PINX1

Chr 8

PIN2 (TERF1) interacting telomerase inhibitor 1

Also known as: Gno1, LPTL, LPTS, Pxr1

NCBI Gene: 54984 ENSG00000258724 UniProt: Q96BK5 OMIM: 606505

The protein binds microtubules and is essential for faithful chromosome segregation, while also inhibiting telomerase activity and mediating telomere-related protein localization to the nucleolus. Mutations cause autosomal recessive developmental delay with short stature, characteristic facies, and variable intellectual disability. The gene shows extreme intolerance to loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

OMIM ResearchSummary from RefSeq, UniProt

Enables telomerase RNA binding activity and telomerase inhibitor activity. Involved in several processes, including negative regulation of telomere maintenance via telomerase; positive regulation of protein localization to nucleolus; and protein localization to nucleolus. Acts upstream of or within telomere maintenance via telomerase. Located in chromosomal region; nuclear lumen; and spindle. Implicated in hepatocellular carcinoma. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.76

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.76LOEUF

pLI 0.000

Z-score -0.40

OE 1.13 (0.72–1.76)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.59Z-score

OE missense 1.54 (1.40–1.70)

280 obs / 181.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.13 (0.72–1.76)

0≤0.351.4

Missense OE?1.54 (1.40–1.70)

0≤0.61.4

Synonymous OE?1.35

0≤1.21.6

LoF obs/exp: 12 / 10.6Missense obs/exp: 280 / 181.7Syn Z: -2.28

Background carrier burden — how many people carry a rare variant somewhere in PINX1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

850 rare PASS variants

Rare truncating (LoF)

1 in 1,700

89 rare PASS variants

Rare synonymous (reference)

1 in 120

356 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PINX1. 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 120	1 in 2,200
South Asian	~43k	1 in 64	1 in 1,300
Remaining (unassigned)	~30k	1 in 80	1 in 1,700
European (Finnish)	~27k	1 in 330	1 in 1,300
Admixed American	~22k	1 in 80	1 in 790
African / African American	~21k	1 in 58	≈ 1 in 5,600
East Asian	~20k	1 in 94	1 in 2,000
Ashkenazi Jewish	~13k	1 in 380	none seen
Middle Eastern	~2,884	1 in 76	≈ 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.

Exome coverage (gnomAD): 3 of 6 coding exons well covered in gnomAD exomes; exons 4, 5 marginal. Genomes: all 6.? see exons ↓