CTDSPL2

Chr 15

CTD small phosphatase like 2

Also known as: HSPC058, HSPC129, SCP4

NCBI Gene: 51496 ENSG00000137770 UniProt: Q05D32 OMIM: 618739

Enables RNA polymerase II CTD heptapeptide repeat phosphatase activity. Involved in positive regulation of gluconeogenesis. Located in nucleus. [provided by Alliance of Genome Resources, Jun 2026]

OMIM Research

Enables RNA polymerase II CTD heptapeptide repeat phosphatase activity. Involved in positive regulation of gluconeogenesis. Located in nucleus. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.17

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.17LOEUF

pLI 1.000

Z-score 4.67

OE 0.04 (0.01–0.17)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.20Z-score

OE missense 0.61 (0.53–0.69)

149 obs / 246.1 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.04 (0.01–0.17)

0≤0.351.4

Missense OE?0.61 (0.53–0.69)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 1 / 27.3Missense obs/exp: 149 / 246.1Syn Z: 0.82

Background carrier burden — how many people carry a rare variant somewhere in CTDSPL2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 260

391 rare PASS variants

Rare truncating (LoF)

1 in 20,000

19 rare PASS variants

Rare synonymous (reference)

1 in 290

200 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CTDSPL2. 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 320	1 in 34,000
South Asian	~43k	1 in 230	1 in 4,500
Remaining (unassigned)	~30k	1 in 320	≈ 1 in 15,000
European (Finnish)	~27k	1 in 1,000	none seen
Admixed American	~22k	1 in 350	≈ 1 in 9,700
African / African American	~21k	1 in 270	≈ 1 in 7,900
East Asian	~20k	1 in 420	≈ 1 in 19,000
Ashkenazi Jewish	~13k	1 in 720	≈ 1 in 3,200
Middle Eastern	~2,884	1 in 230	none seen

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 12 coding exons well covered in gnomAD exomes; exons 4, 7, 8, 9, 10 and 2 more marginal. Genomes: all 12.? see exons ↓