CTR9

Chr 11

CTR9 component of Paf1/RNA polymerase II complex

Also known as: SH2BP1, TSBP, p150, p150TSP

NCBI Gene: 9646 ENSG00000198730 UniProt: Q6PD62 OMIM: 609366

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.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · CTR9-related neurodevelopmental disorder · AD · ClinGen 2025

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.14

LOEUF· LoF intol.

Multiple*

Mechanism· G2P

📖

GeneReview available — CTR9

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.06 (0.03–0.14)

0≤0.351.4

Missense OE?0.52 (0.48–0.57)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

LoF obs/exp: 4 / 67.8Missense obs/exp: 337 / 644.2Syn Z: -0.45

Background carrier burden — how many people carry a rare variant somewhere in CTR9?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 88

992 rare PASS variants

Rare truncating (LoF)

1 in 880

87 rare PASS variants

Rare synonymous (reference)

1 in 74

524 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CTR9. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 110	1 in 3,700
South Asian	~43k	1 in 84	1 in 7,000
Remaining (unassigned)	~30k	1 in 87	1 in 500
European (Finnish)	~27k	1 in 170	≈ 1 in 27,000
Admixed American	~22k	1 in 92	1 in 980
African / African American	~21k	1 in 95	1 in 2,500
East Asian	~20k	1 in 99	1 in 2,600
Ashkenazi Jewish	~13k	1 in 390	1 in 1,500
Middle Eastern	~2,884	1 in 76	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 24 of 25 coding exons well covered in gnomAD exomes; exon 7 marginal. Genomes: all 25.? see exons ↓