4 / 67.8Missense obs/exp: 337 / 644.2Syn Z: -0.45
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateCTR9-related neurodevelopmental disorderDNAD
moderateCTR9-related Wilms tumourLOFAD
DN
0.3594th %ile
GOF
0.4184th %ile
LOF
0.68top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.14

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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