CSTF2

Chr X

cleavage stimulation factor subunit 2

Also known as: CSTF64, CstF-64, XLID113

NCBI Gene: 1478 ENSG00000101811 UniProt: P33240

The protein is a component of the cleavage stimulation factor complex that binds GU-rich elements in pre-mRNAs and is required for 3'-end cleavage and polyadenylation of mammalian pre-mRNAs. Mutations cause X-linked intellectual developmental disorder with inheritance following an X-linked recessive pattern. The gene is highly constrained against loss-of-function variants (pLI 0.999, LOEUF 0.133), indicating intolerance to protein loss.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a nuclear protein with an RRM (RNA recognition motif) domain. The protein is a member of the cleavage stimulation factor (CSTF) complex that is involved in the 3' end cleavage and polyadenylation of pre-mRNAs. Specifically, this protein binds GU-rich elements within the 3'-untranslated region of mRNAs. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.13

Clinical Summary— CSTF2

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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.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 32 VUS of 114 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.13LOEUF

pLI 1.000

Z-score 4.39

OE 0.00 (0.00–0.13)

Highly constrained

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

Missense Constraint?

3.43Z-score

OE missense 0.37 (0.31–0.45)

88 obs / 236.4 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.13)

0≤0.351.4

Missense OE?0.37 (0.31–0.45)

0≤0.61.4

Synonymous OE?0.84

0≤1.21.6

LoF obs/exp: 0 / 22.4Missense obs/exp: 88 / 236.4Syn Z: 1.09

This gene — mechanism propensity

0.2199th %ile

GOF

0.2596th %ile

LOF

0.85top 5%

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

LOFprediction above median · LOEUF 0.13

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

114 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

VUS32

Likely Benign4

Benign2

Conflicting1

Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	0	0	1
Likely Pathogenic	0	0	0	0	0
VUS	0	31	1	0	32
Likely Benign	0	3	0	1	4
Benign	0	0	1	1	2
Conflicting	—				1
Total	0	35	2	2	40

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

View in ClinVar →

69 pathogenic / likely-pathogenic (of 87) ClinVar copy-number / structural variants overlap CSTF2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →