TENT4A

Chr 5

terminal nucleotidyltransferase 4A

Also known as: LAK-1, LAK1, PAPD7, POLK, POLS, TRF4, TRF4-1, TRF41

NCBI Gene: 11044 ENSG00000112941 UniProt: Q5XG87 OMIM: 605198

The protein is a terminal nucleotidyltransferase that modifies RNA 3' poly(A) tails to stabilize mRNAs and functions in post-transcriptional quality control mechanisms. Mutations cause autosomal recessive intellectual disability with microcephaly and seizures, typically presenting in infancy. TENT4A is highly constrained against loss-of-function variants, indicating that haploinsufficiency is not tolerated in the general population.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a DNA polymerase that is likely involved in DNA repair. In addition, the encoded protein may be required for sister chromatid adhesion. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Jan 2010]

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

0.19

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.19LOEUF

pLI 0.999

Z-score 4.50

OE 0.04 (0.01–0.19)

Highly constrained

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

Missense Constraint?

2.31Z-score

OE missense 0.64 (0.58–0.72)

216 obs / 335.0 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.04 (0.01–0.19)

0≤0.351.4

Missense OE?0.64 (0.58–0.72)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 1 / 25.6Missense obs/exp: 216 / 335.0Syn Z: -0.02

Background carrier burden — how many people carry a rare variant somewhere in TENT4A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 59

914 rare PASS variants

Rare truncating (LoF)

1 in 640

48 rare PASS variants

Rare synonymous (reference)

1 in 72

498 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TENT4A. 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 88	1 in 730
South Asian	~43k	1 in 81	1 in 3,400
Remaining (unassigned)	~30k	1 in 55	1 in 480
European (Finnish)	~27k	1 in 160	1 in 670
Admixed American	~22k	1 in 60	≈ 1 in 11,000
African / African American	~21k	1 in 53	1 in 960
East Asian	~20k	1 in 100	1 in 550
Ashkenazi Jewish	~13k	1 in 130	1 in 410
Middle Eastern	~2,884	1 in 80	≈ 1 in 2,800

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): 12 of 13 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 13.? see exons ↓