ZPR1

Chr 11AR

ZPR1 zinc finger

Also known as: GKAF, ZNF259

NCBI Gene: 8882 ENSG00000109917 UniProt: O75312 OMIM: 603901

ZPR1 encodes a cytoplasmic signaling protein that regulates cell cycle progression, enhances pre-mRNA splicing through interaction with survival motor neuron protein (SMN1), and promotes neuronal differentiation and axonal growth. Mutations cause autosomal recessive growth restriction with hypoplastic kidneys, alopecia, and distinctive facies. The gene shows very low constraint against loss-of-function variants (pLI near zero), which is consistent with the recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is found in the cytoplasm of quiescent cells but translocates to the nucleolus in proliferating cells. The encoded protein interacts with survival motor neuron protein (SMN1) to enhance pre-mRNA splicing and to induce neuronal differentiation and axonal growth. Defects in this gene or the SMN1 gene can cause spinal muscular atrophy. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Growth restriction, hypoplastic kidneys, alopecia, and distinctive faciesMIM #619321

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Growth restriction, hypoplastic kidneys, alopecia, and distinctive facies; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.94

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.94LOEUF

pLI 0.000

Z-score 1.81

OE 0.62 (0.43–0.94)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.73Z-score

OE missense 0.87 (0.78–0.97)

216 obs / 248.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.62 (0.43–0.94)

0≤0.351.4

Missense OE?0.87 (0.78–0.97)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 17 / 27.2Missense obs/exp: 216 / 248.2Syn Z: 0.76

Background carrier burden — how many people carry a rare variant somewhere in ZPR1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 90

566 rare PASS variants

Rare truncating (LoF)

1 in 1,600

84 rare PASS variants

Rare synonymous (reference)

1 in 360

212 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZPR1. 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 100	1 in 1,700
South Asian	~43k	1 in 140	1 in 1,100
Remaining (unassigned)	~30k	1 in 100	1 in 1,700
European (Finnish)	~27k	1 in 230	≈ 1 in 8,900
Admixed American	~22k	1 in 110	1 in 2,200
African / African American	~21k	1 in 51	1 in 1,900
East Asian	~20k	1 in 100	1 in 830
Ashkenazi Jewish	~13k	1 in 870	none seen
Middle Eastern	~2,884	1 in 96	≈ 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): 12 of 14 coding exons well covered in gnomAD exomes; exons 1, 13 marginal. Genomes: all 14.? see exons ↓