CRTAP

protein-coding

cartilage associated protein, the group of Prolyl 3-hydroxylase family

Gene summary

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]

MANE transcript

NM_006371.5

Inheritance

AD, AR

ClinVar variants

P:72U:195B:188

Top phenotype

Osteogenesis imperfecta, type VII

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr3:33,114,014-33,147,773

External References & Databases

Ensembl (ENSG00000170275)

Transcript & Mutation Effects

hg38 • Region Span ~33.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

osteogenesis imperfecta type 2SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008147

Submitter: Orphanet

osteogenesis imperfecta type 7STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012536

Submitter: Ambry Genetics

osteogenesis imperfecta type 3SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0009804

Submitter: Orphanet

osteogenesis imperfecta type 7STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0012536

Submitter: Labcorp Genetics (formerly Invitae)

osteogenesis imperfecta type 4SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0008148

Submitter: Orphanet

Clinical Genomic Database (CGD)

Osteogenesis imperfecta, type VIIAR

Manifestation: Musculoskeletal; Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 12110406; 17192541; 17055431; 19862557; 21955071; 21964860; 23613367; 25604815

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CRTAP variants in ClinVar

6 Conditions Cataloged

Osteogenesis imperfecta type 7Total: 491

Inborn genetic diseasesTotal: 68

not providedTotal: 65

not specifiedTotal: 33

CRTAP-related disorderTotal: 27

Osteogenesis imperfectaTotal: 21

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006371.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	175 clinvar	3 clinvar	179
missense	1 clinvar	2 clinvar	190 clinvar	8 clinvar	2 clinvar	203
nonsense	17 clinvar	7 clinvar				24
start loss	1 clinvar	1 clinvar				2
frameshift	24 clinvar	11 clinvar	2 clinvar			37
splice donor/acceptor (+/-2bp)	2 clinvar	6 clinvar	2 clinvar			10
Total	45	27	195	183	5	455

Highest pathogenic variant AF is 0.00016575921

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006371.5	RefSeq	NP_006362.1	7	MANE Select
ENST00000320954.11	Ensembl	ENSP00000323696.5	7	MANE Select
NM_001393363.1	RefSeq	NP_001380292.1	6	Standard
NM_001393364.1	RefSeq	NP_001380293.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Collagen biosynthesis and modifying enzymes
Collagen formation
Extracellular matrix organization

Biological Process

spermatogenesis
peptidyl-proline hydroxylation to 3-hydroxy-L-proline
protein stabilization
chaperone-mediated protein folding
negative regulation of post-translational protein modification

Molecular Function

protein binding

Cellular Component

extracellular space
endoplasmic reticulum
endoplasmic reticulum lumen
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000320954
Coding exons: 7
Length: 33795
Individuals with no LoFs: 125715
Homozygous LoFs: 0
Heterozygous LoFs: 33
Defined: 125748
p: 0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.441	225	207	1.09	0.0000105	2597
Missense (PolyPhen)		46	44.02	1.045		560
Synonymous	-1.62	104	85.0	1.22	0.00000474	733
Loss of Function	2.00	8	16.8	0.475	8.11e-7	209

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00049	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00023	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.00014	0.00013	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Necessary for efficient 3-hydroxylation of fibrillar collagen prolyl residues. {ECO:0000269|PubMed:17055431}.;

Recessive Scores

pRec: 0.110

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.806

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium