CABP4

Chr 11AR

calcium binding protein 4

NCBI Gene: 57010ENSG00000175544UniProt: P57796

Involved in normal synaptic function through regulation of Ca(2+) influx and neurotransmitter release in photoreceptor synaptic terminals and in auditory transmission. Modulator of CACNA1D and CACNA1F, suppressing the calcium-dependent inactivation and shifting the activation range to more hyperpolarized voltages (By similarity)

Primary Disease Associations & Inheritance

Cone-rod synaptic disorder, congenital nonprogressiveMIM #610427
AR
425
ClinVar variants
42
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CABP4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
42 Pathogenic / Likely Pathogenic· 219 VUS of 425 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.
1.54LOEUF
pLI 0.000
Z-score -0.02
OE 1.00 (0.67–1.54)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.52Z-score
OE missense 1.11 (0.99–1.24)
208 obs / 188.0 exp
Tolerant

Tolerant to missense variation

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.1.00 (0.67–1.54)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.11 (0.99–1.24)
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.1.03
0≤1.21.6
LoF obs/exp: 15 / 14.9Missense obs/exp: 208 / 188.0Syn Z: -0.19

ClinVar Variant Classifications

425 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic13
VUS219
Likely Benign103
Benign31
Conflicting29
29
Pathogenic
13
Likely Pathogenic
219
VUS
103
Likely Benign
31
Benign
29
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
1
16
0
29
Likely Pathogenic
6
1
6
0
13
VUS
3
146
66
4
219
Likely Benign
0
10
31
62
103
Benign
0
4
23
4
31
Conflicting
—29
Total2116214270424

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

View in ClinVar →

Protein Context — Lollipop Plot

CABP4 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CABP4-related cone-rod synaptic disorder, congenital nonprogressive

definitive
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cone-rod synaptic disorder, congenital nonprogressive

MIM #610427

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical characterisation of the CABP4-related retinal phenotype.
Khan AO et al.·Br J Ophthalmol
2013
Essential role of Ca2+-binding protein 4, a Cav1.4 channel regulator, in photoreceptor synaptic function.
Haeseleer F et al.·Nat Neurosci
2004
Clinical Characteristics of Patients With Less Common Causes of Leber Congenital Amaurosis/Early-Onset Severe Retinal Dystrophy.
Balbirsingh V et al.·Am J Ophthalmol
2025Cohort
Genetic and Clinical Profile of Retinopathies Due to Disease-Causing Variants in Leber Congenital Amaurosis (LCA)-Associated Genes in a Large German Cohort.
Zobor D et al.·Int J Mol Sci
2023Cohort
Congenital Stationary Night Blindness: Structure, Function and Genotype-Phenotype Correlations in a Cohort of 122 Patients.
Katta M et al.·Ophthalmol Retina
2024Cohort
Novel splice variants implicated in inherited retinal dystrophies in two Moroccan families.
El Khair K et al.·Mol Biol Rep
2025
Identification of a novel CABP4 frameshift variant and a secondary USH2A missense variant in congenital cone-rod synaptic disorder.
Mousawi Z et al.·Ophthalmic Genet
2026
A novel homozygous nonsense variant in CABP4 causing stationary cone/rod synaptic dysfunction.
Hauser BM et al.·Ophthalmic Genet
2024Case report
Clinical Spectrum and Molecular Characteristics of Inherited Ocular Diseases in a Cohort of Pediatric Patients With Infantile Nystagmus Syndrome.
Gong X et al.·Invest Ophthalmol Vis Sci
2025Cohort
Mutation screening of the LRIT3, CABP4, and GPR179 genes in Chinese patients with Schubert-Bornschein congenital stationary night blindness.
Dan H et al.·Ophthalmic Genet
2017Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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