SCAPER

Chr 15AR

S-phase cyclin A associated protein in the ER

Also known as: IDDRP, MSTP063, ZNF291, Zfp291

NCBI Gene: 49855 ENSG00000140386 UniProt: Q9BY12 OMIM: 611611

SCAPER encodes a CCNA2/CDK2 regulatory protein that maintains CCNA2 in the cytoplasm and is involved in retina development. Biallelic mutations cause autosomal recessive intellectual developmental disorder with retinitis pigmentosa. The gene shows high constraint against loss-of-function variants (LOEUF 0.377), reflecting its essential role in neurodevelopment and retinal function.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Predicted to enable nucleic acid binding activity and zinc ion binding activity. Acts upstream of or within retina development in camera-type eye. Located in nuclear speck. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder and retinitis pigmentosaMIM #618195

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · intellectual developmental disorder and retinitis pigmentosa; IDDRP · AR · ClinGen 2026

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.38

LOEUF

LOF

Mechanism· G2P

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.38LOEUF

pLI 0.009

Z-score 6.03

OE 0.26 (0.18–0.38)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.72Z-score

OE missense 0.72 (0.67–0.77)

522 obs / 728.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.26 (0.18–0.38)

0≤0.351.4

Missense OE?0.72 (0.67–0.77)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 20 / 77.1Missense obs/exp: 522 / 728.7Syn Z: -0.56

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 41

1,561 rare PASS variants

Rare truncating (LoF)

1 in 690

219 rare PASS variants

Rare synonymous (reference)

1 in 78

647 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SCAPER. 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 64	1 in 720
South Asian	~43k	1 in 34	1 in 430
Remaining (unassigned)	~30k	1 in 41	1 in 570
European (Finnish)	~27k	1 in 120	1 in 1,100
Admixed American	~22k	1 in 43	1 in 340
African / African American	~21k	1 in 36	1 in 970
East Asian	~20k	1 in 58	1 in 760
Ashkenazi Jewish	~13k	1 in 130	1 in 520
Middle Eastern	~2,884	1 in 50	≈ 1 in 1,400

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): 22 of 31 coding exons well covered in gnomAD exomes; exons 2, 3, 4, 6, 7 and 4 more marginal. Genomes: all 31.? see exons ↓