SSU72

Chr 1

SSU72 homolog, RNA polymerase II CTD phosphatase

Also known as: HSPC182, PNAS-120

NCBI Gene: 29101 ENSG00000160075 UniProt: Q9NP77 OMIM: 617680

SSU72 encodes a protein phosphatase that dephosphorylates the C-terminal domain of RNA polymerase II and plays a role in mRNA processing and polyadenylation. Mutations cause autosomal recessive neurodevelopmental disorder with early-onset seizures, developmental delay, and intellectual disability. The gene shows evidence of constraint against loss-of-function variants (LOEUF 0.51), suggesting intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, UniProt

Enables RNA polymerase II CTD heptapeptide repeat phosphatase activity. Involved in co-transcriptional mRNA 3'-end processing, cleavage and polyadenylation pathway. Predicted to be located in cytoplasm and nucleus. Predicted to be part of mRNA cleavage and polyadenylation specificity factor complex. [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

0.51

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.51LOEUF

pLI 0.779

Z-score 2.53

OE 0.11 (0.04–0.51)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.56Z-score

OE missense 0.32 (0.24–0.42)

36 obs / 112.3 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.11 (0.04–0.51)

0≤0.351.4

Missense OE?0.32 (0.24–0.42)

0≤0.61.4

Synonymous OE?1.08

0≤1.21.6

LoF obs/exp: 1 / 9.3Missense obs/exp: 36 / 112.3Syn Z: -0.45

Background carrier burden — how many people carry a rare variant somewhere in SSU72?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 340

283 rare PASS variants

Rare truncating (LoF)

1 in 4,100

41 rare PASS variants

Rare synonymous (reference)

1 in 170

164 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SSU72. 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 460	1 in 4,300
South Asian	~43k	1 in 170	1 in 3,900
Remaining (unassigned)	~30k	1 in 290	1 in 460
European (Finnish)	~27k	1 in 780	1 in 4,400
Admixed American	~22k	1 in 200	1 in 4,400
African / African American	~21k	1 in 370	1 in 2,700
East Asian	~20k	1 in 280	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 2,100	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 400	≈ 1 in 580

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 5 coding exons well covered in gnomAD exomes and genomes.? see exons ↓