TUT1

Chr 11

terminal uridylyl transferase 1, U6 snRNA-specific

Also known as: PAPD2, RBM21, STARPAP, TENT1, TUTase, URLC6

NCBI Gene: 64852 ENSG00000149016 UniProt: Q9H6E5

This protein functions as a poly(A) polymerase that adds nucleotides to the 3' end of specific mRNAs and also acts as a terminal uridylyltransferase for U6 snRNA, playing essential roles in mRNA processing and gene expression control. Mutations cause autosomal recessive intellectual disability with onset in early childhood. The gene shows strong constraint against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

ResearchSummary from RefSeq, UniProt

This gene encodes a nucleotidyl transferase that functions as both a terminal uridylyltransferase and a nuclear poly(A) polymerase. The encoded enzyme specifically adds and removes nucleotides from the 3' end of small nuclear RNAs and select mRNAs and may function in controlling gene expression and cell proliferation.[provided by RefSeq, Apr 2009]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.83

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.83LOEUF

pLI 0.000

Z-score 2.41

OE 0.58 (0.42–0.83)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.42Z-score

OE missense 0.95 (0.88–1.02)

504 obs / 531.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.58 (0.42–0.83)

0≤0.351.4

Missense OE?0.95 (0.88–1.02)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 23 / 39.3Missense obs/exp: 504 / 531.4Syn Z: -0.61

Background carrier burden — how many people carry a rare variant somewhere in TUT1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 53

1,228 rare PASS variants

Rare truncating (LoF)

1 in 970

203 rare PASS variants

Rare synonymous (reference)

1 in 110

536 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TUT1. 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 82	1 in 1,100
South Asian	~43k	1 in 43	1 in 680
Remaining (unassigned)	~30k	1 in 42	1 in 1,200
European (Finnish)	~27k	1 in 380	1 in 660
Admixed American	~22k	1 in 56	1 in 500
African / African American	~21k	1 in 45	1 in 360
East Asian	~20k	1 in 46	1 in 1,400
Ashkenazi Jewish	~13k	1 in 430	1 in 1,200
Middle Eastern	~2,884	1 in 44	≈ 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.