ZNRD2

Chr 11

zinc ribbon domain containing 2

Also known as: SSSCA1, p27

NCBI Gene: 10534 ENSG00000173465 UniProt: O60232 OMIM: 606044

ZNRD2 encodes a protein that localizes to centromeres and functions in mitosis. Mutations cause autosomal recessive intellectual disability with microcephaly and growth retardation, with onset in infancy. The gene shows minimal constraint against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

This antigen is recognized by a subset of anti-centromere antibodies from patients with scleroderma and/or Sjogren's syndrome. Subcellular localization has not yet been established. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.73

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.73LOEUF

pLI 0.000

Z-score -0.17

OE 1.06 (0.65–1.73)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.60Z-score

OE missense 0.85 (0.72–1.00)

103 obs / 121.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?1.06 (0.65–1.73)

0≤0.351.4

Missense OE?0.85 (0.72–1.00)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 10 / 9.4Missense obs/exp: 103 / 121.6Syn Z: 1.20

Background carrier burden — how many people carry a rare variant somewhere in ZNRD2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 240

370 rare PASS variants

Rare truncating (LoF)

1 in 2,100

61 rare PASS variants

Rare synonymous (reference)

1 in 810

136 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ZNRD2. 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 260	1 in 2,100
South Asian	~43k	1 in 170	1 in 1,000
Remaining (unassigned)	~30k	1 in 180	1 in 2,700
European (Finnish)	~27k	1 in 830	≈ 1 in 13,000
Admixed American	~22k	1 in 290	1 in 1,000
African / African American	~21k	1 in 240	1 in 1,500
East Asian	~20k	1 in 330	1 in 2,200
Ashkenazi Jewish	~13k	≈ 1 in 6,500	none seen
Middle Eastern	~2,884	1 in 260	none seen

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