CTTNBP2

Chr 7

cortactin binding protein 2

Also known as: C7orf8, CORTBP2, Orf4

NCBI Gene: 83992ENSG00000077063UniProt: Q8WZ74

This gene encodes a protein with six ankyrin repeats and several proline-rich regions. A similar gene in rat interacts with a central regulator of the actin cytoskeleton. [provided by RefSeq, Jul 2008]

189
ClinVar variants
24
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CTTNBP2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 133 VUS of 189 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.60LOEUF
pLI 0.000
Z-score 4.23
OE 0.44 (0.33–0.60)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.65Z-score
OE missense 0.94 (0.89–0.99)
833 obs / 887.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.44 (0.33–0.60)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.89–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 30 / 67.6Missense obs/exp: 833 / 887.6Syn Z: 0.12

ClinVar Variant Classifications

189 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic2
VUS133
Likely Benign23
Benign9
22
Pathogenic
2
Likely Pathogenic
133
VUS
23
Likely Benign
9
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
2
0
2
VUS
2
127
4
0
133
Likely Benign
0
10
3
10
23
Benign
0
5
2
2
9
Total21423312189

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CTTNBP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
STRIPAK complexes: structure, biological function, and involvement in human diseases.
Hwang J et al.·Int J Biochem Cell Biol
2014Review
Cortactin-binding protein 2 modulates the mobility of cortactin and regulates dendritic spine formation and maintenance.
Chen YK et al.·J Neurosci
2012
Fine mapping for Weaver syndrome in Brown Swiss cattle and the identification of 41 concordant mutations across NRCAM, PNPLA8 and CTTNBP2.
McClure M et al.·PLoS One
2013
Identification of a novel large deletion and other copy number variations in the CFTR gene in patients with Cystic Fibrosis from a multiethnic population.
Martins RDS et al.·Mol Genet Genomic Med
2019Cohort
Novel RAF Fusions in Pediatric Low-Grade Gliomas Demonstrate MAPK Pathway Activation.
Lind KT et al.·J Neuropathol Exp Neurol
2021Case report
Multi-omics analyses of choroid plexus carcinoma cell lines reveal potential targetable pathways and alterations.
Hesham D et al.·J Neurooncol
2024
A de novo interstitial deletion of 7q31.2q31.31 identified in a girl with developmental delay and hearing loss.
Zhao J et al.·Am J Med Genet C Semin Med Genet
2016Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Sex-biased zinc responses modulate ribosomal protein expression, protein synthesis and social defects in Cttnbp2 mutant mice.
Fang YL et al.·Neurobiol Dis
2025
Sex bias in social deficits, neural circuits and nutrient demand in Cttnbp2 autism models.
Yen TL et al.·Brain
2023🔓 Open AccessFunctional
Dendritic Spine in Autism Genetics: Whole-Exome Sequencing Identifying De Novo Variant of CTTNBP2 in a Quad Family Affected by Autism Spectrum Disorder.
Xie Y et al.·Children (Basel)
2022🔓 Open Access
Phase separation and zinc-induced transition modulate synaptic distribution and association of autism-linked CTTNBP2 and SHANK3.
Shih PY et al.·Nat Commun
2022🔓 Open Access
Autism-linked mutations of CTTNBP2 reduce social interaction and impair dendritic spine formation via diverse mechanisms.
Shih PY et al.·Acta Neuropathol Commun
2020🔓 Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools