CTDSPL

Chr 3

CTD small phosphatase like

Also known as: C3orf8, HYA22, PSR1, RBSP3, SCP3

NCBI Gene: 10217 ENSG00000144677 UniProt: O15194 OMIM: 608592

CTDSPL encodes a phosphatase that dephosphorylates the C-terminal domain of RNA polymerase II and is recruited by REST to silence neuronal genes in non-neuronal cells. The gene shows low constraint to loss-of-function variants (pLI = 0.003, LOEUF = 0.961), and no specific Mendelian diseases have been definitively associated with CTDSPL mutations to date. Further research is needed to establish clear genotype-phenotype correlations for this gene.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable RNA polymerase II CTD heptapeptide repeat phosphatase activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to act upstream of or within negative regulation of G1/S transition of mitotic cell cycle and negative regulation of protein phosphorylation. Located in extracellular exosome. Biomarker of lung non-small cell carcinoma. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.96

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.96LOEUF

pLI 0.003

Z-score 1.67

OE 0.49 (0.27–0.96)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.08Z-score

OE missense 0.54 (0.46–0.65)

89 obs / 164.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.49 (0.27–0.96)

0≤0.351.4

Missense OE?0.54 (0.46–0.65)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 6 / 12.3Missense obs/exp: 89 / 164.1Syn Z: 0.54

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

336 rare PASS variants

Rare truncating (LoF)

1 in 3,100

40 rare PASS variants

Rare synonymous (reference)

1 in 280

150 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CTDSPL. 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 160	1 in 3,200
South Asian	~43k	1 in 110	1 in 1,900
Remaining (unassigned)	~30k	1 in 170	none seen
European (Finnish)	~27k	1 in 540	≈ 1 in 20,000
Admixed American	~22k	1 in 120	1 in 1,300
African / African American	~21k	1 in 180	≈ 1 in 6,300
East Asian	~20k	1 in 120	none seen
Ashkenazi Jewish	~13k	1 in 280	none seen
Middle Eastern	~2,884	1 in 150	≈ 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): 5 of 8 coding exons well covered in gnomAD exomes; exons 1, 3, 5 marginal. Genomes: 7 of 8 (exon 1 below).? see exons ↓