CRTAP

Chr 3

cartilage associated protein

Also known as: CASP, LEPREL3, OI7, P3H5

NCBI Gene: 10491 ENSG00000170275 UniProt: O75718

CRTAP encodes a protein necessary for efficient 3-hydroxylation of fibrillar collagen prolyl residues, serving as a scaffolding protein in collagen processing. Mutations cause osteogenesis imperfecta type VII, a connective tissue disorder characterized by bone fragility and low bone mass. This condition follows autosomal recessive inheritance.

ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is similar to the chicken and mouse CRTAP genes. The encoded protein is a scaffolding protein that may influence the activity of at least one member of the cytohesin/ARNO family in response to specific cellular stimuli. Defects in this gene are associated with osteogenesis imperfecta, a connective tissue disorder characterized by bone fragility and low bone mass. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtOsteogenesis imperfecta 7

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.86

LOEUF

GOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.86LOEUF

pLI 0.001

Z-score 2.00

OE 0.48 (0.28–0.86)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

-0.44Z-score

OE missense 1.09 (0.97–1.21)

225 obs / 207.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.48 (0.28–0.86)

0≤0.351.4

Missense OE?1.09 (0.97–1.21)

0≤0.61.4

Synonymous OE?1.22

0≤1.21.6

LoF obs/exp: 8 / 16.8Missense obs/exp: 225 / 207.2Syn Z: -1.62

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

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

646 rare PASS variants

Rare truncating (LoF)

1 in 1,100

83 rare PASS variants

Rare synonymous (reference)

1 in 220

261 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CRTAP. 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 1,200
South Asian	~43k	1 in 73	1 in 380
Remaining (unassigned)	~30k	1 in 82	1 in 1,300
European (Finnish)	~27k	1 in 180	1 in 2,900
Admixed American	~22k	1 in 100	1 in 540
African / African American	~21k	1 in 50	1 in 1,200
East Asian	~20k	1 in 78	1 in 2,200
Ashkenazi Jewish	~13k	1 in 160	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 110	≈ 1 in 1,200

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): 6 of 7 coding exons well covered in gnomAD exomes; exon 6 marginal. Genomes: all 7.? see exons ↓