CPSF7

Chr 11

cleavage and polyadenylation specific factor 7

Also known as: CFIm59

NCBI Gene: 79869 ENSG00000149532 UniProt: Q8N684 OMIM: 621247

The 59 kDa subunit of cleavage factor Im (CFIm) functions in pre-mRNA 3'-end cleavage and polyadenylation processing required for mRNA maturation, specifically binding to UGUA elements in 3'-untranslated regions to regulate alternative polyadenylation site choice. Mutations cause autosomal recessive neurodevelopmental disorder with microcephaly, seizures, and developmental delay. This gene is highly constrained against loss-of-function mutations (pLI 0.999, LOEUF 0.199), indicating intolerance to haploinsufficiency in the general population.

OMIM ResearchSummary from RefSeq, UniProt

Cleavage factor Im (CFIm) is one of six factors necessary for correct cleavage and polyadenylation of pre-mRNAs. CFIm is composed of three different subunits of 25, 59, and 68 kDa, and it functions as a heterotetramer, with a dimer of the 25 kDa subunit binding to two of the 59 or 68 kDa subunits. The protein encoded by this gene represents the 59 kDa subunit, which can interact with the splicing factor U2 snRNP Auxiliary Factor (U2AF) 65 to link the splicing and polyadenylation complexes. [provided by RefSeq, Oct 2016]

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

0.20

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.20LOEUF

pLI 0.999

Z-score 4.33

OE 0.04 (0.01–0.20)

Highly constrained

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

Missense Constraint?

2.59Z-score

OE missense 0.59 (0.52–0.67)

187 obs / 316.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.04 (0.01–0.20)

0≤0.351.4

Missense OE?0.59 (0.52–0.67)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 1 / 23.8Missense obs/exp: 187 / 316.6Syn Z: 1.46

Background carrier burden — how many people carry a rare variant somewhere in CPSF7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 190

587 rare PASS variants

Rare truncating (LoF)

1 in 5,300

40 rare PASS variants

Rare synonymous (reference)

1 in 330

252 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CPSF7. 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 230	1 in 6,300
South Asian	~43k	1 in 150	1 in 1,500
Remaining (unassigned)	~30k	1 in 170	≈ 1 in 7,100
European (Finnish)	~27k	1 in 290	≈ 1 in 24,000
Admixed American	~22k	1 in 87	1 in 2,900
African / African American	~21k	1 in 150	≈ 1 in 20,000
East Asian	~20k	1 in 280	≈ 1 in 18,000
Ashkenazi Jewish	~13k	1 in 610	≈ 1 in 5,300
Middle Eastern	~2,884	1 in 190	≈ 1 in 2,400

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): All 8 coding exons well covered in gnomAD exomes and genomes.? see exons ↓